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1.  Crystallographic structure determination of B10 mutants of Vitreoscilla hemoglobin: role of Tyr29 (B10) in the structure of the ligand-binding site 
Acta Crystallographica Section F  2013;69(Pt 3):215-222.
The crystal structures of two mutants at position 29 of the dimeric hemoglobin from Vitreoscilla are reported, together with a discussion of the significance of these mutations.
Site-directed mutants of the gene encoding wild-type Vitreoscilla hemoglobin were made that changed Tyr29 (B10) of the wild-type Vitreoscilla hemoglobin (VHb) to either Phe or Ala. The wild-type and the two mutant hemoglobins were expressed in Escherichia coli and purified to homogeneity. The binding of the two mutants to CO was essentially identical to that of wild-type VHb as determined by CO-difference spectra. Circular-dichroism spectra also showed the two mutants to be essentially the same as wild-type VHb regarding overall helicity. All three VHbs were crystallized and their structures were determined at resolutions of 1.7–1.9 Å, which are similar to that of the original wild-type structure determination. The Tyr29Phe mutant has a structure that is essentially indistinguishable from that of the wild type. However, the structure of the Tyr29Ala mutant has significant differences from that of the wild type. In addition, for the Tyr29Ala mutant it was possible to determine the positions of most of the residues in the D region, which was disordered in the originally reported structure of wild-type VHb as well as in the wild-type VHb structure reported here. In the Tyr29Ala mutant, the five-membered ring of proline E8 (Pro54) occupies the space occupied by the aromatic ring of Tyr29 in the wild-type structure. These results are discussed in the context of the proposed role of Tyr29 in the structure of the oxygen-binding pocket.
PMCID: PMC3606562  PMID: 23519792
bacterial hemoglobin; Vitreoscilla; site-directed mutagenesis
2.  A national radiation oncology medical student clerkship survey: Didactic curricular components increase confidence in clinical competency 
Students applying to radiation oncology residency programs complete one or more radiation oncology clerkships. This study assesses student experiences and perspectives during radiation oncology clerkships. The impact of didactic components and number of clerkship experiences in relation to confidence in clinical competency and preparation to function as a first year radiation oncology resident are evaluated.
Methods and Materials
An anonymous, internet-based survey was sent via direct e-mail to all applicants to a single radiation oncology residency program during the 2012–2013 academic year. The survey was composed of three main sections including questions regarding baseline demographic information and prior radiation oncology experience, rotation experiences, and ideal clerkship curriculum content.
The survey response rate was 37% (70/188). Respondents reported 191 unique clerkship experiences. 27% of respondents (19/70) completed at least one clerkship with a didactic component geared towards their level of training. Completing a clerkship with a didactic component was significantly associated with a respondent’s confidence to function as a first- year radiation oncology resident (Wilcoxon rank-sum p = 0.03). However, the total number of clerkships completed did not correlate with confidence to pursue radiation oncology as a specialty (Spearman’s rho p = 0.48) or confidence to function as a first year resident (Spearman’s rho p = 0.43).
Based on responses to this survey, rotating students perceive that the majority of radiation oncology clerkships do not have formal didactic curricula. Survey respondents who completed a clerkship with a didactic curriculum reported feeling more prepared to function as a radiation oncology resident. However, completing an increasing number of clerkships does not appear to improve confidence in the decision to pursue radiation oncology as a career or to function as a radiation oncology resident. These results support further development of structured didactic curricula for the radiation oncology clerkship.
PMCID: PMC4262520  PMID: 24331651
3.  Three dimensional analysis of brace biomechanical efficacy for patients with AIS 
European Spine Journal  2013;22(11):2445-2448.
Corrective three dimensional (3D) effect of different braces is debatable. We evaluated differences in in-brace radiographic correction comparing a custom thoracic-lumbo-sacral-orthosis (TLSO) (T) brace to a Chêneau type TLSO (C) brace using 3D EOS reconstruction technology. Our primary research question was the 3D effect of brace on the spine and in particularly the apical vertebra rotation (AVR).
