Canadian Rheumatology Association/Spondyloarthritis Research Consortium of Canada Living Treatment Recommendations for the Management of Axial Spondyloarthritis.

OBJECTIVE: To provide a set of living treatment recommendations that will give contemporary guidance on the management of patients with axial spondyloarthritis (axSpA) in Canada. METHODS: The Spondyloarthritis Research Consortium of Canada (SPARCC), in conjunction with the Canadian Rheumatology Association, organized a treatment recommendations panel composed of rheumatologists, researchers, allied health professionals, and a patient advocate. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach was used, in which existing guidelines were adopted or adapted to a Canadian context. Recommendations were also placed in a health equity framework. RESULTS: Fifty-six recommendations were made for patients with active axSpA, stable axSpA, active or stable axSpA, for comorbidities, and for assessment, screening, and imaging. Recommendations were also made for principles of management, disease monitoring, and ethical considerations. CONCLUSION: These living treatment recommendations will provide up-to-date guidance for the management of axSpA for Canadian practice. As part of the living model, they will be updated regularly as changes occur in the treatment landscape.

Early Detection of First Carpometacarpal Joint Osteoarthritis Using Magnetic Resonance Imaging Assessment in Women With High Hypermobility Scores.

OBJECTIVE: The aim of this study was to explore association between hypermobility and osteoarthritis (OA) at the first carpometacarpal (CMC) joint, using magnetic resonance imaging (MRI) to identify early change in women at high risk of developing OA but without yet established diagnoses. METHODS: For this observational study, 33 women (aged 30-50 years) with self-reported history of maternal hand OA but without personal diagnoses of OA were recruited. Participants completed a 5-point hypermobility questionnaire. The 20 participants with 2 or more positive responses were categorized with "high hypermobility scores." The remaining 13 were categorized with "low hypermobility scores." Data collection included functional index, hand pain measure, parity, smoking status, and body mass index. Each participant underwent dominant hand radiographic and MRI examination. Imaging studies were interpreted by assessors blinded to hypermobility score categorization. RESULTS: No significant differences in age, body mass index, parity, functional index, or pain scores were observed between higher and lower hypermobility score groups. Similarly, there were no significant differences between groups for radiographic changes. However, significantly higher proportions of women with higher hypermobility scores were observed on MRI to have abnormalities of trapezium cartilage (75% vs. 38%), metacarpal cartilage (80% vs. 38%), and trapezium bone (70% vs. 31%); p < 0.05 for all. CONCLUSIONS: First CMC joint structural abnormalities were more frequently observed in women with higher hypermobility scores. Identification of early preradiographic changes in this group supports the concept that early-life joint laxity may contribute to future OA predisposition. Magnetic resonance imaging may be a preferred imaging test for detection of early cartilage changes in people at high risk of CMC joint OA.

The efficiency of Cytochrome P450 gene-based markers in accessing genetic variability of drumstick (Moringa oleifera Lam.) accessions.

Drumstick (Moringa oleifera Lam.) is an important vegetable as well as forage crop of arid and semi-arid zones of the tropics. The leaves and pods of the plant are rich sources of minerals and vitamins. In the present work, genetic diversity study of 23 genotypes of M. oleifera collected from Kerala, Tamil Nadu and Karnataka states of India was carried out using seven cytochrome P450 (CytP450) markers. By using seven pairs of CytP450 gene-based markers, 88.25% of polymorphism was recorded among the 23 sampled genotypes. The Polymorphic Information Content (PI), Marker Index (MI) and Resolving Power obtained for seven primers were estimated 0.23, 2.96 and 9.83, respectively. The Unweighted Pair Group Method with Arithmetic mean (UPGMA) dendrogram based on this marker data indicate that genotypes from different geographical regions are placed in the same clusters. The dendrogram and Principal Coordinates Analysis (PCoA) plots derived from the binary data matrices were highly concordant. The investigation, in brief, proved that CytP450 based marker system is efficient in the elucidation of genetic diversity in M. oleifera accessions.

