Distraction arthroplasty in osteoarthritis of the foot and ankle

Post-traumatic osteoarthritis(PTOA) is a complex and painful problem in the foot and ankle.Ninety percent of osteoarthritis cases in the foot and ankle can be classified as post-traumatic.PTOA can affect any of the 33 joints in the foot and the ankle.Distraction arthroplasty is a method for treatment of early arthritic joints without fusing or replacing them and its effectiveness has been well documented.The purpose of this case series is to present our successful experiences and positive results using distraction arthroplasty to treat PTOA in the ankle,subtalar,first metatarsophalangeal,and second tarsometatarsal joints,and to present distraction arthroplasty as a viable alternative to invasive joint sacrificing procedures such as arthrodesis or arthroplasty.Distraction Arthroplasty effectively and safely treats PTOA and improves the stability of joints in the Foot and Ankle.Additionally,the use of bone marrow aspirate concentrate as an adjuvant can improve the long-term functional and structural outcomes of the joint,and can prolong the need for further,more aggressive surgical interventions such as fusion or arthroplasty.     

The Maternal Adversity,Vulnerability and Neurodevelopment Project: Theory and Methodology

Objective:

To describe the theory and methodology of the multi-wave, prospective Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) study. The goal of MAVAN is to examine the pre- and postnatal influences, and their interaction, in determining individual differences in mental health.

Method:

MAVAN is a community-based, birth cohort study of pregnant Canadian mothers and their offspring. Dyads are assessed longitudinally, with multiple assessments of both mother and child in home and laboratory across the child’s development. Study measures, including assessments of cognitive and emotional function, are described. The study uses a candidate gene approach to examine gene–environment interdependence in specific developmental outcomes. Finally, the study includes measures of both brain-based phenotypes and metabolism to explore comorbidities associated with child obesity. One of the unique features of the MAVAN protocol is the extensive measures of the mother–child interaction. The relation between these measures will be discussed.

Results:

Evidence from the MAVAN project shows interesting results about maternal care, families, and child outcomes. In our review, preliminary analyses showing the correlations between measures of maternal care are reported. As predicted, early evidence suggests that maternal care measures are positively correlated, over time.

Conclusions:

This review provides evidence for the feasibility and value of laboratory-based measures embedded within a longitudinal birth cohort study. Though retention of the samples has been a challenge of MAVAN, they are within a comparable range to other studies of this nature. Indeed, the trade-off of somewhat greater participant burden has allowed for a rich database. The results yielded from the MAVAN project will not only describe typical development but also possible targets for intervention. Understanding certain endophenotypes will shed light on the pathogenesis of various mental and physical disorders, as well as their interrelation.     

Genetic polymorphisms in NQO1 and SOD2: Interactions with smoking,schistosoma infection,and bladder cancer risk in Egypt

BackgroundBladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in NAD(P)H:quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.MethodsWe assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt. We used unconditional logistic regression to estimate the odds ratios (OR) and confidence intervals (CI) 95%.ResultsWater pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86–10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97–6.74]). Conversely, the risk associated with SH infection was higher among the latter (OR [CI 95%] = 3.59 [2.21–5.84]) than among the former (OR [CI 95%] = 1.86 [1.33–2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much lesser extent. The highest odds for having bladder cancer following SH infection were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR [CI 95%] = 4.41 [2.32–8.38]).ConclusionOur findings suggest that genetic polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder cancer by modulating the effects of known contributing factors such as smoking and SH infection.     

Berberine in Human Oncogenic Herpesvirus Infections and Their Linked Cancers

Human herpesviruses are known to induce a broad spectrum of diseases, ranging from common cold sores to cancer, and infections with some types of these viruses, known as human oncogenic herpesviruses (HOHVs), can cause cancer. Challenges with viral latency, recurrent infections, and drug resistance have generated the need for finding new drugs with the ability to overcome these barriers. Berberine (BBR), a naturally occurring alkaloid, is known for its multiple biological activities, including antiviral and anticancer effects. This paper comprehensively compiles all studies that have featured anti-HOHV properties of BBR along with promising preventive effects against the associated cancers. The mechanisms and pathways induced by BBR via targeting the herpesvirus life cycle and the pathogenesis of the linked malignancies are reviewed. Approaches to enhance the therapeutic efficacy of BBR and its use in clinical practice as an anti-herpesvirus drug are also discussed.     