This was a retrospective comparative analysis of patients with adolescent idiopathic scoliosis who had orthogonal AP and lateral X-rays with and without brace. A 3D image of the spine was reconstructed. Coronal, sagittal and axial spine parameters were measured before bracing and then on the first post-brace X-ray. Brace efficacy in controlling coronal, sagittal and axial parameters was evaluated.
Eighteen patients treated with the C brace and ten patients treated with the T brace were included. No difference was found regarding patients’ age, gender, magnitude of Cobb angle, sagittal parameters or AVR at inclusion. Following bracing, AVR was significantly reduced by the C brace compared to the T brace [average correction of 8.2° vs. 4.9° (P = 0.02)]. Coronal and sagittal correction did not differ significantly between the two groups.
By utilizing a novel 3D reconstruction technology, we were able to demonstrate that braces differ in their immediate effects on the spine. Although clinical relevance should be evaluated in a future trial we feel that the ability to measure treatment effects in 3D, and especially the transverse plane, is an important tool when evaluating different treatments.
PMCID: PMC3886493  PMID: 23873054
Scoliosis; 3D; Apical vertebrae rotation (AVR)
4.  Do obese children experience more severe fractures than nonobese children? A cross-sectional study from a paediatric emergency department 
Paediatrics & Child Health  2014;19(5):251-255.
To determine whether there is an association between childhood obesity and severe extremity fractures. Associations between obesity and complications related to the fracture and/or fracture management were also examined.
The present study was a retrospective, cross-sectional study conducted at a tertiary care children’s emergency department. Eligible cases for review were children (two to 17 years of age) with an extremity fracture. Severe extremity fractures were defined as those requiring manipulation under anesthesia, open operative repair and/or admission to hospital. The primary outcome was the proportion of severe extremity fractures and the secondary outcome was the proportion of complications.
A total of 1340 charts of children who presented with extremity fracture from January 2008 to December 2010 were reviewed. The mean (± SD) age of the study population was 9.1±4.0 years and 62.1% were male. Overall, 19.9% (95% CI 17.8% to 22.0%) were obese and 39.6% (95% CI 36.7% to 39.1%) sustained a severe extremity fracture. The OR of severe extremity fractures among obese versus nonobese children was 1.00 (95% CI 0.76 to 1.32), adjusted for age, sex and mechanism of injury. In addition, the OR of experiencing complications among obese relative to nonobese children was 1.12 (95% CI 0.68 to 1.85).
The results of the present study demonstrated that in children with extremity fractures, obese children were not at increased risk for sustaining more severe extremity fractures or subsequent complications compared with nonobese children.
PMCID: PMC4029229  PMID: 24855428
Child; Emergencies; Fracture; Obesity; Prevention
5.  Origins of cancer symposium report: beyond the tumor cell 
Genes & Cancer  2014;5(11-12):375-377.
The Origins of Cancer Symposium is a meeting organized by graduate students at the Van Andel Research Institute and serves as a forum for focused discussion on factors that contribute to the etiology of cancer. The theme for the fifth annual Origins of Cancer held on July 11th, 2014 was Beyond the Tumor Cell, which focused on the complex influences coming from the environment in which the cancer cell exists. Here we report on the meeting proceedings and briefly discuss the far-reaching implications.
PMCID: PMC4279435
Cancer; extracellular matrix; immunology; symposium; review
6.  GPR40 (FFAR1) – Combined Gs and Gq signaling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo 
Molecular Metabolism  2014;4(1):3-14.
GPR40 (FFAR1), a clinically proven anti-diabetes target, is a Gq-coupled receptor for long chain fatty acids (LCFA) stimulating insulin secretion directly and mediating a major part of the dietary triglyceride-induced secretion of the incretins GLP-1 and GIP. In phase-II studies the GPR40 agonist TAK-875 decreased blood glucose but surprisingly without stimulating incretins.
