Recent studies suggest that cytochrome p450 CYP4F2 enzyme is involved in the ω-hydroxylation of vitamin K. Genetic polymorphism in CYP4F2 is thus likely to affect vitamin K systemic availability, ...which may in turn affect bone development and vascular health in children on long-term anticoagulation therapy with warfarin. There was a...
Patients on warfarin are normally required to stop treatment for a fixed number of days prior to an invasive procedure. However, the anticoagulant activity of warfarin subsides at different rates ...among different patients.
The aim of this study was to investigate the potential influence of CYP2C9 polymorphism on the variable rate of fall in the International Normalized Ratio (INR) in patients withdrawing from warfarin treatment prior to elective surgery.
One hundred and fifty-two patients aged 43-93 years were recruited. Demographic data on age, height, weight, gender, daily warfarin dose, indication for anticoagulation therapy, medical diagnosis, surgical operation planned and concomitant medication were recorded. A blood sample was taken for later CYP2C9 genotyping.
For patients with two CYP2C9 variant alleles (CYP2C9*2*2 or CYP2C9*2*3), the odds of having an INR of ≥ 1.5 before the planned day of surgery were 8.64 times greater (95% confidence interval CI 2.25-33.25) than for other patients. Multiple regression analysis revealed that the rate of fall in the INR was reduced in the presence of two CYP2C9 variant alleles, as well as increasing patient age, weight and number of comorbidities, and increased with increasing initial INR (F5,132 = 242.9, P < 0.0001), all of which accounted for ~ 90% of the interindividual variability in the fall in INR.
A genotype-guided protocol to tailor warfarin withdrawal according to an individual patient's CYP2C9 genotype could reduce cancellation or delays of planned procedures, and could also be beneficial when transitioning patients from warfarin to one of the new oral anticoagulants.
We wished to investigate the influence of metal debris exposure on the subsequent immune response and resulting soft-tissue injury following metal-on-metal (MoM) hip arthroplasty. Some reports have ...suggested that debris generated from the head-neck taper junction is more destructive than equivalent doses from metal bearing surfaces.
We investigated the influence of the source and volume of metal debris on chromium (Cr) and cobalt (Co) concentrations in corresponding blood and hip synovial fluid samples and the observed agglomerated particle sizes in excised tissues using multiple regression analysis of prospectively collected data. A total of 199 explanted MoM hips (177 patients; 132 hips female) were analysed to determine rates of volumetric wear at the bearing surfaces and taper junctions.
The statistical modelling suggested that a greater source contribution of metal debris from the taper junction was associated with smaller aggregated particle sizes in the local tissues and a relative reduction of Cr ion concentrations in the corresponding synovial fluid and blood samples. Metal debris generated from taper junctions appears to be of a different morphology, composition and therefore, potentially, immunogenicity to that generated from bearing surfaces.
The differences in debris arising from the taper and the articulating surfaces may provide some understanding of the increased incidence of soft-tissue reactions reported in patients implanted with MoM total hip arthroplasties compared with patients with hip resurfacings. Cite this article: Bone Joint J 2016;98-B:925-33.
Essentials The once-daily dosing of tinzaparin provides an advantage over other low molecular weight heparins. The recommended age-dependent doses of tinzaparin in children have not previously been ...validated. Once-daily administration of tinzaparin is a safe and effective treatment of childhood thrombosis. Recommended doses are appropriate but monitoring may be required due to inter-individual variation.
Background The recommended starting doses of tinzaparin for the treatment of thrombosis in children have not previously been validated. There are few data to support the efficacy and safety of once-daily tinzaparin dosing in children with thrombosis. Objectives To investigate the use of tinzaparin for the treatment of childhood thrombosis, and to evaluate the age-dependent dosing recommendations and define outcomes in terms of efficacy and safety. Methods This was a retrospective cohort study of children aged 0 to < 16 years treated for thrombosis at a large teaching hospital in the UK between 2008 and 2015. Medical records were reviewed to evaluate tinzaparin dosing, anti-activated factor X (FXa) levels, and patient outcomes. Results Seventy-nine children were identified as having received tinzaparin. Dosing information was available for 57. Younger children required higher doses to reach a therapeutic level. The therapeutic dose requirement varied within age groups, supporting the use of anti-FXa monitoring. Over a median follow-up of 35 months, there were 13 (16%) bleeding episodes (two major; seven clinically relevant but non-major; and four minor). There were two (3%) recurrent episodes of thrombosis. Children were treated for a median duration of 3 months, and the majority (86%) remained on tinzaparin for the duration of their anticoagulant therapy. Conclusion Once-daily tinzaparin is a safe and effective treatment for childhood thrombosis, with rates of recurrence and bleeding similar to those for other anticoagulants used in children. The recommended starting doses are appropriate, but anti-FXa monitoring may be required, owing to interindividual variability in the therapeutic dose requirement.
