Systematic review: plantar fasciitis and prolonged weight bearing.

BACKGROUND: Plantar fasciitis (PF) is one of the most common causes of foot pain. Work can involve factors that may predispose to foot pain. AIMS: To systematically review the evidence of the association between weight bearing (walking or standing) and PF among workers. METHODS: Literature search of relevant indexing databases from inception to May 2012, grey literature, websites of relevant organizations and reference lists for all identified articles. Two reviewers independently selected studies for full review, assessed methodological quality and graded evidence. Findings were summarized qualitatively. RESULTS: Four studies were included; all were assessed as high or unclear risk of bias. Three studies were case-control studies; two used clinic populations and one used volunteers. The other study was cross-sectional involving the workforce of an assembly plant. A number of associations between PF and risk factors were identified including sex, obesity, foot biomechanics and job factors (e.g. job tenure). Two case-control studies and the cross-sectional study found an association with weight bearing, but the assessment of weight bearing varied (e.g. time on feet, time walking or standing). There was low-quality evidence to confirm a causal relationship (Royal College of General Practitioners (RCGP) * grade). CONCLUSIONS: This systematic review found low-quality evidence of an association between PF and weight-bearing tasks such as walking and standing on hard surfaces. The only occupations specifically identified as having higher risk were those associated with the engine assembly plant. Further research is required to fully determine the association between weight bearing and PF.

Diagnostic thresholds for gestational diabetes and their impact on pregnancy outcomes: a systematic review.

AIMS: To assess different diagnostic thresholds for gestational diabetes on outcomes for mothers and their offspring in the absence of treatment for gestational diabetes. This information was used to inform a National Institutes of Health consensus conference on diagnosing gestational diabetes. METHODS: We searched 15 electronic databases from 1995 to May 2012. Study selection was conducted independently by two reviewers. Randomized controlled trials or cohort studies were eligible if they involved women without known pre-existing diabetes mellitus and who did not undergo treatment for gestational diabetes. One reviewer extracted, and a second reviewer verified, data for accuracy. Two reviewers independently assessed methodological quality. RESULTS: Thirty-eight studies were included. Three large, methodologically strong studies showed a continuous positive relationship between increasing glucose levels and the incidence of Caesarean section and macrosomia. When data were examined categorically (i.e. women meeting or not meeting specific diagnostic thresholds), women with gestational diabetes across all glucose criteria had significantly more Caesarean sections, shoulder dystocia, macrosomia (except for International Association of Diabetes in Pregnancy Study Groups' criteria) and large for gestational age. Higher glucose thresholds did not consistently demonstrate greater risk for all outcomes. CONCLUSIONS: Higher glucose thresholds did not consistently demonstrate greater risk, possibly because studies did not compare mutually exclusive groups of women. A pragmatic approach for diagnosis of gestational diabetes using Hyperglycemia and Adverse Pregnancy Outcome Study odds ratio 2.0 thresholds warrants further consideration until additional analysis of the data comparing mutually exclusive groups of women is provided and large randomized controlled trials investigating different diagnostic and treatment thresholds are completed.

Granulocyte colony-stimulating factor for hepatitis C therapy-associated neutropenia: systematic review and economic evaluation.

Hepatitis C virus (HCV) treatment requires maximal adherence to pegylated interferon (Peg-IFN) and ribavirin to achieve a sustained virologic response (SVR). Neutropenia is the most common cause for Peg-IFN dose reduction. Our objectives were to evaluate the effectiveness, safety and cost-effectiveness of granulocyte colony-stimulating factor (G-CSF) versus Peg-IFN dose reduction for HCV therapy-associated neutropenia in treatment naïve adults. We conducted a systematic review to identify controlled trials and observational studies. Study selection, quality assessment and data extraction were completed independently by two investigators. Cost-effectiveness and cost-utility analyses compared G-CSF with dose reduction. Nineteen studies were included. In one trial, the SVR for those receiving G-CSF was 54.5% (95% CI: 34.7-73.1) compared with 26.3% (95% CI: 11.8-48.8) for dose reduction. The remaining studies were case series or retrospective cohorts and provided weak evidence for the relationship between SVR and G-CSF. The risk of adverse events, including infection, associated with G-CSF was low (13.1%; 95% CI: 8.0-20.8) and clinically insignificant. G-CSF had an incremental cost-effectiveness ratio of $41,701 per SVR achieved in genotype 1, and $16,115 per SVR achieved in genotype 2 or 3. Estimates were robust under a variety of resource and intervention scenarios. While administration of G-CSF may enable patients to remain on or resume optimal HCV therapy, there was weak evidence that this improves the likelihood of SVR compared with dose reduction. Adverse effects of G-CSF are mild. The economic evaluation was inconclusive.