Methods and results
Here we find that GPR40 can signal through not only Gq and IP3 but also Gs and cAMP when stimulated with certain agonists such as AM-1638 and AM-5262 in contrast to the endogenous LCFA ligands and agonists such as TAK-875 and AM-837, which only signal through Gq. In competition binding against [3H]AM-1638 and [3H]L358 the Gq + Gs and the Gq-only agonists either competed for or showed positive cooperativity by increasing the binding of the two different radio-ligands, in opposite ways. Nevertheless, both the Gq-only and the Gq + Gs agonists all docked surprisingly well into the binding site for TAK-875 in the X-ray structure of GPR40. In murine intestinal primary cell-cultures the endogenous LCFAs and the Gq-only agonists stimulated GLP-1 secretion with rather poor efficacy as compared with the high efficacy Gq + Gs GPR40 agonists and a prototype GPR119 agonist. Similarly, in fasting both male and female mice the Gq + Gs agonists showed significantly higher efficacy than the Gq-only agonists in respect of increasing plasma GLP-1 and plasma GIP in a GPR40-dependent manner.
It is concluded that stimulation of GPR40 by endogenous LCFAs or by Gq-only synthetic agonists result in a rather limited incretin response, whereas Gq + Gs GPR40 agonists stimulate incretin secretion robustly.
PMCID: PMC4314522
G protein-coupled receptor; Glucagon like peptide 1 (GLP-1); Biased signaling; Ago-allosteric agonist; Long chain fatty acids (LCFAs)
7.  Improved survival time trends for glioblastoma using the SEER 17 population-based registries 
Journal of neuro-oncology  2011;107(1):207-212.
The EORTC/NCIC 22981/26981 study demonstrated an improvement in median overall survival (OS) from 12.1 to 14.6 months in patients with glioblastoma (GBM) who received temozolomide with post-operative radiotherapy (RT). The current study was performed to determine if those results translated into a survival benefit in a population-based cohort. Patients diagnosed between 2000 and 2006 with a GBM who underwent surgery and post-operative RT were selected from the Surveillance, Epidemiology and End Results database. Patients were grouped into time periods: 2000–2001, 2002–2003, 2004 and 2005–2006 (which represented those treated after the EORTC/NCIC trial presentation in 2004). Relative survival (RS) was estimated by the Kaplan–Meier method, and Cox multivariable regression modeling was used to estimate proportional hazard ratios (HR). Over time, there was improvement in the median and 2-year RS of 12 months and 15% for 2000–2001, 13 months and 19% for 2002–2003, 14 months and 24% for 2004, and 15 months and 26% for 2005–2006 (P < 0.0001 compared to 2000–2001 and 2002–2003; P = 0.07 compared to 2004). The estimated adjusted HR showed that patients diagnosed in 2005–2006 had significantly improved survival when compared to patients diagnosed in 2000–2001 (HR = 0.648, 95% CI 0.604–0.696). The median and 2 year RS of 15 months and 26% in 2005–2006 was similar to the median and 2 year OS of 14.6 months and 26% seen in the EORTC/NCIC phase III study. These results are encouraging and suggest that the current treatment of glioblastoma nationwide is now associated with an improved survival compared to previous time cohorts.
PMCID: PMC4077033  PMID: 21984115
Glioblastoma; Radiation; Temozolomide; SEER
8.  A Catalytic Mechanism for d-Tyr-tRNATyr Deacylase Based on the Crystal Structure of Hemophilus influenzae HI0670* 
The Journal of biological chemistry  2003;278(15):13496-13502.