The effect of silver nitrate on micropropagation of Moringa oleifera Lam. an important vegetable crop of tropics with substantial nutritional value.

An improved micropropagation protocol facilitating continuous multiplication of elite germplasm of Moringa oleifera has been developed. Initial culture of nodal explant in MS medium supplemented with 2.5 µM BA resulted in the formation of 12.5 shoots per explant with high frequency of leaf fall (84.3%). To confirm whether the leaf fall is due to accumulation of ethylene in the culture vessel, effect of ethylene releasing agent CEPA in the medium was tested. In order to reduce leaf fall and improve multiplication, varying concentration of anti-ethylene agent, AgNO3 was incorporated in the medium. Addition of 2.5 µM AgNO3 in combination with 2.5 µM BA produced maximum number of shoots (17.6) including shoots originated from the base of the explant and shoots from the axillary buds of the primary shoots, where significant reduction in leaf fall (20.6%) was noticed. This enabled sustained multiplication of M. oleifera through continuous subculture without adversely affecting shoot number or shoot quality in terms of shoot length. Microshoots obtained from fourth subculture onwards were used for ex vitro rooting and found that by treating 50 µM NAA for 30 s, maximum numbers of microshoots (83.3%) were rooted. Rooted plants were acclimatized, survived and were successfully transferred to field. Genetic fidelity analysis using 10 ISSR primers revealed more than 95% monomorphic bands among plants raised in MS medium containing low concentration (2.5 µM) of AgNO3 and BA (2.5 µM). The addition of AgNO3 in the medium sustained in vitro growth and effectively prevented leaf fall compared to control, thus demonstrating efficient micropropagation of M. oleifera.

Transcriptional Regulation of Brain-derived Neurotrophic Factor Coding Exon IX: ROLE OF NUCLEAR RESPIRATORY FACTOR 2.

Brain-derived neurotrophic factor (BDNF) is an active neurotrophin abundantly expressed throughout the nervous system. It plays an important role in synaptic transmission, plasticity, neuronal proliferation, differentiation, survival, and death. The Bdnf gene in rodents has eight non-coding exons and only a single coding exon (IX). Despite its recognized regulation by neuronal activity, relatively little is known about its transcriptional regulation, and even less about the transcription factor candidates that may play such a role. The goal of the present study was to probe for such a candidate that may regulate exon IX in the rat Bdnf gene. Our in silico analysis revealed tandem binding sites for nuclear respiratory factor 2 (NRF-2) on the promoter of exon IX. NRF-2 is of special significance because it co-regulates the expressions of mediators of energy metabolism (cytochrome c oxidase) and mediators of neuronal activity (glutamatergic receptors). To test our hypothesis that NRF-2 also regulates the Bdnf gene, we performed electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), promoter cloning, and site-directed mutagenesis, real-time quantitative PCR (RT-qPCR), and Western blotting analysis. Results indicate that NRF-2 functionally regulates exon IX of the rat Bdnf gene. The binding sites of NRF-2 are conserved between rats and mice. Overexpressing NRF-2 up-regulated the expression of Bdnf exon IX, whereas knocking down NRF-2 down-regulated such expression. These findings are consistent with our hypothesis that NRF-2, in addition to regulating the coupling between neuronal activity and energy metabolism, also regulates the expression of BDNF, which is intimately associated with energy-demanding neuronal activity.

Specificity protein 4 (Sp4) transcriptionally regulates inhibitory GABAergic receptors in neurons.

