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Background: Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome that predominantly affects women. Its pathophysiology remains unclear but connective tissue disorders (CTD) and other vasculopathies have been observed in many SCAD patients. A genetic component for SCAD is increasingly appreciated, although few genes have been robustly implicated. We sought to clarify the genetic cause of SCAD using targeted and genome-wide methods in a cohort of sporadic cases to identify both common and rare disease-associated variants. Methods: A cohort of 91 unrelated sporadic SCAD cases was investigated for rare, deleterious variants in genes associated with either SCAD or CTD, while new candidate genes were sought using rare variant collapsing analysis and identification of novel loss-of-function variants in genes intolerant to such variation. Finally, 2 SCAD polygenic risk scores were applied to assess the contribution of common variants. Results: We identified 10 cases with at least one rare, likely disease-causing variant in CTD-associated genes, although only one had a CTD phenotype. No genes were significantly associated with SCAD from genome-wide collapsing analysis, however, enrichment for TGF (transforming growth factor)-β signaling pathway genes was found with analysis of 24 genes harboring novel loss-of-function variants. Both polygenic risk scores demonstrated that sporadic SCAD cases have a significantly elevated genetic SCAD risk compared with controls. Conclusions: SCAD shares some genetic overlap with CTD, even in the absence of any major CTD phenotype. Consistent with a complex genetic architecture, SCAD patients also have a higher burden of common variants than controls.

Telomerase is the ribonucleoprotein reverse transcriptase that catalyzes the synthesis of telomeres at the ends of linear chromosomes and contributes to proper telomere-loop (T-loop) formation. Formation of the T-loop, an obligate step before cell division can proceed, requires the generation of a 3′-overhang on the G-rich strand of telomeric DNA via telomerase or C-strand specific nucleases. Here, it is discovered that telomerase activity is critical for efficient cell-cycle progression using transient chemical inhibition by the telomerase inhibitor, imetelstat. Telomerase inhibition changed cell cycle kinetics and increased the proportion of cells in G2-phase, suggesting delayed clearance through this checkpoint. Investigating the possible contribution of unstructured telomere ends to these cell-cycle distribution changes, it was observed that imetelstat treatment induced γH2AX DNA damage foci in a subset of telomerase-positive cells but not telomerase-negative primary human fibroblasts. Chromatin-immunoprecipitation with γH2AX antibodies demonstrated imetelstat treatment-dependent enrichment of this DNA damage marker at telomeres. Notably, the effects of telomerase inhibition on cell cycle profile alterations were abrogated by pharmacological inhibition of the DNA-damage-repair transducer, ATM. Also, imetelstat potentiation of etoposide, a DNA-damaging drug that acts preferentially during S–G2 phases of the cell cycle, depends on functional ATM signaling. Thus, telomerase inhibition delays the removal of ATM-dependent DNA damage signals from telomeres in telomerase-positive cancer cells and interferes with cell cycle progression through G2.Implications: This study demonstrates that telomerase activity directly facilitates the progression of the cell cycle through modulation of transient telomere dysfunction signals. Mol Cancer Res; 16(8); 1215–25. ©2018 AACR.

Supplementary Figure 1. Imetelstat reduces cell number in telomerase positive cell lines in a dose-dependent manner following 7-day incubation. Supplementary Figure 2. Imetelstat inhibits telomerase activity in a dose dependent manner. Supplementary Figure 3. Secondary-antibody alone controls for imetelstat induced DNA damage foci. Supplementary Figure 4. Short-term Imetelstat treatment does not increase cell death. Supplementary Figure 5. KU55933 does not affect telomerase inhibition by imetelstat.

Supplementary Methods, Figure Legends 1-3 from Telomerase Inhibition Potentiates the Effects of Genotoxic Agents in Breast and Colorectal Cancer Cells in a Cell Cycle–Specific Manner

Supplementary Figure 2A from Telomerase Inhibition Potentiates the Effects of Genotoxic Agents in Breast and Colorectal Cancer Cells in a Cell Cycle–Specific Manner

Supplementary Figure 3 from Telomerase Inhibition Potentiates the Effects of Genotoxic Agents in Breast and Colorectal Cancer Cells in a Cell Cycle–Specific Manner

Supplementary Figure 1 from Telomerase Inhibition Potentiates the Effects of Genotoxic Agents in Breast and Colorectal Cancer Cells in a Cell Cycle–Specific Manner

