Protein restriction for diabetic renal disease

Background Diabetic renal disease (diabetic nephropathy) is a leading cause of end‐stage renal failure. Once the process has started, it cannot be reversed by glycaemic control, but progression might be slowed by control of blood pressure and protein restriction. Objectives To assess the effects of dietary protein restriction on the progression of diabetic nephropathy in patients with diabetes. Search methods We searched The Cochrane Library, MEDLINE, EMBASE, ISI Proceedings, Science Citation Index Expanded and bibliographies of included studies. Selection criteria Randomised controlled trials (RCTs) and before and after studies of the effects of a modified or restricted protein diet on diabetic renal function in people with type 1 or type 2 diabetes following diet for at least four months were considered. Data collection and analysis Two reviewers performed data extraction and evaluation of quality independently. Pooling of results was done by means of random‐effects model. Main results Twelve studies were included, nine RCTs and three before and after studies. Only one study explored all‐cause mortality and end‐stage renal disease (ESRD) as endpoints. The relative risk (RR) of ESRD or death was 0.23 (95% confidence interval (CI) 0.07 to 0.72) for patients assigned to a low protein diet (LPD). Pooling of the seven RCTs in patients with type 1 diabetes resulted in a non‐significant reduction in the decline of glomerular filtration rate (GFR) of 0.1 ml/min/month (95% CI ‐0.1 to 0.3) in the LPD group. For type 2 diabetes, one trial showed a small insignificant improvement in the rate of decline of GFR in the protein‐restricted group and a second found a similar decline in both the intervention and control groups. Actual protein intake in the intervention groups ranged from 0.7 to 1.1 g/kg/day. One study noted malnutrition in the LPD group. We found no data on the effects of LPDs on health‐related quality of life and costs. Authors' conclusions The results show that reducing protein intake appears to slightly slow progression to renal failure but not statistically significantly so. However, questions concerning the level of protein intake and compliance remain. Further longer‐term research on large representative groups of patients with both type 1 and type 2 diabetes mellitus is necessary. Because of the variability amongst patients, there might perhaps be a six month therapeutic trial of protein restriction in all individuals, with continuation only in those who responded best. Trials are required of different types of protein

ERPs reveal the temporal dynamics of auditory word recognition in specific language impairment.

We used event-related potentials (ERPs) to compare auditory word recognition in children with specific language impairment (SLI group; N=14) to a group of typically developing children (TD group; N=14). Subjects were presented with pictures of items and heard auditory words that either matched or mismatched the pictures. Mismatches overlapped expected words in word-onset (cohort mismatches; see: DOLL, hear: dog), rhyme (CONE -bone), or were unrelated (SHELL -mug). In match trials, the SLI group showed a different pattern of N100 responses to auditory stimuli compared to the TD group, indicative of early auditory processing differences in SLI. However, the phonological mapping negativity (PMN) response to mismatching items was comparable across groups, suggesting that just like TD children, children with SLI are capable of establishing phonological expectations and detecting violations of these expectations in an online fashion. Perhaps most importantly, we observed a lack of attenuation of the N400 for rhyming words in the SLI group, which suggests that either these children were not as sensitive to rhyme similarity as their typically developing peers, or did not suppress lexical alternatives to the same extent. These findings help shed light on the underlying deficits responsible for SLI

Darcin: a male pheromone that stimulates female memory and sexual attraction to an individual male's odour

<p>Abstract</p> <p>Background</p> <p>Among invertebrates, specific pheromones elicit inherent (fixed) behavioural responses to coordinate social behaviours such as sexual recognition and attraction. By contrast, the much more complex social odours of mammals provide a broad range of information about the individual owner and stimulate individual-specific responses that are modulated by learning. How do mammals use such odours to coordinate important social interactions such as sexual attraction while allowing for individual-specific choice? We hypothesized that male mouse urine contains a specific pheromonal component that invokes inherent sexual attraction to the scent and which also stimulates female memory and conditions sexual attraction to the airborne odours of an individual scent owner associated with this pheromone.</p> <p>Results</p> <p>Using wild-stock house mice to ensure natural responses that generalize across individual genomes, we identify a single atypical male-specific major urinary protein (MUP) of mass 18893Da that invokes a female's inherent sexual attraction to male compared to female urinary scent. Attraction to this protein pheromone, which we named darcin, was as strong as the attraction to intact male urine. Importantly, contact with darcin also stimulated a strong learned attraction to the associated airborne urinary odour of an individual male, such that, subsequently, females were attracted to the airborne scent of that specific individual but not to that of other males.</p> <p>Conclusions</p> <p>This involatile protein is a mammalian male sex pheromone that stimulates a flexible response to individual-specific odours through associative learning and memory, allowing female sexual attraction to be inherent but selective towards particular males. This 'darcin effect' offers a new system to investigate the neural basis of individual-specific memories in the brain and give new insights into the regulation of behaviour in complex social mammals.</p> <p>See associated Commentary <url>http://www.biomedcentral.com/1741-7007/8/71</url></p

Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice

This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic 'carrier' status to assess future reproductive risks. The study also examined participants' level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child's future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.221

Study of the 7Be(p,γ)8B^7Be(p,\gamma)^8B and 7Li(n,γ)8Li^7Li(n,\gamma)^8Li capture reactions using the shell model embedded in the continuum

We apply the realistic shell model which includes the coupling between many-particle (quasi-)bound states and the continuum of one-particle scattering states to the spectroscopy of mirror nuclei: $^8$B and $^8$Li, as well as to the description of low energy cross sections (the astrophysical S factors) in the capture reactions:$^7Be(p,\gamma)^8B$ and $^7Li(n,\gamma)^8Li$.Comment: 36 pages, 10 figure

Is routine hospital episode data sufficient for identifying individuals with chronic kidney disease?

