Case Study: Chronic Recurrent Multifocal Osteomyelitis in the Femoral Diaphysis of a Young Female

Chronic recurrent multifocal osteomyelitis (CRMO) is relatively uncommon. Even though the name suggests it is the result of infection, this is not likely the case. Instead it is more likely the result of genetic, autoimmune, or autoinflammatory causes. Although CRMO has a benign course and responds well to anti-inflammatory medications, it can have a very aggressive clinical and imaging presentation overlapping with infectious osteomyelitis and malignancy. Therefore, radiologists and clinicians need to be aware of its clinical and imaging presentation to avoid morbidity associated with more aggressive treatment. We present the case of a ten-year-old female with CRMO as a solitary expansile-mixed lytic and sclerotic lesion in the distal femoral diaphysis. The diaphyseal location and mixed lytic and sclerotic appearance are less common and have an aggressive imaging appearance. We also review the pathophysiology, imaging findings, and therapeutic approach to this uncommon but clinically important condition

Novel Molecular Targets of Azadirachta indica Associated with Inhibition of Tumor Growth in Prostate Cancer

Advanced prostate cancer has significant long-term morbidity, and there is a growing interest in alternative and complimentary forms of therapy that will improve the outcomes of patients. Azadirachta indica (common name: neem) contains multiple active compounds that have potent anti-inflammatory and anticancer properties. The present study investigates the novel targets of the anticancer activity of ethanol extract of neem leaves (EENL) in vitro and evaluates the in vivo efficacy in the prostate cancer models. Analysis of the components in the EENL by mass spectrometry suggests the presence of 2′,3′-dehydrosalannol, 6-desacetyl nimbinene, and nimolinone. Treatment of C4-2B and PC-3M-luc2 prostate cancer cells with EENL inhibited the cell proliferation. Genome-wide expression profiling, using oligonucleotide microarrays, revealed genes differentially expressed with EENL treatment in prostate cancer cells. Functional analysis unveiled that most of the up-regulated genes were associated with cell death, and drug metabolism, and the down-regulated genes were associated with cell cycle, DNA replication, recombination, and repair functions. Quantitative PCR confirmed significant up-regulation of 40 genes and immunoblotting revealed increase in the protein expression levels of HMOX1, AKR1C2, AKR1C3, and AKR1B10. EENL treatment inhibited the growth of C4-2B and PC-3M-luc2 prostate cancer xenografts in nude mice. The suppression of tumor growth is associated with the formation of hyalinized fibrous tumor tissue and the induction of cell death by apoptosis. These results suggest that EENL-containing natural bioactive compounds could have potent anticancer property and the regulation of multiple cellular pathways could exert pleiotrophic effects in prevention and treatment of prostate cancer

A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity.

BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Utilization, access and outcome of surgical lumbar discectomy in British Columbia

Lumbar discectomy is the most commonly performed operation on the spine. This thesis includes four studies on the utilization, access and outcome of lumbar discectomy in British Columbia. Studies 1 and 2 estimate temporal trends and regional variations in age- and sex adjusted lumbar discectomy rates using administrative data from the BC Linked Health Database. Study 1 shows that discectomy rates in public hospitals declined by 61% between 1990/91 and 2003/04. Rates declined faster after 2000/01 when lumbar discectomy became accessible in private clinics, preferentially for workers' compensation beneficiaries. Evidence of the diversion of compensated surgical patients from the public to private sectors was observed, however with no obvious attenuation of the decline in surgical rates for noncompensated patients remaining in the public system. In Study 2, rates of lumbar discectomy varied significantly between health service delivery areas (HSDAs), by almost five-fold during 2000/01-2003/04, up from 3.4 fold in 1990/91-1993/94. Studies 3 and 4 are based on prospective registry data on surgically treated lumbar disc patients at Vancouver General Hospital between November 1999 and December 2003. Study 3 identified significant sociodemographic and clinical determinants of waiting times in this population. Clinical severity (symptom duration, pain intensity) were appropriately associated, while most sociodemographic variables (age, sex, compensation status) were appropriately not associated with access to surgery. However professional occupation predicted waiting time, suggesting that access to surgery may not be based on clinical need alone. Study 4 estimated the effect of waiting 12 weeks or longer on the odds of pain improvement after lumbar discectomy. In propensity score-adjusted ordinal regression models, patients waiting 12 weeks or longer for surgery had a 41% lower odds of pain improvement. In the absence of declining disease prevalence, the implications of declining back surgery rates possibly include declining access to care and rising prevalence of disability in the community. This thesis research indicates that delayed access matters, and that "treatment within 12 weeks" may have utility as both a quality-of-care measure in health services research and as a benchmark for defining a maximum appropriate wait for lumbar discectomy.Medicine, Faculty ofPopulation and Public Health (SPPH), School ofGraduat

Guideline implementation in the Canadian chiropractic setting: a pilot cluster randomized controlled trial and parallel study

Background: Feasibility and pilot studies are recommended prior to embarking on large-scale costly confirmatory trials. The objectives were to determine the feasibility of conducting a cluster randomized controlled trial (C-RCT) to evaluate a complex knowledge translation (KT) intervention to improve the management of people with neck pain, and to identify challenges and potential solutions to conducting a fully powered C-RCT in the chiropractic setting. Methods: Pilot C-RCT involving a nationally representative sample of chiropractors and patients. We invited 400 chiropractors and 150 patients to participate. Clinicians were randomized to receive either an online theory-based KT educational and brief action plan (BAP) intervention (intervention group) or a copy of a clinical practice guideline (control group). Study-related challenges were ascertained via mid-study phone interviews and end-of-study feedback questionnaires. Analyses focused on descriptive estimates of likely recruitment, retention, and adherence rates, and documentation of potential barriers. Results: In total, 47 chiropractors (12%) agreed to participate and were randomized after resampling. Fifteen withdrew from the study, leaving a total of 32 (8%) participants. Eleven chiropractors in the intervention group completed the webinars and e-learning modules, two partially completed them and three did not register. Participating chiropractors recruited a total of 29 patients. Sixty-three percent (n = 7) of intervention and 56% (n = 10) of control group patients completed all outcome measures at both baseline and 3-months follow-up, attended follow-up visits and performed home exercises. Patients in the intervention group reported significant reductions in pain (mean 1.6, 95% CI 0.26–2.94, P = 0.027) and disability scores (9.8, 95% CI 3.68–15.91, P = 0.033) from baseline to 3-month follow-up. Key barriers to participation reported by chiropractors included lack of time, difficulties in recruiting patients, problems with the administration of study questionnaires, concern that the clinician-patient relationship might be jeopardized, and lack of assistance from office staff. Over half (55%) of the respondents in the intervention group encountered some difficulty registering or completing the educational modules. Conclusion: Recruitment of clinicians and patients for a trial of a complex intervention can be challenging, and retention of participants after enrolment may be low. Future trials of this nature likely require multiple recruitment strategies to achieve desired sample sizes. Moreover, time-constraint issues are perceived particularly by clinicians as a major barrier to both study enrolment before, and protocol adherence during, their actual participation in a trial. Trial registration: The study was registered at, NCT02483091 , on 17th June 2015.Medicine, Faculty ofOther UBCNon UBCOrthopaedic Surgery, Department ofPopulation and Public Health (SPPH), School ofReviewedFacult