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Background This study sought to determine the impact of the pandemic response to healthcare delivery on outcomes in patients with cardiovascular disease. Methods This is a population-based cohort study performed in the province of Nova Scotia (population 979,499), between Pre-COVID (March 1, 2017 – March 16, 2020) and in-COVID (March 17, 2020 – December 31, 2020) periods. Adult patients (≥18 years) with new onset or existing cardiovascular disease were included for comparison between periods. The main outcome measures included: cardiovascular emergency department visits or hospitalizations, mortality, and out-of-hospital cardiac arrest. Results In the first month of the in-COVID period, emergency department visits (n=51,750) for cardiac symptoms decreased by 20.8% (95% CI 14.0% - 27.0%, p, Restrictions in healthcare resources due to COVID-19 was associated with increased morbidity/mortality in patients with cardiovascular disease. In a population with low burden of COVID-19 disease, increased rates of out-of-hospital cardiac arrest and myocardial infarction were observed, with increased mortality in patients awaiting coronary revascularization procedures. As the world recovers from the pandemic, steps should be taken to inform policy surrounding healthcare delivery for future pandemic relief and an increased burden of cardiovascular disease.

Chromosome segregation is mediated by spindle microtubules that attach to the kinetochore via dynamic protein complexes, such as Ndc80, Ska, Cdt1 and ch-TOG during mitotic metaphase. While experimental studies have previously shown that these proteins and protein complexes are all essential for maintaining a stable kinetochore-microtubule (kMT) interface, their exact roles in this mitotic metaphase remains elusive. In this study, we employed experimental and computational methods in order to characterize how these proteins can strengthen kMT attachments in both nonload-bearing and load-bearing conditions, typical of prometaphase and metaphase, respectively. Immunofluorescence staining of HeLa cells showed that the levels of Ska and Cdt1 significantly increased from prometaphase to metaphase, while levels of the Ndc80 complex remained unchanged. Our new computational model showed that by incorporating binding and unbinding of each protein complex coupled with a biased diffusion mechanism, the displacement of a possible complex formed by Ndc80-Ska-Cdt1 is significantly higher than that of Ndc80 alone or Ndc80-Ska. In addition, when we incorporate Ndc80/ch-TOG in the model, rupture force and time of attachment of the kMT interface increases. These results support the hypothesis that Ndc80-associated proteins strengthen kMT attachments, and that the interplay between kMT protein complexes in metaphase ensures stable attachments.

Background Low back pain is one of the most common and disabling health problems in Canada and internationally. In most cases, low back pain is a benign, self-limiting condition that can be managed with little diagnostic investigation or treatment. Yet contrary to clinical practice guideline recommendations, diagnostic imaging (here meaning X-ray, MRI, CT) is commonly used in the assessment of low back pain. Diagnostic imaging is of limited value in most cases, exposing patients to unnecessary radiation and leading to increased health services use and worse patient health outcomes. The Choosing Wisely campaign has highlighted the need to reduce diagnostic imaging for low back pain; however, no clinical decision rules are available. Methods This project will develop a clinical decision support tool for appropriate use of diagnostic imaging for patients with low back pain in the emergency department. We will conduct a prospective cohort study at five Canadian emergency departments. The study will follow recommendations for prediction model development and testing. The study population will be 4000 patients presenting to the emergency department with low back pain. We will assess potential clinical indications of emergent-cause (i.e., “red flag” items), including clinical characteristics and past history. Our outcome, emergent-cause for low back pain such as fracture, cancer, infection, or cauda equina syndrome, will be assessed at discharge and at 1-, 3-, and 12-month follow-up periods using information from self-report and health administrative data. We will construct and assess the performance of a multivariable prediction model that has strong measurement properties, presented as a clinical decision support tool acceptable to knowledge users. Discussion Practice guidelines describe “red flags” for which diagnostic imaging is likely appropriate. However, recommendations across guidelines are discordant, and few studies have evaluated these criteria to determine which characteristics best predict emergent etiology that warrant diagnostic imaging. A clinical decision support tool, that recommends diagnostic imaging where appropriate, has the potential to improve clinical care and patient outcomes and reduce costs associated with managing low back pain patients. Electronic supplementary material The online version of this article (10.1186/s41512-019-0047-8) contains supplementary material, which is available to authorized users.

