Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

Natural variation in life history and aging phenotypes is associated with mitochondrial DNA deletion frequency in Caenorhabditis briggsae

<p>Abstract</p> <p>Background</p> <p>Mutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial dysfunction in aging processes has been the lack of model systems with relevant, naturally occurring mitochondrial genetic variation. Toward the goal of developing such a model system, we studied natural variation in life history, metabolic, and aging phenotypes as it relates to levels of a naturally-occurring heteroplasmic mitochondrial <it>ND5 </it>deletion recently discovered to segregate among wild populations of the soil nematode, <it>Caenorhabditis briggsae</it>. The normal product of <it>ND5 </it>is a central component of the mitochondrial electron transport chain and integral to cellular energy metabolism.</p> <p>Results</p> <p>We quantified significant variation among <it>C. briggsae </it>isolates for all phenotypes measured, only some of which was statistically associated with isolate-specific <it>ND5 </it>deletion frequency. We found that fecundity-related traits and pharyngeal pumping rate were strongly inversely related to <it>ND5 </it>deletion level and that <it>C. briggsae </it>isolates with high <it>ND5 </it>deletion levels experienced a tradeoff between early fecundity and lifespan. Conversely, oxidative stress resistance was only weakly associated with <it>ND5 </it>deletion level while ATP content was unrelated to deletion level. Finally, mean levels of reactive oxygen species measured <it>in vivo </it>showed a significant non-linear relationship with <it>ND5 </it>deletion level, a pattern that may be driven by among-isolate variation in antioxidant or other compensatory mechanisms.</p> <p>Conclusions</p> <p>Our findings suggest that the <it>ND5 </it>deletion may adversely affect fitness and mitochondrial functioning while promoting aging in natural populations, and help to further establish this species as a useful model for explicit tests of hypotheses in aging biology and mitochondrial genetics.</p

Gender, ethnicity, health behaviour & self-rated health in Singapore

10.1186/1471-2458-7-184BMC Public Health718

Identification of ejaculated proteins in the house mouse (Mus domesticus) via isotopic labeling

<p>Abstract</p> <p>Background</p> <p>Seminal fluid plays an important role in successful fertilization, but knowledge of the full suite of proteins transferred from males to females during copulation is incomplete. The list of ejaculated proteins remains particularly scant in one of the best-studied mammalian systems, the house mouse (<it>Mus domesticus</it>), where artificial ejaculation techniques have proven inadequate. Here we investigate an alternative method for identifying ejaculated proteins, by isotopically labeling females with ¹⁵N and then mating them to unlabeled, vasectomized males. Proteins were then isolated from mated females and identified using mass spectrometry. In addition to gaining insights into possible functions and fates of ejaculated proteins, our study serves as proof of concept that isotopic labeling is a powerful means to study reproductive proteins.</p> <p>Results</p> <p>We identified 69 male-derived proteins from the female reproductive tract following copulation. More than a third of all spectra detected mapped to just seven genes known to be structurally important in the formation of the copulatory plug, a hard coagulum that forms shortly after mating. Seminal fluid is significantly enriched for proteins that function in protection from oxidative stress and endopeptidase inhibition. Females, on the other hand, produce endopeptidases in response to mating. The 69 ejaculated proteins evolve significantly more rapidly than other proteins that we previously identified directly from dissection of the male reproductive tract.</p> <p>Conclusion</p> <p>Our study attempts to comprehensively identify the proteins transferred from males to females during mating, expanding the application of isotopic labeling to mammalian reproductive genomics. This technique opens the way to the targeted monitoring of the fate of ejaculated proteins as they incubate in the female reproductive tract.</p

Switching Virally Suppressed, Treatment-Experienced Patients to a Raltegravir-Containing Regimen Does Not Alter Levels of HIV-1 DNA

Background: Current HIV-1 antiretroviral therapy (ART) greatly reduces virus replication but does not significantly affect the viral reservoir. Raltegravir, a recently introduced integrase inhibitor, could, at least theoretically, reduce residual viremia in patients on ART and affect the viral reservoir size. The aim of this study was to assess whether switching therapy in treatment-experienced patients that were virally suppressed to a raltegravir-containing regimen reduces the size of the viral reservoir, and if such treatment leads to a change in levels of HIV 2-LTR circles in this patient group. Methods: 14 ART experienced individuals with a suppressed viral load (,50 HIV-1 RNA copies/mL plasma) at baseline (for at least 2 months) were switched to a raltegravir-containing regimen. Blood samples were taken at baseline and at $2 timepoints up to 4866 weeks. Levels of total HIV-1 DNA and 2-LTR circles in peripheral blood mononuclear cells (PBMCs) were measured using real-time PCR assays. Results: There was no significant change in HIV-1 total DNA levels over the study duration (p = 0.808), median slope 0.24 (conservative nonparametric 95 % CI: 211.78, 26.23). Low levels of 2-LTR circles were detected in 2 patients. One had 16 copies/10 6 PBMCs at baseline and the other had 34 copies/10 6 PBMCs at week 51. Conclusions: The switch to a raltegravir containing regimen was not associated with a significant change in HIV-1 total DNA levels in this cohort. There were no observed changes in the levels of HIV-1 2-LTR circles associated with raltegravi

Project FIT: Rationale, design and baseline characteristics of a school- and community-based intervention to address physical activity and healthy eating among low-income elementary school children