The focus of this study was to isolate, evaluate and characterize endophytic actinobacteria from cocoyam roots collected in the localities around Mount Cameroon for their potential antagonistic activities against Pythium myriotylum (the major pathogen that limits growth and productivity of this crop in Cameroon) and their ability to promote plant growth. A total of 171 actinobacteria were isolated from healthy cocoyams and were screened for their antagonistic activities against P. myriotylum, Phytophthora megakarya, Fusarium oxysporum and Colletotrichum gloeosporioides. Four isolates (PERM1, PERM2, PERM4 and PERM5) were selected based on of their strongest antagonistic activity in vitro against P. myriotylum. These four isolates were subsequently identified using phenotypic and molecular tests, characterized for extracellular hydrolytic enzymes, plant growth-promoting (PGP) traits, and their effects were evaluated on tissue culture-derived cocoyam plantlets. The sequencing of the 16S rRNA genes and alignment with sequences retrieved through the EzTaxon program indicated that PERM2, PERM4 and PERM5 have low similarity percentages with S. samsunensis EU077190 (92.4% sequence similarity), S. roietensis KX394336 (81% sequence similarity), S. flavoviridis AB184842 (91% sequence similarity) respectively. The comparison of some physiological and biochemical properties of PERM2,PERM4 and PERM5 with the most closely related Streptomyces species showed that these strains differ phenotypically. PERM2, PERM4 and PERM5 might represent new species. All selected Streptomyces were able to produce siderophores, indole-3-acetic acid (IAA), aminocyclopropane-1-carboxylate (ACC) deaminase, and solubilized tricalcium phosphate. With 20.30 μg/ml of IAA, the PERM2 isolate significantly increased the length of roots as compared to the positive control. These results suggest the possibility of using endophytic Streptomyces strains, especially isolate PERM2 in the protection of cocoyams against root rot disease and the promotion of root growth.

Background In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. Methods We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR

International audience; No abstract available

Given the success of combination antiretroviral therapy (cART) in treating HIV viremia, drug toxicity remains an area of interest in HIV research. Despite newer integrase strand transfer inhibitors (InSTIs), such as dolutegravir (DTG) and raltegravir (RAL), having excellent clinical tolerance, there is emerging evidence of off-target effects and toxicities. Although limited in number, recent reports have highlighted the vulnerability of mitochondria to these toxicities. The aim of the present study is to quantify changes in cellular and mitochondrial health following exposure to current cART regimens at pharmacological concentrations. A secondary objective is to determine whether any cART-associated toxicities would be modulated by human telomerase reverse transcriptase (hTERT).We longitudinally evaluated markers of cellular (cell count, apoptosis), and mitochondrial health [mitochondrial reactive oxygen species (mtROS), membrane potential (MMP) and mass (mtMass)] by flow cytometry in WI-38 human fibroblast with differing hTERT expression/localization and peripheral blood mononuclear cells. This was done after 9 days of exposure to, and 6 days following the removal of, seven current cART regimens, including three that contained DTG. Mitochondrial morphology was assessed by florescence microscopy and quantified using a recently developed deep learning-based pipeline.Exposure to DTG-containing regimens increased apoptosis, mtROS, mtMass, induced fragmented mitochondrial networks compared with non-DTG-containing regimens, including a RAL-based combination. These effects were unmodulated by telomerase expression. All effects were fully reversible following removal of drug pressure.Taken together, our observations indicate that DTG-containing regimens negatively impact cellular and mitochondrial health and may be more toxic to mitochondria, even among the generally well tolerated InSTI-based cART.

Ideas of reference (IOR) are often implicated in predicting psychosis onset. They have been conceptualized to present on a continuum, from oversensitive psychological reactions to delusional thoughts. It is however unknown to what extent IOR may be triggered by collective environmental stress. We obtained timely data from 9873 individuals to assess IOR in relation to trauma exposure in the 2019–2020 social unrest in Hong Kong. Two levels of IOR are distinguished: attenuated IOR (IOR-A), being the experience of feeling particularly referred to within a group; and exclusive IOR (IOR-E), the experience of feeling exclusively referred to while others are not. Logistic regressions showed that event-based rumination was a shared predictor for IOR-A (OR = 1.07, CI = 1.03–1.10) and IOR-E (OR = 1.09, CI = 1.02–1.17). For IOR-A, three categories of social unrest-related traumatic events (TEs) were significant predictors, including being attacked or having experienced sexual violence (OR = 4.14, CI = 1.93–8.85), being arrested (OR = 4.48, CI = 1.99–10.10), and being verbally abused (OR = 2.66, CI = 1.28–5.53). Being arrested was significant for IOR-E (OR = 3.87, CI = 1.03–14.52), though not when rumination was included. Education level also significantly predicted IOR-E (OR = 0.72, CI = 0.52–0.99). Further analysis revealed that rumination significantly mediated between TEs and IOR severity (β = 0.26, SE = 0.01, CI = 0.24–0.28). The findings are consistent with the hypothesis that IOR-A and IOR-E occur as levels on a continuum, but each has some distinctive correlates. Extrinsic events may play a more prominent role in IOR-A, while intrinsic factors, such as cognitive capacity, may play a more prominent role in IOR-E. The involvement of rumination across the IOR spectrum suggests an opportunity for intervention.

