Management of knee and hip osteoarthritis: an opportunity for the Canadian chiropractic profession

Knee and hip osteoarthritis (OA) place a significant burden on the Canadian health system and are a major public health challenge. This brief commentary discusses the recently published Osteoarthritis Research Society International guideline and the American College of Rheumatology guideline for the management of OA. Special attention has been given to the role of manual therapy, exercise, and patient education for the treatment of knee and hip OA. This article also reviews the Good Life with osteoArthritis in Denmark (GLA:D^®) treatment program for knee and hip OA and the implementation of this program in Canada. Lastly, the authors discuss the opportunity for the Canadian chiropractic profession to embrace treatment programs like GLA:D^® and take an active role in the strengthening of the Canadian health system from a musculoskeletal perspective.     

Contribution of bacterial cells as nucleation centers in microbiologically induced CaCO3 precipitation—A mathematical modeling approach

The microbiologically induced calcite precipitation (MICP) has been extensively studied for geotechnical engineering through simultaneous action of natural phenomena and engineering processes. The focus of bacterial contribution to the MICP has been directed to calcium carbonate productivity, while the additional bacterial role as a crystal nucleation center was not explained especially from a mathematical prediction modeling point of view. Therefore, this study provides explanations and a mathematical modeling approach of bacterial influence on the MICP induced by newly-isolated ureolytic Bacillus strains and Sporosarcina pasteurii DSM 33. Using the obtained results of low-cost, rapid, and simple assays, artificial neural network modeling was applied for cell surface predispositions, pH changes as well as calcium-involved function in biofilm formation during the MICP, for the first time. Based on the obtained contribution of the alkalophilic/alkaloresistant bacteria, calcite precipitation can be significantly directed by the presence, of ureolytic bacterial cells as nucleation centers during CaCO₃ precipitation as well as their morphology, surface characteristics, potential to form a biofilm, and/or generate pH changes.     

X-linked angiotensin II type 2 receptor gene polymorphism -1332A/G in male patients with essential hypertension

BACKGROUND: The role of AT2R in regulation of blood pressure (BP) was mainly investigated in animal models. It is proposed to be a negative regulator of BP. X-linked AT2R -1332 A/G polymorphism has been denoted as functional. This polymorphism was associated with certain cardiovascular phenotypes in hypertensive patients, but it was poorly investigated in essential hypertension. The aim of our study was to evaluate possible association of -1332 A/G gene polymorphism with essential hypertension in males from Serbian population. METHODS: The study group included 304 men of Caucasian origin, 190 normotensive (NT) and 114 hypertensive (HT), free of cardiovascular disorders. Genotyping was done by PCR RFLP method. RESULTS: G/- genotype was in association with HT (OR 1.6, CI=1.0-2.6, p=0.04). Stratification by age (<40 years, mean 31.65+/-5.29 and >40 years, mean 51.36+/-8.32) pronounced significance only in older males (OR 2.4, CI=1.2-5.0, p=0.02). After adjustment for confounding factors the OR for hypertension remained unchanged and significant (adjusted OR 2.3, CI=1.0-5.4, p=0.04). Conclusion: Hemizygosity for the G allele was found to be susceptibility factor for hypertension in males. Still, clarifying the role of AT2R in development of human hypertension requires further replication studies in larger and different populations.     

The association of V249I and T280M fractalkine receptor haplotypes with disease course of multiple sclerosis

We investigated the association of CX3CR1 genotypes/haplotypes with MS and performed the prediction analysis of protein sequence variants' effects on CX3CL1/CX3CR1 interaction. We found no association of CX3CR1 with MS susceptibility. Frequency of I(249)T(280) haplotype was significantly lower in SP compared to RR patients (RR>10 years, OR=0.30, 95%CI=0.11-0.79, p=0.01; OR=0.53, 95%CI=0.18-1.56, p=0.2, in SP<10 years vs. RR>10 years). Prediction analysis showed that I249 T280 protein variant would significantly affect CX3CL1/CX3CR1 interaction. Our results suggest that CX3CR1 I???T??? haplotype could have protective effect for switch to SP MS. Further research is warranted to validate and replicate currently observed results.     