d-Tyr-tRNATyr deacylase is an editing enzyme that removes d-tyrosine and other d-amino acids from charged tRNAs, thereby preventing incorrect incorporation of d-amino acids into proteins. A model for the catalytic mechanism of this enzyme is proposed based on the crystal structure of the enzyme from Haemophilus influenzae determined at a 1.64-Å resolution. Structural comparison of this dimeric enzyme with the very similar structure of the enzyme from Escherichia coli together with sequence analyses indicate that the active site is located in the dimer interface within a depression that includes an invariant threonine residue, Thr-80. The active site contains an oxyanion hole formed by the main chain nitrogen atoms of Thr-80 and Phe-79 and the side chain amide group of the invariant Gln-78. The Michaelis complex between the enzyme and d-Tyr-tRNA was modeled assuming a nucleophilic attack on the carbonyl carbon of d-Tyr by the Thr-80 Oγ atom and a role for the oxyanion hole in stabilizing the negatively charged tetrahedral transition states. The model is consistent with all of the available data on substrate specificity. Based on this model, we propose a substrate-assisted acylation/deacylation-catalytic mechanism in which the amino group of the d-Tyr is deprotonated and serves as the general base.
PMCID: PMC3762893  PMID: 12571243
9.  Open reduction and internal fixation of unstable slipped capital femoral epiphysis by means of surgical dislocation does not decrease the rate of avascular necrosis: a preliminary study 
The treatment of unstable slipped capital femoral epiphysis (SCFE) remains controversial. Surgical dislocation and open reduction has the potential to significantly reduce the rate of avascular necrosis (AVN) by allowing direct preservation of the femoral head blood supply. The purpose of this study was to determine if open reduction of the unstable SCFE by means of surgical hip dislocation reduced the risk of AVN compared with closed reduction and percutaneous pinning.
We reviewed the medical records and radiographs of patients treated at our institution between the years 2000 and 2008. Sex, age, side of slip, precipitating event, pre- and post-operative anterior physeal separation (APS) and slip angle, slip severity, time between inciting event and surgical treatment, number of screws used, development of AVN, and need for subsequent surgery were evaluated. Statistical analysis was performed to compare risk factors and occurrence of AVN.
From 2004 to 2008, we treated 12 patients with unstable SCFEs: six had closed reduction and percutaneous pinning and six underwent open reduction by means of surgical hip dislocation. There were no statistically significant differences between the two groups regarding sex, age, slip angle, APS, time to surgery, and AVN rate. At follow-up, 4 (66.7 %) patients had AVN in the group which had open reduction, while 2 (33.3 %) patients had AVN in the group which underwent closed reduction. (p = 0.57).
Open reduction of the unstable SCFE by means of surgical dislocation of the hip does not decrease the rate of AVN when compared to closed reduction.
PMCID: PMC3425698  PMID: 23904893
Slipped capital femoral epiphysis; Closed reduction; Open reduction; Surgical dislocation of the hip; Percutaneous pinning; Avascular necrosis
10.  The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes 
ACS Medicinal Chemistry Letters  2012;3(6):484-489.
A structure–activity relationship study of the imidazolyl-β-tetrahydrocarboline series identified MK-4256 as a potent, selective SSTR3 antagonist, which demonstrated superior efficacy in a mouse oGTT model. MK-4256 reduced glucose excursion in a dose-dependent fashion with maximal efficacy achieved at doses as low as 0.03 mg/kg po. As compared with glipizide, MK-4256 showed a minimal hypoglycemia risk in mice.
PMCID: PMC4025728  PMID: 24900499
SSTR3; antagonist; type 2 diabetes; β-tetrahydrocarboline
11.  Establishing a surgical partnership between Addis Ababa, Ethiopia, and Toronto, Canada 
Canadian Journal of Surgery  2013;56(3):E19-E23.
Academic partnerships between high-and low/middle-income countries can improve the quality of surgical education and health care delivery in each setting. We report the perceived needs related to collaborative surgical education in a resource-limited setting.
We used qualitative methods to elicit the opinions of surgical faculty members and surgical residents and quantitative methods to outline surgical procedure type and volume.
Ethiopian faculty members identified the management of trauma and emergency surgical care as a priority. They identified supervision in the operating room (OR), topic-specific lectures and supervising resident assessments in the clinic as appropriate roles for partners. Residents were in agreement with faculty members, highlighting a desire for supervision in the OR and topic-specific lectures.
We present specific experiences and needs of a surgical teaching unit in a low-income country, paving the way to form a meaningful and responsive relationship between 2 surgical departments in 2 universities.