PurposeTo assess the changes in diabetic retinopathy (DR) in type 2 diabetes (T2DM) patients post bariatric surgery and report on the risk factors that may be associated with it.Patients and ...methodsRetrospective observational study of T2DM patients who underwent bariatric surgery in a UK specialist bariatric unit between 2009 and 2015. Preoperative and postoperative weight, HbA1c, and annual DR screening results were collected from medical records. Patients with preoperative retinal screening and at least one postoperative retinal screening were eligible for analysis. Multivariate analysis was used to explore significant clinical predictors on postoperative worsening in DR.ResultsA total of 102 patients were eligible for analysis and were followed up for 4 years. Preoperatively, 68% of patients had no DR compared to 30% with background retinopathy, 1% pre-proliferative retinopathy, and 1% proliferative retinopathy. In the first postoperative visit, 19% of patients developed new DR compared to 70% stable and 11% improved. These proportions remained similar for each postoperative visit over time. Young age, male gender, high preoperative HbA1c, and presence of preoperative retinopathy were the significant predictors of worsening postoperatively.ConclusionBariatric surgery does not prevent progression of DR. Young male patients with pre-existing DR and poor preoperative glycaemic control are most at risk of progression. All diabetic patients should attend regular DR screening post bariatric surgery to allow early detection of potentially sight-threatening changes, particularly among those with identifiable risk factors. Future prospective studies with prolonged follow-up are required to clarify the duration of risk.
During 2005-2010, the Canadian Integrated Program for Antimicrobial Resistance Surveillance identified increased prevalence of ciprofloxacin (a fluororquinolone) resistance among Campylobacter ...isolates from retail chicken in British Columbia (4%-17%) and Saskatchewan (6%-11%), Canada. Fluoroquinolones are critically important to human medicine and are not labeled for use in poultry in Canada.
The insects evaluated were susceptible to infection by the Hypocreales fungus, Ifr, in the product PFR 97™ and Ifr 3581 when applied as a spray to seedlings, leaves or leaf discs. This is the first ...report indicating that H. vitripennis, T. citricidus and D. abbreviatus were susceptible to Ifr strains under laboratory conditions. The results suggest that Ifr provides a potential biological control agent for these and other pests of agricultural crops, and may provide a product for organic growers, as well as an additional tool to augment standard IPM programs.
Since the 1930s, California's Sierra Nevada has warmed by an average of 1.2
C. Warming directly primes forests for easier wildfire ignition, but the change in climate also affects vegetation species ...composition. Different types of vegetation support unique fire regimes with distinct probabilities of catastrophic wildfire, and anticipating vegetation transitions is an important but undervalued component of long-term wildfire management and adaptation. Vegetation transitions are more likely where the climate has become unsuitable but the species composition remains static. This vegetation climate mismatch (VCM) can result in vegetation conversions, particularly after a disturbance like wildfire. Here we produce estimates of VCM within conifer-dominated forests in the Sierra Nevada. Observations from the 1930s Wieslander Survey provide a foundation for characterizing the historical relationship between Sierra Nevada vegetation and climate before the onset of recent, rapid climate change. Based on comparing the historical climatic niche to the modern distribution of conifers and climate, ∼19.5% of modern Sierra Nevada coniferous forests are experiencing VCM, 95% of which is below an elevation of 2356 m. We found that these VCM estimates carry empirical consequences: likelihood of type-conversion increased by 9.2% for every 10% decrease in habitat suitability. Maps of Sierra Nevada VCM can help guide long-term land management decisions by distinguishing areas likely to transition from those expected to remain stable in the near future. This can help direct limited resources to their most effective uses-whether it be protecting land or managing vegetation transitions-in the effort to maintain biodiversity, ecosystem services, and public health in the Sierra Nevada.
We previously reported Clostridium difficile in 20% of retail meat in Canada, which raised concerns about potential foodborne transmissibility. Here, we studied the genetic diversity of C. difficile ...in retail meats, using a broad Canadian sampling infrastructure and 3 culture methods. We found 6.1% prevalence and indications of possible seasonality (highest prevalence in winter).
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•Four fungal strains can infect and kill Xyleborus glabratus, vector of laurel wilt.•Spores adhere to beetles walking on fungus-treated wood.•Initial tunneling activity is not ...inhibited but beetles die inside the tunnels.•Beauveria bassiana kills Xyleborus glabratus faster than other tested fungi.•Fungal pathogens are potential biological control agents of Xyleborus glabratus.
The redbay ambrosia beetle (RAB), Xyleborus glabratus, is a wood-boring insect that vectors the fungal pathogen, Raffaelea lauricola, which causes laurel wilt, a lethal disease of avocado. The objective of this study was to determine the susceptibility of RAB to infection and subsequent death by exposure to three commercial strains of entomopathogenic fungi two strains of Isaria fumosorosea (Ifr 3581 and PFR), and strain GHA of Beauveria bassiana. RAB females were dipped in fungal spore solutions and their median survivorship times (MST) determined. Contact with any of the biopesticides resulted in death of all RAB females. MSTs of RAB females ranged from 3days (B. bassiana) to 5days (I. fumosorosea PFR). B.bassiana killed RAB females faster, followed by Ifr 3581 and PFR. RAB females dipped in B. bassiana suspensions had the highest number of viable spores attached to their bodies, followed by Ifr 3581. Beetles dipped in PFR suspension had significantly less viable spores attached to their bodies. No significant differences were observed in the mortality of beetles exposed to entomopathogenic fungi by dipping in a fungal suspension or walking on treated avocado bolts. Beetles bored into the logs and constructed galleries, but they were found dead inside the galleries a few days after exposure to the entomopathogens. Entomopathogenic fungal infection in dead beetles was confirmed through molecular techniques. This is the first study to demonstrate that entomopathogenic fungi are potential biological control agents against RAB.
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