Controlling spontaneous emission with metamaterials.

We have observed, in metamaterial with hyperbolic dispersion (an array of silver nanowires in alumina membrane), a sixfold reduction of the emission lifetime of dye deposited onto the metamaterial's surface. This serves as evidence of an anomalously high density of photonic states in hyperbolic metamaterials, demonstrates the feasibility of an earlier-predicted single-photon gun, and paves the road for the use of metamaterials in quantum optics.

Medical illness, medication use and suicide in seniors: a population-based case-control study.

BACKGROUND: Suicide among seniors is a significant health problem in north America, particularly for men in whom the rates rise steadily after 50 years of age. The goal of this study was to examine elder suicides identified from a large population-based database using case-control methods to determine disease and medication factors related to suicide. METHODS: A population-based 1 : 5 case-control study was conducted comparing seniors aged 66 years and older who had died by suicide with age and sex-matched controls. Case data were obtained through British Columbia (BC) Vital Statistics, whereas controls were randomly selected from the BC Health Insurance Registry. Cases and controls were linked to the provincial PharmaCare database to determine medication use and the provincial Physician Claims and Inpatient Hospitalization databases to determine co-morbidity. RESULTS: Between 1993 and 2002 a total of 602 seniors died by suicide in BC giving an annual rate of 13.2 per 100,000. Firearms were the most common mechanism (28%), followed by hanging/suffocation (25%), self-poisoning (21%), and jumping from height (7%). In the adjusted logistic model, variables related to suicide included: lower socioeconomic status, depression/psychosis, neurosis, stroke, cancer, liver disease, parasuicide, benzodiazepine use, narcotic pain killer use and diuretic use. There was an elevated risk for those prescribed inappropriate benzodiazepines and for those using strong narcotic pain killers. CONCLUSION: This study is consistent with previous studies that have identified a relationship between medical or psychiatric co-morbidity and suicide in seniors. In addition, new and potentially useful information confirms that certain types and dosages of benzodiazepines are harmful to seniors and their use should be avoided.

DNA mimicry by proteins.

It has been discovered recently, via structural and biophysical analyses, that proteins can mimic DNA structures in order to inhibit proteins that would normally bind to DNA. Mimicry of the phosphate backbone of DNA, the hydrogen-bonding properties of the nucleotide bases and the bending and twisting of the DNA double helix are all present in the mimics discovered to date. These mimics target a range of proteins and enzymes such as DNA restriction enzymes, DNA repair enzymes, DNA gyrase and nucleosomal and nucleoid-associated proteins. The unusual properties of these protein DNA mimics may provide a foundation for the design of targeted inhibitors of DNA-binding proteins.

StpA protein from Escherichia coli condenses supercoiled DNA in preference to linear DNA and protects it from digestion by DNase I and EcoKI.

The nucleoid-associated protein, StpA, of Escherichia coli binds non-specifically to double-stranded DNA (dsDNA) and apparently forms bridges between adjacent segments of the DNA. Such a coating of protein on the DNA would be expected to hinder the action of nucleases. We demonstrate that StpA binding hinders dsDNA cleavage by both the non-specific endonuclease, DNase I, and by the site-specific type I restriction endonuclease, EcoKI. It requires approximately one StpA molecule per 250-300 bp of supercoiled DNA and approximately one StpA molecule per 60-100 bp on linear DNA for strong inhibition of the nucleases. These results support the role of StpA as a nucleoid-structuring protein which binds DNA segments together. The inhibition of EcoKI, which cleaves DNA at a site remote from its initial target sequence after extensive DNA translocation driven by ATP hydrolysis, suggests that these enzymes would be unable to function on chromosomal DNA even during times of DNA damage when potentially lethal, unmodified target sites occur on the chromosome. This supports a role for nucleoid-associated proteins in restriction alleviation during times of cell stress.

Single molecule fluorescence imaging and its application to the study of DNA condensation.

