Gender differences in the use of transportation services to community rehabilitation programs

<p>Abstract</p> <p>Background</p> <p>Prevention and reduction of disability among community-dwelling older adults have been an important health policy concern in Japan. Moreover, it has also become a gendered issue due to the recent rapid growth in older females than males with disability living in their own homes. The aim of this study is to examine whether there is a gender difference in the use of community rehabilitation programs in Japan, and if so, whether the lack of transportation services and accompanying caregivers are the reasons for the gender difference.</p> <p>Methods</p> <p>This study was based on surveys of the program administrators and the primary caregivers of the program participants from 55 randomly selected community rehabilitation programs (CRP) in the Tokyo metropolitan area. Questions included sociodemographic characteristics of program participants, types of transportation services provided by the CRP, caregiver's relationship to participant, and the nature of family support. Bivariate statistical analysis was conducted.</p> <p>Results</p> <p>Although there were more females than males with disability residing in communities, our findings showed that females were less likely to use CRP than males (1.3% and 2.3%, respectively; <it>X</it>²= 93.0, p < 0.0001). Lower CRP use by females was related to lower availability of transportation services (36% without transportation service and 46% door-to-door services) and fewer caregivers accompanying the participants to CRP.</p> <p>Conclusion</p> <p>This study builds on previous research findings, which suggest gender inequality in access to CRP.</p

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Pharmacokinetics of Teriparatide (rhPTH[1–34]) and Calcium Pharmacodynamics in Postmenopausal Women with Osteoporosis

Teriparatide (rhPTH[1–34]) affects calcium metabolism in a pattern consistent with the known actions of endogenous parathyroid hormone (PTH). This report describes the pharmacokinetics and resulting serum calcium response to teriparatide in postmenopausal women with osteoporosis. Pharmacokinetic samples for this analysis were obtained from 360 women who participated in the Fracture Prevention Trial. Postmenopausal women with osteoporosis received daily subcutaneous injections of either teriparatide 20 μg (4.86 μmol) or placebo, median 21 months’ treatment. Serum teriparatide and calcium concentrations were measured throughout the study. An indirect-response model was developed to describe the pharmacokinetic–pharmacodynamic relationship between teriparatide concentrations and serum calcium response. The pharmacokinetics of teriparatide were characterized by rapid absorption (maximum concentration achieved within 30 min) and rapid elimination (half-life of 1 h), resulting in a total duration of exposure to the peptide of approximately 4 h. Teriparatide transiently increased serum calcium, with the maximum effect observed at approximately 4.25 h (median increase 0.4 mg/dl [0.1 mmol/l]). Calcium concentrations returned to predose levels by 16–24 h after each dose. Persistent hypercalcemia was not observed; one teriparatide 20 μg-treated patient had a predose serum calcium value above the normal range but <11.0 mg/dl (2.75 mmol/l). Following once-daily subcutaneous administration, teriparatide produces a modest but transient increase in serum calcium, consistent with the known effects of endogenous PTH on mineral metabolism. The excursion in serum calcium is brief, due to the short length of time that teriparatide concentrations are elevated

Inverse correlation between PDGFC expression and lymphocyte infiltration in human papillary thyroid carcinomas

<p>Abstract</p> <p>Background</p> <p>Members of the PDGF family have been suggested as potential biomarkers for papillary thyroid carcinomas (PTC). However, it is known that both expression and stimulatory effect of PDGF ligands can be affected by inflammatory cytokines. We have performed a microarray study in a collection of PTCs, of which about half the biopsies contained tumour-infiltrating lymphocytes or thyroiditis. To investigate the expression level of PDGF ligands and receptors in PTC we measured the relative mRNA expression of all members of the PDGF family by qRT-PCR in 10 classical PTC, eight clinically aggressive PTC, and five non-neoplastic thyroid specimens, and integrated qRT-PCR data with microarray data to enable us to link PDGF-associated gene expression profiles into networks based on recognized interactions. Finally, we investigated potential influence on PDGF mRNA levels by the presence of tumour-infiltrating lymphocytes.</p> <p>Methods</p> <p>qRT-PCR was performed on <it>PDGFA</it>, <it>PDGFB</it>, <it>PDGFC</it>, <it>PDGFD</it>, <it>PDGFRA PDGFRB </it>and a selection of lymphocyte specific mRNA transcripts. Semiquantitative assessment of tumour-infiltrating lymphocytes was performed on the adjacent part of the biopsy used for RNA extraction for all biopsies, while direct quantitation by qRT-PCR of lymphocyte-specific mRNA transcripts were performed on RNA also subjected to expression analysis. Relative expression values of PDGF family members were combined with a cDNA microarray dataset and analyzed based on clinical findings and PDGF expression patterns. Ingenuity Pathway Analysis (IPA) was used to elucidate potential molecular interactions and networks.</p> <p>Results</p> <p>PDGF family members were differentially regulated at the mRNA level in PTC as compared to normal thyroid specimens. Expression of <it>PDGFA </it>(p = 0.003), <it>PDGFB </it>(p = 0.01) and <it>PDGFC </it>(p = 0.006) were significantly up-regulated in PTCs compared to non-neoplastic thyroid tissue. In addition, expression of <it>PDGFC </it>was significantly up-regulated in classical PTCs as compared to clinically aggressive PTCs (p = 0.006), and <it>PDGFRB </it>were significantly up-regulated in clinically aggressive PTCs (p = 0.01) as compared to non-neoplastic tissue. Semiquantitative assessment of lymphocytes correlated well with quantitation of lymphocyte-specific gene expression. Further more, by combining TaqMan and microarray data we found a strong inverse correlation between <it>PDGFC </it>expression and the expression of lymphocyte specific mRNAs.</p> <p>Conclusion</p> <p>At the mRNA level, several members of the PDGF family are differentially expressed in PTCs as compared to normal thyroid tissue. Of these, only the <it>PDGFC </it>mRNA expression level initially seemed to distinguish classical PTCs from the more aggressive PTCs. However, further investigation showed that <it>PDGFC </it>expression level correlated inversely to the expression of several lymphocyte specific genes, and to the presence of lymphocytes in the biopsies. Thus, we find that <it>PDGFC </it>mRNA expression were down-regulated in biopsies containing infiltrated lymphocytes or thyroiditis. No other PDGF family member could be linked to lymphocyte specific gene expression in our collection of PTCs biopsies.</p

