Emerging Agents for the Management of Nephrotic Syndrome: Progress to Date

Nephrotic Syndrome is a rare condition associated with high morbidity in the 20–40 % of children and adolescents who fail to respond to standard immunosuppressive therapies. Novel non-immunologic mechanisms of widely used immunosuppressive therapies, as well as emerging anti-inflammatory drugs, and anti-fibrotics may play a crucial role in the treatment of patients with refractory disease. This article will review some of these treatments and their various stages of investigation

An organizational impression management perspective on the formation of corporate reputations

Researchers have only recently turned their attention to the study of corporate reputation. As is characteristic of many early areas of management inquiry, the field is decidedly multidisciplinary and disconnected. This article selectively reviews reputation research conducted mainly during the past decade. A framework is proposed that views reputation from the perspective of organizational impression management. Corporations are viewed as social actors, intent on enhancing their respectability and impressiveness in the eyes of constituents

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Ação do napsilato de propoxifeno durante a prenhez da rata albina (Rattus norvegicus albinus, Rodentia, Mammalia): ensaio biológico

Utilizamos 50 ratas prenhes que foram divididas em cinco grupos de dez. Todas as ratas receberam diariamente, por gavagem 1 ml de solucao, desde o zero ate o 20º dia de prenhez. O grupo I foi considerado controle, recebeu agua destilada. As ratas do grupo II, assim como os grupos restantes receberam solucao de acacia a 5% em solucao aquosa, associado ou nao ao napsilato de propoxifeno. As ratas do grupo III receberam 5 mg/kg de peso de napsilato de propoxifeno. O quarto grupo 15 mg/kg por dia e o quinto grupo 45 mg/kg por dia de napsilato de propoxifeno. Os pesos maternos foram considerados no inicio e ao 7º, 14ºe 20º dia da prenhez. No 20º dia, as matrizes foram sacrificadas. Nossos resultados mostraram que a solucao de acacia e o napsilato de propoxifeno em altas dosagens interferiu no ganho de peso materno, embora estas diferencas nao tenham sido significantes. Com relacao ao peso individual dos fetos, das ninhadas e das placentas, observou-se maior ganho de peso no grupo controle quando comparado ao grupo que recebeu 45 mg/kg de peso de napsilato de propoxifeno. Quanto as reabsorcoes, numero de fetos, numero de implantacoes e o numero de placentas nossos resultados que as doses de napsilato de propoxifeno administradas nao alteraram essas variaveisBV UNIFESP: Teses e dissertaçõe

Surface-exposed epitopes on the major outer-membrane protein of Chlamydia trachomatis defined with peptide antisera

The surface exposure of computer-predicted, linear B-cell epitopes on the major outer-membrane protein (MOMP) of Chlamydia trachomatis serovar B was assessed using antibodies raised against synthetic peptides in conjunction with immunogold transmission electron microscopy. Several of the chosen peptides elicited antibodies which reacted with both denatured and native MOMP. The majority of the exposed epitopes were found within the variable segments of MOMP. For each of the epitopes identified, the extent of their surface accessibility varied both among individual organisms and different developmental forms. Evidence for two distinct subspecies-specific epitopes within VS4 is presented

Imaging brain activity in conscious monkeys following oral MDMA (¿Ecstasy¿).

NoRecreational use of 3,4-methylenedioxymethamphetamine (MDMA;¿ecstasy¿) poses worldwide potential health problems. Clinical studies show that repeated exposure to low oral doses of MDMA has toxic effects on the brain, altering cognitive and psychosocial behavior. Functional magnetic resonance imaging in conscious marmoset monkeys was used to evaluate the sensitivity of the brain to an oral dose of MDMA (1 mg/kg). Following MDMA administration, the midbrain raphe nuclei and substantia nigra, major sources of serotonin and dopamine, were activated as were the hippocampus, hypothalamus and amygdala. The corticostriatal circuit of dorsal thalamus, sensorimotor cortex and basal ganglia showed a robust, coherent activation pattern. Two key reward areas, the nucleus accumbens and prefrontal cortex, and most other cortical regions showed little activation. The visual cortex, however, showed intense activation without applied visual stimuli. These data identify brain areas and functional circuits sensitive to a recreational dose of MDMA, some of which may be vulnerable to long-term intermittent exposure to this drug

The major outer-membrane proteins of Chlamydia trachomatis serovars A and B: intra-serovar amino acid changes do not alter specificities of serovar- and C subspecies-reactive antibody-binding domains

The major outer-membrane protein (MOMP) of Chlamydia trachomatis is a promising candidate antigen for chlamydial vaccine development. We have sequenced the MOMP genes for a serovar A and a serovar B isolate and have compared these new sequences with those already reported. Intra-serovar changes in the inferred amino acid sequences of the surface-exposed variable segments known to be responsible for binding of neutralizing antibody were observed. Nevertheless, epitope mapping with solid-phase peptides showed that these intra-serovar changes did not affect the binding of serovar- and subspecies-specific, potentially protective antibodies. Variable segment 1 of C. trachomatis serovar A contained two adjacent antibody-binding sites, one of which was C-subspecies specific while the other was serovar A specific. Therefore the subspecies binding site for C-complex organisms is in variable segment 1, whilst that for B-complex organisms is in variable segment 4. This work shows that MOMP sequences are relatively stable within the serovar categorization for isolates taken decades apart from different continents. Within a given serovar, however, limited interchange of functionally related amino acids may occur without impairing the binding of serovar-specific antibody

Analysis of James Ross Island volcanic complex and sedimentary basin based on high-resolution aeromagnetic data

High-resolution aeromagnetic surveys provide a geophysical tool to help image the subsurface structure of volcanoes and their tectonic framework. Here we interpret high-resolution aeromagnetic data and models for James Ross archipelago and surrounding regions to provide a new perspective on Neogene magmatism emplaced along the eastern margin of the Antarctic Peninsula. Based on the analysis and modelling of magnetic anomalies we were able to image the subglacial extent of Miocene to Recent alkaline rocks of the James Ross Island Volcanic Group and map tectonic structures that appear to have exerted important controls on Neogene magmatism. High-amplitude linear anomalies detected over Mount Haddington stratovolcano were modelled as caused by subvertical feeder bodies extending to a depth of at least 3 km. These feeder bodies may have been emplaced along a N–S oriented volcano-tectonic rift zone. We also identified several effusive subglacial centres and imaged two concentric magnetic arcs, which we related to Neogene volcanic and subvolcanic lineaments, likely controlled by Mid-Cretaceous strike-slip fault belts and associated deformation zones. The regional magnetic quiet zone that encompasses James Ross Island is caused by the thick sedimentary infill of the Larsen Basin, and a low-amplitude magnetic high within the basin is inferred to reflect a basement push-up structure associated with strike-slip faulting along the eastern edge of the Antarctic Peninsula. In the offshore regions magnetic anomalies southwest of Tabarin Peninsula and west of Vega Island may reflect recent volcanic structures that have yet to emerge from the sea-floor