Work Disability among Employees with Diabetes: Latent Class Analysis of Risk Factors in Three Prospective Cohort Studies

Background

Studies of work disability in diabetes have examined diabetes as a homogeneous disease. We sought to identify subgroups among persons with diabetes based on potential risk factors for work disability.

Methods

Participants were 2,445 employees with diabetes from three prospective cohorts (the Finnish Public Sector study, the GAZEL study, and the Whitehall II study). Work disability was ascertained via linkage to registers of sickness absence and disability pensions during a follow-up of 4 years. Study-specific latent class analysis was used to identify subgroups according to prevalent comorbid disease and health-risk behaviours. Study-specific associations with work disability at follow-up were pooled using fixed-effects meta-analysis.

Results

Separate latent class analyses for men and women in each cohort supported a two-class solution with one subgroup (total n = 1,086; 44.4%) having high prevalence of chronic somatic diseases, psychological symptoms, obesity, physical inactivity and abstinence from alcohol and the other subgroup (total n = 1,359; 55.6%) low prevalence of these factors. In the adjusted meta-analyses, participants in the ‘high-risk’ group had more work disability days (pooled rate ratio = 1.66, 95% CI 1.38–1.99) and more work disability episodes (pooled rate ratio = 1.33, 95% CI 1.21–1.46). These associations were similar in men and women, younger and older participants, and across occupational groups.

Conclusions

Diabetes is not a homogeneous disease in terms of work disability risk. Approximately half of people with diabetes are assigned to a subgroup characterised by clustering of comorbid health conditions, obesity, physical inactivity, abstinence of alcohol, and associated high risk of work disability; the other half to a subgroup characterised by a more favourable risk profile.     

Dosimetric impact of different multileaf collimators on prostate intensity modulated treatment planning

AimThe main purpose of this study is to perform a dosimetric comparison on target volumes and organs at risks (OARs) between prostate intensity modulated treatment plans (IMRT) optimized with different multileaf collimators (MLCs).BackgroundThe use of MLCs with a small leaf width in the IMRT optimization may improve conformity around the tumor target whilst reducing the dose to normal tissues.Materials and methodsTwo linacs mounting MLCs with 5 and 10 mm leaf-width, respectively, implemented in Pinnacle³ treatment planning system were used for this work. Nineteen patients with prostate carcinoma undergoing a radiotherapy treatment were enrolled. Treatment planning with different setup arrangements (7 and 5 beams) were performed for each patient and each machine. Dose volume histograms (DVHs) cut-off points were used in the treatment planning comparison.ResultsComparable planning target volume (PTV) coverage was obtained with 7- and 5-beam configuration (both with 5 and 10 mm MLC leaf-width). The comparison of bladder and rectum DVH cut-off points for the 5-beam arrangement shows that 52.6% of the plans optimized with a larger leaf-width did not satisfy at least one of the OARs’ constraints. This percentage is reduced to 10.5% for the smaller leaf-width. If a 7-beam arrangement is used the value of 52.6% decreases to 21.1% while the value of 10.5% remains unchanged.ConclusionMLCs collimators with different widths and number of leaves lead to a comparable prostate treatment planning if a proper adjustment is made of the number of gantry angles.     

The pheromonal gland of Lymantria dispar: Morphology and evidence for its innervation

The morphological features of the glandular epithelium that secretes pheromone in the polyphagous pest gypsy moth Lymantria dispar are described by light and electron microscopy. The monolayered gland cells are covered by the folded cuticle of the intersegmental membrane between the 8th and 9th abdominal segments showing neither sites of discontinuity nor distinct openings on its external surface. The cells bear a large, often irregularly shaped nucleus, and contain granules of variable amount and electron‐density. These granules are mostly located in the basal compartment of the cytoplasm, in a labyrinthine zone laying on a basement membrane. The apical membrane of the gland cells bear microvilli and cell–cell contact is established by different junctional structures. Nerve fibers enwrapped in glia are found beneath the basement membrane, in close contact with the secretory cells. This latter finding represents the first evidence of the innervation of the pheromonal gland in L. dispar. J. Morphol. 2009. © 2008 Wiley‐Liss, Inc.     