Renin‐angiotensin‐aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66‐72 years; congestive heart failure [CHF] in 11%‐19%; diabetes in 43%‐54%; serum potassium ≥5 in 20%‐35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had diabetes, hypertension, or less advanced CKD. In conclusion, RAASi prescription patterns vary by country, and by demographic and clinical characteristics. RAASi appear to be underused, even among patients with strong class‐specific recommendations. Although the reasons for this variation could not be fully identified in this cross‐sectional observation, our data indicate that the risk of hyperkalemia may contribute to the underuse of this class of agents in moderate to advanced CKD.

Background Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. Methods The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. Results Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. Conclusions Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.

Previously lacking in the literature, we describe longitudinal patterns of anemia prescriptions for non-dialysis-dependent chronic kidney disease (NDD-CKD) patients under nephrologist care. We analyzed data from 2818 Stage 3-5 NDD-CKD patients from Brazil, Germany, and the US, naïve to anemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrollment in the CKDopps. We report the cumulative incidence function (CIF) of medication initiation stratified by baseline characteristics. Even in patients with hemoglobin (Hb)

Holistic processing (HP) has long been considered a characteristic of right hemisphere (RH) processing. Indeed, holistic face processing is typically associated with left visual field (LVF)/RH processing advantages. Nevertheless, expert Chinese character recognition involves reduced HP and increased RH lateralization, presenting a counterexample. Recent modeling research suggests that RH processing may be associated with an increase or decrease in HP, depending on whether spacing or component information was used respectively. Since expert Chinese character recognition involves increasing sensitivity to components while deemphasizing spacing information, RH processing in experts may be associated with weaker HP than novices. Consistent with this hypothesis, in a divided visual field paradigm, novices exhibited HP only in the LVF/RH, whereas experts showed no HP in either visual field. This result suggests that the RH may flexibly switch between part-based and holistic representations, consistent with recent fMRI findings. The RH's advantage in global/low spatial frequency processing is suggested to be relative to the task relevant frequency range. Thus, its use of holistic and part-based representations may depend on how attention is allocated for task relevant information. This study provides the first behavioral evidence showing how type of information used for processing modulates perceptual representations in the RH.

Background There is increasing evidence that patients with spontaneous coronary artery dissection (SCAD) have an underlying genetic susceptibility (Goel et al JAMA Intern Med175:821–826, 2015). Moreover, in a collaborative study involving 1,055 SCAD cases and 7,190 controls, we recently reported the first risk allele for SCAD, a variant (rs9349379-A) in the PHACTR1/EDN1 genetic locus (Adlam et al J Amer Coll Cardiol73:58–66, 2019). Purpose We sought to determine the clinical characteristics and initial genetic data for 11 families, in which more than one member has had an episode of SCAD. Methods Participants were recruited largely via a social media platform. Informed consent was obtained in all cases for analysis of genetic information using whole genome sequencing, as well as collection of clinical information. SCAD was confirmed by review of coronary angiogram images and clinical data collected by phone interview, as well as review of specialist letters and hospital records. Results Of 235 participants recruited to date, 23 cases showed familial clustering involving sister-sister pairs in six families, three first-degree cousins in one family (picture), two first-degree cousins in two families, a mother-son pair, and a family with concordant monozygotic twins, that is both twins having had SCAD. In an additional family, SCAD is discordant in monozygotic twins. A comparison of symptoms, age at SCAD, clinical syndrome, cardiovascular risk factors, SCAD risk factors, environmental triggers, SCAD location, acute management, left ventricular function and recurrent SCAD events in these families versus isolated cases, will be presented. Three sister-sister pairs have undergone whole genome sequencing and these data sets are undergoing segregation analysis to identify rare variants that are present exclusively in affected family members. Family E Pedigree. Shaded circles represent first cousins affected with SCAD. The top number represents age (in years) of the SCAD event and the bottom number represents current age (in years). Conclusions To our knowledge, this is the largest assembly of SCAD cases with familial clustering reported to date. It provides strong evidence supporting an underlying genetic basis for SCAD, which most likely is a multi-genic disorder that also involves important gene-environment interactions.