PMCID: PMC3672439  PMID: 23706853
12.  Stimulation of Glucose-Dependent Insulin Secretion by a Potent, Selective sst3 Antagonist 
ACS Medicinal Chemistry Letters  2012;3(4):289-293.
This letter provides the first pharmacological proof of principle that the sst3 receptor mediates glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. To enable these studies, we identified the selective sst3 antagonist (1R,3R)-3-(5-phenyl-1H-imidazol-2-yl)-1-(tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-β-carboline (5a), with improved ion channel selectivity and mouse pharmacokinetic properties as compared to previously described tetrahydro-β-carboline imidazole sst3 antagonists. We demonstrated that compound 5a enhances GSIS in pancreatic β-cells and blocks glucose excursion induced by dextrose challenge in ipGTT and OGTT models in mice. Finally, we provided strong evidence that these effects are mechanism-based in an ipGTT study, showing reduction of glucose excursion in wild-type but not sst3 knockout mice. Thus, we have shown that antagonism of sst3 represents a new mechanism with potential in treating type 2 diabetes mellitus.
PMCID: PMC4025754  PMID: 24900466
somatostatin; type 2 diabetes; sst3; glucose-stimulated insulin secretion
14.  Structural basis for the mechanism and substrate specificity of glycocyamine kinase, a phosphagen kinase family member†‡ 
Biochemistry  2010;49(9):2031-2041.
Glycocyamine kinase (GK), a member of the phosphagen kinase family, catalyzes the Mg2+-dependent reversible phosphoryl group transfer of the N-phosphoryl group of phospho glycocyamine to ADP to yield glycocyamine and ATP. This reaction helps to maintain the energy homeostasis of the cell in some multicelullar organisms that encounter high and variable energy turnover. GK from the marine worm Namalycastis sp. is heterodimeric, with two homologous polypeptide chains, α and β, derived from a common pre mRNA by mutually exclusive N-terminal alternative exons. The N-terminal exon of GKβ encodes a peptide that is different in sequence and is sixteen amino acids longer than that encoded by the N-terminal exon of GKα. The crystal structures of recombinant GKαβ and GKββ from Namalycastis sp. were determined at 2.6 Å and 2.4 Å resolution, respectively. In addition, the structure of the GKββ was determined at 2.3 Å resolution in complex with a transition state analog, Mg2+-ADP-NO3--glycocyamine. Consistent with the sequence homology, the GK subunits adopt the same overall fold as that of other phosphagen kinases of known structure (the homodimeric creatine kinase (CK) and the monomeric arginine kinase (AK)). As with CK, the GK N-termini mediate the dimer interface. In both heterodimeric and homodimeric GK forms, the conformations of the two N-termini are asymmetric and the asymmetry is different than that reported previously for the homodimeric CKs from several organisms. The entire polypeptide chains of GKαβ are structurally defined and the longer N-terminus of the β subunit is anchored at the dimer interface. In GKββ the 24 N-terminal residues of one subunit and 11 N-terminal residues of the second subunit are disordered. This observation is consistent with a proposal that the GKαβ amino acids involved in the interface formation were optimized once a heterodimer emerged as the physiological form of the enzyme. As a consequence, the homodimer interface (either solely α or solely β chains) has been corrupted. In the unbound state, GK exhibits an open conformation analogous to that observed with ligand-free CK or AK. Upon binding the transition state analog, both subunits of GK undergo the same closure motion that clasps the transition state analog, in contrast to the transition state analog complexes of CK, where the corresponding transition state analog occupies only one subunit, which undergoes domain closure. The active site environments of the GK, CK and AK at the bound states reveal the structural determinants of substrate specificity. Despite the equivalent binding in both active sites of the GK heterodimer, the conformational asymmetry of the N-termini is retained. Thus, the coupling between the structural asymmetry and negative cooperativity previously proposed for CK is not supported in the case of GK.
