Enteric pathogen testing importance for children with acute gastroenteritis: A modified Delphi study

The application of clinical diagnostics for gastroenteritis in children has implications for a broad collection of stakeholders, impacting clinical care, communicable disease control, and laboratory utilization. To support diagnostic stewardship as gastroenteritis testing options continue to advance, it is critical to understand which enteropathogens constitute priorities for testing across stakeholder groups. Using a modified Delphi technique, we elicited opinions of subject matter experts to determine clinical and public health testing priorities. There was a high level of overall agreement (≥80%) among stakeholders (final roun

Youth Single-Sport Specialization in Professional Baseball Players.

Background: An increasing number of youth baseball athletes are specializing in playing baseball at younger ages. Purpose: The purpose of our study was to describe the age and prevalence of single-sport specialization in a cohort of current professional baseball athletes. In addition, we sought to understand the trends surrounding single-sport specialization in professional baseball players raised within and outside the United States (US). Study Design: Cross-sectional study; Level of evidence, 3. Methods: A survey was distributed to male professional baseball athletes via individual team athletic trainers. Athletes were asked if and at what age they had chosen to specialize in playing baseball at the exclusion of other sports, and data were then collected pertaining to this decision. We analyzed the rate and age of specialization, the reasons for specialization, and the athlete\u27s perception of injuries related to specialization. Results: A total of 1673 professional baseball athletes completed the survey, representing 26 of the 30 Major League Baseball (MLB) organizations. Less than half (44.5%) of professional athletes specialized in playing a single sport during their childhood/adolescence. Those who reported specializing in their youth did so at a mean age of 14.09 ± 2.79 years. MLB players who grew up outside the US specialized at a significantly earlier age than MLB players native to the US (12.30 ± 3.07 vs 14.89 ± 2.24 years, respectively; Conclusion: This study challenges the current trends toward early youth sport specialization, finding that the majority of professional baseball athletes studied did not specialize as youth and that those who did specialize did so at a mean age of 14 years. With the potential cumulative effects of pitching and overhead throwing on an athlete\u27s arm, the trend identified in this study toward earlier specialization within baseball is concerning

The flexibility and dynamics of protein disulphide-isomerase

We have studied the mobility of the multi-domain folding catalyst, protein disulphide-isomerase (PDI), by a coarse-graining approach based on exibility. We analyse our simulations of yeast PDI (yPDI) using measures of backbone movement, relative positions and orientations of domains, and distances between functional sites. We nd that there is interdomain exibility at every interdomain junction but these show very di erent characteristics. The extent of interdomain exibility is such that yPDI's two active sites can approach much more closely than is found in crystal structures | and indeed hinge motion to bring these sites into proximity is the lowest energy normal mode of motion of the protein. The exibility predicted for yPDI (based on one structure) includes the other known conformation of yPDI and is consistent with (i) the mobility observed experimentally for mammalian PDI and (ii) molecular dynamics. We also observe intradomain exibility and clear di erences between the domains in their propensity for internal motion. Our results suggest that PDI exibility enables it to interact with many di erent partner molecules of widely di erent sizes and shapes, and highlights considerable similarities of yPDI and mammalian PDI

A revised Cepheid distance to NGC 4258 and a test of the distance scale

In a previous paper (Maoz et al. 1999), we reported a Hubble Space Telescope (HST) Cepheid distance to the galaxy NGC 4258 obtained using the calibrations and methods then standard for the Key Project on the Extragalactic Distance Scale. Here, we reevaluate the Cepheid distance using the revised Key Project procedures described in Freedman et al. (2001). These revisions alter the zero points and slopes of the Cepheid Period-Luminosity (P-L) relations derived at the Large Magellanic Cloud (LMC), the calibration of the HST WFPC2 camera, and the treatment of metallicity differences. We also provide herein full information on the Cepheids described in Maoz et al. 1999. Using the refined Key Project techniques and calibrations, we determine the distance modulus of NGC 4258 to be 29.47 +/- 0.09 mag (unique to this determination) +/- 0.15 mag (systematic uncertainties in Key Project distances), corresponding to a metric distance of 7.8 +/- 0.3 +/- 0.5 Mpc and 1.2 sigma from the maser distance of 7.2 +/- 0.5 Mpc. We also test the alternative Cepheid P-L relations of Feast (1999), which yield more discrepant results. Additionally, we place weak limits upon the distance to the LMC and upon the effect of metallicity in Cepheid distance determinations.Comment: 26 pages in emulateapj5 format, including 6 figures and 5 tables. Accepted for publication in the Astrophysical Journa

Oral ondansetron administration to nondehydrated children with diarrhea and associated vomiting in emergency departments in Pakistan: A randomized controlled trial

Study objective: We determine whether single-dose oral ondansetron administration to children with vomiting as a result of acute gastroenteritis without dehydration reduces administration of intravenous fluid rehydration.Methods: In this 2-hospital, double-blind, placebo-controlled, emergency department–based, randomized trial conducted in Karachi Pakistan, we recruited children aged 0.5 to 5.0 years, without dehydration, who had diarrhea and greater than or equal to 1 episode of vomiting within 4 hours of arrival. Patients were randomly assigned (1:1), through an Internet-based randomization service using a stratified variable-block randomization scheme, to single-dose oral ondansetron or placebo. The primary endpoint was intravenous rehydration (administration of 20 mL/kg of an isotonic fluid during 4 hours) within 72 hours of randomization.Results: Participant median age was 15 months (interquartile range 10 to 26) and 59.4% (372/626) were male patients. Intravenous rehydration use was 12.1% (38/314) and 11.9% (37/312) in the placebo and ondansetron groups, respectively (odds ratio 0.98; 95% confidence interval [CI] 0.60 to 1.61; difference 0.2%; 95% CI of the difference –4.9% to 5.4%). Bolus fluid administration occurred within 72 hours of randomization in 10.8% (34/314) and 10.3% (27/312) of children administered placebo and ondansetron, respectively (odds ratio 0.95; 95% CI 0.56 to 1.59). A multivariable regression model fitted with treatment group and adjusted for antiemetic administration, antibiotics, zinc prerandomization, and vomiting frequency prerandomization yielded similar results (odds ratio 0.91; 95% CI 0.55 to 1.53). There was no interaction between treatment group and age, greater than or equal to 3 stools in the preceding 24 hours, or greater than or equal to 3 vomiting episodes in the preceding 24 hours.Conclusion: Oral administration of a single dose of ondansetron did not result in a reduction in intravenous rehydration use. In children without dehydration, ondansetron does not improve clinical outcomes

Data for 'Something in the way she moves': the functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI)

Protein disulfide isomerase (PDI) has diverse functions in the endoplasmic reticulum as catalyst of redox transfer, disulfide isomerization and oxidative protein folding, as molecular chaperone and in multi-subunit complexes. It interacts with an extraordinarily wide range of substrate and partner proteins, but there is only limited structural information on these interactions. Extensive evidence on the flexibility of PDI in solution is not matched by any detailed picture of the scope of its motion. A new rapid method for simulating the motion of large proteins provides detailed molecular trajectories for PDI demonstrating extensive changes in the relative orientation of its four domains, great variation in the distances between key sites and internal motion within the core ligand-binding domain. The review shows that these simulations are consistent with experimental evidence and provide insight into the functional capabilities conferred by the extensive flexible motion of PDI