Tuberculosis (TB) infection of bones and joints accounts for 6.7% of TB cases in England, and is associated with significant morbidity and disability. Public Health England reports that patients with ...TB experience delays in diagnosis and treatment. Our aims were to determine the demographics, presentation and investigation of patients with a TB infection of bones and joints, to help doctors assessing potential cases and to identify avoidable delays.
This was a retrospective observational study of all adults with positive TB cultures on specimens taken at a tertiary orthopaedic centre between June 2012 and May 2014. A laboratory information system search identified the patients. The demographics, clinical presentation, radiology, histopathology and key clinical dates were obtained from medical records.
A total of 31 adult patients were identified. Their median age was 37 years (interquartile range (IQR): 29 to 53); 21 (68%) were male; 89% were migrants. The main sites affected were joints (10, 32%), the spine (8, 26%) and long bones (6, 19%); 8 (26%) had multifocal disease. The most common presenting symptoms were pain (29/31, 94%) and swelling (26/28, 93%). 'Typical' symptoms of TB, such as fever, sweats and weight loss, were uncommon. Patients waited a median of seven months (IQR 3 to 13.5) between the onset of symptoms and referral to the tertiary centre and 2.3 months (IQR 1.6 to 3.4.)) between referral and starting treatment. Radiology suggested TB in 26 (84%), but in seven patients (23%) the initial biopsy specimens were not sent for mycobacterial culture, necessitating a second biopsy. Rapid Polymerase Chain Reaction-based testing for TB using Xpert MTB/RIF was performed in five patients; 4 (80%) tested positive for TB. These patients had a reduced time between the diagnostic biopsy and starting treatment than those whose samples were not tested (median eight days
36 days, p = 0.016).
Patients with bone and joint TB experience delays in diagnosis and treatment, some of which are avoidable. Maintaining a high index of clinical suspicion and sending specimens for mycobacterial culture are crucial to avoid missing cases. Rapid diagnostic tests reduce delays and should be performed on patients with radiological features of TB. Cite this article:
2018;100-B:119-24.
In the nematode Caenorhabditis elegans, longevity in response to germline ablation, but not in response to reduced insulin/IGF1-like signaling, is strongly dependent on the conserved protein kinase ...minibrain-related kinase 1 (MBK-1). In humans, the MBK-1 ortholog DYRK1A is associated with a variety of disorders, most prominently with neurological defects observed in Down syndrome. To better understand mbk-1's physiological roles and their dependence on genetic background, we analyzed the influence of mbk-1 loss on the transcriptomes of wildtype and long-lived, germline-deficient or insulin-receptor defective, C. elegans strains by RNA-sequencing.
mbk-1 loss elicited global changes in transcription that were less pronounced in insulin-receptor mutant than in germline-deficient or wildtype C. elegans. Irrespective of genetic background, mbk-1 regulated genes were enriched for functions in biological processes related to organic acid metabolism and pathogen defense. qPCR-studies confirmed mbk-1 dependent induction of all three C. elegans Δ9-fatty acid desaturases, fat-5, fat-6 and fat-7, in wildtype, germline-deficient and insulin-receptor mutant strains. Conversely, mbk-1 dependent expression patterns of selected pathogen resistance genes, including asp-12, dod-24 and drd-50, differed across the genetic backgrounds examined. Finally, cth-1 and cysl-2, two genes which connect pathogen resistance to the metabolism of the gaseous messenger and lifespan regulator hydrogen sulfide (H
S), were commonly suppressed by mbk-1 loss only in wildtype and germline-deficient, but not in insulin-receptor mutant C. elegans.