Single molecule fluorescence imaging incorporated with optical tweezers and a laminar flow cell has been used to monitor the kinetic process of DNA condensation induced by spermidine. It was found that at least two steps were involved in the condensation process of the hydrodynamically-stretched linear DNA; a lag period followed by a rapid collapse of DNA. The lag time increased with the flow speed and the collapse time remained short within the range of the flow speed studied. The effect of salt concentration on the condensation process was examined, and the results suggest that the longer lag time observed in the higher salt buffer probably results from the displacement of bound cations and rearrangement of spermidine on the DNA. The flow-speed dependence of the lag time suggests that a nucleation event at the free end of the DNA, i.e. formation of a loop, may play a vital role in the kinetic process of condensation.

Utilization of health services following spinal cord injury: a 6-year follow-up study.

STUDY DESIGN: Cohort study with 6-years follow-up. OBJECTIVE: To describe the utilization of health services by persons with spinal cord injury (SCI) and compare it with that of the general population. SETTING: Alberta, Canada. METHODS: All persons who sustained an SCI in Alberta between April 1992 and March 1994 were followed from date of injury to 6 years postinjury. Cases were matched (1:5) with controls randomly selected from the general population and matched for age, gender, and region of residence. Administrative data from centralized health care databases were compiled to provide a complete picture of health care use, including hospitalizations, physician contacts, long-term care admissions, home care services, and the occurrence of secondary complications. RESULTS: In all, 233 individuals with SCI and 1165 matched controls were followed for 6 years. Compared with the control group, persons with SCI were rehospitalized 2.6 times more often, spent 3.3 more days in hospital, were 2.7 times more likely to have a physician contact, and required 30 times more hours of home care services. Of those with SCI, 47.6% were treated for a urinary tract infection, 33.8% for pneumonia, 27.5% for depression, and 19.7% for decubitus ulcer. CONCLUSION: SCI places a heavy burden on the health care system. Persons with SCI have greater rates of contact with the health system compared with the general population. Secondary complications continue to affect persons with SCI long after the acute trauma.

Unusual 2-aminopurine fluorescence from a complex of DNA and the EcoKI methyltransferase.

The methyltransferase, M.EcoKI, recognizes the DNA sequence 5'-AACNNNNNNGTGC-3' and methylates adenine at the underlined positions. DNA methylation has been shown by crystallography to occur via a base flipping mechanism and is believed to be a general mechanism for all methyltransferases. If no structure is available, the fluorescence of 2-aminopurine is often used as a signal for base flipping as it shows enhanced fluorescence when its environment is perturbed. We find that 2-aminopurine gives enhanced fluorescence emission not only when it is placed at the M.EcoKI methylation sites but also at a location adjacent to the target adenine. Thus it appears that 2-aminopurine fluorescence intensity is not a clear indicator of base flipping but is a more general measure of DNA distortion. Upon addition of the cofactor S-adenosyl-methionine to the M.EcoKI:DNA complex, the 2-aminopurine fluorescence changes to that of a new species showing excitation at 345 nm and emission at 450 nm. This change requires a fully active enzyme, the correct cofactor and the 2-aminopurine located at the methylation site. However, the new fluorescent species is not a covalently modified form of 2-aminopurine and we suggest that it represents a hitherto undetected physicochemical form of 2-aminopurine.

Interaction of the ocr gene 0.3 protein of bacteriophage T7 with EcoKI restriction/modification enzyme.

The ocr protein, the product of gene 0.3 of bacteriophage T7, is a structural mimic of the phosphate backbone of B-form DNA. In total it mimics 22 phosphate groups over approximately 24 bp of DNA. This mimicry allows it to block DNA binding by type I DNA restriction enzymes and to inhibit these enzymes. We have determined that multiple ocr dimers can bind stoichiometrically to the archetypal type I enzyme, EcoKI. One dimer binds to the core methyltransferase and two to the complete bifunctional restriction and modification enzyme. Ocr can also bind to the component subunits of EcoKI. Binding affinity to the methyltransferase core is extremely strong with a large favourable enthalpy change and an unfavourable entropy change. This strong interaction prevents the dissociation of the methyltransferase which occurs upon dilution of the enzyme. This stabilisation arises because the interaction appears to involve virtually the entire surface area of ocr and leads to the enzyme completely wrapping around ocr.

Structure of Ocr from bacteriophage T7, a protein that mimics B-form DNA.

We have solved, by X-ray crystallography to a resolution of 1.8 A, the structure of a protein capable of mimicking approximately 20 base pairs of B-form DNA. This ocr protein, encoded by gene 0.3 of bacteriophage T7, mimics the size and shape of a bent DNA molecule and the arrangement of negative charges along the phosphate backbone of B-form DNA. We also demonstrate that ocr is an efficient inhibitor in vivo of all known families of the complex type I DNA restriction enzymes. Using atomic force microscopy, we have also observed that type I enzymes induce a bend in DNA of similar magnitude to the bend in the ocr molecule. This first structure of an antirestriction protein demonstrates the construction of structural mimetics of long segments of B-form DNA.