PMCID: PMC3519428  PMID: 20121101
15.  Helmet use in BIXI cyclists in Toronto, Canada: an observational study 
BMJ Open  2012;2(3):e001049.
To investigate the use of helmets for cyclists choosing to use BIXI bikes in comparison to personal bike riders in the City of Toronto.
Cross-sectional study design.
Cyclists were observed in Toronto, Canada.
Of the 6732 sample size, 306 cyclists on BIXI bikes and 6426 personal bike riders were observed.
Outcome measure
The outcome of interest was helmet use.
Overall, 50.3% of cyclists wore helmets. The proportion of BIXI bike riders using helmets was significantly lower than the proportion of helmet users on personal bikes (20.9% vs 51.7%, respectively, p<0.0001).
Although the BIXI bike programme has provided an alternate means for Torontonians to use a bicycle, cyclists using BIXI bikes are much less likely to wear a helmet. Since the prevalence of helmet use in cyclists in general is already low, helmet use should be especially promoted in BIXI bike riders in order to promote a safe and healthy environment for cyclists.
Article summary
Article focus
We investigated the use of helmets for cyclists choosing to use BIXI bikes in comparison to personal bike riders in the City of Toronto.
We hypothesised that the proportion of helmet users using BIXI bikes would be significantly lower than those on personal bikes.
Key messages
Cyclists using BIXI bikes in Toronto are less likely to wear a helmet than cyclists riding their own bike; only 20.9% of all BIXI cyclists wear helmets compared with 51.7% of cyclists riding a personal bike.
More men than women ride bicycles in Toronto.
Women in Toronto were more likely to wear a helmet while cycling.
Strengths and limitations of this study
This is the first study (to our knowledge) investigating helmet use in a bike-sharing system. Additional strengths include the prospective study design, number of observations, randomly selected observation sites and stratified analyses by sex.
The data were collected by one of the observer not blinded to the study hypothesis; observations were limited to presumed commuter hours in the downtown core of Toronto and we were unable to account for variables previously associated with helmet use, including income, education and age.
PMCID: PMC3378939  PMID: 22710130
16.  Child automobile restraints 
PMCID: PMC3114897  PMID: 21398232
17.  Corruption in the health care sector: A barrier to access of orthopaedic care and medical devices in Uganda 
Globally, injuries cause approximately as many deaths per year as HIV/AIDS, tuberculosis and malaria combined, and 90% of injury deaths occur in low- and middle- income countries. Given not all injuries kill, the disability burden, particularly from orthopaedic injuries, is much higher but is poorly measured at present. The orthopaedic services and orthopaedic medical devices needed to manage the injury burden are frequently unavailable in these countries. Corruption is known to be a major barrier to access of health care, but its effects on access to orthopaedic services is still unknown.
A qualitative case study of 45 open-ended interviews was conducted to investigate the access to orthopaedic health services and orthopaedic medical devices in Uganda. Participants included orthopaedic surgeons, related healthcare professionals, industry and government representatives, and patients. Participants’ experiences in accessing orthopaedic medical devices were explored. Thematic analysis was used to analyze and code the transcripts.
Analysis of the interview data identified poor leadership in government and corruption as major barriers to access of orthopaedic care and orthopaedic medical devices. Corruption was perceived to occur at the worker, hospital and government levels in the forms of misappropriation of funds, theft of equipment, resale of drugs and medical devices, fraud and absenteeism. Other barriers elicited included insufficient health infrastructure and human resources, and high costs of orthopaedic equipment and poverty.
This study identified perceived corruption as a significant barrier to access of orthopaedic care and orthopaedic medical devices in Uganda. As the burden of injury continues to grow, the need to combat corruption and ensure access to orthopaedic services is imperative. Anti-corruption strategies such as transparency and accountability measures, codes of conduct, whistleblower protection, and higher wages and benefits for workers could be important and initial steps in improving access orthopaedic care and OMDs, and managing the global injury burden.
PMCID: PMC3492067  PMID: 22554349
18.  The impact of pedestrian countdown signals on pedestrian–motor vehicle collisions: a quasi-experimental study 
Injury Prevention  2011;18(4):210-215.
