The PedsQL in type 1 and type 2 diabetes: reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales and type 1 Diabetes Module

OBJECTIVE: The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents aged 2-18 years. The PedsQL 4.0 Generic Core Scales are child self-report and parent proxy-report scales developed as the generic core measure to be integrated with the PedsQL disease-specific modules. The PedsQL 3.0 Type 1 Diabetes Module was designed to measure diabetes-specific HRQOL. RESEARCH DESIGN AND METHODS: The PedsQL Generic Core Scales and Diabetes Module were administered to 300 pediatric patients with type 1 or type 2 diabetes and 308 parents. RESULTS: Internal consistency reliability for the PedsQL Generic Core Total Scale score (alpha = 0.88 child, 0.89 parent-report) and most Diabetes Module scales (average alpha = 0.71 child, 0.77 parent-report) was acceptable for group comparisons. The PedsQL 4.0 distinguished between healthy children and children with diabetes. The Diabetes Module demonstrated intercorrelations with dimensions of generic and diabetes-specific HRQOL. CONCLUSIONS: The results demonstrate the reliability and validity of the PedsQL in diabetes. The PedsQL may be used as an outcome measure for diabetes clinical trials and research.     

Antioxidant properties of beta-carboline alkaloids are related to their antimutagenic and antigenotoxic activities

The beta-carboline alkaloids found in medical plants and in a variety of foods, beverages and cigarette smoke have a range of action in various biological systems. In vitro studies have demonstrated that these alkaloids can act as scavengers of reactive oxygen species. In this paper, we report the in vivo antioxidative properties of the aromatic (harmane, harmine, harmol) and dihydro-beta-carbolines (harmaline and harmalol) studied by using Saccharomyces cerevisiae strains proficient and deficient in antioxidant defenses. Their antimutagenic activity was also assayed in S. cerevisiae and the antigenotoxicity was tested by the comet assay in V79 cell line, when both eukaryotic systems were exposed to H(2)O(2). We show that the alkaloids have a significant protective effect against H(2)O(2) and paraquat oxidative agents in yeast cells, and that their ability to scavenge hydroxyl radicals contributes to their antimutagenic and antigenotoxic effects.     

Disassembly of layer-by-layer films of plasmid DNA and reducible TAT polypeptide

This paper reports the disassembly of layer-by-layer (LbL) films of plasmid DNA and a reducible cationic polypeptide. To utilize a reducing microenvironment of cellular plasma membrane as a potential trigger, LbL films are assembled to contain both DNA and the TAT-based polypeptide (PTAT) with reducible disulfide bonds in the backbone. The assembly and disassembly processes are monitored by goniometry, ellipsometry, and atomic force microscopy (AFM). The structure of the PTAT films is compared with that of non-reducible poly(L-lysine) (PLL) films. Both PTAT and PLL films exhibit exponential growth but with the contact angle alternating between characteristic values. Ellipsometry and AFM show a gradual and complete disassembly of the PTAT but not the PLL films in a 24h period in the reducing environment in vitro. This study suggests a potential of using reducible LbL films for controlled DNA delivery.     

Meckel syndrome in the Hutterite population is actually a Joubert-related cerebello-oculo-renal syndrome

Meckel syndrome (MKS) is a rare lethal autosomal recessive disorder characterized by the presence of occipital encephalocele, cystic kidneys, fibrotic changes of the liver and polydactyly. Joubert syndrome (JS)-related disorders (JSRDs) or cerebello-oculo-renal syndromes (CORS) are a group of recessively inherited conditions characterized by a molar tooth sign (MTS) on cranial MRI, a set of core clinical features (developmental delay/mental retardation, hypotonia, ataxia, episodic breathing abnormalities, abnormal eye movements) and variable involvement of other systems including renal, ocular, central nervous system, craniofacial, hepatic, and skeletal. A significant clinical overlap between MKS and JSRD/CORS has been recognized in the literature. We describe a group of 10 Hutterite patients, of which 7 had been previously diagnosed with MKS, with a JSRD. Clinical features include variable early mortality, cognitive handicap, a characteristic dysmorphic facial appearance, hypotonia, ataxia, abnormal breathing pattern, nystagmus, and MTS on MRI. Additional features include occipital encephalocele, posterior fossa fluid collections resembling Dandy-Walker malformation, hydrocephalus, coloboma, and renal disease. This JSRD is a recognizable dysmorphic syndrome characterized by hypertelorism, deep-set eyes, down-slanting palpebral fissures, ptosis, arched eyebrows with medial sparseness, square nasal tip, short philtrum with tented upper lip, open mouth with down-turned corners, and posteriorly rotated low-set ears. Renal disease is present in 70% of patients and is characterized by cystic kidneys, abnormalities in renal function and hypertension. Homozygous deletions of NPHP1 and the known loci for JS/JSRD and MKS were excluded by identity-by-descent mapping studies suggesting that this condition in the Hutterites represents yet another locus for a JSRD.     