An MTA phosphorylase gene discovered in the metagenomic library derived from Antarctic top soil during screening for lipolytic active clones confers strong pink fluorescence in the presence of rhodamine B

Eubacteria encode proteins that are required for nucleoid organization and for regulation of DNA-dependent processes. Of these histone-like proteins (Hlps), Escherichia coli HU has been shown to associate with the nucleoid and to regulate processes such as DNA repair and recombination. In contrast, the divergent HU homologs encoded by mycobacteria have been variously identified as involved in the physiology of dormancy, in the response to cold shock, or as laminin-binding proteins associated with the cell envelope. We show here, contrary to previous reports that the HU-related Hlp from Mycobacterium smegmatis associates with the nucleoid in vivo . Using indirect fluorescent antibody microscopy we show that cold shock causes Hlp to accumulate in the cytoplasm of M. smegmatis . No evidence of surface-associated Hlp was found in M. smegmatis cells treated for cell wall permeabilization. Quantitative Western blots indicate that exponentially growing cells contain c . 120 molecules per cell, with upregulation of Hlp after cold shock estimated to be c . 10-fold. That Hlp associates with the nucleoid in vivo suggests functions in DNA metabolism, perhaps in adaptation to environmental stress.     

Low- versus high-baseline epinephrine output shapes opposite innate cytokine profiles: presence of Lewis- and Fischer-like neurohormonal immune phenotypes in humans?

Immunogenetic mechanisms operating within the immune system are known to influence cytokine profiles and disease susceptibility. Yet the role of the individual's neurohormonal background in these processes remains undefined. Hormonal imbalances are documented in immune-related diseases, but it is unclear whether this represents a secondary phenomenon or a primary "defect" related to specific neurohormonal immune phenotype(s). We report that in a large subpopulation of healthy humans the baseline epinephrine output (but not cortisol and sex steroid hormones) correlated inversely with proinflammatory and positively with anti-inflammatory cytokine production. Thus, low vs high epinephrine excretors had a 2- to 5-fold higher TNF-alpha and IL-12 production but 2-fold lower IL-10 production induced by LPS ex vivo. In alternative settings, we found low baseline levels and profoundly blunted stress-induced epinephrine responses but high TNF-alpha levels in Lewis vs Fischer inbred rats. Additionally, isoproterenol, a beta adrenoreceptor agonist suppressed LPS-induced TNF-alpha production, with more pronounced effect in Lewis than in Fischer rats. In human monocytes, epinephrine and the beta(2) adrenoreceptor agonist fenoterol potently inhibited LPS-induced TNF-alpha and IL-12, but stimulated IL-10 production. The order of potency for hormones able to inhibit IL-12 production ex vivo was: epinephrine > norepinephrine > or = 1,25-(OH)(2) vitamin D(3) > hydrocortisone. This indicates that baseline epinephrine conditions cytokine responsiveness and through this mechanism intrinsic hypo- or hyperactive adrenal medullas in some individuals may shape opposite cytokine profiles. Since Lewis and Fischer rats have opposite susceptibility to experimental immunological diseases, this suggests that the parallel human phenotypes could be linked to differing responsiveness and susceptibility to infections and immune/inflammatory-related conditions.     

IgA1 levels in milk and serum samples from intestinal parasite-infected or normal puerperae

In this study, IgA1 levels in the milk and serum of puerperae were compared and a correlation was established between the levels of this immunoglobulin and the occurrence of parasitism. Eighty-three paired milk and serum samples were obtained from puerperal and IgA1 levels were analyzed. In addition, the presence of intestinal parasites in stool samples from these puerperae was determined. Twelve puerperae tested positive for intestinal parasites and all their samples presented an IgA1 ELISA Index > 1. There was a correlation between serum and milk IgA1 levels and puerperae with any parasite in their stool (r = 0.6723; p = 0.0166). This finding may reinforce the importance of breast-feeding for the protection of neonates.     