Gastrointestinal (GI) bleeding is a common problem in patients with portal hypertension. One of the most common causes of GI bleeding are varices (e.g., esophageal varices). In some instances, varices can develop between an intestinal stoma and the abdominal wall vasculature, known as parastomal varices. Specifically, parastomal varices are common in patients with a preexisting stoma and concurrent chronic portal hypertension. These patients often present with recurrent bleeding and may require regular transfusions. Herein, we report on a patient with parastomal varices and portal hypertension without hepatic cirrhosis. Given the high morbidity and mortality associated with surgical interventions, most clinical guidelines encourage observation and medical management of bleeding from parastomal varices. Among the nonsurgical interventions, manual compression and local maneuvers often successfully stop the bleeding. However, subsequent rebleeding from parastomal varices can remain a problem requiring additional treatment. Further research is needed to investigate appropriate medical or surgical alternatives for managing parastomal varices bleeding.

Previous studies have described the use of cefazolin with probenecid to treat uncomplicated skin and soft-tissue infections. Some prescribers are extrapolating from this evidence to treat more invasive infections, which have a greater potential for poor outcomes, including treatment failure that could lead to increased morbidity and mortality. Information supporting cefazolin with probenecid as effective treatment in this context is needed.To describe prescribing patterns and outcomes for patients who received cefazolin with probenecid for the treatment of bone and joint infections.This single-centre retrospective study involved adult outpatients for whom cefazolin and probenecid were prescribed for bone and joint infections between April 1, 2012, and March 31, 2017. Patient charts were reviewed, and data were collected for clinical and microbiological variables using a standardized data collection form.In a total of 80 cases, the patient received cefazolin and probenecid for treatment of a bone or joint infection, of which 69 cases met the inclusion criteria. In most cases (The effectiveness of cefazolin and probenecid for the treatment of bone and joint infections appears to be similar to that of standard treatment, as reported in the literature. Antibiotic effectiveness is difficult to determine conclusively in a retrospective analysis, so these results should be interpreted with caution, but they may stimulate further research.Des études précédentes ont décrit l’utilisation de la céfazoline et du probénécide pour traiter les infections cutanées et les infections de tissus mous. Quelques prescripteurs extrapolent ces éléments probants pour traiter des infections plus invasives, dont les résultats risquent d’être défavorables, comme un échec du traitement pouvant entraîner une morbidité et une mortalité accrues. De l’information supplémentaire étayant l’efficacité du traitement à l’aide de la céfazoline et du probénécide dans ce contexte est nécessaire.Décrire les modes de prescription et les résultats obtenus par des patients ayant reçu de la céfazoline et du probénécide pour traiter des infections osseuses et articulaires.Cette étude rétrospective unicentrique porte sur des patients ambulatoires adultes à qui on a prescrit de la céfazoline et du probénécide pour traiter des infections osseuses et articulaires entre le 1Les patients, soit 80 cas en tout, ont reçu de la céfazoline et du probénécide pour traiter une infection osseuse ou articulaire et 69 de ces cas répondaient aux critères d’inclusion. Dans la plupart des cas (L’efficacité de la céfazoline et du probénécide dans le traitement des infections osseuses et articulaires semble être similaire à celle des traitements standard, comme le rapporte la littérature scientifique. L’efficacité des antibiotiques est difficile à déterminer de façon concluante dans une analyse rétrospective, ces résultats doivent donc être interprétés avec prudence, mais ils pourraient stimuler des recherches supplémentaires.

Pathogen-driven selection and past interbreeding with archaic human lineages have resulted in differences in human leukocyte antigen (HLA)-allele frequencies between modern human populations. Whether or not this variation affects pathogen subtype diversification is unknown. Here we show a strong positive correlation between ethnic diversity in African countries and both human immunodeficiency virus (HIV)-1 p24gag and subtype diversity. We demonstrate that ethnic HLA-allele differences between populations have influenced HIV-1 subtype diversification as the virus adapted to escape common antiviral immune responses. The evolution of HIV Subtype B (HIV-B), which does not appear to be indigenous to Africa, is strongly affected by immune responses associated with Eurasian HLA variants acquired through adaptive introgression from Neanderthals and Denisovans. Furthermore, we show that the increasing and disproportionate number of HIV-infections among African Americans in the USA drive HIV-B evolution towards an Africa-centric HIV-1 state. Similar adaptation of other pathogens to HLA variants common in affected populations is likely. ispartof: VIRUS EVOLUTION vol:6 issue:2 ispartof: location:England status: published

Background: Previous studies have described the use of cefazolin with probenecid to treat uncomplicated skin and soft-tissue infections. Some prescribers are extrapolating from this evidence to treat more invasive infections, which have a greater potential for poor outcomes, including treatment failure that could lead to increased morbidity and mortality. Information supporting cefazolin with probenecid as effective treatment in this context is needed.Objectives: To describe prescribing patterns and outcomes for patients who received cefazolin with probenecid for the treatment of bone and joint infections.Methods: This single-centre retrospective study involved adult outpatients for whom cefazolin and probenecid were prescribed for bone and joint infections between April 1, 2012, and March 31, 2017. Patient charts were reviewed, and data were collected for clinical and microbiological variables using a standardized data collection form.Results: In a total of 80 cases, the patient received cefazolin and probenecid for treatment of a bone or joint infection, of which 69 cases met the inclusion criteria. In most cases (n = 67), the patients were treated with cefazolin 2 g IV plus probenecid 1 g PO, both given twice daily. Completion of prescribed treatment occurred in 56 patient cases (81%), resolution of signs and symptoms in 53 (77%), readmission to hospital in 11 (16%), recurrence of infection in 6 (9%), and treatment failure requiring a change in therapy in 7 (10%).Conclusions: The effectiveness of cefazolin and probenecid for the treatment of bone and joint infections appears to be similar to that of standard treatment, as reported in the literature. Antibiotic effectiveness is difficult to determine conclusively in a retrospective analysis, so these results should be interpreted with caution, but they may stimulate further research.RÉSUMÉContexte : Des études précédentes ont décrit l’utilisation de la céfazoline et du probénécide pour traiter les infections cutanées et les infections de tissus mous. Quelques prescripteurs extrapolent ces éléments probants pour traiter des infections plus invasives, dont les résultats risquent d’être défavorables, comme un échec du traitement pouvant entraîner une morbidité et une mortalité accrues. De l’information supplémentaire étayant l’efficacité du traitement à l’aide de la céfazoline et du probénécide dans ce contexte est nécessaire.Objectifs : Décrire les modes de prescription et les résultats obtenus par des patients ayant reçu de la céfazoline et du probénécide pour traiter des infections osseuses et articulaires.Méthodes : Cette étude rétrospective unicentrique porte sur des patients ambulatoires adultes à qui on a prescrit de la céfazoline et du probénécide pour traiter des infections osseuses et articulaires entre le 1er avril 2012 et le 31 mars 2017. L’examen des dossiers médicaux des patients a permis la récolte de données sur les variables cliniques et microbiologiques à l’aide d’un formulaire de recueil de données standard.Résultats : Les patients, soit 80 cas en tout, ont reçu de la céfazoline et du probénécide pour traiter une infection osseuse ou articulaire et 69 de ces cas répondaient aux critères d’inclusion. Dans la plupart des cas (n = 67), les patients étaient traités avec de la céfazoline IV dosée à 2 g et du probénécide dosé à 1 g PO, les deux produits étant administrés deux fois par jour. Le traitement a été appliqué au complet dans 56 cas (81 %), la résolution des signes et des symptômes a eu lieu dans 53 cas (77 %), la réadmission à l’hôpital s’est produite dans 11 cas (16 %), les infections ont récidivé dans 6 cas (9 %) et le traitement s’est soldé par un échec et a nécessité un changement de thérapie dans 7 cas (10 %).Conclusions : L’efficacité de la céfazoline et du probénécide dans le traitement des infections osseuses et articulaires semble être similaire à celle des traitements standard, comme le rapporte la littérature scientifique. L’efficacité des antibiotiques est difficile à déterminer de façon concluante dans une analyse rétrospective, ces résultats doivent donc être interprétés avec prudence, mais ils pourraient stimuler des recherches supplémentaires.