Identification of Three Novel and One Known Mutation in the WFS1 Gene in Four Unrelated Turkish Families: The Role of Homozygosity Mapping in the Early Diagnosis

Objective:Bi-allelic mutations in the wolframin gene (WFS1) cause Wolfram syndrome 1 (WS1 or DIDMOAD) characterized by non-autoimmune diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural deafness, urinary tract abnormalities, and neuropsychiatric disorders. Patients presenting with an incomplete phenotype of WS1 were evaluated using homozygosity mapping and subsequent whole-exome sequencing.Methods:Four unrelated consanguineous Turkish families, including seven affected children, and their unaffected parents and siblings were evaluated. Homozygosity mapping was performed, followed by whole-exome sequencing of WFS1. Mutations were classified according to results of “in silico” analyses, protein prediction, and functional consequences.Results:Homozygosity mapping confirmed shared homozygous regions on chromosome 4 (chr4p16.1) between the affected individuals, that was absent in their unaffected siblings. Exome sequencing identified three novel (c.1215T>A, c.554G>A, c.1525_1540dup) and one known (c.1522_1523delTA) mutations in WFS1. All mutations were predicted to cause stop codon leading to early termination of protein synthesis and complete loss-of-function. All patients were found to be homozygous for the change, with parents and other unaffected siblings being carriers.Conclusion:Our study expands the mutation spectrum of WSF1 mutations with three novel mutations. Homozygosity mapping may provide enrichment for molecular genetic analysis and early diagnosis of WS1 patients with incomplete phenotype, particularly in consanguineous pedigrees.     

The mechanism of appearance of specific antibody-forming cells in lungs of inbred mice after intratracheal immunization with sheep erythrocytes

Immunization, ablation, and adoptive transfer studies were performed in inbred mice to define in vivo the cellular mechanisms for the appearance of specific antibody-forming cells (AFC) in pulmonary parenchyma. Mice were immunized locally or systemically with sheep erythrocytes (SRBC), and the concentrations of IgM- and IgG-producing AFC were measured in lung and extrapulmonary lymphoid tissues with a hemolytic-plaque assay. Splenectomized mice and recipients of adoptively transferred, sensitized lymphocytes were examined. We found that primary intratracheal (IT) immunization regularly failed to induce the appearance of AFC in lungs, whereas IT boosting of primed animals consistently succeeded. Immunization experiments showed that mice could be primed by any of a variety of local or systemic routes, but that the IT route of boosting was an absolute requirement for the induction of pulmonary AFC in primed mice. Recruitment of AFC into lungs by IT boosting of systemically primed and boosted animals was antigen-specific. Splenectomy performed prior to priming reduced, but did not ablate, the pulmonary AFC-response to IT boosting. Adoptive transfer of sensitized lymphocytes to naive recipient mice substituted for antigen-priming, which is required for induction of pulmonary AFC by IT challenge. Results of adoptive transfer studies demonstrate that IT challenge with specific antigen recruits systemically administered sensitized lymphocytes into the lung. We conclude that local primary immunization of mice results in the generation of AFC in extrapulmonary lymphoid tissues and that the major mechanism for the appearance of AFC in lungs is through recruitment of sensitized cells from systemic sources by intrapulmonary boosting with specific antigen.     

Stem cell transplantation for patients with Fanconi anemia with low-dose cyclophosphamide and antithymocyte globulins without the use of radiation therapy

In all, 22 patients with confirmed Fanconi anemia (FA) underwent stem cell transplantation (SCT) from HLA-matched, related donors at KFSHRC. Median age at SCT was 7.6 years (range, 2.5-14.6 years). Conditioning regimen consisted of cyclophosphamide (CY) 15 mg/kg/day intravenously (i.v.) for 4 consecutive days, in addition to equine antithymocyte globulins (ATG) given i.v. at 40 mg/kg/day for four doses pre-SCT. No radiation therapy was given. For graft-versus-host disease prophylaxis, we used cyclosporin at the standard doses; ATG was added at 20 mg/kg/dose i.v. on days 2, 4, 6, 8, 10, and 12 post-SCT (total of six doses). All patients engrafted and are alive and transfusion independent with a median follow-up time of 20.2 months (range, 3.3-59 months). One patient however developed a decrease in her WBC and platelet count. Her work-up revealed slightly hypocellular bone marrow, and a series of chimerism studies over 1 year confirmed that she has stable mixed chimerism; she remains transfusion independent. We conclude that low-dose CY without radiation therapy can be used satisfactorily in the conditioning of patients with FA undergoing related SCT.     

A survey-based assessment of the Canadian pediatric surgery workforce

Background

There is significant lack of information regarding the Canadian pediatric surgery workforce.

Methods

An IRB-approved survey aimed at assessing workforce issues was administered to pediatric surgeons and pediatric surgery chiefs in Canada in 2012.

Results

The survey was completed by 98% of practicing surgeons and 13 of the 18 division chiefs. Only 6% of surgeons are older than 60 years, and only a fifth anticipate retirement over the next decade. The workforce is stable, with 82% of surgeons unlikely to change current positions. Surgical volume showed essentially no growth during the 5-year period 2006–2010. The majority of surgeons felt they were performing the right number or too few cases and anticipated minimal or no future growth in their individual practices or that of their group. Based on anticipated vacancies, the best estimate is a need for 20 new pediatric surgeons over the next decade. This need is significantly surpassed by the current output from the Canadian training programs.

Conclusions

The Canadian pediatric surgery workforce is currently saturated. The mismatch between the number of graduating trainees and the available positions over the next decade has significant repercussions for current surgery and pediatric surgery residents wishing to practice in Canada.