Dietary Assessment of Individuals with Chronic Kidney Disease

Examining the quality and quantity of food intake by appropriate methods is critical in the management of patients with chronic kidney disease (CKD). The four commonly used dietary assessment methods in CKD patients include short‐term dietary recalls, several days of food records with or without dietary interviews, urea kinetic based estimates such as protein nitrogen appearance calculation, and food histories including food screeners and food frequency questionnaires (FFQ). There are a number of strengths and limitations of these dietary assessment methods. Accordingly, none of the four methods is suitable in and of itself to give sufficiently accurate dietary information for all purposes. Food frequency questionnaires, which is the preferred method for epidemiological studies, should be used for dietary comparisons of patients within a given population rather than individual assessment. Food histories including FFQ and dietary recalls may underestimate important nutrients, especially in CKD patients. Given the large and increasing number of dialysis patients and work responsibilities of renal dietitians, routine analysis of dietary records and recalls is becoming less feasible. Ongoing and future studies will ascertain additional strengths and limitations of dietary assessment methods in CKD populations including the assessment of food intake during an actual hemodialysis treatment.     

Dietary Protein Intake in Patients with Advanced Chronic Kidney Disease and on Dialysis

Many patients with chronic kidney disease (CKD), particularly those with stage 5 CKD, have protein wasting. The degree to which increased morbidity and mortality seen in these patients is due to protein depletion rather than to the often accompanying comorbidity is not clear. High protein diets lead to the accumulation of metabolites of protein that are potentially toxic. The MDRD Study, which investigated the effects of three levels of dietary protein and phosphorus intakes and two blood pressure goals on the progression of CKD, has several limitations. Several meta‐analyses have examined the effects of low protein diets (LPD) on the progression of CKD. It is possible that the lower SUN levels or lesser degree of uremic symptoms may have contributed to the positive findings of LPD in the meta‐analyses of Fouque and Pedrini et al., when compared with the study of Kasiske et al. A number of published reports indicate that LPD provide adequate protein for almost all clinically stable CKD patients and do not adversely affect body composition. In general, there are no large differences in the protein intake recommended by different expert groups for a given stage of CKD.     

Troponin utilization in patients presenting with atrial fibrillation/flutter to the emergency department: retrospective chart review

Background

There are few recommendations about the use of cardiac markers in the investigation and management of atrial fibrillation/flutter. Currently, it is unknown how many patients with atrial fibrillation/flutter undergo troponin testing, and how positive troponin results are managed in the emergency department. We sought to look at the emergency department troponin utilization patterns.

Methods

We performed a retrospective chart review of patients with atrial fibrillation/flutter presenting to the emergency department at three centers. Outcome measures included the rates of troponins ordered by emergency doctors, number of positive troponins, and those with positive troponins treated as acute coronary syndrome (ACS) by consulting services.

Results

Four hundred fifty-one charts were reviewed. A total of 388 (86%) of the patients had troponins ordered, 13.7% had positive results, and 4.9% were treated for ACS.

Conclusions

Troponin tests are ordered in a high percentage of patients with atrial fibrillation/flutter presenting to emergency departments. Five percent of our total patient cohort was diagnosed as having acute coronary syndrome by consulting services.

     

Dynamic mechanical thermal analysis of two light-cured dental composites.

OBJECTIVES: Clinical observations suggest that some composite resins are more often linked to post-operative sensitivity than others. These differences may relate to differences in modulus of elasticity and polymerization rates among materials. The aim of this study was to identify viscoelastic behavior of two light curable composites and determine whether significant differences in viscoelastic behavior exist between the two materials when light cured at each of three different irradiance values. METHODS: Two composites (Z100 and Z250 by 3M ESPE) were evaluated. Six specimens per composite and irradiance value (250, 500 and 850 mW/cm2) were made. The curing times were chosen to produce a fixed energy value of 30 J/cm2 independent of irradiation value. Dynamic mechanical thermal analysis (DMTA) was performed in single cantilever clamped mode. RESULTS: There were significant differences in transition temperatures between the two materials and the three frequencies at their glass transition temperatures, while significant differences did not exist at the lower transitions. The glass transition of Z250 was lower and narrower than that of Z100. Z250 exhibited lower storage modulus values. The irradiance values did not affect any of the transition temperatures significantly. SIGNIFICANCE: The lower and more distinct T(g) of Z250 suggests that Z250 cures more efficiently than Z100. The lower storage modulus of Z250 suggests that Z250 develops less stress in the tooth than Z100 during curing if shrinkage is the same for the two materials. The findings suggest that the material chosen, rather than irradiance, determines the stress level developed during light curing.     