To determine whether pedestrian countdown signals (PCS) reduce pedestrian–motor vehicle collisions in the city of Toronto, Canada.
A quasi-experimental study design was used to evaluate the effect of PCS on the number of pedestrian–motor vehicle collisions in the city of Toronto, from January 2000 to December 2009. Each intersection acted as its own control. We compared the number of pedestrian–motor vehicle collisions per intersection-month before and after the intervention. Stratified models were used to evaluate effect modification by pedestrian age, injury severity and location (urban vs inner suburbs). Poisson regression analysis with repeated measures (generalised estimating equations) was used to estimate the RR and 95% CI.
The analysis included 9262 pedestrian–motor vehicle collisions at 1965 intersections. The RR of collisions after PCS installation was 1.014 (95% CI 0.958 to 1.073), indicating no statistically significant effect of PCS on collisions. There was no evidence to suggest effect modification between PCS and collisions by age, injury severity or location.
The installation of PCS at 1965 signalised intersections in Toronto did not reduce the number of pedestrian–motor vehicle collisions at these intersections.
PMCID: PMC3406612  PMID: 22157206
Accidents; bicycle; Canada; child; database; epidemiology; evaluation; MVTC; occupational; pedestrians; playground; public health; restraint; safety; surveillance; traffic/prevention and control; training
20.  Low-income Countries’ Orthopaedic Information Needs: Challenges and Opportunities 
The Internet should, in theory, facilitate access to peer-reviewed scientific articles for orthopaedic surgeons in low-income countries (LIC). However, there are major barriers to access, and most full-text journal articles are available only on a subscription basis, which many in LIC cannot afford. Various models exist to remove such barriers. We set out to examine the potential, and reality, of journal article access for surgeons in LIC by studying readership patterns and journal access through a number of Internet-based initiatives, including an open access journal (“PLoS Medicine”), and programs from the University of Toronto (The Ptolemy Project) and World Health Organization (WHO) (Health InterNetwork Access to Research Initiative [HINARI]).
Do Internet-based initiatives that focus on peer-reviewed journal articles deliver clinically relevant information to those who need it? More specifically: (1) Can the WHO’s program meet the information needs of practicing surgeons in Africa? (2) Are healthcare workers across the globe aware of, and using, open access journals in a manner that reflects global burden of disease (GBD)?
We compared actual Ptolemy use to HINARI holdings. We also compared “PLoS Medicine” readership patterns among low-, middle-, and high-income regions.
Many of the electronic resources used through Ptolemy are not available through HINARI. In contrast to higher-income regions, “PLoS Medicine” readership in Africa is proportional to both the density of healthcare workers and the GBD there.
Free or low-cost Internet-based initiatives can improve access to the medical literature in LIC. Open access journals are a key component to providing clinically relevant literature to the regions and healthcare workers who need it most.
PMCID: PMC3049618  PMID: 20431972
21.  Keeping children safe: rethinking how we design our surroundings 
PMCID: PMC2845685  PMID: 19805499
22.  Purification and crystallization of Cor a 9, a major hazelnut allergen 
The major hazelnut allergen Cor a 9 was purified from the natural source and crystallized. Diffraction data were collected to 1.9 Å resolution using a synchrotron-radiation source.
Hazelnut (Corylus avellana) is one of the food sources that induce allergic reaction in a subpopulation of people with food allergy. The 11S legumin-like seed-storage protein from hazelnut has been identified as one of the major hazelnut allergens and named Cor a 9. In this study, Cor a 9 was extracted from hazelnut kernels using a high-salt solution and was purified by desalting out and FPLC to a highly purified state. Diffraction-quality single crystals were obtained using the hanging-drop vapour-diffusion method. Diffraction data were collected and a structure solution has been obtained by molecular-replacement calculations. Further refinement of the structure is currently in progress.