Crystallization and preliminary X-ray analysis of ocr, the product of gene 0.3 of bacteriophage T7.

Ocr, the product of gene 0.3 of bacteriophage T7, prevents the action of restriction endonucleases of the host bacteria. The amino-acid sequence of ocr has less than 20% similarity to any protein of known three-dimensional structure. Ocr has been crystallized in a number of different crystal forms and X-ray data for the seleno-L-methionine-substituted form has been collected to a resolution of 1.8 A. The presence of caesium was found to be required for good crystal growth. Anomalous X-ray data was used to identify possible positions for Se and Cs atoms in the unit cell.

Nucleoside triphosphate-dependent restriction enzymes.

The known nucleoside triphosphate-dependent restriction enzymes are hetero-oligomeric proteins that behave as molecular machines in response to their target sequences. They translocate DNA in a process dependent on the hydrolysis of a nucleoside triphosphate. For the ATP-dependent type I and type III restriction and modification systems, the collision of translocating complexes triggers hydrolysis of phosphodiester bonds in unmodified DNA to generate double-strand breaks. Type I endonucleases break the DNA at unspecified sequences remote from the target sequence, type III endonucleases at a fixed position close to the target sequence. Type I and type III restriction and modification (R-M) systems are notable for effective post-translational control of their endonuclease activity. For some type I enzymes, this control is mediated by proteolytic degradation of that subunit of the complex which is essential for DNA translocation and breakage. This control, lacking in the well-studied type II R-M systems, provides extraordinarily effective protection of resident DNA should it acquire unmodified target sequences. The only well-documented GTP-dependent restriction enzyme, McrBC, requires methylated target sequences for the initiation of phosphodiester bond cleavage.

Shape of Ocr, the gene 0.3 protein of bacteriophage T7: modeling based on light scattering experiments.

Ocr, the first protein expressed by bacteriophage T7, inhibits type Iota DNA restriction enzymes by preventing them from binding to DNA. This inhibition allows the phage to successfully infect the host. The shape of ocr is modeled on the basis of static and dynamic light scattering measurements. The static light scattering data confirm previous observations that ocr exists in solution as a dimer. The diffusion constant determined by dynamic light scattering indicates a nonspherical shape of the ocr dimer. Hydrodynamic models of ellipsoids are presented, and it is argued that ocr is best described by a prolate ellipsoid with dimensions of 10.4 nm by 2.6 nm. The size and shape predicted by this model are consistent with ocr acting as a mimic of the DNA structure bound by type Iota restriction enzymes.

Characterisation of the structure of ocr, the gene 0.3 protein of bacteriophage T7.

The product of gene 0.3 of bacteriophage T7, ocr, is a potent inhibitor of type I DNA restriction and modification enzymes. We have used biophysical methods to examine the mass, stability, shape and surface charge distribution of ocr. Ocr is a dimeric protein with hydrodynamic behaviour equivalent to a prolate ellipsoid of axial ratio 4.3 +/- 0.7:1 and mass of 27 kDa. The protein is resistant to denaturation but removal of the C-terminal region reduces stability substantially. Six amino acids, N4, D25, N43, D62, S68 and W94, are all located on the surface of the protein and N4 and S68 are also located at the interface between the two 116 amino acid monomers. Negatively charged amino acid side chains surround W94 but these side chains are not part of the highly acidic C-terminus after W94. Ocr is able to displace a short DNA duplex from the binding site of a type I enzyme with a dissociation constant of the order of 100 pM or better. These results suggest that ocr is of a suitable size and shape to effectively block the DNA binding site of a type I enzyme and has a large negatively charged patch on its surface. This charge distribution may be complementary to the charge distribution within the DNA binding site of type I DNA restriction and modification enzymes.

DNA recognition by the methyl-CpG binding domain of MeCP2.