Our work reveals previously unknown roles of C. elegans mbk-1 in the regulation of fatty acid desaturase- and H
S metabolic-genes. These roles are only partially dependent on genetic background. Considering the particular importance of fatty acid desaturation and H
S for longevity of germline-deficient C. elegans, we propose that these processes at least in part account for the previous observation that mbk-1 preferentially regulates lifespan in these worms.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Mucins are large complex glycoproteins that protect intestinal mucosal surfaces by limiting access of environmental matter to their epithelial cells. Several mucin genes have been ...described, including MUC3 that is a membrane associated mucin of the small intestine. Increased MUC3 mRNA transcription is induced by incubation of intestinal epithelial cells with a Lactobacillus strain known to be adherent to them. Aims: To determine whether increased epithelial cell MUC3 mucin expression in response to Lactobacillus strains results in increased extracellular secretion of MUC3 mucins and the importance of epithelial cell adherence in modulation of MUC3 mucin expression. Methods: HT29 cells grown to enhance expression of MUC3 mucins were incubated with selected Lactobacillus strains. Spent cell culture medium was collected for detection of secreted MUC3 mucins using dot blot immunoassay with a generated MUC3 antibody. Post-incubation HT29 cell RNA was collected for analysis of MUC3 expression by northern blot analysis using a MUC3 cDNA probe. In vitro binding studies using Lactobacillus strains incubated alone or coincubated with enteropathogenic Escherichia coli strain E2348/69 were used for adherence and inhibition of adherence studies, respectively. Results:Lactobacillus strains with minimal ability to adhere to HT29 cells failed to induce upregulation of mucin gene expression. There was a direct correlation between upregulation of MUC3 mucin mRNA expression and extracellular secretion of MUC3 mucin. The same Lactobacillus strains that increased extracellular secretion of MUC3 mucin led to reduced adherence of enteropathogen E coli E2348/69 during coincubation experiments. Conclusion: Probiotic microbes induce MUC3 mucin transcription and translation with extracellular secretion of the MUC3 mucins. Epithelial cell adherence enhances the effects of probiotics on eukaryotic mucin expression.
Background:
Few population-based descriptive studies on the incidence of anterior cruciate ligament (ACL) reconstruction and concomitant pathology exist.
Hypothesis:
Incidence of ACL reconstruction ...has increased from 2002 to 2014.
Study Design:
Descriptive clinical epidemiology study.
Level of Evidence:
Level 3.
Methods:
The Truven Health Analytics MarketScan Commercial Claims and Encounters database, which contains insurance enrollment and health care utilization data for approximately 158 million privately insured individuals younger than 65 years, was used to obtain records of ACL reconstructions performed between 2002 and 2014 and any concomitant pathology using Current Procedures Terminology (CPT) and International Classification of Diseases, Ninth Revision (ICD-9) codes. The denominator population was defined as the total number of person-years (PYs) for all individuals in the database. Annual rates were computed overall and stratified by age, sex, and concomitant procedure.
Results:
There were 283,810 ACL reconstructions and 385,384,623 PYs from 2002 to 2014. The overall rate of ACL reconstruction increased 22%, from 61.4 per 100,000 PYs in 2002 to 74.6 per 100,000 PYs in 2014. Rates of isolated ACL reconstruction were relatively stable over the study period. However, among children and adolescents, rates of both isolated ACL reconstruction and ACL reconstruction with concomitant meniscal surgery increased substantially. Adolescents aged 13 to 17 years had the highest absolute rates of ACL reconstruction, and their rates increased dramatically over the 13-year study period (isolated, +37%; ACL + meniscal repair, +107%; ACL + meniscectomy, +63%). Rates of isolated ACL reconstruction were similar for males and females (26.1 vs 25.6 per 100,000 PYs, respectively, in 2014), but males had higher rates of ACL reconstruction with concomitant meniscal surgery than females.
Conclusion:
Incidence rates of isolated ACL reconstruction and rates of concomitant meniscal surgery have increased, particularly among children and adolescents.
Clinical Relevance:
A renewed focus on adoption of injury prevention programs is needed to mitigate these trends. In addition, more research is needed on long-term patient outcomes and postoperative health care utilization after ACL reconstruction, with a focus on understanding the sex-based disparity in concomitant meniscal surgery.
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FSPLJ, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Health administrative databases can be used to track chronic diseases. The aim of this study was to validate a case ascertainment definition of paediatric-onset inflammatory bowel disease (IBD) using ...administrative data and describe its epidemiology in Ontario, Canada.
A population-based clinical database of patients with IBD aged <15 years was used to define cases, and patient information was linked to health administrative data to compare the accuracy of various patterns of healthcare use. The most accurate algorithm was validated with chart data of children aged <18 years from 12 medical practices. Administrative data from the period 1991-2008 were used to describe the incidence and prevalence of IBD in Ontario children. Changes in incidence were tested using Poisson regression.