FISHing in the dark: How the combination of FISH and conventional karyotyping improves the diagnostic yield in CpG‐stimulated chronic lymphocytic leukemia

Despite significant advances in molecular genetic approaches, fluorescence in situ hybridization (FISH) remains the gold standard for the diagnostic evaluation of genomic aberrations in patients with chronic lymphocytic leukemia (CLL). Efforts to improve the diagnostic utility of molecular cytogenetic testing have led to the expansion of the traditional 4‐probe CLL FISH panel. Not only do these efforts increase the cost of testing, they remain hindered by the inherent limitations of FISH studies ‐ namely the inability to evaluate genomic changes outside of the targeted loci. While array‐based profiling and next generation sequencing (NGS) have critically expanded our understanding of the molecular pathogenesis of CLL, these methodologies are not routinely used by diagnostic laboratories to evaluate copy number changes or the mutational profile of this disease. Mitogenic stimulation of CLL specimens with CpG‐oligonucleotide (CpG‐ODN) has been identified as a reliable and reproducible means of obtaining a karyotype, facilitating a low‐resolution genome‐wide analysis. Across a cohort of 1255 CpG‐ODN‐stimulated CLL specimens, we describe the clinical utility associated with the combinatorial use of FISH and karyotyping. Our testing algorithm achieves a higher diagnostic yield (～10%) through the detection of complex karyotypes, well‐characterized chromosomal aberrations not covered by the traditional CLL FISH panel and through the detection of concurrent secondary malignancies. Moreover, the single cell nature of this approach permits the evaluation of emerging new clinical concepts including clonal dynamics and clonal evolution. This approach can be broadly applied by diagnostic laboratories to improve the utility of traditional and molecular cytogenetic studies of CLL. Am. J. Hematol. 91:978–983, 2016. © 2016 Wiley Periodicals, Inc.     

Abnormal ultrasonographic findings of the kidneys obtained with a portable echosonographic device in the patients with infectious diseases--a five-year study

BACKGROUND/AIM: Ultrasonographic kidney changes might be a part of the clinical picture, or consequence of the various infections diseases. The aim of this study was to establish ultrasonographic findings obtained by portable devices, the frequency of abnormal findings of the kidneys in the non-selected group of the patients with infections diseases. METHODS: Over a five-year period (January 1, 2000-December 31, 2004), the kidneys were examined by ultrasonography in 2,718 patients, 1,452 males and 1,266 females, mean age 47.52 +/- 17 years, (16-92 years). The examination included the measurement of the size of the kidneys, evaluation of the condition of parenchyma and pyelo-calix, detection of simple cysts, calculi and tumor. The conventional portable ultrasonographic devices ALOKA SSD-500 and SSD-1000 (B-mode) with a convex 3.5 and 5 MHz sonde were used. RESULTS: The size of kidneys was normal in 95% of the patients, while they were enlarged in 1.3% and reduced in 1.5% of the patients. A normal ultrasonographic recording was noted in 68.9% of the patients, double pelvis in 0.1%, while hydronephrosis was revealed in 0.9% of the patients. A reduced renal parenchyma was observed in 16.1% of the patients. Nephrolithiasis was found in 10.9% of the patients, and simple cysts of kidneys in 8.9% of the patients. The finding of polycystic kidneys was seen in 0.5% of the patients. An ultrasonographic recording of angiomyolipoma was noted in 0.4% of the patients, and the finding of other tumors in 0.1% of the patients. Adrenal tumors were found in 0.1% of the patients. CONCLUSION: Portable ultrasonographic units may be highly useful for the standard morphological diagnostics of renal changes during infections, as well as in clinical-epidemiological studies and screening of hereditary and the acquired diseases of this organ.     

Postgraduate training in family medicine in Albania

In the Balkan context education in general practice varies greatly and it is in different stages of reorganisation and curriculum development. The postgraduate training in family medicine in Albania started in January 1997 with the goal of providing future family doctors with the proper knowledge, skills, attitudes, and professional values that will enable them to address the medical problems in the community. This paper describes the structure and content of the training programme and discusses some of its key elements.     