Previous studies in our laboratory have shown that the neuron-specific specificity protein 4 (Sp4) transcriptionally regulates many excitatory neurotransmitter receptor subunit genes, such as those for GluN1, GluN2A, and GluN2B of N-methyl-d-aspartate (NMDA) receptors and Gria2 of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. It also regulates Atp1a1 and Atp1b1 subunit genes of Na(+)/K(+)-ATPase, a major energy-consuming enzyme, as well as all 13 subunits of cytochrome c oxidase (COX), an important energy-generating enzyme. Thus, there is a tight coupling between energy consumption, energy production, and excitatory neuronal activity at the transcriptional level in neurons. The question is whether inhibitory neurotransmitter receptors are also regulated by Sp4. In the present study, we tested our hypothesis that Sp4 regulates receptor subunit genes of a major inhibitory neurotransmitter, GABA, specifically GABAA receptors. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, real-time quantitative PCR, chromatin immunoprecipitation, promoter mutational analysis, over-expression and shRNA of Sp4, functional assays, and western blots, we found that Sp4 functionally regulates the transcription of Gabra1 (GABAA α1) and Gabra2 (GABAA α2), but not Gabra3 (GABAA α3) subunit genes. The binding sites of Sp4 are conserved among rats, humans, and mice. Thus, our results substantiate our hypothesis that Sp4 plays a key role in regulating the transcription of GABAA receptor subunit genes. They also indicate that Sp4 is in a position to transcriptionally regulate the balance between excitatory and inhibitory neurochemical expressions in neurons.

Assessment of heavy metals in Averrhoa bilimbi and A. carambola fruit samples at two developmental stages.

Though the fruits of Averrhoa bilimbi and A. carambola are economically and medicinally important, they remain underutilized. The present study reports heavy metal quantitation in the fruit samples of A. bilimbi and A. carambola (Oxalidaceae), collected at two stages of maturity. Heavy metals are known to interfere with the functioning of vital cellular components. Although toxic, some elements are considered essential for human health, in trace quantities. Heavy metals such as Cr, Mn, Co, Cu, Zn, As, Se, Pb, and Cd were analyzed by atomic absorption spectroscopy (AAS). The samples under investigation included, A. bilimbi unripe (BU) and ripe (BR), A. carambola sour unripe (CSU) and ripe (CSR), and A. carambola sweet unripe (CTU) and ripe (CTR). Heavy metal analysis showed that relatively higher level of heavy metals was present in BR samples compared to the rest of the samples. The highest amount of As and Se were recorded in BU samples while Mn content was highest in CSU samples and Co in CSR. Least amounts of Cr, Zn, Se, Cd, and Pb were noted in CTU while, Mn, Cu, and As were least in CTR. Thus, the sweet types of A. carambola (CTU, CTR) had comparatively lower heavy metal content. There appears to be no reason for concern since different fruit samples of Averrhoa studied presently showed the presence of various heavy metals in trace quantities.

Nuclear respiratory factor 2 regulates the transcription of AMPA receptor subunit GluA2 (Gria2).

Neuronal activity is highly dependent on energy metabolism. Nuclear respiratory factor 2 (NRF-2) tightly couples neuronal activity and energy metabolism by transcriptionally co-regulating all 13 subunits of an important energy-generating enzyme, cytochrome c oxidase (COX), as well as critical subunits of excitatory NMDA receptors. AMPA receptors are another major class of excitatory glutamatergic receptors that mediate most of the fast excitatory synaptic transmission in the brain. They are heterotetrameric proteins composed of various combinations of GluA1-4 subunits, with GluA2 being the most common one. We have previously shown that GluA2 (Gria2) is transcriptionally regulated by nuclear respiratory factor 1 (NRF-1) and specificity protein 4 (Sp4), which also regulate all subunits of COX. However, it was not known if NRF-2 also couples neuronal activity and energy metabolism by regulating subunits of the AMPA receptors. By means of multiple approaches, including electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutations, real-time quantitative PCR, and western blot analysis, NRF-2 was found to functionally regulate the expression of Gria2, but not of Gria1, Gria3, or Gria4 genes in neurons. By regulating the GluA2 subunit of the AMPA receptor, NRF-2 couples energy metabolism and neuronal activity at the transcriptional level through a concurrent and parallel mechanism with NRF-1 and Sp4.

Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2).