Short-term outcomes and their predictors for patients hospitalized with community-acquired pneumonia

PURPOSE: This study of patients who were hospitalized with pneumonia describes 4 short-term outcomes and the relative value of 4 variables for predicting the outcomes. METHOD: We prospectively documented 4 short-term outcomes (hospital length of stay, discharge location, death, 30-day readmission) among 213 adults (mean age = 72.5 years) with pneumonia who were admitted to the hospital. Relationships between the Pneumonia Severity Index (PSI), preadmission walking, malnutrition, grip strength, and outcomes were examined with correlations and multiple logistic regression. RESULTS: The mean (SD) hospital stay was 8.8 (10.4) days. Many patients (51.6%) were not discharged to their homes; 13.6% died during admission or within 30 days of discharge. Of 205 patients discharged alive, 23.9% were readmitted within 30 days. All predictor variables correlated significantly with length of stay, discharge, and death. Except for grip strength, all predictor variables correlated significantly with readmission. Regression showed that the PSI contributed significantly to the prediction of all outcomes but that other variables also contributed (R(2) =.099 [readmitted] to.484 [discharged to home]). CONCLUSIONS: Because malnutrition and physical performance measures independently predicted or added to the PSI's prediction of untoward outcomes, the measures merit inclusion when assessing patients with pneumonia.     

Lack of difference between retinoic acid and retinol in stimulating progesterone production by luteinizing granulosa cells in vitro

Receptors for retinoids in the immature rat ovary and the effects of retinol and retinoic acid on luteinizing granulosa cells were studied. Radioreceptor assay demonstrated the presence of specific cellular retinol-binding protein and cellular retinoic acid-binding protein in the ovaries of rats injected with PMSG alone or PMSG and hCG. In addition, when luteinizing granulosa cell from PMSG/hCG-injected immature rats were cultured with or without retinoic acid, the morphology, viability, number of cells in culture, and progesterone (P) accumulation were not affected by up to 10 microM retinoic acid. Beyond 10 microM, the cells began to round up, which was associated with a decrease in cell viability. Surprisingly, the deleterious concentrations of retinoic acid increased progesterone accumulation significantly higher than the medium control value. This increase in progesterone, however, was not accompanied by an increase in cAMP. When cells preincubated for 2 days with 1 microM of either retinoic acid or retinol were subsequently incubated in retinoid-free medium containing various substrates for steroidogenesis, the following results were obtained. Basal progesterone and its accumulation in response to human low density lipoprotein were significantly higher in cells preincubated with retinoids than in the control cells. However, no difference was seen in the degree of stimulation between retinol and retinoic acid pretreatments. Both 25-hydroxycholesterol, a substrate for side-chain cleavage enzyme, and pregnenolone, a substrate for 3 beta-hydroxysteroid dehydrogenase, significantly stimulated the accumulation of progesterone in cells preincubated with retinoids over the control value. Again, no appreciable difference was observed between retinol and retinoic acid pretreatments. Our results suggest that receptors for retinoids are present in gonadotropin-primed immature rat ovaries, retinoids increase luteal cell progesterone accumulation, and no difference exists between retinol and retinoic acid in their ability to increase the accumulation of progesterone by these cells.     

Evaluating Responses to Gluten Challenge: A Randomized,Double-Blind, 2-Dose Gluten Challenge Trial

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Readability of online patient education materials on adult reconstruction Web sites

Recommended readability of patient education materials is sixth-grade level or lower. Readability of 212 patient education materials pertaining to adult reconstruction topics available from the American Academy of Orthopaedic Surgeons, American Association of Hip and Knee Surgeons, and 3 other specialty and private practitioner Web sites was assessed using the Flesch-Kincaid grade formula. The mean Flesch-Kincaid score was 11.1 (range, 3-26.5). Only 5 (2%) articles had a readability level of sixth grade or lower. Readability of most of the articles for patient education on adult reconstruction Web sites evaluated may be too advanced for a substantial portion of patients. Further studies are needed to assess the optimal readability level of health information on the Internet.     

Metabolic Syndrome,C-Reactive Protein,and Mortality in U.S. Blacks and Whites: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

OBJECTIVE

We evaluate associations of metabolic syndrome (MetS), C-reactive protein (CRP), and a CRP-incorporated definition of MetS (CRPMetS) with risk of all-cause mortality in a biracial population.

RESEARCH DESIGN AND METHODS

We studied 23,998 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, an observational study of black and white adults ≥45 years old across the U.S. Elevated CRP was defined as ≥3 mg/L and MetS by the revised Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III; ATP III) criteria (three of five components). CRPMetS was defined as presence of three out of six components, with elevated CRP added to ATP III criteria as a sixth component. Cox models were used to calculate hazard ratios (HRs) for all-cause mortality, and population attributable risk (PAR) was calculated. Stratified analyses based on race and diabetes status were performed.

RESULTS

There were 9,741 participants (41%) with MetS and 12,179 (51%) with CRPMetS at baseline. Over 4.8 years of follow-up, 2,050 participants died. After adjustment for multiple confounders, MetS, elevated CRP, and CRPMetS were each significantly associated with increased mortality risk (HRs 1.26 [95% CI 1.15–1.38], 1.55 [1.41–1.70], and 1.34 [1.22–1.48], respectively). The PAR was 9.5% for MetS, 18.1% for CRP, and 14.7% for CRPMetS. Associations of elevated CRP and of CRPMetS with mortality were significantly greater in whites than blacks, while no differences in associations were observed based on diabetes status.

CONCLUSIONS

By definition, CRPMetS identifies more people at risk than MetS but still maintains a similar mortality risk. Incorporating CRP into the definition for MetS may be useful in identifying additional high-risk populations to target for prevention.