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic form of coronary artery disease of unknown cause that predominantly affects women (>90%; mean age 44–55 years) and can be fatal. The finding of familial clustering, including the concordant involvement of monozygotic twins, and its association with the PHACTR1/EDN1 genetic locus, indicate a genetic predisposition to its pathophysiology. A human induced pluripotent stem cell line (hiPSC) was generated from a patient who had survived an episode of SCAD. This disease-specific hiPSC line will be useful for the study of SCAD after differentiation into blood vessel-forming cells. Keywords: SCAD, Induced pluripotent stem cells, Disease modeling, Cardiovascular biology, Reprogramming

The purpose of this review was to systematically identify, summarize, and critically appraise studies on dietary salt relating to health outcomes that were published from August to November 2015. The search strategy was adapted from a previous systematic review on dietary salt and health. Overall, 15 studies were included in the review: one study assessed cardiovascular events, five studies assessed blood pressure or hypertension incidence, six studies assessed surrogate outcomes for cardiovascular or kidney diseases, and three studies assessed other outcomes (age‐related cataracts, rheumatoid arthritis, and bone mineral density, respectively). Four studies were selected for detailed appraisal and commentary.

Studies identified from an updated systematic review (from June 2014 to May 2015) on the impact of dietary salt intake on clinical and population health are reviewed. Randomized controlled trials, cohort studies, and meta‐analyses of these study types on the effect of sodium intake on blood pressure, or any substantive adverse health outcomes were identified from MEDLINE searches and quality indicators were used to select studies that were relevant to clinical and public health. From 6920 studies identified in the literature search, 144 studies were selected for review, of which only three (n=233,680) met inclusion criteria. Between them, the three studies demonstrated a harmful association between excess dietary salt and all‐cause mortality, noncardiovascular and cardiovascular disease mortality, and headache. None of the included studies found harm from lowering dietary salt. The findings of this systematic review are consistent with the large body of research supportive of efforts to reduce population salt intake and congruent with our last annual review from June 2013 to May 2014.

Background International variation in anemia assessment and management practices in chronic kidney disease (CKD) is poorly understood. Methods We performed a cross-sectional analysis of anemia laboratory monitoring, prevalence and management in the prospective Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps). A total of 6766 participants with CKD Stages 3a–5ND from nephrology clinics in Brazil, France, Germany and the USA were included. Results Among patients with anemia (hemoglobin Conclusions Hemoglobin and iron stores are measured less frequently than per guidelines. Among all regions, there was a substantial proportion of anemic patients with iron deficiency who were not treated with iron, highlighting an area for practice improvement in CKD care.

Objective(s) Malnutrition and protein–energy wasting are associated with morbidity and mortality in hemodialysis patients. Existing nutritional scores rely primarily on cross-sectional data. Using readily available nutritional indicators, we developed models to predict the risk of mortality and hospitalization in prevalent hemodialysis patients. Design and Methods In this retrospective study, we constructed prediction models of 1-year mortality and hospitalization using generalized linear models, generalized additive models (GAM), classification tree, and random forest models. The models were compared using area under the receiver-operating characteristics curve (AUC) and calibration curves. Model predictors included nutritional and inflammation indicators, demographics, comorbidities, and slopes of all continuous variables over 6 months. Patients were randomly split in the ratio 2:1:1 into training, testing, and validation cohorts, respectively. We included patients with hemodialysis vintage ≥1 year from Fresenius Medical Care North America clinics from July 2011 to December 2012 (N = 21,802 in mortality analysis; N = 13,892 in hospitalization analysis).The outcome variables were 1-year mortality and hospitalization. Results For mortality prediction, GAM was the best model (AUC = 0.85, 95% confidence interval=0.83-0.86), comprised of neutrophil-to-lymphocyte ratio slope, serum bicarbonate slope, and vintage as nonlinear predictors, and age, serum albumin, and creatinine as linear predictors. For hospitalization prediction, GAM was also the best model (AUC = 0.70, 95% confidence interval = 0.62-0.79) and included neutrophil-to-lymphocyte ratio slope, bicarbonate slope, volume of urea distribution, vintage, and phosphate slope as nonlinear predictors, in addition to albumin, congestive heart failure, age, phosphate, equilibrated normalized protein catabolic rate, and creatinine as linear predictors. Both models demonstrated good calibration, with mild overestimation of hospitalization risk at the highest risk interval. Conclusions The GAM model can accurately predict the risk of mortality and hospitalization. Application of these prediction models could inform allocation of nutritional interventions to patients at highest nutritional risk.

