Rural–urban disparities in the incidence and treatment intensity of periodontal disease among patients with diabetes

BackgroundDiabetes threatens population health, especially in rural areas. Diabetes and periodontal diseases have a bidirectional relationship. A persistence of rural–urban disparities in diabetes may indicate a rural–urban difference in periodontal disease among patients with diabetes; however, the evidence is lacking. This retrospective study aimed to investigate rural–urban discrepancies in the incidence and treatment intensity of periodontal disease among patients who were newly diagnosed with type 2 diabetes in the year 2010.MethodsThe present study was a retrospective cohort design, with two study samples: patients with type 2 diabetes and those who were further diagnosed with periodontal disease. The data sources included the 2010 Diabetes Mellitus Health Database at the patient level, the National Geographic Information Standardization Platform and the Department of Statistics, Ministry of Health and Welfare in Taiwan at the township level. Two dependent variables were a time-to-event outcome for periodontal disease among patients with type 2 diabetes and the treatment intensity measured for patients who were further diagnosed with periodontal disease. The key independent variables are two dummy variables, representing rural and suburban areas, with urban areas as the reference group. The Cox and Poisson regression models were applied for analyses.ResultsOf 68,365 qualified patients, 49% of them had periodontal disease within 10 years after patients were diagnosed with diabetes. Compared to urban patients with diabetes, rural (HR = 0.83, 95% CI: 0.75–0.91) and suburban patients (HR = 0.86, 95% CI: 0.83–0.89) had a lower incidence of periodontal disease. Among 33,612 patients with periodontal disease, rural patients received less treatment intensity of dental care (Rural: RR = 0.87, 95% CI: 0.83, 0.92; suburban: RR = 0.93, 95% CI: 0.92, 0.95) than urban patients.ConclusionGiven the underutilization of dental care among rural patients with diabetes, a low incidence of periodontal disease indicates potentially undiagnosed periodontal disease, and low treatment intensity signals potentially unmet dental needs. Our findings provide a potential explanation for the persistence of rural–urban disparities in poor diabetes outcomes. Policy interventions to enhance the likelihood of identifying periodontal disease at the early stage for proper treatment would ease the burden of diabetes care and narrow rural–urban discrepancies in diabetes outcomes

Interferon-b Modulates Inflammatory Response in Cerebral Ischemia

BACKGROUND: Stroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon-β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well-characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke. METHODS AND RESULTS: We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4(+) T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. CONCLUSIONS: Our results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator

Generation and Evolution of Spin Entanglement in NRQED

A complete analysis on the generation of spin entanglement from NRQED is presented. The results of entanglement are obtained with relativistic correction to the leading order of (v/c)^2. It is shown that to this order the degree of entanglement of a singlet state does not change under time evolution whereas the triplet state can change.Comment: 8 pages, 1 figure, to appear in Phys. Rev.

Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation

Many biochemical pathways involved in hair and skin development have not been investigated. Here, we reported on the lesions and investigated the mechanism underlying hair and skin abnormalities in Zdhhc13skc4 mice with a deficiency in DHHC13, a palmitoyl-acyl transferase encoded by Zdhhc13. Homozygous affected mice showed ragged and dilapidated cuticle of the hair shaft (CUH, a hair anchoring structure), poor hair anchoring ability, and premature hair loss at early telogen phase of the hair cycle, resulting in cyclic alopecia. Furthermore, the homozygous affected mice exhibited hyperproliferation of the epidermis, disturbed cornification, fragile cornified envelope (CE, a skin barrier structure), and impaired skin barrier function. Biochemical investigations revealed that cornifelin, which contains five palmitoylation sites at cysteine residues (C58, C59, C60, C95, and C101), was a specific substrate of DHHC13 and that it was absent in the CUH and CE structures of the affected mice. Furthermore, cornifelin levels were markedly reduced when two palmitoylated cysteines were replaced with serine (C95S and C101S). Taken together, our results suggest that DHHC13 is important for hair anchoring and skin barrier function and that cornifelin deficiency contributes to cyclic alopecia and skin abnormalities in Zdhhc13skc4 mice

Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis.