CD44‐Targeted Docetaxel Conjugate for Cancer Cells and Cancer Stem‐Like Cells: A Novel Hyaluronic Acid‐Based Drug Delivery System

A CD44‐targeted macromolecular conjugate of docetaxel was prepared via a pH‐sensitive linkage to hyaluronic acid and was characterized using NMR, gel permeation chromatography, and differential scanning calorimetry. The conjugated species were further evaluated in terms of drug release, cytotoxicity, cellular uptake, cell cycle inhibition, and subacute toxicity in mice. Cellular microscopic studies revealed that CD44‐expressing cells including MCF‐7 cancer stem cells and MDA‐MB‐231 metastatic breast cancer cells had internalized the conjugates via a selective receptor‐mediated mechanism, leading to cell cycle arrest in the G2/M phase. Hyaluronic acid–docetaxel conjugates showed specific toxicity only in CD44‐expressing cells in vitro, along with a decreased risk of neutropenia and dose‐dependent mortality in vivo. Hyaluronic acid–drug conjugates represent a promising and efficient platform for solubilization of sparingly soluble molecules as well as active and selective targeted delivery to cancer cells and cancer stem cells.     

Overexpressed eIF4E is functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway.

PURPOSE: Overexpression of eIF4E in surgical margins of head and neck cancer patients is an independent risk factor for recurrence. We hypothesize that overexpressed eIF4E is functionally active in tumor margins through activation of the Akt/mammalian target of rapamycin (mTOR) pathway EXPERIMENTAL DESIGN: Western blots and/or immunohistochemistry were performed to determine whether phosphorylation of mTOR and activation of its downstream molecules eIF4E-binding protein-1 (4E-BP1) and p70 S6 kinase and the upstream modulator of mTOR, Akt, were expressed in margins overexpressing eIF4E. RESULTS: There was a significant association between phospho-4E-BP1 and eIF4E expression of a margin or a significant difference in phospho-4E-BP1 expression between the eIF4E-positive and -negative margins (P < 0.01). A significant association between eIF4E and phospho-p70 S6 kinase as well as eIF4E and phospho-mTOR was also noted (P < 0.05). Western blot analysis indicated a highly significant difference in the phosphorylation status of 4E-BP1 between tumors and resection margins. A total of 89% of the 4E-BP1-expressing margins expressed more of the phosphorylated (beta, gamma, and delta) isoforms, whereas 81% of the 4E-BP1-expressing tumors expressed more of the unphosphorylated alpha isoform. A similar difference in Akt activation was noted between eIF4E-positive margins and tumors (P < 0.05). CONCLUSIONS: Overexpression of eIF4E is functionally active in tumor margins through activation of the Akt/mTOR signaling pathway. The greater degree of expression of downstream targets and upstream regulators of mTOR in margins compared with the tumors indicates preferential activation of the Akt/mTOR signaling pathway in margins overexpressing eIF4E. Rapamycin analogs can potentially be used as adjuvant therapy for patients with eIF4E-positive margins.     

Helicobacter pylori Infection Impairs the Mucin Production Rate and Turnover in the Murine Gastric Mucosa

To protect the surface of the stomach, the epithelial cells secrete a mucus layer, which is mainly comprised of the MUC5AC mucin. Further protection is provided by a thick glycocalyx on the apical surface of the epithelial cell, with the cell surface mucin MUC1 as a major component. Here, we investigate the production rate and turnover of newly synthesized mucin in mice and analyze the effects of early colonization and chronic infection with H. pylori. Metabolic incorporation of an azido GalNAc analog (GalNAz) was used as a nonradioactive method to perform pulse experiments in the whole animal. First, the subcellular movement of newly synthesized mucin and mucin turnover was determined in uninfected mice. Based on the time line for mucin transport and dissemination, 2, 6, and 12 h after GalNAz injection was selected to collect the stomachs from mice infected with H. pylori strain SS1 during early colonization (7 days) and chronic infection (90 days). The results demonstrated that the speed from the start of glycosylation to the final destination is faster for the membrane-bound mucin to reach the glycocalyx (2 h) than for the secretory mucins to become secreted into the mucus layer (5 h). Furthermore, infection with H. pylori reduces the rate of mucin turnover and decreases the levels of Muc1. Since H. pylori colonizes this mucus niche, the decreased turnover rate indicates that H. pylori creates a more stable and favorable environment for itself by impairing the defense mechanism for clearing the mucosal surface of pathogens by mucus flow.