Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies

Background The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. Aim To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. Methods Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1–2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. Results The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of −53.0 μmol/L (P \u3c 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. Conclusions Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function

Review of rehabilitation and habilitation strategies for children and young people with homonymous visual field loss caused by cerebral vision impairment

Partial and homonymous visual field loss (HVFL) is a common consequence of post-chiasmatic injury to the primary visual pathway or injury to the primary visual cortex. Different approaches to rehabilitation have been reported for older adults with HVFL and there is evidence to support the use of compensatory training over other proposed therapies. We reviewed the literature to investigate the current state of the art of rehabilitation and habilitation strategies for children and young people with HVFL, and whether there is enough evidence to support the use of these strategies in the paediatric population. We have provided an overview of the existing literature on children and young people with HVFL, a brief overview of rehabilitation strategies for adults with HVFL, and evidence on whether these different interventions have been applied with children and young people effectively. We found that there have been very few studies to investigate these strategies with children and young people, and the quality of evidence is currently low. New research is required to evaluate which strategies are effective for children and young people with HVFL and whether new strategies need to be developed

Rabl's model of the interphase chromosome arrangement tested in Chinise hamster cells by premature chromosome condensation and laser-UV-microbeam experiments

In 1885 Carl Rabl published his theory on the internal structure of the interphase nucleus. We have tested two predictions of this theory in fibroblasts grown in vitro from a female Chinese hamster, namely (1) the Rabl-orientation of interphase chromosomes and (2) the stability of the chromosome arrangement established in telophase throughout the subsequent interphase. Tests were carried out by premature chromosome condensation (PCC) and laser-UV-microirradiation of the interphase nucleus. Rabl-orientation of chromosomes was observed in G1 PCCs and G2 PCCs. The cell nucleus was microirradiated in G1 at one or two sites and pulse-labelled with 3H-thymidine for 2h. Cells were processed for autoradiography either immediately thereafter or after an additional growth period of 10 to 60h. Autoradiographs show unscheduled DNA synthesis (UDS) in the microirradiated nuclear part(s). The distribution of labelled chromatin was evaluated in autoradiographs from 1035 cells after microirradiation of a single nuclear site and from 253 cells after microirradiation of two sites. After 30 to 60h postincubation the labelled regions still appeared coherent although the average size of the labelled nuclear area fr increased from 14.2% (0h) to 26.5% (60h). The relative distance dr, i.e. the distance between two microirradiated sites divided by the diameter of the whole nucleus, showed a slight decrease with increasing incubation time. Nine metaphase figures were evaluated for UDS-label after microirradiation of the nuclear edge in G1. An average of 4.3 chromosomes per cell were labelled. Several chromosomes showed joint labelling of both distal chromosome arms including the telomeres, while the centromeric region was free from label. This label pattern is interpreted as the result of a V-shaped orientation of these particular chromosomes in the interphase nucleus with their telomeric regions close to each other at the nuclear edge. Our data support the tested predictions of the Rabl-model. Small time-dependent changes of the nuclear space occupied by single chromosomes and of their relative positions in the interphase nucleus seem possible, while the territorial organization of interphase chromosomes and their arrangement in general is maintained during interphase. The present limitations of the methods used for this study are discussed

Research in psychobiology

Research in brain-behavior relationships, perception and learning, and comparative and developmental psycholog

GMFilter and SXTestPlate: software tools for improving the SNPlex™ genotyping system

<p>Abstract</p> <p>Background</p> <p>Genotyping of single-nucleotide polymorphisms (SNPs) is a fundamental technology in modern genetics. The SNPlex™ mid-throughput genotyping system (Applied Biosystems, Foster City, CA, USA) enables the multiplexed genotyping of up to 48 SNPs simultaneously in a single DNA sample. The high level of automation and the large amount of data produced in a high-throughput laboratory require advanced software tools for quality control and workflow management.</p> <p>Results</p> <p>We have developed two programs, which address two main aspects of quality control in a SNPlex™ genotyping environment: GMFilter improves the analysis of SNPlex™ plates by removing wells with a low overall signal intensity. It enables scientists to automatically process the raw data in a standardized way before analyzing a plate with the proprietary GeneMapper software from Applied Biosystems. SXTestPlate examines the genotype concordance of a SNPlex™ test plate, which was typed with a control SNP set. This program allows for regular quality control checks of a SNPlex™ genotyping platform. It is compatible to other genotyping methods as well.</p> <p>Conclusion</p> <p>GMFilter and SXTestPlate provide a valuable tool set for laboratories engaged in genotyping based on the SNPlex™ system. The programs enhance the analysis of SNPlex™ plates with the GeneMapper software and enable scientists to evaluate the performance of their genotyping platform.</p

Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured

Executive function and intelligence in the resolution of temporary syntactic ambiguity: An individual differences investigation

In the current study, we examined the role of intelligence and executive functions in the resolution of temporary syntactic ambiguity using an individual differences approach. Data were collected from 174 adolescents and adults who completed a battery of cognitive tests as well as a sentence comprehension task. The critical items for the comprehension task consisted of object/subject garden paths (e.g. While Anna dressed the baby that was small and cute played in the crib.), and participants answered a comprehension question (e.g. Did Anna dress the baby?) following each one. Previous studies have shown that garden-path misinterpretations tend to persist into final interpretations. Results showed that both intelligence and processing speed interacted with ambiguity. Individuals with higher intelligence and faster processing were more likely to answer the comprehension questions correctly, and specifically, following ambiguous as opposed to unambiguous sentences. Inhibition produced a marginal effect, but the variance in inhibition was largely shared with intelligence. Conclusions focus on the role of individual differences in cognitive ability and their impact on syntactic ambiguity resolution