From the Cover: Desorption electrospray ionization mass spectrometry reveals surface-mediated antifungal chemical defense of a tropical seaweed

Organism surfaces represent signaling sites for attraction of allies and defense against enemies. However, our understanding of these signals has been impeded by methodological limitations that have precluded direct fine-scale evaluation of compounds on native surfaces. Here, we asked whether natural products from the red macroalga Callophycus serratus act in surface-mediated defense against pathogenic microbes. Bromophycolides and callophycoic acids from algal extracts inhibited growth of Lindra thalassiae, a marine fungal pathogen, and represent the largest group of algal antifungal chemical defenses reported to date. Desorption electrospray ionization mass spectrometry (DESI-MS) imaging revealed that surface-associated bromophycolides were found exclusively in association with distinct surface patches at concentrations sufficient for fungal inhibition; DESI-MS also indicated the presence of bromophycolides within internal algal tissue. This is among the first examples of natural product imaging on biological surfaces, suggesting the importance of secondary metabolites in localized ecological interactions, and illustrating the potential of DESI-MS in understanding chemically-mediated biological processes.     

Endoscopic necrosectomy of organized pancreatic necrosis: a currently practiced NOTES procedure

Background

Endoscopic necrosectomy is now an established minimally invasive method for treatment of organized pancreatic necrosis.

Methods

Review of methods and results of endoscopic treatment of pancreatic necrosis.

Results

Reports by multiple groups have demonstrated favorable results of endoscopic necrosectomy. The mortality of critically ill patients undergoing endoscopic treatment in several series is approximately 10%. Some patients will eventually also require surgery for situations such as complete pancreatic duct disruption, but even in these cases endoscopic necrosectomy is useful because pancreatic surgery can often be delayed until the patient is stable.

Conclusions

Endoscopic necrosectomy will likely assume an increasing role in the treatment of pancreatic necrosis. This should result in reduced morbidity and mortality in these critically ill patients.     

Long-term impaired quality of life in Cushing's syndrome despite initial improvement after surgical remission

CONTEXT: Cushing's syndrome (CS) is associated with symptoms that may impair health-related quality of life (HRQL). METHODS: We used the short-form 36 survey to evaluate HRQL in 23 patients with Cushing's disease before and after transsphenoidal surgery (age, 42.7 +/- 12.0 yr; 19 women and four men) and in a cross-section of 343 CS patients (age, 48.2 +/- 14.1 yr; 265 women and 78 men) in remission for up to 25.8 yr after surgery (adrenal, 5%; ectopic, 6%). The z-scores were calculated for short-form 36 domains, and physical (PCS) and mental (MCS) summary scores were compared with those of age- and sex-matched controls (n = 6742). RESULTS: Active Cushing's disease was associated with low PCS and MCS scores (P < 0.05). Despite residual postoperative impairment, primarily of physical domains, all HRQL parameters improved after treatment with transsphenoidal surgery (3.2 +/- 1.5 yr; P < 0.05). In the cross-section in remission at follow-up, there was a small, but significant (P < 0.05), impairment of both PCS and MCS. A longitudinal postoperative analysis confirmed stable, but impaired, HRQL over time. Logistic regression demonstrated that previous pituitary radiation and current glucocorticoid use had little effect on HRQL outcomes. CONCLUSION: CS is associated with impaired HRQL, which partially resolves after treatment. At longer-term follow-up, however, there is residual impairment of HRQL. Determination of modifiable factors that contribute to impaired HRQL may help reduce the physical and psychosocial burden of this disease.     

Effect of disease-related pain on the health-related quality of life of children and adolescents with cystic fibrosis

OBJECTIVES: The authors' objective was to describe the effect of recurrent pain symptoms on the health-related quality of life (HRQOL) of children and adolescents with cystic fibrosis (CF). Frequent pain, independent of disease severity, was hypothesized to be associated with broad decrements in physical, psychological, and social functioning. METHODS: Forty-six children and adolescents (mean age 12.9 years; 52% female) completed the Cystic Fibrosis Questionnaire-Revised (CFQ-R) to assess their HRQOL and a retrospective pain interview to assess pain location, frequency, intensity, duration, and bother during a routine clinic visit. Forced expiratory volume in 1 second as percent of predicted (FEV1%) was recorded from medical charts to assess the children's disease severity. RESULTS: As hypothesized, pain symptoms were related to children's physical, emotional, and role functioning, CF-related symptoms, and overall perception of their health. Children with frequent pain had significantly reduced physical functioning, vitality, role limitations, and overall perceptions of their health, and increased eating disturbances, treatment burden, respiratory, and digestive symptoms compared with children with no pain or less frequent pain. After controlling for the effects of disease severity, pain frequency continued to predict children's HRQOL in each of these areas. DISCUSSION: Children with frequent CF-related pain experienced broad decrements in their HRQOL. These findings are similar to those found in other populations of children experiencing disease-related pain, suggesting a pervasive impact of pain on overall health and well-being. Future research is needed to evaluate treatments to reduce pain symptoms and improve HRQOL in children with cystic fibrosis.     

PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys

Dopamine neurotransmission is associated with high susceptibility to cocaine abuse. Positron emission tomography was used in 12 rhesus macaques to determine if dopamine D2 receptor availability was associated with the rate of cocaine reinforcement, and to study changes in brain dopaminergic function during maintenance of and abstinence from cocaine. Baseline D2 receptor availability was negatively correlated with rates of cocaine self-administration. D2 receptor availability decreased by 15-20% within 1 week of initiating self-administration and remained reduced by approximately 20% during 1 year of exposure. Long-term reductions in D2 receptor availability were observed, with decreases persisting for up to 1 year of abstinence in some monkeys. These data provide evidence for a predisposition to self-administer cocaine based on D2 receptor availability, and demonstrate that the brain dopamine system responds rapidly following cocaine exposure. Individual differences in the rate of recovery of D2 receptor function during abstinence were noted.     

Comparison of Concordance Correlation Coefficient Estimating Approaches with Skewed Data

The concordance correlation coefficient (CCC) is an index that assesses the agreement between continuous measures made by different observers. At least four methods are used to estimate the CCC: two (Lin's method, Variance Components) which are defined on the basis that data are normally distributed, and the two others (U-statistics, GEE) which do not assume any particular distribution of the data. Here the four methods are compared with skewed data from a model in which the subject means follow a log-normal distribution while the within-subject variability is assumed to be normally distributed. An example of alcohol consumption is considered and a simulation study is performed.     

The Concordance Correlation Coefficient for Repeated Measures Estimated by Variance Components

The concordance correlation coefficient (CCC) is an index that is commonly used to assess the degree of agreement between observers on measuring a continuous characteristic. Here, a CCC for longitudinal repeated measurements is developed through the appropriate specification of the intraclass correlation coefficient from a variance components linear mixed model. A case example and the results of a simulation study are provided.