Immediate allergic reactions to cephalosporins and penicillins and their cross-reactivity in children

Penicillins and cephalosporins are the most important betalactams inducing IgE-mediated reactions. The safety of administering cephalosporins to penicillin-allergic children is a particular problem, because cephalosporin allergenic determinants have not been properly identified. A study was undertaken to evaluate the frequency of anaphylactic reactions to cephalosporins and penicillins and their cross-reactivity in a pediatric population. A prospective survey was conducted in a group of 1170 children with suspected immediate allergic reactions to cephalosporins and/or penicillins, which were examined during a period of 8 yr. In vivo (skin tests and challenges) and in vitro tests (for specific IgE) were performed with standard concentration of penicillins and cephalosporins. When 1170 children with a clinical history of allergy to penicillins and/or cephalosporins were tested in vivo for immediate hypersensitivity to betalactams, 58.3% cases overall were found to be skin or challenge test positive. Among them, 94.4% patients were positive to penicillins and 35.3% to cephalosporins. The frequency of positive reactions in the in vivo testing was in the range from 36.4% to 88.1% for penicillins and from 0.3% to 29.2% for cephalosporins. However, 31.5% of the penicillin allergic children cross-reacted to some cephalosporin. If a child was allergic to a cephalosporin, the frequency of positive reactions to penicillin was 84.2%. The cross-reactivity between cephalosporins and penicillins varied between 0.3% and 23.9%. The cross-reactivity among different generations of cephalosporins varied between 0% and 68.8%, being the highest for first and second-generation cephalosporins and 0% for third generation cephalosporins. The frequency of immediate allergic reactions to cephalosporins is considerably lower compared to penicillins, and the degree of cross-reactivity between cephalosporins and penicillins depends on the generation of cephalosporins, being higher with earlier generation cephalosporins. The cross-reactivity among cephalosporins is lower compared to cross-reactivity between penicillins and cephalosporins.     

Microbiota and viral hepatitis: State of the art of a complex matter

Changes in gut microbiota influence both the gut and liver, which are strictly connected by the so-called “gut–liver axis”. The gut microbiota acts as a major determinant of this relationship in the onset and clinical course of liver diseases. According to the results of several studies, gut dysbiosis is linked to viral hepatitis, mainly hepatitis C virus and hepatitis B virus infection. Gut bacteria-derived metabolites and cellular components are key molecules that affect liver function and modulate the pathology of viral hepatitis. Recent studies showed that the gut microbiota produces various molecules, such as peptidoglycans, lipopolysaccharides, DNA, lipoteichoic acid, indole-derivatives, bile acids, and trimethylamine, which are translocated to the liver and interact with liver immune cells causing pathological effects. Therefore, the existence of crosstalk between the gut microbiota and the liver and its implications on host health and pathologic status are essential factors impacting the etiology and therapeutic approach. Concrete mechanisms behind the pathogenic role of gut-derived components on the pathogenesis of viral hepatitis remain unclear and not understood. In this review, we discuss the current findings of research on the bidirectional relationship of the components of gut microbiota and the progression of liver diseases and viral hepatitis and vice versa. Moreover, this paper highlights the current therapeutic and preventive strategies, such as fecal transplantation, used to restore the gut microbiota composition and so improve host health.     

TMZ regulates GBM stemness via MMP14-DLL4-Notch3 pathway

Glioblastoma (GBM) is one of the most aggressive primary brain tumors with frequent recurrences following the standard methods of treatment—temozolomide (TMZ), ionizing radiation and surgical resection. The objective of our study was to investigate GBM resistance mediated via MMP14 (matrix metalloproteinase 14). We used multiple PDX GBM models and established glioma cell lines to characterize expression and subcellular localization of MMP14 after TMZ treatment. We performed a Kiloplex ELISA-based array to evaluate changes in cellular proteins induced by MMP14 expression and translocation. Lastly, we conducted functional and mechanistic studies to elucidate the role of DLL4 (delta-like canonical notch ligand 4) in regulation of glioma stemness, particularly in the context of its relationship to MMP14. We detected that TMZ treatment promotes nuclear translocation of MMP14 followed by extracellular release of DLL4. DLL4 in turn stimulates cleavage of Notch3, its nuclear translocation and induction of sphering capacity and stemness.