Miner1 is a redox-active 2Fe2S cluster protein. Mutations in Miner1 result in Wolfram Syndrome, a metabolic disease associated with diabetes, blindness, deafness, and a shortened lifespan. Embryonic fibroblasts from Miner1(-/-) mice displayed ER stress and showed hallmarks of the unfolded protein response. In addition, loss of Miner1 caused a depletion of ER Ca(2+) stores, a dramatic increase in mitochondrial Ca(2+) load, increased reactive oxygen and nitrogen species, an increase in the GSSG/GSH and NAD(+)/NADH ratios, and an increase in the ADP/ATP ratio consistent with enhanced ATP utilization. Furthermore, mitochondria in fibroblasts lacking Miner1 displayed ultrastructural alterations, such as increased cristae density and punctate morphology, and an increase in O2 consumption. Treatment with the sulphydryl anti-oxidant N-acetylcysteine reversed the abnormalities in the Miner1 deficient cells, suggesting that sulphydryl reducing agents should be explored as a treatment for this rare genetic disease

Inhibition of gap junctional Intercellular communication in WB-F344 rat liver epithelial cells by triphenyltin chloride through MAPK and PI3-kinase pathways

<p>Abstract</p> <p>Background</p> <p>Organotin compounds (OTCs) have been widely used as stabilizers in the production of plastic, agricultural pesticides, antifoulant plaints and wood preservation. The toxicity of triphenyltin (TPT) compounds was known for their embryotoxic, neurotoxic, genotoxic and immunotoxic effects in mammals. The carcinogenicity of TPT was not well understood and few studies had discussed the effects of OTCs on gap junctional intercellular communication (GJIC) of cells.</p> <p>Method</p> <p>In the present study, the effects of triphenyltin chloride (TPTC) on GJIC in WB-F344 rat liver epithelial cells were evaluated, using the scrape-loading dye transfer technique.</p> <p>Results</p> <p>TPTC inhibited GJIC after a 30-min exposure in a concentration- and time-dependent manner. Pre-incubation of cells with the protein kinase C (PKC) inhibitor did not modify the response, but the specific MEK 1 inhibitor PD98059 and PI3K inhibitor LY294002 decreased substantially the inhibition of GJIC by TPTC. After WB-F344 cells were exposed to TPTC, phosphorylation of Cx43 increased as seen in Western blot analysis.</p> <p>Conclusions</p> <p>These results show that TPTC inhibits GJIC in WB-F344 rat liver epithelial cells by altering the Cx43 protein expression through both MAPK and PI3-kinase pathways.</p

Isolation of Mouse Cerebral Microvasculature for Molecular and Single-Cell Analysis

Brain microvasculature forms a specialized structure, the blood-brain barrier (BBB), to maintain homeostasis and integrity of the central nervous system (CNS). The BBB dysfunction is emerging as a critical contributor to multiple neurological disorders, including stroke, traumatic brain injury, autoimmune multiple sclerosis, and neurodegenerative diseases. The brain microvasculature exhibits highly cellular and regional heterogeneity to accommodate dynamic changes of microenvironment during homeostasis and diseases. Thus, investigating the underlying mechanisms that contribute to molecular or cellular changes of the BBB is a significant challenge. Here, we describe an optimized protocol to purify microvessels from the mouse cerebral cortex using mechanical homogenization and density-gradient centrifugation, while maintaining the structural integrity and functional activity of the BBB. We show that the isolated microvessel fragments consist of BBB cell populations, including endothelial cells, astrocyte end-feet, pericytes, as well as tight junction proteins that seal endothelial cells. Furthermore, we describe the procedures to generate single-cell suspensions from isolated microvessel fragments. We demonstrate that cells in the single-cell suspensions are highly viable and suitable for single-cell RNA-sequencing analysis. This protocol does not require transgenic mice and cell sorting equipment to isolate fluorescence-labeled endothelial cells. The optimized procedures can be applied to different disease models to generate viable cells for single-cell analysis to uncover transcriptional or epigenetic landscapes of BBB component cells

Phonon-assisted Kondo Effect in a Single-Molecule Transistor out of Equilibrium

The joint effect of the electron-phonon interaction and Kondo effect on the nonequilibrium transport through the single molecule transistor is investigated by using the improved canonical transformation scheme and extended equation of motion approach. Two types of Kondo phonon-satellites with different asymmetric shapes are fully confirmed in the spectral function, and are related to the electron spin singlet or hole spin singlet, respectively. Moreover, when a moderate Zeeman splitting is caused by a local magnetic field, the Kondo satellites in the spin resolved spectral function are found disappeared on one side of the main peak, which is opposite for different spin component. All these peculiar signatures that manifest themselves in the nonlinear differential conductance, are explained with a clear physics picture.Comment: 12 pages, 6 figure