<p>Abstract</p> <p>Background</p> <p>This paper describes Project FIT, a collaboration between the public school system, local health systems, physicians, neighborhood associations, businesses, faith-based leaders, community agencies and university researchers to develop a multi-faceted approach to promote physical activity and healthy eating toward the general goal of preventing and reducing childhood obesity among children in Grand Rapids, MI, USA.</p> <p>Methods/design</p> <p>There are four overall components to Project FIT: school, community, social marketing, and school staff wellness - all that focus on: 1) increasing access to safe and affordable physical activity and nutrition education opportunities in the schools and surrounding neighborhoods; 2) improving the affordability and availability of nutritious food in the neighborhoods surrounding the schools; 3) improving the knowledge, self-efficacy, attitudes and behaviors regarding nutrition and physical activity among school staff, parents and students; 4) impacting the 'culture' of the schools and neighborhoods to incorporate healthful values; and 5) encouraging dialogue among all community partners to leverage existing programs and introduce new ones.</p> <p>Discussion</p> <p>At baseline, there was generally low physical activity (70% do not meet recommendation of 60 minutes per day), excessive screen time (75% do not meet recommendation of < 2 hours per day), and low intake of vegetables and whole grains and high intake of sugar-sweetened beverages, French fries and chips and desserts as well as a high prevalence of overweight and obesity (48.5% including 6% with severe obesity) among low income, primarily Hispanic and African American 3^rd-5^thgrade children (n = 403).</p> <p>Trial registration</p> <p><b>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01385046">NCT01385046</a></b></p

Revised cutoff values of ALT and HBV DNA level can better differentiate HBeAg (-) chronic inactive HBV patients from active carriers

<p>Abstract</p> <p>Background and Aims</p> <p>ELISA is still used as primary test for diagnosis HBV disease. However, ELISA-positive patients were marked as HBV inactive after confirmation with PCR and vice versa. Our aim was to assess the performance of new cut-off value of ALT, HBV DNA load and significance of AST as screening tool for HBeAg (-) chronic active or inactive patients in Pakistani population.</p> <p>Materials and methods</p> <p>In a cross-sectional, cohort study, 567 HBeAg (-) patients followed for one year were selected. Patients with persistent elevated ALT than normal and HBV DNA ≥ 100,000 copies/mL were taken as active chronic. Diagnostic values for ALT, AST and HBV DNA load in HBV HBeAg (-) chronic active and inactive patients compared using receiver operation characteristic (ROC) curves.</p> <p>Results</p> <p>Of 567 HBeAg (-) patients, 228 were classified as chronic inactive and 339 as active. HBV infection was dominant in male. Serum ALT, AST and HBV DNA levels showed significant and high AUROC to differentiate chronic HBeAg (-) inactive patients from active. AUROC for Serum ALT, AST and HBV DNA were observed 0.997, 0.969 and 1.000, respectively. For revised cut off value for ALT (30 IU/L for male and 19 IU/L for female) and HBV DNA load ≥100,000 copies/mL, a PPV of 97%, NPV of 94%, a sensitivity of 98%, and a specificity of 92% was observed to discriminate active carriers from inactive carriers. We also observed 93.5% specificity, 83.1% sensitivity, 82% PPV and 89.5% NPV for AST ≤20 IU/L to differentiate inactive carriers from active ones in our study group.</p> <p>Conclusions</p> <p>Revised cut off value of ALT and NIH derived HBV DNA value can better discriminate between HBeAg (-) chronic active and inactive patients.</p

Molecular evolution of a gene cluster of serine proteases expressed in the Anopheles gambiae female reproductive tract

<p>Abstract</p> <p>Background</p> <p>Genes involved in post-mating processes of multiple mating organisms are known to evolve rapidly due to coevolution driven by sexual conflict among male-female interacting proteins. In the malaria mosquito <it>Anopheles gambiae </it>- a monandrous species in which sexual conflict is expected to be absent or minimal - recent data strongly suggest that proteolytic enzymes specifically expressed in the female lower reproductive tissues are involved in the processing of male products transferred to females during mating. In order to better understand the role of selective forces underlying the evolution of proteins involved in post-mating responses, we analysed a cluster of genes encoding for three serine proteases that are down-regulated after mating, two of which specifically expressed in the atrium and one in the spermatheca of <it>A. gambiae </it>females.</p> <p>Results</p> <p>The analysis of polymorphisms and divergence of these female-expressed proteases in closely related species of the <it>A. gambiae </it>complex revealed a high level of replacement polymorphisms consistent with relaxed evolutionary constraints of duplicated genes, allowing to rapidly fix novel replacements to perform new or more specific functions. Adaptive evolution was detected in several codons of the 3 genes and hints of episodic selection were also found. In addition, the structural modelling of these proteases highlighted some important differences in their substrate specificity, and provided evidence that a number of sites evolving under selective pressures lie relatively close to the catalytic triad and/or on the edge of the specificity pocket, known to be involved in substrate recognition or binding. The observed patterns suggest that these proteases may interact with factors transferred by males during mating (e.g. substrates, inhibitors or pathogens) and that they may have differently evolved in independent <it>A. gambiae </it>lineages.</p> <p>Conclusions</p> <p>Our results - also examined in light of constraints in the application of selection-inference methods to the closely related species of the <it>A. gambiae </it>complex - reveal an unexpectedly intricate evolutionary scenario. Further experimental analyses are needed to investigate the biological functions of these genes in order to better interpret their molecular evolution and to assess whether they represent possible targets for limiting the fertility of <it>Anopheles </it>mosquitoes in malaria vector control strategies.</p