The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors mediating fast excitatory synaptic transmission in the brain. The regulation of the four subunits of AMPA receptors, GluA1-4, is poorly understood. Excitatory synaptic transmission is highly energy-demanding, and this energy is derived mainly from the oxidative pathway. Recently, we found that specificity factor regulates all subunits of cytochrome c oxidase (COX), a critical energy-generating enzyme. COX is also regulated by nuclear respiratory factor 1 (NRF-1), which transcriptionally controls the Gria2 (GluA2) gene of AMPA receptors. The goal of the present study was to test our hypothesis that Sp-factors (Sp1, Sp3, and/or Sp4) also regulate AMPA subunit genes. If so, we wish to determine if Sp-factors and NRF-1 function via a complementary, concurrent and parallel, or a combination of complementary and concurrent/parallel mechanism. By means of multiple approaches, including electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutations, real-time quantitative PCR, and western blot analysis, we found that Sp4, but not Sp1 or Sp3, regulates the Gria2, but not Gria1, 3, or 4, subunit gene of the AMPA receptor in a concurrent and parallel manner with NRF-1. Thus, Sp4 and NRF-1 both mediate the tight coupling between neuronal activity and energy metabolism at the transcriptional level.

Fabrication of Epoxy Vesicles using Self-Assembling Polystyrene-Montmorillonite Nanocomposite Reusable Template.

We report the fabrication of thermoset vesicles using a thermoplastic-clay nanocomposite vesicle reusable template. Epoxy polymer vesicles (EPV) of micrometer diameters were synthesized from bisphenol-A diglycidyl ether resin encapsulated within a self-assembled, polystyrene-montmorillonite hybrid nanocomposite (PCN) template and in situ cross-linked with polyamine curing agent. The size and wall thickness of the EPV vesicles were shown to be controlled by the epoxy resin concentration up to a critical epoxy concentration of 20 wt %, beyond which the wall thickness alone was found to be increasing. The EPVs dispersed in a polystyrene matrix at a loading of 2 wt % were found to reduce the dielectric constant of polystyrene from 3.1 to 2.0, and a linear decrease with decreasing wall thickness of the EPV, attributed to the increase in free volume involving the intrinsic porosity from the rigid epoxy vesicles and the composite, exhibited improved thermal stability also. The result suggests that vesicles produced by micromolding using self-assembled PCN can be utilized for the synthesis of polymer microcomposites having good interfacial bonding as well as low dielectric constant and good thermal stability for use in electronic packaging applications.

Reduced levels of brain-derived neurotrophic factor contribute to synaptic imbalance during the critical period of respiratory development in rats.

Previously, our electrophysiological studies revealed a transient imbalance between suppressed excitation and enhanced inhibition in hypoglossal motoneurons of rats on postnatal days (P) 12-13, a critical period when abrupt neurochemical, metabolic, ventilatory and physiological changes occur in the respiratory system. The mechanism underlying the imbalance is poorly understood. We hypothesised that the imbalance was contributed by a reduced expression of brain-derived neurotrophic factor (BDNF), which normally enhances excitation and suppresses inhibition. We also hypothesised that exogenous BDNF would partially reverse this synaptic imbalance. Immunohistochemistry/single-neuron optical densitometry, real-time quantitative PCR (RT-qPCR) and whole-cell patch-clamp recordings were done on hypoglossal motoneurons in brainstem slices of rats during the first three postnatal weeks. Our results indicated that: (1) the levels of BDNF and its high-affinity tyrosine receptor kinase B (TrkB) receptor mRNAs and proteins were relatively high during the first 1-1.5 postnatal weeks, but dropped precipitously at P12-13 before rising again afterwards; (2) exogenous BDNF significantly increased the normally lowered frequency of spontaneous excitatory postsynaptic currents but decreased the normally heightened amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) during the critical period; (3) exogenous BDNF also decreased the normally heightened frequency of miniature IPSCs at P12-13; and (4) the effect of exogenous BDNF was partially blocked by K252a, a TrkB receptor antagonist. Thus, our results are consistent with our hypothesis that BDNF and TrkB play an important role in the synaptic imbalance during the critical period. This may have significant implications for the mechanism underlying sudden infant death syndrome.

Polyhedral oligomeric silsesquioxane-F68 hybrid vesicles for folate receptor targeted anti-cancer drug delivery.

