- Pro: The rationale for dietary therapy for patients with advanced chronic kidney disease. [Journal Article]
- NDNephrol Dial Transplant 2018 Feb 19
- Dietary treatment offers many benefits to patients with advanced chronic kidney disease (CKD) who are approaching the need for renal replacement therapy. A large number of these benefits are independ...
Dietary treatment offers many benefits to patients with advanced chronic kidney disease (CKD) who are approaching the need for renal replacement therapy. A large number of these benefits are independent of whether diets slow the rate of progression of CKD. These diets are low in protein and many minerals, and provide adequate energy for the CKD patient. The diets can reduce accumulation of potentially toxic metabolic products derived from protein and amino acid degradation, maintain a healthier balance of body water, sodium, potassium, phosphorus, calcium and other minerals, and prevent or improve protein-energy wasting. Such diets may enable patients to safely delay the onset of chronic dialysis therapy or kidney transplantation. Dietary therapy may also augment the effectiveness of infrequent or incremental dialysis by maintaining healthier metabolic and clinical status and may enable some end-stage renal disease patients to avoid the need for temporary placement of hemodialysis catheters while their arterial venous fistulae or grafts mature. The anxiety that many advanced CKD patients commonly experience with regard to starting dialysis may incentivize them to accept and adhere to dietary therapy.
- Awareness of the New Kidney Allocation System among United States Dialysis Providers with Low Waitlisting. [Journal Article]
- AJAm J Nephrol 2018 Feb 22; 47(2):115-119
- It is unknown whether dialysis facility staff are aware of the new kidney allocation system implemented in December 2014, which changed how deceased donor kidneys are allocated and waiting time is ca...
It is unknown whether dialysis facility staff are aware of the new kidney allocation system implemented in December 2014, which changed how deceased donor kidneys are allocated and waiting time is calculated. U.S. dialysis facilities with low annual waitlisting (<15.2%) were surveyed as part of a large randomized study. Among 653 facilities, 57.9% of staff were aware of the policy change, with medical directors (84.4%) being more aware than social workers (73.3%), facility administrators (53.1%), nurse managers (46.4%), and other staff (43.8%). Targeted education among dialysis facilities with low waitlisting may help extend the reach of the new policy.
- An Ovine Model for Studying the Pathophysiology of Septic Acute Kidney Injury. [Journal Article]
- MMMethods Mol Biol 2018; 1717:207-218
- The development of acute kidney injury (AKI) is both a significant and independent prognostic factor of mortality in patients with sepsis, but its pathophysiology remains unclear. Herein, we describe...
The development of acute kidney injury (AKI) is both a significant and independent prognostic factor of mortality in patients with sepsis, but its pathophysiology remains unclear. Herein, we describe an ovine model of sepsis evoked by the administration of live Escherichia coli in which there is hypotension, peripheral vasodilatation with a large increase in cardiac output; a similar hyperdynamic state to that commonly reported in humans. Interestingly, in this sheep model of sepsis, despite an increase in global kidney blood flow, there is a progressive reduction in renal function. Although renal hyperperfusion develops, renal tissue hypoxia due to redistribution of intrarenal blood flow may contribute to the pathogenesis of septic AKI. We have, therefore, developed a novel methodology to chronically implant combination probes to monitor intrarenal tissue perfusion and oxygen tension during the development of septic AKI in conscious sheep with hyperdynamic sepsis.
- InForm software: a semi-automated research tool to identify presumptive human hepatic progenitor cells, and other histological features of pathological significance. [Journal Article]
- SRSci Rep 2018 Feb 21; 8(1):3418
- Hepatic progenitor cells (HPCs) play an important regenerative role in acute and chronic liver pathologies. Liver disease research often necessitates the grading of disease severity, and pathologists...
Hepatic progenitor cells (HPCs) play an important regenerative role in acute and chronic liver pathologies. Liver disease research often necessitates the grading of disease severity, and pathologists' reports are the current gold-standard for assessment. However, it is often impractical to recruit pathologists in large cohort studies. In this study we utilise PerkinElmer's "InForm" software package to semi-automate the scoring of patient liver biopsies, and compare outputs to a pathologist's assessment. We examined a cohort of eleven acute hepatitis samples and three non-alcoholic fatty liver disease (NAFLD) samples, stained with HPC markers (GCTM-5 and Pan Cytokeratin), an inflammatory marker (CD45), Sirius Red to detect collagen and haematoxylin/eosin for general histology. InForm was configured to identify presumptive HPCs, CD45+veinflammatory cells, areas of necrosis, fat and collagen deposition (p < 0.0001). Hepatitis samples were then evaluated both by a pathologist using the Ishak-Knodell scoring system, and by InForm through customised algorithms. Necroinflammation as evaluated by a pathologist, correlated with InForm outputs (r2 = 0.8192, p < 0.05). This study demonstrates that the InForm software package provides a useful tool for liver disease research, allowing rapid, and objective quantification of the presumptive HPCs and identifies histological features that assist with assessing liver disease severity, and potentially can facilitate diagnosis.