Internationally, investment in the availability of routine health care data for improving health, health surveillance and health care is increasing. We assessed the validity of hospital episode data for identifying individuals with chronic kidney disease compared to biochemistry data in a large population-based cohort, the Grampian Laboratory Outcomes, Morbidity and Mortality Study-II (n = 70,435). Grampian Laboratory Outcomes, Morbidity and Mortality Study-II links hospital episode data to biochemistry data for all adults in a health region with impaired kidney function and random samples of individuals with normal and unmeasured kidney function in 2003. We compared identification of individuals with chronic kidney disease by hospital episode data (based on International Classification of Diseases-10 codes) to the reference standard of biochemistry data (at least two estimated glomerular filtration rates 97%). Using routine health care data from multiple sources offers the best opportunity to identify individuals with chronic kidney disease

Shifting attention in viewer- and object-based reference frames after unilateral brain injury

The aims of the present study were to investigate the respective roles that object- and viewer-based reference frames play in reorienting visual attention, and to assess their influence after unilateral brain injury. To do so, we studied 16 right hemisphere injured (RHI) and 13 left hemisphere injured (LHI) patients. We used a cueing design that manipulates the location of cues and targets relative to a display comprised of two rectangles (i.e., objects). Unlike previous studies with patients, we presented all cues at midline rather than in the left or right visual fields. Thus, in the critical conditions in which targets were presented laterally, reorienting of attention was always from a midline cue. Performance was measured for lateralized target detection as a function of viewer-based (contra- and ipsilesional sides) and object-based (requiring reorienting within or between objects) reference frames. As expected, contralesional detection was slower than ipsilesional detection for the patients. More importantly, objects influenced target detection differently in the contralesional and ipsilesional fields. Contralesionally, reorienting to a target within the cued object took longer than reorienting to a target in the same location but in the uncued object. This finding is consistent with object-based neglect. Ipsilesionally, the means were in the opposite direction. Furthermore, no significant difference was found in object-based influences between the patient groups (RHI vs. LHI). These findings are discussed in the context of reference frames used in reorienting attention for target detection

Daisyworld: a review

Daisyworld is a simple planetary model designed to show the long-term effects of coupling between life and its environment. Its original form was introduced by James Lovelock as a defense against criticism that his Gaia theory of the Earth as a self-regulating homeostatic system requires teleological control rather than being an emergent property. The central premise, that living organisms can have major effects on the climate system, is no longer controversial. The Daisyworld model has attracted considerable interest from the scientific community and has now established itself as a model independent of, but still related to, the Gaia theory. Used widely as both a teaching tool and as a basis for more complex studies of feedback systems, it has also become an important paradigm for the understanding of the role of biotic components when modeling the Earth system. This paper collects the accumulated knowledge from the study of Daisyworld and provides the reader with a concise account of its important properties. We emphasize the increasing amount of exact analytic work on Daisyworld and are able to bring together and summarize these results from different systems for the first time. We conclude by suggesting what a more general model of life-environment interaction should be based on

Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV.IMPORTANCESevere acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and 2003, and infected patients developed an atypical pneumonia, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) leading to pulmonary fibrosis and death. We identified sets of differentially expressed genes that contribute to ALI and ARDS using lethal and sublethal SARS-CoV infection models. Mathematical prioritization of our gene sets identified the urokinase and extracellular matrix remodeling pathways as the most enriched pathways. By infecting Serpine1-knockout mice, we showed that the urokinase pathway had a significant effect on both lung pathology and overall SARS-CoV pathogenesis. These results demonstrate the effective use of unbiased modeling techniques for identification of high-priority host targets that regulate disease outcomes. Similar transcriptional signatures were noted in 1918 and 2009 H1N1 influenza virus-infected mice, suggesting a common, potentially treatable mechanism in development of virus-induced ALI

Approaches to ascertaining comorbidity information: validation of routine hospital episode data with clinician-based case note review

Background In clinical practice, research, and increasingly health surveillance, planning and costing, there is a need for high quality information to determine comorbidity information about patients. Electronic, routinely collected healthcare data is capturing increasing amounts of clinical information as part of routine care. The aim of this study was to assess the validity of routine hospital administrative data to determine comorbidity, as compared with clinician-based case note review, in a large cohort of patients with chronic kidney disease. Methods A validation study using record linkage. Routine hospital administrative data were compared with clinician-based case note review comorbidity data in a cohort of 3219 patients with chronic kidney disease. To assess agreement, we calculated prevalence, kappa statistic, sensitivity, specificity, positive predictive value and negative predictive value. Subgroup analyses were also performed. Results Median age at index date was 76.3 years, 44% were male, 67% had stage 3 chronic kidney disease and 31% had at least three comorbidities. For most comorbidities, we found a higher prevalence recorded from case notes compared with administrative data. The best agreement was found for cerebrovascular disease (κ = 0.80) ischaemic heart disease (κ = 0.63) and diabetes (κ = 0.65). Hypertension, peripheral vascular disease and dementia showed only fair agreement (κ = 0.28, 0.39, 0.38 respectively) and smoking status was found to be poorly recorded in administrative data. The patterns of prevalence across subgroups were as expected and for most comorbidities, agreement between case note and administrative data was similar. Agreement was less, however, in older ages and for those with three or more comorbidities for some conditions. Conclusions This study demonstrates that hospital administrative comorbidity data compared moderately well with case note review data for cerebrovascular disease, ischaemic heart disease and diabetes, however there was significant under-recording of some other comorbid conditions, and particularly common risk factors