Myelinated axons contain beta-actin mRNA and ZBP-1 in periaxoplasmic ribosomal plaques and depend on cyclic AMP and F-actin integrity for in vitro translation

Periaxoplasmic ribosomal plaques (PARPs) are periodic structural formations containing ribosomes, which are likely cortical sites of translation along myelinated fibers. β-actin mRNA, and its trans- acting binding factor, zipcode-binding protein-1, were co-distributed within PARP domains of axoplasmic whole-mounts isolated from goldfish Mauthner, rabbit and rat nerve fibers. The distribution of co-localization signals of fluorophore pixels, however, was asymmetric in PARP domains, possibly indicative of endpoint trafficking of RNPs. β-actin mRNA in RNA extracted from axoplasm of single Mauthner fibers was confirmed by RT-PCR. A metabolically active isolated Mauthner fiber system, which required cAMP to activate translation, was developed in order to probe cycloheximide-sensitivity, and the importance of the actin cytoskeleton. cAMP greatly stimulated protein synthesis in axoplasm after a period of pre-incubation, while being inhibited strongly by cycloheximide, or by cytochalasin D. Cytochalasin D reduced incorporation only modestly in the associated myelin sheath. We conclude that mechanisms for targeting and localizing β-actin mRNA to discrete PARP domains are probably similar to those described for dendritic synaptic domains. Moreover, optimal translation in axoplasm depends on the integrity of the actin cytoskeleton, and can be modulated by cAMP as well.     

Syndecan-4 contributes to endothelial tubulogenesis through interactions with two motifs inside the pro-angiogenic N-terminal domain of thrombospondin-1

Thrombospondin-1 (TSP-1) is an extracellular matrix protein that modulates focal adhesion in mammalian cells and exhibits dual roles in angiogenesis. In a previous work, we showed that a recombinant 18 kDa protein encompassing the N-terminal residues 1-174 of human TSP-1 (TSP18) induced tubulogenesis of human umbilical vein endothelial cells and protected them from apoptosis. Our results indicated that these effects were possibly mediated by syndecan-4 proteoglycan, since binding of TSP18 to endothelial extracts was inhibited by anti-syndecan-4 antibody. Syndecan-4 is a heparan-sulfate proteoglycan that regulates cell-matrix interactions and is the only member of its family present in focal adhesions. In this report, we demonstrate that a monoclonal antibody against syndecan-4 blocks TSP18-induced tubulogenesis. Furthermore, through 2D adhesion and 3D angiogenic assays, we demonstrate that two sequences, TSP Hep I and II, retain the major pro-angiogenic activity of TSP18. These TSP-1 motifs also compete with the fibronectin Hep II domain for binding to syndecan-4 on endothelial cell surface, indicating that they may exert their effects by interfering with the recognition of fibronectin by syndecan-4. Additionally, TSP18 and its derived peptides activate the PKC-dependent Akt-PKB signaling pathway. Blockage of PKC activation prevented HUVEC spreading when seeded on TSP18 fragment, and on TSP Hep I and TSP Hep II peptides, but not on gelatin-coated substrates. Our results identify syndecan-4 as a novel receptor for the N-terminus of TSP-1 and suggest that TSP-1 N-terminal pro-angiogenic activity is linked to its capacity of interfering with syndecan-4 functions in the course of cell adhesion.     

Carqueja (Baccharis sect. Caulopterae), a critical review of its history,phytochemistry and medicinal use: problems of ethnopharmacology in Latin America

Phytochemistry Reviews - The Latin American medicinal plant carqueja got its name from a morphologically similar plant from the Iberian peninsula. The popular name came in general use to indicate...