Polyhedral Oligomeric Silsesquioxane (POSS)-F68 hybrid vesicles with an average diameter of 700 nm are produced using a stable solution of heterofunctional POSS having 3-aminopropyl and vinyl groups and pluronic F68 in ethanol-water mixture. Thermogram and zeta potential values evidence the spontaneous self-assembly of POSS into bilayers through H-bonding interaction between the aminopropyl groups, and the effective stabilization of the POSS-bilayers by amphiphilic F68 during solvent-evaporation to form the vesicles. The vesicles are noncytotoxic and dispersible in aqueous solvents through steric stabilization provided by the hydrophilic F68. A highly facile coinclusion method has been used for making doxorubicin and folic acid loaded vesicles. Doxorubicin loaded in the vesicles exhibits a controlled release profile in phosphate buffered saline. Confocal microscopic and flow cytometric studies on the endocytosis of the vesicles by HeLa and HOS cells prove that a noncovalent entrapment of excess folic acid in the vesicles through H-bonding is sufficient to enhance the uptake significantly. POSS-F68 vesicles in combination with folic acid and a chemotherapeutic can have potential for targeted intracellular anti-cancer drug delivery.

Increased nocturnal periodic limb movements in rheumatoid arthritis patients meeting questionnaire diagnostic criteria for restless legs syndrome.

BACKGROUND: Based on questionnaire criteria, the sensorimotor disorder restless legs syndrome (RLS) has been reported to have a higher prevalence in rheumatoid arthritis (RA) patients than in the general population. There has been some speculation that peripheral arthritic symptoms may allow false positive responses to questionnaire criteria. This study evaluates whether RA patients meeting RLS questionnaire criteria also have objective evidence of increased periodic limb movements (PLMs) characteristic of RLS. METHODS: Participants were recruited from RA clinic. Questionnaire data collected at study entry included: pain scores, rheumatoid arthritis disease activity index, Epworth sleepiness scale, Pittsburgh sleep quality index and RLS diagnostic criteria. Each participant was provided a PAM-RL actigraphic monitor, which attached to the ankle. This device was worn for two consecutive nights then returned for data download. Laboratory data including hemoglobin, iron studies, renal function and C-reactive protein levels were collected. RESULTS: Of the 57 participants, 23 met RLS diagnostic criteria. Those who met RLS criteria demonstrated higher mean frequency of nocturnal PLMs (19.63/hour; SD:21.13) than those who did not meet RLS criteria (11.13/hour; SD:12.10; p=0.033). There were no significant differences between groups in terms of patient characteristics, disease activity or duration measures. Patients meeting RLS criteria did have poorer sleep quality measures (p <0.001). CONCLUSIONS: RA patients who met RLS diagnostic criteria demonstrated higher frequencies of nocturnal PLMs than RA patients who did not meet criteria for RLS. This finding supports use of the RLS diagnostic criteria in helping to differentiate between RA arthritic symptoms and RLS.

Obstructive sleep apnoea in relation to rheumatic disease.

Sleep problems are common concerns in rheumatology patients and have been independently linked to increased pain perception and fatigue severity. Evidence supports an increased prevalence of primary sleep disorders, including sleep apnoea, in some rheumatic disease populations, particularly RA. Obstructive sleep apnoea is a significant public health concern and contributes to increased cardiovascular morbidity and mortality. Patients with obstructive sleep apnoea have also been found to have elevations in circulating acute-phase markers and pro-inflammatory cytokines. Co-existence of sleep apnoea in rheumatic disease patients may influence the severity of reported symptoms of pain and fatigue, accelerate the risk of cardiovascular events and possibly influence levels of circulating inflammatory markers and mediators. In this article we review the risk factors, prevalence and impact of sleep apnoea from a rheumatological perspective. Additionally, we recommend considering sleep apnoea screening in patients with rheumatic disease and, when appropriate, referral to a specialized sleep disorders clinic.

A 2-yr Randomized Controlled Trial on Creatine Supplementation during Exercise for Postmenopausal Bone Health.