PMCID: PMC2628846  PMID: 19153454
hazelnuts; 11S seed-storage proteins; food allergies; tree-nut allergens
23.  Cast versus splint in children with minimally angulated fractures of the distal radius: a randomized controlled trial 
Minimally angulated fractures of the distal radius are common in children and have excellent outcomes. We conducted a randomized controlled trial to determine whether the use of a prefabricated splint is as effective as a cast in the recovery of physical function.
We included 96 children 5 to 12 years of age who were treated for a minimally angulated (≤ 15°) greenstick or transverse fracture of the wrist between April 2007 and September 2009 at a tertiary care pediatric hospital. Participants were randomly assigned to receive either a prefabricated wrist splint or a short arm cast for four weeks. The primary outcome was physical function at six weeks, measured using the performance version of the Activities Scale for Kids. Additional outcomes included the degree of angulation, range of motion, grip strength and complications.
Of the 96 children, 46 received a splint and 50 a cast. The mean Activities Scale for Kids score at six weeks was 92.8 in the splint group and 91.4 in the cast group (difference 1.44, 95% confidence interval [CI] −1.75 to 4.62). Thus, the null hypothesis that the splint is less effective by at least seven points was rejected. The between-group difference in angulation at four weeks was not statistically significant (9.85° in the splint group and 8.20° in the cast group; mean difference 1.65°, 95% CI −1.82° to 5.11°), nor was the between-group differences in range of motion, grip strength and complications.
In children with minimally angulated fractures of the distal radius, use of a splint was as effective as a cast with respect to the recovery of physical function. In addition, the devices were comparable in terms of the maintenance of fracture stability and the occurrence of complications. ( trial register no. NCT00610220.)
PMCID: PMC2950182  PMID: 20823169
24.  Safety standards and socioeconomic disparities in school playground injuries: a retrospective cohort study 
BMC Public Health  2010;10:542.
Playground injuries are fairly common and can require hospitalization and or surgery. Previous research has suggested that compliance with guidelines or standards can reduce the incidence of such injuries, and that poorer children are at increased risk of playground injuries.
The objective of this study was to determine the association between playground injury and school socioeconomic status before and after the upgrading of playground equipment to meet CSA guidelines.
Injury data were collected from January 1998-December 1999 and January 2004 - June 2007 for 374 elementary schools in Toronto, Canada. The objective of this study was to investigate the effect of a program of playground assessment, upgrading, and replacement on school injury rates and socio-economic status. Injury rates were calculated for all injuries, injuries that did not occur on equipment, and injuries on play equipment. Poisson regression was performed to determine the relationship between injury rates and school socio-economic status.
Prior to upgrading the equipment there was a significant relationship between socio-economic status and equipment-related injuries with children at poorer schools being at increased risk (Relative risk: 1.52 [95% CI = 1.24-1.86]). After unsafe equipment was upgraded, the relationship between injury and SES decreased and was no longer significant (RR 1.13 [95% CI = 0.95-1.32]).
Improvements in playground equipment can result in an environment in which students from schools in poorer neighbourhoods are no longer at increased risk of injuries on play equipment.
PMCID: PMC2949768  PMID: 20825679
25.  Purification, crystallization and initial crystallographic characterization of the Ginkgo biloba 11S seed globulin ginnacin 
The crystallization of ginnacin, the 11S seed storage protein from G. biloba, is reported.
Ginkgo biloba, a well known ‘living fossil’ native to China, is grown worldwide as an ornamental shade plant. Medicinal and nutritional uses of G. biloba in Asia have a long history. However, ginkgo seed proteins have not been well studied at the biochemical and molecular level. In this study, the G. biloba 11S seed storage protein ginnacin was purified by sequential anion-exchange and gel-filtration chromatography. A crystallization screen was performed and well diffracting single crystals were obtained by the vapor-diffusion method. A molecular-replacement structural solution has been obtained. There are six protomers in an asymmetric unit. Structure refinement is currently in progress.
PMCID: PMC2443976  PMID: 18607097
cupins; ginnacin; allergens; seed storage proteins; herbal medicine

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