The Effect of Azithromycin on Ivermectin Pharmacokinetics—A Population Pharmacokinetic Model Analysis

This paper describes the use of a modeling and simulation approach to explore a reported pharmacokinetic interaction between two drugs (ivermectin and azithromycin), which along with albendazole, are being developed for combination use in neglected tropical diseases. This approach is complementary to more traditional pharmacokinetic and safety studies that need to be conducted to support combined use of different health interventions. A mathematical model of ivermectin pharmacokinetics was created and used to simulate multiple trials, and the probability of certain outcomes (very high peak blood ivermectin levels when given in combination) was determined. All simulated peak blood levels were within ranges known to be safe and well tolerated. Additional field studies are needed to confirm these findings

IFN-gamma Impairs Release of IL-8 by IL-1beta-stimulated A549 Lung Carcinoma Cells

Background Production of interferon (IFN)-gamma is key to efficient anti-tumor immunity. The present study was set out to investigate effects of IFNgamma on the release of the potent pro-angiogenic mediator IL-8 by human A549 lung carcinoma cells. Methods A549 cells were cultured and stimulated with interleukin (IL)-1beta alone or in combination with IFNgamma. IL-8 production by these cells was analyzed with enzyme linked immuno sorbent assay (ELISA). mRNA-expression was analyzed by real-time PCR and RNase protection assay (RPA), respectively. Expression of inhibitor-kappaBalpha, cellular IL-8, and cyclooxygenase-2 was analyzed by Western blot analysis. Results Here we demonstrate that IFNgamma efficiently reduced IL-8 secretion under the influence of IL-1beta. Surprisingly, real-time PCR analysis and RPA revealed that the inhibitory effect of IFNgamma on IL-8 was not associated with significant changes in mRNA levels. These observations concurred with lack of a modulatory activity of IFNgamma on IL-1beta-induced NF-kappaB activation as assessed by cellular IkappaB levels. Moreover, analysis of intracellular IL-8 suggests that IFNgamma modulated IL-8 secretion by action on the posttranslational level. In contrast to IL-8, IL-1beta-induced cyclooxygenase-2 expression and release of IL-6 were not affected by IFNgamma indicating that modulation of IL-1beta action by this cytokine displays specificity. Conclusions Data presented herein agree with an angiostatic role of IFNgamma as seen in rodent models of solid tumors and suggest that increasing T helper type 1 (Th1)-like functions in lung cancer patients e.g. by local delivery of IFNgamma may mediate therapeutic benefit via mechanisms that potentially include modulation of pro-angiogenic IL-8

The Formation of Collective Silk Balls in the Spider Mite Tetranychus urticae Koch

Tetranychus urticae is a phytophagous mite that forms colonies of several thousand individuals. These mites construct a common web to protect the colony. When plants become overcrowded and food resources become scarce, individuals gather at the plant apex to form a ball composed of mites and their silk threads. This ball is a structure facilitating group dispersal by wind or animal transport. Until now, no quantitative study had been done on this collective form of migration. This is the first attempt to understand the mechanisms that underlie the emergence and growth of the ball. We studied this collective behaviour under laboratory conditions on standardized infested plants. Our results show that the collective displacement and the formation of balls result from a recruitment process: by depositing silk threads on their way up to the plant apex, mites favour and amplify the recruitment toward the balls. A critical threshold (quorum response) in the cumulative flow of mites must be reached to observe the emergence of a ball. At the beginning of the balls formation, mites form an aggregate. After 24 hours, the aggregated mites are trapped inside the silk balls by the complex network of silk threads and finally die, except for recently arrived individuals. The balls are mainly composed of immature stages. Our study reconstructs the key events that lead to the formation of silk balls. They suggest that the interplay between mites' density, plant morphology and plant density lead to different modes of dispersions (individual or collective) and under what conditions populations might adopt a collective strategy rather than one that is individually oriented. Moreover, our results lead to discuss two aspects of the cooperation and altruism: the importance of Allee effects during colonization of new plants and the importance of the size of a founding group

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA