Prevalence of Deep Surgical Site Infection After Repair of Periarticular Knee Fractures: A systematic review and meta-analysis

Importance Surgical management of periarticular knee fractures can be challenging, and adverse outcomes may be severe. Recent literature indicates that the rate of periarticular knee surgical site infection (SSI) may range from 2% to 88% depending on the fracture site. Objective To examine the prevalence of deep SSI and the rate of septic arthritis after surgical repair of fractures around the knee. Data Sources The electronic databases MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception to July 1, 2018. Study Selection Eligible studies had to specifically report deep SSI rates and include fractures in the distal femur, patella, tibial plateau, or proximal tibia. Risk factors that were associated with increased the risk of deep SSI were also examined. Data Extraction and Synthesis This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were extracted by multiple investigators. Comprehensive Meta-Analysis software was used for the pooling of data, using either random-effects or fixed-effects models, with respect to the degree of statistical heterogeneity present. Data analyses were conducted in October 2018. Main Outcomes and Measures The primary outcome was overall prevalence of deep SSI after periarticular knee fracture repair. The secondary outcomes were the overall prevalence of septic arthritis, risk factors associated with deep SSI, and the most commonly cultured bacteria specimens found periarticular knee infections. Results Of 6928 articles screened, 117 articles met inclusion criteria and were included in analysis. Among 11 432 patients included in analysis, 653 patients (5.7%) experienced deep SSIs, most commonly among patients with proximal tibia fractures (56 of 872 patients [6.4%]). Among studies that included information on septic arthritis, 38 of 1567 patients (2.4%) experienced septic arthritis. The 2 most commonly reported bacteria were methicillin-resistant Staphylococcus aureus, found in 67 SSIs, and methicillin-susceptible S aureus, found in 53 SSIs. Sixty-two studies (53.0%) in the sample received a Coleman Methodological Score of poor (<50 points). Conclusions and Relevance Deep SSIs occurred in nearly 6% of periarticular knee fracture repairs, and 2.4% of SSIs were associated with septic arthritis. Surgeons managing these injuries should be vigilant when wounds are not pristine. Efforts should be made to elevate the quality of research conducted not only in this subject but also in orthopedic surgery as a whole

Reconstructing CNV genotypes using segregation analysis: combining pedigree information with CNV assay

<p>Abstract</p> <p>Background</p> <p>Repeated blocks of genome sequence have been shown to be associated with genetic diversity and disease risk in humans, and with phenotypic diversity in model organisms and domestic animals. Reliable tests are desirable to determine whether individuals are carriers of copy number variants associated with disease risk in humans and livestock, or associated with economically important traits in livestock. In some cases, copy number variants affect the phenotype through a dosage effect but in other cases, allele combinations have non-additive effects. In the latter cases, it has been difficult to develop tests because assays typically return an estimate of the sum of the copy number counts on the maternally and paternally inherited chromosome segments, and this sum does not uniquely determine the allele configuration. In this study, we show that there is an old solution to this new problem: segregation analysis, which has been used for many years to infer alleles in pedigreed populations.</p> <p>Methods</p> <p>Segregation analysis was used to estimate copy number alleles from assay data on simulated half-sib sheep populations. Copy number variation at the Agouti locus, known to be responsible for the recessive self-colour black phenotype, was used as a model for the simulation and an appropriate penetrance function was derived. The precision with which carriers and non-carriers of the undesirable single copy allele could be identified, was used to evaluate the method for various family sizes, assay strategies and assay accuracies.</p> <p>Results</p> <p>Using relationship data and segregation analysis, the probabilities of carrying the copy number alleles responsible for black or white fleece were estimated with much greater precision than by analyzing assay results for animals individually. The proportion of lambs correctly identified as non-carriers of the undesirable allele increased from 7% when the lambs were analysed alone to 80% when the lambs were analysed in half-sib families.</p> <p>Conclusions</p> <p>When a quantitative assay is used to estimate copy number alleles, segregation analysis of related individuals can greatly improve the precision of the estimates. Existing software for segregation analysis would require little if any change to accommodate the penetrance function for copy number assay data.</p

Are Canadian General Internal Medicine training program graduates well prepared for their future careers?

BACKGROUND: At a time of increased need and demand for general internists in Canada, the attractiveness of generalist careers (including general internal medicine, GIM) has been falling as evidenced by the low number of residents choosing this specialty. One hypothesis for the lack of interest in a generalist career is lack of comfort with the skills needed to practice after training, and the mismatch between the tertiary care, inpatient training environment and "real life". This project was designed to determine perceived effectiveness of training for 10 years of graduates of Canadian GIM programs to assist in the development of curriculum and objectives for general internists that will meet the needs of graduates and ultimately society. METHODS: Mailed survey designed to explore perceived importance of training for and preparation for various aspects of Canadian GIM practice. After extensive piloting of the survey, including a pilot survey of two universities to improve the questionnaire, all graduates of the 16 universities over the previous ten years were surveyed. RESULTS: Gaps (difference between importance and preparation) were demonstrated in many of the CanMEDS 2000/2005(® )competencies. Medical problems of pregnancy, perioperative care, pain management, chronic care, ambulatory care and community GIM rotations were the medical expert areas with the largest gaps. Exposure to procedural skills was perceived to be lacking. Some procedural skills valued as important for current GIM trainees and performed frequently (example ambulatory ECG interpretation) had low preparation ratings by trainees. Other areas of perceived discrepancy between training and practice included: manager role (set up of an office), health advocate (counseling for prevention, for example smoking cessation), and professional (end of life issues, ethics). CONCLUSION: Graduates of Canadian GIM training programs over the last ten years have identified perceived gaps between training and important areas for practice. They have identified competencies that should be emphasized in Canadian GIM programs. Ongoing review of graduate's perceptions of training programs as it applies to their current practice is important to ensure ongoing appropriateness of training programs. This information will be used to strengthen GIM training programs in Canada

A stochastic automaton shows how enzyme assemblies may contribute to metabolic efficiency

<p>Abstract</p> <p>Background</p> <p>The advantages of grouping enzymes into metabolons and into higher order structures have long been debated. To quantify these advantages, we have developed a stochastic automaton that allows experiments to be performed in a virtual bacterium with both a membrane and a cytoplasm. We have investigated the general case of transport and metabolism as inspired by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) for glucose importation and by glycolysis.</p> <p>Results</p> <p>We show that PTS and glycolytic metabolons can increase production of pyruvate eightfold at low concentrations of phosphoenolpyruvate. A fourfold increase in the numbers of enzyme EI led to a 40% increase in pyruvate production, similar to that observed <it>in vivo </it>in the presence of glucose. Although little improvement resulted from the assembly of metabolons into a hyperstructure, such assembly can generate gradients of metabolites and signaling molecules.</p> <p>Conclusion</p> <p><it>in silico </it>experiments may be performed successfully using stochastic automata such as HSIM (Hyperstructure Simulator) to help answer fundamental questions in metabolism about the properties of molecular assemblies and to devise strategies to modify such assemblies for biotechnological ends.</p

Dot Display Affects Approximate Number System Acuity and Relationships with Mathematical Achievement and Inhibitory Control

Much research has investigated the relationship between the Approximate Number System (ANS) and mathematical achievement, with continued debate surrounding the existence of such a link. The use of different stimulus displays may account for discrepancies in the findings. Indeed, closer scrutiny of the literature suggests that studies supporting a link between ANS acuity and mathematical achievement in adults have mostly measured the ANS using spatially intermixed displays (e.g. of blue and yellow dots), whereas those failing to replicate a link have primarily used spatially separated dot displays. The current study directly compared ANS acuity when using intermixed or separate dots, investigating how such methodological variation mediated the relationship between ANS acuity and mathematical achievement. ANS acuity was poorer and less reliable when measured with intermixed displays, with performance during both conditions related to inhibitory control. Crucially, mathematical achievement was significantly related to ANS accuracy difference (accuracy on congruent trials minus accuracy on incongruent trials) when measured with intermixed displays, but not with separate displays. The findings indicate that methodological variation affects ANS acuity outcomes, as well as the apparent relationship between the ANS and mathematical achievement. Moreover, the current study highlights the problem of low reliabilities of ANS measures. Further research is required to construct ANS measures with improved reliability, and to understand which processes may be responsible for the increased likelihood of finding a correlation between the ANS and mathematical achievement when using intermixed displays