Accurate identification of children with IBD required four physician contacts or two hospitalisations (with International Classification of Disease (ICD) codes for IBD) within 3 years if they underwent colonoscopy and seven contacts or three hospitalisations within 3 years in those without colonoscopy (children <12 years old, sensitivity 90.5%, specificity >99.9%; children <15 years old, sensitivity 89.6%, specificity >99.9%; children <18 years old, sensitivity 91.1%, specificity 99.5%). Age- and sex-standardised prevalence per 100 000 population of paediatric IBD has increased from 42.1 (in 1994) to 56.3 (in 2005). Incidence per 100 000 has increased from 9.5 (in 1994) to 11.4 (in 2005). Statistically significant increases in incidence were noted in 0-4 year olds (5.0%/year, p = 0.03) and 5-9 year olds (7.6%/year, p<0.0001), but not in 10-14 or 15-17 year olds.
Ontario has one of the highest rates of childhood-onset IBD in the world, and there is an accelerated increase in incidence in younger children.
The Good Behavior Game (GBG) is a classroom management strategy that uses an interdependent group-oriented contingency to promote prosocial behavior and decrease problem behavior. This meta-analysis ...synthesized single-case research (SCR) on the GBG across 21 studies, representing 1,580 students in pre-kindergarten through Grade 12. The TauU effect size across 137 phase contrasts was .82 with a confidence interval 95% CI = 0.78, 0.87, indicating a substantial reduction in problem behavior and an increase in prosocial behavior for participating students. Five potential moderators were examined: emotional and behavioral disorder (EBD) risk status, reinforcement frequency, target behaviors, GBG format, and grade level. Findings suggest that the GBG is most effective in reducing disruptive and off-task behaviors, and that students with or at risk for EBD benefit most from the intervention. Implications for research and practice are discussed.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The proton is one of the main building blocks of all visible matter in the Universe
. Among its intrinsic properties are its electric charge, mass and spin
. These properties emerge from the complex ...dynamics of its fundamental constituents-quarks and gluons-described by the theory of quantum chromodynamics
. The electric charge and spin of protons, which are shared among the quarks, have been investigated previously using electron scattering
. An example is the highly precise measurement of the electric charge radius of the proton
. By contrast, little is known about the inner mass density of the proton, which is dominated by the energy carried by gluons. Gluons are hard to access using electron scattering because they do not carry an electromagnetic charge. Here we investigated the gravitational density of gluons using a small colour dipole, through the threshold photoproduction of the J/ψ particle. We determined the gluonic gravitational form factors of the proton
from our measurement. We used a variety of models
and determined, in all cases, a mass radius that is notably smaller than the electric charge radius. In some, but not all cases, depending on the model, the determined radius agrees well with first-principle predictions from lattice quantum chromodynamics
. This work paves the way for a deeper understanding of the salient role of gluons in providing gravitational mass to visible matter.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
General labels tend to obscure objective realities upon which disability rights are based and can deny individuals with disabilities their educational and civil rights. Undoubtedly, stigma can come ...from labels unnecessarily categorizing people into separate groups. However, stigma does not reside primarily in disability categories/terms but in what people think of words’ referents. The replacement of the old disability categories/terms with new ones is a case of what is called the “euphemism treadmill,” showing how concepts and mentally represented realities, not words, are the key issue. However, in the case of disabilities, scientific names are unavoidable for the purposes of research, education, advocacy, and social welfare. Some people try to avoid naming special education and its derivatives just as they do in the case of disability categories. We argue that scientifically validated disability and special education labels are necessary and legitimate classifications required for progress in disability research and practice. They provide the most direct route to legally protecting and serving individuals with educational disabilities.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
We consider dark matter annihilation into standard model particles and show that the least detectable final states, namely, neutrinos, define an upper bound on the total cross section. Calculating ...the cosmic diffuse neutrino signal, and comparing it to the measured terrestrial atmospheric neutrino background, we derive a strong and general bound. This can be evaded if the annihilation products are dominantly new and truly invisible particles. Our bound is much stronger than the unitarity bound at the most interesting masses, shows that dark matter halos cannot be significantly modified by annihilations, and can be improved by a factor of 10-100 with existing neutrino experiments.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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