Citations

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.

Objectives To investigate whether demographic (age and education) adjustments for the Mini‐Mental State Examination ( MMSE ) attenuate mean score discrepancies between African‐American and Caucasian adults and whether demographically adjusted MMSE scores improve the diagnostic classification accuracy of dementia in African‐American adults over unadjusted MMSE scores. Design Cross‐sectional study. Setting Community‐dwelling adults participating in the Mayo Clinic A lzheimer's Disease Patient Registry and A lzheimer's Disease Research Center. Participants Three thousand two hundred fifty‐four adults (2,819 Caucasian, 435 African American) aged 60 and older. Measurements MMSE score at study entry. Results African‐American adults had significantly lower unadjusted MMSE scores (23.0 ± 7.4) than Caucasian adults (25.3 ± 5.4). This discrepancy persisted despite adjustment of MMSE scores for age and years of education using established regression weights or newly derived weights. Controlling for dementia severity at baseline and adjusting MMSE scores for age and quality of education attenuated this discrepancy. In African‐American adults, an age‐ and education‐adjusted MMSE cut score of 23/24 provided optimal dementia classification accuracy, but this represented only a modest improvement over an unadjusted MMSE cut score of 22/23. The posterior probability of dementia in African‐American adults is presented for various unadjusted MMSE cut scores and prevalence rates of dementia. Conclusion Age, dementia severity at study entry, and quality of educational experience are important explanatory factors in understanding the existing discrepancies in MMSE performance between Caucasian and African‐American adults. These findings support the use of unadjusted MMSE scores when screening older African Americans for dementia, with an unadjusted MMSE cut score of 22/23 yielding optimal classification accuracy.

AbstractIt has been well established that a high level of stress is associated with medical problems, mental health difficulties and absenteeism at the workplace. The aim of this single‐arm study design was to examine the potential effectiveness of a 12‐session multidisciplinary stress reduction programme on reducing perceived stress and improving health behaviours and quality of life. One hundred and four women participated in a programme that incorporated group support, skill building and cognitive behavioural and relaxation techniques. A series of Bonferroni corrected t‐tests found that the participants reported having significantly (p < 0.001) lower levels of perceived stress, improved health behaviours (sleep, nutrition, physical activity) improved overall health and improved quality of life at the end of the 12 week programme and at 1‐month follow‐up. Although the effect sizes for improvement were all large, there was no control group, so regression to the mean or selection bias may have impacted the results. Therefore, these results provide initial support for the implementation of gender‐based worksite stress reduction programmes and provide guidance in designing an effective worksite stress reduction programme. Further research using randomized controlled trials is warranted. Copyright © 2011 John Wiley & Sons, Ltd.

AbstractBackgroundBloating, flatulence, early satiety, and dysphagia resolve in more than 90% of patients early after fundoplication. Gastric dysfunction can persist, however, and a small number of patients develop severe gastric dysfunction (gastroparesis). Management of gastroparesis after antireflux procedures is generally conservative, but gastroparesis can become refractory to medical therapy. The aim of this study was to assess the role of gastric resection in the management of the unusual patient with severe postfundoplication gastric dysfunction.MethodsFrom January 1990 to October 2010, a total of 5,129 gastric resections were performed at our institution. From this cohort, we identified nine patients with postfundoplication gastric dysfunction managed with gastric resection. Clinical records were reviewed retrospectively for preoperative evaluation, perioperative course, and long‐term outcomes.ResultsOver 20 years, nine patients were treated with gastric resection for debilitating gastric dysfunction after antireflux surgery. Seven of the nine patients were female; the median preoperative body mass index was 25 kg/m2 (18–31 kg/m2). Median follow‐up was 23 months (1–97 months). Preoperatively, five patients required enteral feeding. Postoperatively, although there were no deaths, one patient required operative drainage of a subphrenic abscess, one developed temporary respiratory failure, and one was readmitted for partial small bowel obstruction. Six of the nine patients maintain their nutrition orally, but three are maintained with enteral nutrition. Only two patients are subjectively asymptomatic.ConclusionsOutcomes after gastric resection for postfundoplication gastric dysfunction are poor, with three of the nine patients requiring supplemental nutrition and seven of the nine having persistent symptoms.

Background and Purpose CGS 19755 is a competitive N -methyl- d -aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models. The objectives of this multicenter (7 centers), randomized, double-blind, placebo-controlled, ascending-dose phase IIa study were to evaluate the safety and tolerability of CGS 19755 and obtain pharmacokinetic and preliminary data on its efficacious dose range in patients treated within 12 hours of hemispheric ischemic stroke. Methods At each dose level, 6 patients were randomized to one or two intravenous bolus doses of CGS 19755, and 2 patients were randomized to placebo. An unblinded safety and monitoring committee evaluated results at each dose before ascending to the next level. All patients at the first level (1 mg/kg) received two doses separated by 12 hours. The first 2 patients at 2 mg/kg received two doses, but adverse experiences occurred in both; subsequent patient groups received single doses of 2.0, 1.75, or 1.5 mg/kg. Results Adverse experiences (agitation, hallucinations, confusion, paranoia, and delirium) occurred in all 6 patients treated with 2 mg/kg, and in 3 of 5 at 1.75 mg/kg. Similar but milder adverse experiences were noted in 4 of 7 patients at 1.5 mg/kg and 1 of 6 patients at 1.0 mg/kg. Adverse experiences began between 20 minutes and 22 hours (mean, 8 hours) after treatment and lasted 2 to 60 hours (mean, 24 hours). Mortality was 1 of 8 in patients receiving placebo and 3 of 24 in treated patients. In treated survivors, median and mean percent improvement in National Institutes of Health Stroke Scale scores from baseline to terminal visit (mean, 86 days) was comparable at all doses, and 95% of treated patients had Barthel Index scores of ≥70 at the terminal visit. Conclusions We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.