PURPOSE: Our purpose was to examine the effects of 2 yr of creatine monohydrate supplementation and exercise on bone health in postmenopausal women. METHODS: Two hundred and thirty-seven postmenopausal women (mean age, 59 yr) were randomized to receive creatine (0.14 g·kg -1 ·d -1 ) or placebo during a resistance training (3 d·wk -1 ) and walking (6 d·wk -1 ) program for 2 yr. Our primary outcome was the femoral neck bone mineral density (BMD), with lumbar spine BMD and proximal femur geometric properties as the secondary outcomes. RESULTS: Compared with placebo, creatine supplementation had no effect on BMD of the femoral neck (creatine: 0.725 ± 0.110 to 0.712 ± 0.100 g·cm -2 ; placebo: 0.721 ± 0.102 to 0.706 ± 0.097 g·cm -2 ), total hip (creatine: 0.879 ± 0.118 to 0.872 ± 0.114 g·cm -2 ; placebo: 0.881 ± 0.111 to 0.873 ± 0.109 g·cm -2 ), or lumbar spine (creatine: 0.932 ± 0.133 to 0.925 ± 0.131 g·cm -2 ; placebo: 0.923 ± 0.145 to 0.915 ± 0.143 g·cm -2 ). Creatine significantly maintained section modulus (1.35 ± 0.29 to 1.34 ± 0.26 vs 1.34 ± 0.25 to 1.28 ± 0.23 cm 3 (placebo), P = 0.0011), predictive of bone bending strength, and buckling ratio (10.8 ± 2.6 to 11.1 ± 2.2 vs 11.0 ± 2.6 to 11.6 ± 2.7 (placebo), P = 0.011), predictive of reduced cortical bending under compressive loads, at the narrow part of the femoral neck. Creatine reduced walking time over 80 m (48.6 ± 5.6 to 47.1 ± 5.4 vs 48.3 ± 4.5 to 48.2 ± 4.9 s (placebo), P = 0.0008) but had no effect on muscular strength (i.e., one-repetition maximum) during bench press (32.1 ± 12.7 to 42.6 ± 14.1 vs 30.6 ± 10.9 to 41.4 ± 14 kg (placebo)) and hack squat (57.6 ± 21.6 to 84.4 ± 28.1 vs 56.6 ± 24.0 to 82.7 ± 25.0 kg (placebo)). In the subanalysis of valid completers, creatine increased lean tissue mass compared with placebo (40.8 ± 5.7 to 43.1 ± 5.9 vs 40.4 ± 5.3 to 42.0 ± 5.2 kg (placebo), P = 0.046). CONCLUSIONS: Two years of creatine supplementation and exercise in postmenopausal women had no effect on BMD; yet, it improved some bone geometric properties at the proximal femur.

Poly(lactide-co-glycolide)-laponite-F68 nanocomposite vesicles through a single-step double-emulsion method for the controlled release of doxorubicin.

Poly(lactide-co-glycolide) (PLGA)-laponite-F68 nanocomposite (PNC) vesicles were prepared through a technically facile, single-step water/oil/water double-emulsion method using ethyl acetate/water mixture. Vesicles of diameter 100 nm to 1.2 µm and average membrane thickness 30 nm were produced. Encapsulation with chemotherapeutic drug doxorubicin revealed unilamellar nature of the vesicle wall. PNC exhibited exfoliated morphology, enhanced thermal stability over neat PLGA, and a glass transition temperature of 54.29 °C. The zeta potential of -14.1 ± 0.231 for the vesicles revealed that the negatively charged PLGA surface is covered with neutral F68 in the vesicle wall. F68-Assisted formation of water/oil/water double emulsion of PNC in ethyl acetate/water mixture is proposed for the formation of the vesicles. Release characteristics of doxorubicin in phosphate-buffered saline (pH 7.4), cytotoxicity of bare and drug-loaded PNC vesicles with L929 cells, and uptake of doxorubicin with C6 fibroblast glioma cell line were also investigated.

Improved dielectric and mechanical properties of polystyrene-hybrid silica sphere composite induced through bifunctionalization at the interface.