Past studies have shown that multimodal presentation of story can improve story-retelling performance in the first language. The purpose of the present study was to investigate whether similar multimedia effects can be observed in second language learning and graphic novel reading. A total of 51 Chinese elementary school children, aged 7–8, who were learning English as a second language were recruited. They were randomly assigned to one of the three experimental conditions that differed in the format of story presentation: English text, English text with pictorial illustrations or graphic novel. After reading the same story, the children retold the story in English. The narratives produced were then rated by two independent raters. The results of group comparison showed that children from the three experimental groups had similar performance, indicating that multimedia presentation may not always facilitate narrative production in English as a second language. Within-subject comparison further showed that the children were relatively strong in language skills and capturing the main ideas of the story, while showing weakness in story structure awareness, elaboration, as well as local and global cohesion. Suggestions for the application of multimodal presentation of narrative texts are discussed.

Background and objectives Dialysis patients have a high risk for inadequate nutrition. Their nutritional status is particularly susceptible to deterioration when faced with intercurrent events such as hospitalization. This study was conducted to improve the understanding of the temporal evolution of nutritional parameters as a foundation for rational and proactive nutritional intervention. Design, setting, participants, & measurements A retrospective cohort study was performed to investigate the temporal evolution of nutritional parameters (serum albumin, serum phosphate, serum creatinine, equilibrated normalized protein catabolic rate, and interdialytic weight gain) and a composite nutritional score derived from these parameters, in two populations: ( 1 ) incident hemodialysis (HD) patients who started HD between January 2006 and December 2011 and were followed for up to 54 months (median 16.3), and ( 2 ) prevalent patients with HD vintage ≥2.5 years who were hospitalized between January 2006 and December 2011 and followed from 6 months before to 6 months after hospitalization. Results In incident patients ( n =126,964), each of the nutritional parameters improved after HD initiation, with a mean composite nutritional score at the 24th percentile at the start of HD and reaching a plateau at the 57th percentile toward the end of the second year on dialysis. Nutritional parameters increased more rapidly and reached higher values among patients who survived longer. In hospitalized patients ( n =14,193), the nutritional parameters and the composite score began to decline 1–2 months before hospitalization, reached their lowest level in the month after hospitalization, and then partially recovered in the subsequent 5 months. The degree of recovery of the nutritional score was inversely related to the number of rehospitalizations. Conclusions This study increases the understanding of nutritional resilience and its determinants in HD patients. Application of the nutritional score, pending further validation, may facilitate targeted and timely interventions to avert the negative consequences of inadequate nutrition in chronic HD patients.

The purpose of this review is to identify, summarize, and critically appraise studies on dietary salt and health outcomes that were published from April to July 2016. The search strategy was adapted from a previous systematic review on dietary salt and health. We have revised our criteria for methodological quality and health outcomes, which are applied to select studies for detailed critical appraisals and written commentary. Overall, 28 studies were identified and are summarized in this review. Four of the 28 studies met criteria for methodological quality and health outcomes and five studies underwent detailed critical appraisals and commentary. Three of these studies found adverse effects of salt on health outcomes (chronic kidney disease and blood pressure) and two were neutral (fracture risk/bone mineral density and cognitive impairment).

Background: Frequent hemodialysis (HD) may be associated with an increased risk of vascular access complications. Studies addressing vascular access outcomes in frequent HD show conflicting results. Methods: We searched Medline for trials looking at vascular access outcomes in frequent HD. Results: Nineteen studies met the inclusion criteria; only studies with a control group were included for analysis (n = 15). The vascular access event rate was higher in intensive HD as compared to conventional HD (difference of 6.7 events per 100 patient-years, p = 0.009). Overall event rates were not significantly different between conventional and intensive HD when stratified for access type, but were notably higher in the arteriovenous grafts and catheter group as compared to the arteriovenous fistula (AVF) group. Conclusion: Intensive HD is associated with an increased risk of vascular access complications. Overall reported event rates were lower in the AVF group. Further controlled studies should investigate whether a ‘fistula first' strategy may be recommended also for intensive HD.