Iliotibial band (ITB) syndrome is a common running injury that has been the cause of much pain in the active population. The ITB originates on the pelvis, crosses the hip joint, travels along the lateral thigh and inserts on the lateral, proximal tibia and fibula. Irritation and pain occur when there is excessive friction of the ITB as it crosses the lateral femoral condyle in the region of the knee joint. It has been shown that runners that have ITB syndrome tend to run with a narrower step width. This narrower step width would presumably stretch the ITB to a greater extent and increase the potential for ITB syndrome. This study was designed to test the hypothesis that strain and rate of strain development in the ITB would increase as the step width becomes narrower. Fifteen recreational or competitive runners ran at their preferred 5k running pace. Each subject ran at their preferred step width, their preferred step width +5% of their leg length and their preferred step width -5% of their leg length. Results showed that there was a significant difference in strain across all conditions (p < .0001). There was an increase in strain rate across all conditions with the highest strain rate in the narrow running condition and the lowest strain rate in the wide running condition but only the narrow and wide (p = .003) and wide and normal (p = .016) comparisons were significant. There was a relationship between a runner’s step width and the strain on the ITB. Results indicated that there may be a benefit to widening the step width in runners prone to ITB syndrome. Further analysis should be conducted to insure that this suggested running style does not cause abnormal stresses or anatomical alignments that could induce injury.

A common origin of the celiac trunk and superior mesenteric artery (SMA), also termed as celiomesenteric trunk (CMT), is a rare occurrence. We report a rare case of symptomatic CMT stenosis requiring multiple interventions. The patient underwent an initial superior mesenteric artery bypass graft but required a subsequent endoluminal intervention. We present this case for the rarity of CMT stenosis and its potential to cause recurrent mesenteric ischemia. The treatment outcome in this patient suggests that revascularization of the SMA alone can result in adequate perfusion of the entire mesenteric bed and resolve symptoms of mesenteric ischemia including weight loss and food avoidance.

Virophages and polintons are part of a complex system that also involves eukaryotes, giant viruses, as well as other viruses and transposable elements. Virophages are cosmopolitan, being found in environments ranging from the Amazon River to Antarctic hypersaline lakes, while polintons are found in many single celled and multicellular eukaryotes. Virophages and polintons have a shared ancestry, but their exact origins are unknown and obscured by antiquity and extensive horizontal gene transfer (HGT). Paleovirology can help disentangle the complicated gene flow between these two, as well as their giant viral and eukaryotic hosts. We outline the evidence and theoretical support for polintons being descended from viruses and not vice versa. In order to disentangle the natural history of polintons and virophages, we suggest that there is much to be gained by embracing rigorous metagenomics and evolutionary analyses. Methods from paleovirology will play a pivotal role in unravelling ancient relationships, HGT and patterns of cross-species transmission.

The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated Streptococcus pneumoniae (Non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if Non-Ec-Sp evolve sporadically, if they have high antibiotic non-susceptiblity rates and a unique, specific gene content. Here, whole genome sequencing of 131 Non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multi-locus sequences types ST344 (n=39) and ST448 (n=40). All ST344 and nine ST448 isolates had high non-susceptiblity rates to β-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic Non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic Non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic Non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P=0.005). In contrast, sporadic Non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, Non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of pneumococcal conjugate vaccines, Non-Ec-Sp may become more prevalent.

This study assessed the effect of step width during running on factors related to iliotibial band (ITB) syndrome. Three-dimensional (3D) kinematics and kinetics were recorded from 15 healthy recreational runners during overground running under various step width conditions (preferred and at least +/- 5% of their leg length). Strain and strain rate were estimated from a musculoskeletal model of the lower extremity. Greater ITB strain and strain rate were found in the narrower step width condition (p < 0.001, p = 0.040). ITB strain was significantly (p < 0.001) greater in the narrow condition than the preferred and wide conditions and it was greater in the preferred condition than the wide condition. ITB strain rate was significantly greater in the narrow condition than the wide condition (p = 0.020). Polynomial contrasts revealed a linear increase in both ITB strain and strain rate with decreasing step width. We conclude that relatively small decreases in step width can substantially increase ITB strain as well as strain rates. Increasing step width during running, especially in persons whose running style is characterized by a narrow step width, may be beneficial in the treatment and prevention of running-related ITB syndrome.

A new emulsion stability model analyzes various reported and newly generated experimental data demonstrating that this model can provide quantitative insight into the mechanism of emulsion decomposition and formation. A variety of emulsion stability data is accurately correlated by means of the new emulsion stability model. The decomposition and formation rate constants, reaction order, limiting emulsion fraction, and emulsion half-life are determined from linearized experimental data. This study reconfirms that the order of the quiescent emulsion decomposition reaction is equal to 0.4, similar to Civan and Weers [SPE Production and Facilities (2001) 260], while the order of the emulsion formation reaction by mixing varies from 0.18 to 1.73 depending on the solvent conditions for the emulsions considered in this study.

Objective. The objective was to determine the prevalence of the polymorphisms of the microsomal epoxide hydrolase (Ephx1), glutathione S-transferase µ1 (GSTM1), θ1 (GSTT1), and π1 (GSTP1) genes in patients with oropharyngeal carcinoma. Study design. Gene polymorphisms in 137 patients with oropharyngeal carcinoma were determined by polymerase chain reaction and restriction enzyme digestion for xenobiotic metabolizing enzymes that have been implicated in the carcinogenesis of tobacco-related neoplasias and compared with a population sample of 99 persons. Results. At Ephx1 (microsomal epoxide hydrolase) codon 113, an overrepresentation of the greater activity genotype (Tyr/Tyr) was observed for male ever-smokers alone, both male and female ever-smokers, female never-smokers alone, and in both male and female never-smokers, compared with a control population sample. At codon 139, Ephx1 showed no differences. There was an overrepresentation of homozygosity for the GSTT1 (glutathione S-transferase θ1) null allele [but not for the GSTM1 (glutathione S-transferase µ1) null allele] in ever-smokers, when compared with controls. Polymorphisms at the GSTP1 (glutathione S-transferase π1) locus did not show differences versus controls, although in the never-smoker cancer sample there was a higher prevalence of the B/B genotype compared with ever-smokers. Conclusion. The Ephx1 codon 113 Tyr/Tyr variant, as well as homozygosity for the GSTT1 null allele, is associated with oropharyngeal carcinogenesis. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:440-5)

Corrosion inhibitors are known to adsorb to a variety of corrosion product layers. Under conditions of high shear, the fracture of corrosion product scale is one important aspect affecting...

The kinetics of formation of vesicles by dilution with water from a hydrotrope solution of the vesicle forming surfactants and the reverse formation of them to hydrotrope stabilized micelles were investigated using the stopped flow technique. The relaxation time for the formation of vesicles varied from 0.09 s to several seconds depending on the concentration of the vesicle forming surfactant, while the corresponding time for the formation of hydrotrope stabilized micelles from the vesicular solution was found to be 0.24 s irrespective of the concentrations involved.