Hybrid silica spheres (HS) of size 270-350 nm with vinyl and aminopropyl surface groups were incorporated in polystyrene (PS), and its effect on dielectric properties, coefficient of thermal expansion (CTE), and strength of PS-HS composite was studied. Incorporation of HS in PS followed a decrease in the dielectric constant from 3.2 for PS to 2.6 for composite with 7.5 vol % HS. The decrease in the dielectric constant was attributed to (i) increased interfacial porosity, (ii) formation of anhydrous HS having low dielectric constant, during hot processing of the composites, and (iii) dispersion and preservation of the anhydrous HS in the hydrophobic matrix. The dielectric constant of the composites with HS content up to 7.5 vol % does not vary much with temperature in the range from -20 to 65 °C. These composites also exhibited reduced CTE and improved flexural strength/stiffness due to good interfacial bonding through HS vinyl groups and dispersion of the filler in the matrix. The dielectric loss increased with HS content, and the loss measured for 7.5 vol % PS-HS composite was 6 × 10(-3), as compared to 10(-4) for PS. At HS loading above 7.5 vol %, the tendency of HS to agglomerate and form percolated structure lead to an increase in the dielectric constant and decrease in the mechanical properties of the composites.

Higher mortality rates associated with rheumatoid arthritis in Saskatchewan, Canada, 2001-2019.

OBJECTIVES: To estimate provincial all-cause mortality rates of Saskatchewan people with rheumatoid arthritis (RA) for comparison with the general population over time and between different geographic regions. METHODS: Saskatchewan provincial administrative health databases (2001-2019) were utilized as data sources. Two RA case definitions were employed: (1) ≥ 3 physician billing diagnoses, at least 1 from a specialist (rheumatologist, general internist or orthopaedic surgeon) within 2 years; (2) ≥ 1 hospitalization diagnosis (ICD-9 code 714, and ICD-10-CA codes M05, M06). Data from these definitions were combined to create an administrative data RA cohort. All-cause mortality rates across geographic regions, between rural/urban residences and between sexes were examined. RESULTS: Over an 18-year span, between fiscal-year 2001-2002 and fiscal-year 2018-2019, age- and sex-adjusted mortality rates ranged from 17.10 to 21.04 (95% CI 14.77, 19.44; 18.03, 24.05)/1000 RA person-years, compared with mortality rates for the general Saskatchewan population without RA, which ranged from 9.37 to 10.88 (95% CI 9.23, 9.51; 10.72, 11.05)/1000 person-years. Fiscal-year mortality rate ratios ranged from 1.82 to 2.13 (95% CI 1.56, 2.13; 1.83, 2.46). Provincial mortality rates were higher in men than in women for both general and RA populations. Northern Saskatchewan mortality rates were significantly higher in the general population but did not achieve significance compared with other provincial regions for the RA population. Regression analysis identified age, male sex, RA and geographic region as factors contributing to increased mortality. A trend towards lower mortality rates over time was observed. CONCLUSION: Higher mortality rates were observed in the RA population overall. Men had higher mortality rates, as did residents of Northern Saskatchewan compared with residents of other regions for the general population.