Family Influences on the Long Term Post-Disaster Recovery of Puerto Rican Youth

This study focused on characteristics of the family environment that may mediate the relationship between disaster exposure and the presence of symptoms that met DSM-IV diagnostic criteria for symptom count and duration for an internalizing disorder in children and youth. We also explored how parental history of mental health problems may moderate this meditational model. Approximately 18 months after Hurricane Georges hit Puerto Rico in 1998, participants were randomly selected based on a probability household sample using 1990 US Census block groups. Caregivers and children (N=1,886 dyads) were interviewed with the Diagnostic Interview Schedule for Children and other questionnaires in Spanish. Areas of the family environment assessed include parent-child relationship quality, parent-child involvement, parental monitoring, discipline, parents’ relationship quality and parental mental health. SEM models were estimated for parents and children, and by age group. For children (4–10 years old), parenting variables were related to internalizing psychopathology, but did not mediate the exposure-psychopathology relationship. Exposure had a direct relationship to internalizing psychopathology. For youth (11–17 years old), some parenting variables attenuated the relation between exposure and internalizing psychopathology. Family environment factors may play a mediational role in psychopathology post-disaster among youth, compared to an additive role for children. Hurricane exposure had a significant relation to family environment for families without parental history of mental health problems, but no influence for families with a parental history of mental health problems

A Geometrical Model for DNA Organization in Bacteria

Recent experimental studies have revealed that bacteria, such as C. crescentus, show a remarkable spatial ordering of their chromosome. A strong linear correlation has been found between the position of genes on the chromosomal map and their spatial position in the cellular volume. We show that this correlation can be explained by a purely geometrical model. Namely, self-avoidance of DNA, specific positioning of one or few DNA loci (such as origin or terminus) together with the action of DNA compaction proteins (that organize the chromosome into topological domains) are sufficient to get a linear arrangement of the chromosome along the cell axis. We develop a Monte-Carlo method that allows us to test our model numerically and to analyze the dependence of the spatial ordering on various physiologically relevant parameters. We show that the proposed geometrical ordering mechanism is robust and universal (i.e. does not depend on specific bacterial details). The geometrical mechanism should work in all bacteria that have compacted chromosomes with spatially fixed regions. We use our model to make specific and experimentally testable predictions about the spatial arrangement of the chromosome in mutants of C. crescentus and the growth-stage dependent ordering in E. coli

Graded Smad2/3 Activation Is Converted Directly into Levels of Target Gene Expression in Embryonic Stem Cells

The Transforming Growth Factor (TGF) β signalling family includes morphogens, such as Nodal and Activin, with important functions in vertebrate development. The concentration of the morphogen is critical for fate decisions in the responding cells. Smad2 and Smad3 are effectors of the Nodal/Activin branch of TGFβ signalling: they are activated by receptors, enter the nucleus and directly transcribe target genes. However, there have been no studies correlating levels of Smad2/3 activation with expression patterns of endogenous target genes in a developmental context over time. We used mouse Embryonic Stem (ES) cells to create a system whereby levels of activated Smad2/3 can be manipulated by an inducible constitutively active receptor (Alk4*) and an inhibitor (SB-431542) that blocks specifically Smad2/3 activation. The transcriptional responses were analysed by microarrays at different time points during activation and repression. We identified several genes that follow faithfully and reproducibly the Smad2/3 activation profile. Twenty-seven of these were novel and expressed in the early embryo downstream of Smad2/3 signalling. As they responded to Smad2/3 activation in the absence of protein synthesis, they were considered direct. These immediate responsive genes included negative intracellular feedback factors, like SnoN and I-Smad7, which inhibit the transcriptional activity of Smad2/3. However, their activation did not lead to subsequent repression of target genes over time, suggesting that this type of feedback is inefficient in ES cells or it is counteracted by mechanisms such as ubiquitin-mediated degradation by Arkadia. Here we present an ES cell system along with a database containing the expression profile of thousands of genes downstream of Smad2/3 activation patterns, in the presence or absence of protein synthesis. Furthermore, we identify primary target genes that follow proportionately and with high sensitivity changes in Smad2/3 levels over 15–30 hours. The above system and resource provide tools to study morphogen function in development

Understanding diabetes in patients with HIV/AIDS

This paper reviews the incidence, pathogenetic mechanisms and management strategies of diabetes mellitus in patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). It classifies patients based on the aetiopathogenetic mechanisms, and proposes rational methods of management of the condition, based on aetiopathogenesis and concomitant pharmacotherapy