Background and Objectives: The pathogenesis of anemia in hemodialysis (HD) patients is dependent on multiple factors, with decreased red blood cell life span (RBCLS) being a significant contributor. Although the impact of reduced RBCLS on anemia is recognized, it is still a subject that is not well researched. The objective of this study was to investigate the relationship between RBCLS and inflammatory biomarkers in chronic HD patients. Design, Setting, Participants, and Measurements: RBCLS was calculated from alveolar carbon monoxide concentrations measured by gas chromatography. Interleukins (IL) IL-6, IL-18, IL-10, and high sensitivity C-reactive protein were measured using bead-based multiplex assay. Measurements were carried out at baseline and during follow-up. The associations between RBCLS and inflammatory biomarkers were evaluated using linear mixed effects models. Results: RBCLS measurements were available for 54 HD patients. Their average age was 58.5 ± 14.4 years, 68.5% were males, 48.1% were diabetics, and the HD vintage was 51 ± 48 months. In 4 patients, RBCLS was measured once, while in 50 patients, up to 5 repeated RBCLS measurements were available. RBCLS was 73.2 ± 17.8 days (range 37.7-115.8 days). No association was found between RBCLS and any of the inflammatory biomarkers. Of note, RBCLS was positively correlated with levels of uric acid (p = 0.02) and blood urea nitrogen (BUN; p = 0.01), respectively. Conclusion: Our study suggests that inflammation pathways reported by these biomarkers only have a limited role in causing premature RBC death. The positive correlation with uric acid and BUN warrants further studies.

The purpose of this review was to identify, summarize, and critically appraise studies on dietary salt relating to health outcomes that were published from December 2015 to March 2016. The search strategy was adapted from a previous systematic review on dietary salt and health. Overall, 13 studies were included in the review: one study assessed cardiovascular events, nine studies assessed prevalence or incidence of blood pressure or hypertension, one study assessed kidney disease, and two studies assessed other health outcomes (obesity and nonalcoholic fatty liver disease). Four studies were selected for detailed appraisal and commentary. One study met the minimum methodologic criteria and found an increased risk associated with lower sodium intake in patients with heart failure. All other studies identified in this review demonstrated positive associations between dietary salt and adverse health outcomes.

BackgroundHigh interdialytic weight gain (IDWG) is associated with adverse outcomes in hemodialysis (HD) patients. We identified temporal and regional trends in IDWG, predictors of IDWG, and associations of IDWG with clinical outcomes.Study DesignAnalysis 1: sequential cross-sections to identify facility- and patient-level predictors of IDWG and their temporal trends. Analysis 2: prospective cohort study to assess associations between IDWG and mortality and hospitalization risk.Setting & Participants21,919 participants on HD therapy for 1 year or longer in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 2 to 5 (2002-2014).PredictorsAnalysis 1: study phase, patient demographics and comorbid conditions, HD facility practices. Analysis 2: relative IDWG, expressed as percentage of post-HD weight (

A technique is developed for a North Sea chalk reservoir to estimate the Hatchell-ROste R factors using a reservoir engineering constraint. This provides a way of defining the uncertainty on the R values, given the range of mechanical properties for the field of interest. In our case study the average R for the reservoir and overburden appears to be in the range 7 to 22. R factors are also calculated for regions of pressure relaxation and drawdown identified in the field, and the results confirm the current understanding determined by laboratory experiment and previous studies that the magnitude varies as a function of strain polarity, with the asymmetry being at most a factor of three. These results are validated with full geomechanical modelling followed by time shift modelling, showing that the observed time shifts cannot be created unless this asymmetry is present

Summary A simple spectrophotometric method has been developed for the determination of water-soluble synthetic food colours in soft drinks involving ion-pair formation with octadecyltrimethyl ammonium bromide at pH 5.6 and extraction of the ion-pair into n-butanol. The proposed method has been applied to determine amaranth, carmoisine, Green S, Orange G, Patent blue V, Ponceau 4R, Sunset yellow and tartrazine singly in soft drinks. The optimum experimental conditions for the method were reported. The percent-age extraction for all the colours except Green S under the optimum conditions ranged from 98 to 100. The precision of the proposed method was in the range 1–2.4% at the level of 8.0 μg ml−1 for the food colours.