Accurate placement of emulsions containing formulated inhibitors in the casing-tubing annulus can provide more effective and long term well treatment than the standard batch methods. This paper presents the results of experimental investigation and correlation of experimental data based on a large-scale model well constructed to simulate flow within the typical well annulus. The wellhead and bottom hole assemblies were designed to closely simulate those found in producing oil and gas fields. Various chemicals were injected at the wellhead to flow through the annulus, to determine the role of viscosity, density, and surface tension, which were then followed by brine flush. The flow of emulsion and flush through the annulus was recorded at fixed positions and with mobile cameras. The observation and identification of the flow patterns during the treatment was made. A set of pins was inserted into the casing wall. This allowed the measurement of thickness of the emulsion coating the annular surface. The surface area coated by the emulsion was traced and measured. Downhole emulsion delivery was thus determined by performing the emulsion material balance. The amount of emulsion retained in the system is based on deposited chemical thickness, coated surface area and concentration of chemical in the annular fluids after the tests. The results were correlated using dimensionless groups to allow extrapolation to well depths encountered in a typical oilfield production. The effectiveness of emulsion delivery and the flow patterns in the annulus were determined to strongly depend on the application type and conditions.

Liquid holdup may decrease the productivity of gas producing wells. The use of foaming agents is a popular method of reducing fluid levels and increasing well production. However, corrosion rates may still be excessive in these cases requiring a mitigation strategy. The use of chemicals that act as foaming agents and corrosion inhibitors have great utility in gas wells with excessive water holdup. The underlying physical principles and measurable parameters include dynamic interfacial tension, foaming ability, and corrosion inhibition. A mechanistic description to predict the performance of chemical foamers is developed based upon measurable parameters demonstrating that the dominant factor is foam density. In addition, the effectiveness of a chemical program to unload a well and inhibit corrosion is demonstrated.

For over 20 years, high molecular weight polymers and surfactants have been used to reduce pressure drop and enhance flow in oil and aqueous systems from production pipelines to water injection systems. The mode of action has been attributed to a reduction in energy loss by a suppression of turbulent fluctuations. However, surface modifications also play a role gas transmission systems. As will be shown with laboratory and field data, the alteration either in the surface or in the fluid flow properties can also improve other aspects of oilfield production. Such as in this paper, four particular instances of drag reduction will be related to corrosion performance. In a first case, two model surfactant corrosion inhibitors, cetyltrimethylammonium chloride (CTAC) and cetylpyridinium chloride (CPC) were chemically modified to drag reducing agents by exchange of the chloride with salycilate counterion. The modified surfactants (cation exchanged) and the corresponding halides were compared in a corrosion test under conditions were drag reduction occurred. Drag reduction promoted corrosion inhibition in a standard corrosion test. In a second case, the introduction of a low foam surfactant into a brine system resulted in a reduction in the corrosion rate as shown by laboratory data. In a third case, utilizing a cleaner/antifoulant surfactant, the pressure drop was reduced and the production increased in a gas gathering system. As a side benefit of the removal of solid deposits, the uninhibited corrosion rate was decreased by a factor of seven. In a final case, a foaming surfactant was utilized to remove liquid hold-up in a production well. By removing the liquid hold-up, the corrosion rate was decreased. Utilizing a drag reduction chemical in an oil or gas production system can lead to additional performance enhancements as demonstrated for the case of corrosion control.

A significantly increased uptake of 65Zn administered intravenously was detected in healing bones of rats compared with control rats. The parameters used for measuring osteogenesis included: histologic examination, radiographic studies, and Ca 45 uptake in bone. The accumulation of 65Zn appeared to be correlated with bone formation. The data suggest a mobilization of zinc to the site of bone repair.