The methyl-CpG binding domain (MBD) of the transcriptional repressor MeCP2 has been proposed to recognize a single symmetrically methylated CpG base pair via hydrophobic patches on an otherwise positively charged DNA binding surface. We have tested this binding model by analysis of mutant derivatives of the MeCP2 MBD in electrophoretic mobility shift assays complemented by NMR structural analysis. Exposed arginine side chains on the binding face, in particular Arg-111, were found to be critical for binding. Arg-111 was found to interact with the conserved aspartate side chain Asp-121, which is proposed to orientate the arginine side chain to allow specific contacts with the DNA. The conformational flexibility of the disordered B-C loop region, which forms part of the binding face, was also shown to be important. In contrast, mutation of the exposed hydrophobic side chains had a less severe effect on DNA binding. This suggests that the Arg-111 side chain may contribute to sequence-specific recognition of the CpG site rather than simply making nonspecific contacts with the phosphate backbone. The majority of missense mutations within the MBD found in the human genetic disorder Rett syndrome were shown or predicted to affect folding of the domain rather than the DNA recognition event directly.

Personal risk factors associated with injury among female recreational ice hockey players.

INTRODUCTION: Women's ice hockey is a rapidly growing sport, however little is known about the injuries sustained by this group of athletes. PURPOSE: The objective of this research was to identify risk factors associated with injury among female recreational ice hockey players. METHODS: This prospective study followed players from two women's ice hockey leagues in Edmonton, Canada during the 1997-98 hockey season. The occurrence of injuries was monitored during the season through standardized telephone follow-up. Risk factors were determined using multiple logistic regression. RESULTS: The initial study sample consisted of 314 players, however as the season progressed 19 (6%) were lost to follow-up. The results of the study are based on 295 (94%) participants. A total of 125 injuries were reported; the injury rate was 7.5 injuries/1,000 player-exposures. Risk factors found to be significantly related to the occurrence of injury were: injury in the past year (OR= 1.57), more than 5 years of hockey experience (OR=1.49), and high exposure level (OR=1.41). CONCLUSION: This research is the first to quantify personal risk factors associated with injury among female recreational ice hockey players. A sports injury in the previous 12 months appears to be highly associated with injury and further research is required to more fully understand this relationship. The importance of controlling for level of exposure when investigating risk factors for sports injury was demonstrated.

Epidemiology of women's recreational ice hockey injuries.

INTRODUCTION: Participation in ice hockey by women is increasing in many parts of North America; however, research into injuries and the patterns of injury among female players associated with this activity is limited. PURPOSE: The purpose of this research was to examine the incidence and nature of injuries suffered by female recreational ice hockey players. METHODS: This prospective study followed 314 female players from 33 teams in Edmonton, Canada, during the 1997-1998 hockey season. Injury and game attendance data were collected using monthly telephone interviews throughout the season. Diagnostic information for individuals who received medical treatment was solicited from the attending health professional. RESULTS: A total of 102 players reported a total of 125 injuries for a rate 7.5 injuries/1000 player exposures. The anatomic region most often injured was the lower extremity (31.2%), and the most common diagnosis was sprain/strain (52.0%). The predominant injury mechanism was player contact, either as a result of collision with another player or a body check (40.0%). Of all injuries, 65.6% occurred during league games, 27.2% during play-off, tournament, or exhibition games, and 7.2% during practices. Although less than 1% of injuries resulted in hospitalization, 17.6% of injuries resulted in an absence from hockey of 8 or more days. CONCLUSION: The diagnostic and anatomic distribution of injury in the women's hockey league was similar to that in leagues where full facial protection is mandatory. The observed injury rate was lower than the rates reported for male recreational and collegiate ice hockey players. Female recreational ice hockey players are at risk for injuries and further research is required to identify areas for injury prevention.

Translocation-independent dimerization of the EcoKI endonuclease visualized by atomic force microscopy.

Bacterial type I restriction/modification systems are capable of performing multiple actions in response to the methylation pattern on their DNA recognition sequences. The enzymes making up these systems serve to protect the bacterial cells against viral infection by binding to their recognition sequences on the invading DNA and degrading it after extensive ATP-driven translocation. DNA cleavage has been thought to occur as the result of a collision between two translocating enzyme complexes. Using atomic force microscopy (AFM), we show here that EcoKI dimerizes rapidly when bound to a plasmid containing two recognition sites for the enzyme. Dimerization proceeds in the absence of ATP and is also seen with an EcoKI mutant (K477R) that is unable to translocate DNA. Only monomers are seen when the enzyme complex binds to a plasmid containing a single recognition site. Based on our results, we propose that the binding of EcoKI to specific DNA target sequences is accompanied by a conformational change that leads rapidly to dimerization. This event is followed by ATP-dependent translocation and cleavage of the DNA.