RéSUMé: OBJECTIFS: Estimer les taux de mortalité provinciaux, toutes causes confondues, des habitants de la Saskatchewan atteints de polyarthrite rhumatoïde (PR) pour les comparer aux taux dans la population générale au fil du temps et entre différentes régions géographiques. MéTHODE: Nos données sont extraites des bases de données administratives sur la santé de la Saskatchewan (2001­2019). Deux définitions de cas ont été employées pour la PR : 1) ≥ 3 factures de diagnostic médical, dont au moins une d'un(e) spécialiste (rhumatologue, interniste général[e] ou chirurgien[ne] orthopédiste) en l'espace de deux ans; 2) ≥ 1 diagnostic d'hospitalisation (code CIM-9 714 et codes CIM-10-CA M05 et M06). Les données de ces définitions ont été combinées pour créer une cohorte de personnes atteintes de PR dans les données administratives. Les taux de mortalité toutes causes confondues entre les régions géographiques, entre les lieux de résidence urbains et ruraux et entre les sexes ont été examinés. RéSULTATS: En l'espace de 18 ans, entre les exercices 2001-2002 et 2018-2019, les taux de mortalité rajustés selon l'âge et le sexe ont varié entre 17,10 et 21,04 (IC de 95 % : 14,77-19,44; 18,03-24,05)/1000 personnes-années pour les personnes atteintes de PR, tandis que les taux de mortalité de la population générale de la Saskatchewan non atteinte de PR se sont situés entre 9,37 et 10,88 (IC de 95 % : 9,23-9,51; 10,72-11,05)/1000 personnes-années. Les rapports de taux de mortalité par exercice ont varié entre 1,82 et 2,13 (IC de 95 % : 1,56-2,13; 1,83-2,46). Les taux de mortalité provinciaux des hommes étaient supérieurs à ceux des femmes, tant dans la population générale que chez les personnes atteintes de PR. Les taux de mortalité dans le Nord de la Saskatchewan étaient sensiblement plus élevés que dans les autres régions de la province pour la population générale, mais pas sensiblement plus élevés pour la population atteinte de PR. Selon les analyses de régression, l'âge, le sexe masculin, la PR et la région géographique étaient des facteurs contribuant à une mortalité accrue. Une tendance à la baisse des taux de mortalité au fil du temps a été observée. CONCLUSION: Dans la population atteinte de PR, des taux de mortalité plus élevés ont été observés globalement. Dans la population générale, les taux de mortalité des hommes et ceux des résidents du Nord de la Saskatchewan étaient plus élevés que ceux des résidents des autres régions.

Comparative Evaluation of Genotoxicity in Tobacco Users versus Nontobacco Users.

BACKGROUND: Many of the contents of cigarette smoke are genotoxic in nature, and consequently, cytogenetic injury seems to be a trustworthy biomarker for deciding the influence of exposure to chromosome damaging agents in smoke. The cytokinesis-block micronucleus assay (CBMN assay) has been proven to be an effectual tool for the study of micronuclei (MN) that will help in estimating the genotoxicity in tobacco users alone which will further help in early cancer detection. OBJECTIVE: The objective is to find out whether there is pronounced contrast in genotoxicity between tobacco users and nonusers by determining MN number in peripheral blood lymphocytes using CBMN assay. METHODOLOGY: MN frequency in peripheral blood lymphocytes was estimated in 5 ml of fresh blood obtained from sixty individuals using tobacco either smoking, chewing, or combination of both and also from thirty individuals with no habit of tobacco use. All were in the age group of 20-40 years. RESULTS: There was a significant increase in genotoxicity in tobacco users when compared to that of nontobacco users. A positive correlation was also obtained between smoking index and MN frequency in the study. CONCLUSION: Approximation of frequency of MN by CBMN assay can be used to evaluate the genotoxicity present in blood and helps in identifying tobacco users who are at a high risk for the presence of cancer even before the appearance of clinical changes.

Micropatterned surfaces through moisture-induced phase-separation of polystyrene-clay nanocomposite particles.

We report micropatterned polystyrene-clay nanocomposite (PCN) surfaces with concavities by moisture-induced phase separation of PCN particles. Micropatterned film with concavity size of 800 nm to 1.3 microm and a high number density of 2 x 10(8) features/cm(2) was obtained by drop-casting PCN solution (20 mg/mL PCN/THF) under ambient relative humidity of 70-80%. It is proposed that water droplets were channeled through the hydrophilic interfaces between the PCN particles, and the two-dimensional array of concavities was formed by spontaneous phase separation due to the presence of rigid clay platelets. The concavity size and number density can be tuned by varying the solvent for PCN. Micropatterned film with concavity size in the range of 650 nm to 1.1 microm with a number density of 5 x 10(7) features/cm(2) was obtained using chloroform as solvent, whereas a concavity size of 150-740 nm and number density of 10(8) features/cm(2) were obtained using carbon disulfide.