- Is there relationship between epicardial fat and cardiovascular parameters in incident kidney transplant patients? A post-hoc analysis. [Journal Article]
- PlosPLoS One 2018; 13(2):e0191009
- CONCLUSIONS: The impact of EF gain on ventricular mass after KTX could not be definitely confirmed. Further prospective studies in a large sample of KTX patients should be considered to address a possible causal relationship between EF gain and cardiac hypertrophy in this population.
- Extreme disorder in an ultrahigh-affinity protein complex. [Journal Article]
- NatNature 2018 Feb 21
- Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise comp...
Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.
- Blood pressure variability increases with advancing chronic kidney disease stage: a cross-sectional analysis of 16 546 hypertensive patients. [Journal Article]
- JHJ Hypertens 2018 Feb 20
- CONCLUSIONS: An increase in short-term SBP-variability was present with advancing CKD stages in a large cohort. This increased SBP-variability may be involved in the sharp elevation of cardiovascular risk with worsening renal function.
- High status of mercury and selenium in false killer whales (Pseudorca crassidens, Owen 1846) stranded on Southern South America: A possible toxicological concern? [Journal Article]
- CChemosphere 2018 Feb 10; 199:637-646
- The study was carried out to determine Hg and Se concentrations in false killer whales stranded on the Estrecho de Magallanes, Chile, South America. Tissue samples of five mature specimens were analy...
The study was carried out to determine Hg and Se concentrations in false killer whales stranded on the Estrecho de Magallanes, Chile, South America. Tissue samples of five mature specimens were analyzed (two females and three males). Mean Hg concentration in liver 1068 (234) μg g-1dry weight (DW) (standard deviation in parenthesis) was markedly higher than those in kidney 272 (152) μg g-1DW, lung 423 (325) μg g-1DW, spleen 725 (696) μg g-1DW, muscle 118 (94) μg g-1DW and testicle 18.0 (2.8) μg g-1DW. Mean Se concentration in liver, 398 (75) μg g-1DW, was higher than those in kidney 162 (69) μg g-1DW, lung 128 (84) μg g-1DW, spleen 268 (245) μg g-1DW, muscle 47 (38) μg g-1DW and testicle 25.4 (2.1) μg g-1DW. Positive correlations were found between Hg and Se molar concentrations in muscle, lung, spleen and kidney. Molar ratio of Se/Hg in liver, lung and muscle were <1, but those in kidney and testicle were markedly >1 suggesting a Se protection against Hg toxicity. In all the examined specimens Hg values exceeded the toxic thresholds defined for hepatic damage in marine mammals, with Se/Hg molar ratios below 1 implying limited protective action of Se. Generally, our results showed that individuals are carrying a significant burden, reflecting a high exposure to this toxic metal. This constitutes the first report on Hg and Se levels for a large subantarctic odontocete in South America region, providing insights into their contamination status and with information to the understanding of possible impacts on wild populations.
- ATP-binding cassette subfamily A, member 4 intronic variants c.4773+3A>G and c.5461-10T>C cause Stargardt disease due to defective splicing. [Journal Article]
- AOActa Ophthalmol 2018 Feb 20
- CONCLUSIONS: Two intronic variants c.4773+3A>G and c.5461-10T>C, both predicted to affect splicing, are indeed disease-causing mutations due to skipping of exons 33, 34, 39 and 40 of ABCA4 gene. The experimental proof that ABCA4 mutations in STGD patients affect protein function is crucial for their inclusion to future clinical trials; therefore, functional testing of all ABCA4 intronic variants associated with Stargardt disease by minigene technology is desirable.
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- Long-term results of intestinal transplantation in children: survival after 10 years, intestinal function, quality of life. [Journal Article]
- COCurr Opin Organ Transplant 2018 Feb 15
- CONCLUSIONS: For children more than 10 years out from ITx, growth and weight gain are sustained; oral aversion and dependence on supplemental tube feeds remain prevalent issues. Most recipients are successfully managed with frequent outpatient visits and multiple daily medications. Post-transplant lymphoproliferative disorder and chronic kidney disease are long-term concerns. Though many children require special education, most are high functioning and report good health-related quality of life.