Frequency and severity of exacerbations of COPD associated with future Risk of exacerbations and mortality: A UK routine health care data study

Background: Studies have shown that chronic obstructive pulmonary disease (COPD) exacerbation events are related to future events; however, previous literature typically reports frequent vs infrequent exacerbations per patient-year and no studies have investigated increasing number of severe exacerbations in relation to COPD outcomes. Objective: To investigate the association between baseline frequency and severity of exacerbations and subsequent mortality and exacerbation risk in a COPD cohort. Methods: Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics data were used to identify patients registered at general practices in the UK, who had a diagnosis of COPD, were over the age of 40 years, were smokers or ex-smokers and had data recorded from 2004 onwards. Frequency and severity of exacerbations in the baseline year were identified as moderate exacerbations (general practice events) and severe exacerbations (hospitalised events). Patients were categorised as having: none, 1 moderate only, 2 moderate only, 3+ moderate only, 1 severe (and any moderate), 2 severe (and any moderate), and 3+ severe (and any moderate exacerbations). Poisson regression was used to investigate the association between baseline exacerbation frequency/severity and exacerbation events and mortality over follow-up. Results: Overall, 340,515 COPD patients were included. Patients had higher rates of future exacerbations with increasing frequency and severity of baseline exacerbations compared to no baseline exacerbations. Adjusted incidence rate ratios (IRR) for patients with 1, 2, and 3+ moderate exacerbations compared to 0 exacerbations were 1.70 (95% CI 1.66– 1.74), 2.31 (95% CI 2.24– 2.37), and 3.52 (95% CI 3.43– 3.62), respectively. Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion. Conclusion: Increasing number and severity of exacerbations were associated with increasing risk of subsequent exacerbations, all-cause mortality and COPD-related mortality. Even a single moderate event increases the risk of future events, illustrating that every exacerbation counts

Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration >= 5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Methodology/Principal Findings: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin

Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering

Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs

Clinical and laboratory findings associated with severe scrub typhus

<p>Abstract</p> <p>Background</p> <p>Scrub typhus is a mite-borne bacterial infection of humans caused by <it>Orientia tsutsugamushi </it>that causes a generalized vasculitis that may involve the tissues of any organ system. The aim of this study was to identify factors associated to severe complications from scrub typhus.</p> <p>Methods</p> <p>We conducted this prospective, case-control study on scrub typhus patients who presented to the Department of Internal Medicine at Chosun University Hospital between September, 2004 and December, 2006. Cases were 89 scrub typhus patients with severe complications and controls were 119 scrub typhus patients without severe complications.</p> <p>Results</p> <p>There were significant differences in the absence of eschar, white blood cell (WBC) counts, hemoglobin, albumin, serum creatinine, fibrinogen, C-reactive protein (CRP), and active partial thromboplastin time (aPTT) between the two groups. Multivariate analysis demonstrated that only the following four factors were significantly associated with the severe complications of scrub typhus: (1) age ≥ 60 years (odd ratio [OR] = 3.13, <it>P </it>= 0.002, confidence interval [CI] = 1.53-6.41), (2) the absence of eschar (OR = 6.62, <it>P </it>= 0.03, CI = 1.22-35.8, (3) WBC counts > 10, 000/mm3 (OR = 3.6, <it>P </it>= 0.001, CI = 1.65-7.89), and (4) albumin ≤ 3.0 g/dL (OR = 5.01, <it>P </it>= 0.004, CI = 1.69-14.86).</p> <p>Conclusions</p> <p>Our results suggest that clinicians should be aware of the potential for complications, when scrub typhus patients are older (≥ 60 years), presents without eschar, or laboratory findings such as WBC counts > 10, 000/mm3, and serum albumin level ≤ 3.0 g/dL. Close observation and intensive care for scrub typhus patients with the potential for complications may prevent serious complications with subsequent reduction in its mortality rate.</p

Genetic divergence of rubber tree estimated by multivariate techniques and microsatellite markers

Genetic diversity of 60 Hevea genotypes, consisting of Asiatic, Amazonian, African and IAC clones, and pertaining to the genetic breeding program of the Agronomic Institute (IAC), Brazil, was estimated. Analyses were based on phenotypic multivariate parameters and microsatellites. Five agronomic descriptors were employed in multivariate procedures, such as Standard Euclidian Distance, Tocher clustering and principal component analysis. Genetic variability among the genotypes was estimated with 68 selected polymorphic SSRs, by way of Modified Rogers Genetic Distance and UPGMA clustering. Structure software in a Bayesian approach was used in discriminating among groups. Genetic diversity was estimated through Nei's statistics. The genotypes were clustered into 12 groups according to the Tocher method, while the molecular analysis identified six groups. In the phenotypic and microsatellite analyses, the Amazonian and IAC genotypes were distributed in several groups, whereas the Asiatic were in only a few. Observed heterozygosity ranged from 0.05 to 0.96. Both high total diversity (HT' = 0.58) and high gene differentiation (G st' = 0.61) were observed, and indicated high genetic variation among the 60 genotypes, which may be useful for breeding programs. The analyzed agronomic parameters and SSRs markers were effective in assessing genetic diversity among Hevea genotypes, besides proving to be useful for characterizing genetic variability

Left ventricular T2 distribution in Duchenne Muscular Dystrophy

<p>Abstract</p> <p>Background</p> <p>Although previous studies have helped define the natural history of Duchenne Muscular Dystrophy (DMD)-associated cardiomyopathy, the myocardial pathobiology associated with functional impairment in DMD is not yet known.</p> <p>The objective of this study was to assess the distribution of transverse relaxation time (T2) in the left ventricle (LV) of DMD patients, and to determine the association of myocardial T2 heterogeneity to the severity of cardiac dysfunction. DMD patients (n = 26) and normal control subjects (n = 13) were studied by Cardiovascular Magnetic Resonance (CMR). DMD subject data was stratified based on subject age and LV Ejection Fraction (EF) into the following groups: A (<12 years old, n = 12); B (≥12 years old, EF ≤ 55%, n = 8) and C (≥12 years old, EF = 55%, n = 6). Controls were also stratified by age into Groups N1 (<12 years, n = 6) and N2 (>12 years, n = 5). LV mid-slice circumferential myocardial strain (ε_cc) was calculated using tagged CMR imaging. T2 maps of the LV were generated for all subjects using a black blood dual spin echo method at two echo times. The Full Width at Half Maximum (<it>FWHM</it>) was calculated from a histogram of LV T2 distribution constructed for each subject.</p> <p>Results</p> <p>In DMD subject groups, <it>FWHM </it>of the T2 histogram rose progressively with age and decreasing EF (Group A <it>FWHM</it>= 25.3 ± 3.8 ms; Group B <it>FWHM</it>= 30.9 ± 5.3 ms; Group C <it>FWHM</it>= 33.0 ± 6.4 ms). Further, <it>FWHM </it>was significantly higher in those with reduced circumferential strain (|ε_cc| ≤ 12%) (Group B, and C) than those with |ε_cc| > 12% (Group A). Group A <it>FWHM </it>was not different from the two normal groups (N1 <it>FWHM </it>= 25.3 ± 3.5 ms; N2 <it>FWHM</it>= 24.0 ± 7.3 ms).</p> <p>Conclusion</p> <p>Reduced EF and ε_cccorrelates well with increased T2 heterogeneity quantified by <it>FWHM</it>, indicating that subclinical functional impairments could be associated with pre-existing abnormalities in tissue structure in young DMD patients.</p

Functional significance of the hemadsorption activity of influenza virus neuraminidase and its alteration in pandemic viruses

Human influenza viruses derive their genes from avian viruses. The neuraminidase (NA) of the avian viruses has, in addition to the catalytic site, a separate sialic acid binding site (hemadsorption site) that is not present in human viruses. The biological significance of the NA hemadsorption activity in avian influenza viruses remained elusive. A sequence database analysis revealed that the NAs of the majority of human H2N2 viruses isolated during the influenza pandemic of 1957 differ from their putative avian precursor by amino acid substitutions in the hemadsorption site. We found that the NA of a representative pandemic virus A/Singapore/1/57 (H2N2) lacks hemadsorption activity and that a single reversion to the avian-virus-like sequence (N367S) restores hemadsorption. Using this hemadsorption-positive NA, we generated three NA variants with substitutions S370L, N400S and W403R that have been found in the hemadsorption site of human H2N2 viruses. Each substitution abolished hemadsorption activity. Although, there was no correlation between hemadsorption activity of the NA variants and their enzymatic activity with respect to monovalent substrates, all four hemadsorption-negative NAs desialylated macromolecular substrates significantly slower than did the hemadsorption-positive counterpart. The NA of the 1918 pandemic virus A/Brevig Mission/1/18 (H1N1) also differed from avian N1 NAs by reduced hemadsorption activity and less efficient hydrolysis of macromolecular substrates. Our data indicate that the hemadsorption site serves to enhance the catalytic efficiency of NA and they suggest that, in addition to changes in the receptor-binding specificity of the hemagglutinin, alterations of the NA are needed for the emergence of pandemic influenza viruses

Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33 000 women from the general population

<p>Abstract</p> <p>Background</p> <p>Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women.</p> <p>Methods</p> <p>Dietary intake was estimated using a food frequency questionnaire among 33 623 women aged 30-49 years at enrolment (1991/92). Information on psychotic-like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic-like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression.</p> <p>Results</p> <p>18 411 women were classified as having a low level of psychotic-like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic-like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic-like symptoms.</p> <p>Conclusion</p> <p>Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic-like symptoms.</p

A Role for Non-Antimicrobial Actions of Tetracyclines in Combating Oxidative Stress in Periodontal and Metabolic Diseases: A Literature Review

This review addresses the role of adjunctive tetracycline therapy in the management of periodontal diseases and its efficacy in reducing inflammatory burden, oxidative stress and its sequelae in patients with coexisting features of metabolic syndrome. Removal of the dimethylamine group at C4 of the tetracycline molecule reduces its antibiotic properties, enhancing its non-antimicrobial actions; this strategy has aided the development of several chemically modified tetracyclines such as minocycline and doxycycline, by altering different regions of the molecule for focused action on biological targets. Tetracyclines are effective in reducing inflammation by inhibiting matrix metalloproteinases, preventing excessive angiogenesis, inhibiting apoptosis and stimulating bone formation. There are important applications for tetracyclines in the management of diabetic, dyslipidaemic periodontal patients who smoke. The diverse mechanisms of action of tetracyclines in overcoming oxidative stress and enhancing matrix synthesis are discussed in this review