220 research outputs found

    A Cross-Sectional Study of HPV Vaccine Acceptability in Gaborone, Botswana

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    Background Cervical cancer is the most common cancer among women in Botswana and elsewhere in Sub-Saharan Africa. We sought to examine whether HPV vaccine is acceptable among parents in Botswana, which recently licensed the vaccine to prevent cervical cancer. Methods and Findings We conducted a cross-sectional survey in 2009, around the time the vaccine was first licensed, with adults recruited in general medicine and HIV clinics in Gaborone, the capital of Botswana. Although only 9% (32/376) of respondents had heard of HPV vaccine prior to the survey, 88% (329/376) said they definitely will have their adolescent daughters receive HPV vaccine. Most respondents would get the vaccine for their daughters at a public or community clinic (42%) or a gynecology or obstetrician\u27s office (39%), and 74% would get it for a daughter if it were available at her school. Respondents were more likely to say that they definitely will get HPV vaccine for their daughters if they had less education (OR = 0.20, 95% CI = 0.07–0.58) or lived more than 30 kilometers from the capital, Gaborone (OR = 2.29, 95% CI = 1.06–4.93). Other correlates of acceptability were expecting to be involved in the decision to get HPV vaccine, thinking the vaccine would be hard to obtain, and perceiving greater severity of HPV-related diseases. Conclusions HPV vaccination of adolescent girls would be highly acceptable if the vaccine became widely available to the daughters of healthcare seeking parents in Gaborone, Botswana. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine as well as work to minimize barriers

    Luminescence spectra and kinetics of disordered solid solutions

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    We have studied both theoretically and experimentally the luminescence spectra and kinetics of crystalline, disordered solid solutions after pulsed excitation. First, we present the model calculations of the steady-state luminescence band shape caused by recombination of excitons localized in the wells of random potential induced by disorder. Classification of optically active tail states of the main exciton band into two groups is proposed. The majority of the states responsible for the optical absorption corresponds to the group of extended states belonging to the percolation cluster, whereas only a relatively small group of “radiative” states forms the steady-state luminescence band. The continuum percolation theory is applied to distinguish the “radiative” localized states, which are isolated in space and have no ways for nonradiative transitions along the tail states. It is found that the analysis of the exciton-phonon interaction gives the information about the character of the localization of excitons. We have shown that the model used describes quite well the experimental cw spectra of CdS(1−c)Sec and ZnSe(1−c)Tec solid solutions. Further, the experimental results are presented for the temporal evolution of the luminescence band. It is shown that the changes of band shape with time come from the interplay of population dynamics of extended states and spatially isolated “radiative” states. Finally, the measurements of the decay of the spectrally integrated luminescence intensity at long delay times are presented. It is shown that the observed temporal behavior can be described in terms of relaxation of separated pairs followed by subsequent exciton formation and radiative recombination. Electron tunneling processes are supposed to be responsible for the luminescence in the long-time limit at excitation below the exciton mobility edge. At excitation by photons with higher energies the diffusion of electrons can account for the observed behavior of the luminescence

    Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis

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    Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl(4)-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B(hi) F4/80(int) Ly-6C(lo) macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter–diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C(hi) monocytes, a common origin with profibrotic Ly-6C(hi) macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C(lo) subset, compared with Ly-6C(hi) macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process

    Intestinal BMP-9 locally upregulates FGF19 and is down-regulated in obese patients with diabetes

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    believed to be mainly produced in the liver. The serum levels of BMP-9 were reported to be reduced in newly diagnosed diabetic patients and BMP-9 overexpression ameliorated steatosis in the high fat diet-induced obesity mouse model. Furthermore, injection of BMP-9 in mice enhanced expression of fibroblast growth factor (FGF)21. However, whether BMP-9 also regulates the expression of the related FGF19 is not clear. Because both FGF21 and 19 were described to protect the liver from steatosis, we have further investigated the role of BMP-9 in this context. We first analyzed BMP-9 levels in the serum of streptozotocin (STZ)-induced diabetic rats (a model of type I diabetes) and confirmed that BMP-9 serum levels decrease during diabetes. Microarray analyses of RNA samples from hepatic and intestinal tissue from BMP-9 KO- and wild-type mice (C57/Bl6 background) pointed to basal expression of BMP-9 in both organs and revealed a down-regulation of hepatic Fgf21 and intestinal Fgf19 in the KO mice. Next, we analyzed BMP-9 levels in a cohort of obese patients with or without diabetes. Serum BMP-9 levels did not correlate with diabetes, but hepatic BMP-9 mRNA expression negatively correlated with steatosis in those patients that did not yet develop diabetes. Likewise, hepatic BMP-9 expression also negatively correlated with serum LPS levels. In situ hybridization analyses confirmed intestinal BMP-9 expression. Intestinal (but not hepatic) BMP-9 mRNA levels were decreased with diabetes and positively correlated with intestinal E-Cadherin expression. In vitro studies using organoids demonstrated that BMP-9 directly induces FGF19 in gut but not hepatocyte organoids, whereas no evidence of a direct induction of hepatic FGF21 by BMP-9 was found. Consistent with the in vitro data, a correlation between intestinal BMP-9 and FGF19 mRNA expression was seen in the patients’ samples. In summary, our data confirm that BMP-9 is involved in diabetes development in humans and in the control of the FGF-axis. More importantly, our data imply that not only hepatic but also intestinal BMP-9 associates with diabetes and steatosis development and controls FGF19 expression. The data support the conclusion that increased levels of BMP-9 would most likely be beneficial under pre-steatotic conditions, making supplementation of BMP-9 an interesting new approach for future therapies aiming at prevention of the development of a metabolic syndrome and liver steatosis

    Recycling Attitudes and Behavior among a Clinic-Based Sample of Low-Income Hispanic Women in Southeast Texas

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    We examined attitudes and behavior surrounding voluntary recycling in a population of low-income Hispanic women. Participants (N = 1,512) 18–55 years of age completed a self-report survey and responded to questions regarding household recycling behavior, recycling knowledge, recycling beliefs, potential barriers to recycling (transportation mode, time), acculturation, demographic characteristics (age, income, employment, marital status, education, number of children, birth country), and social desirability. Forty-six percent of participants (n = 810) indicated that they or someone else in their household recycled. In a logistic regression model controlling for social desirability, recycling behavior was related to increased age (P<0.05), lower acculturation (P<0.01), knowing what to recycle (P<0.01), knowing that recycling saves landfill space (P<0.05), and disagreeing that recycling takes too much time (P<0.001). A Sobel test revealed that acculturation mediated the relationship between recycling knowledge and recycling behavior (P<0.05). We offer new information on recycling behavior among Hispanic women and highlight the need for educational outreach and intervention strategies to increase recycling behavior within this understudied population

    Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFβ cell cycle arrest

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    <p>Abstract</p> <p>Background</p> <p>TGFβ is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFβ in disease. We asked how <it>Rb</it>-deficiency would affect responses to TGFβ-induced cell cycle arrest.</p> <p>Results</p> <p>Primary hepatocytes isolated from <it>Rb-floxed </it>mice were infected with an adenovirus expressing CRE-recombinase to delete the <it>Rb </it>gene. In control cells treatment with TGFβ prevented cells to enter S phase via decreased cMYC activity, activation of P16<sup>INK4A </sup>and P21<sup>Cip </sup>and reduction of E2F activity. In <it>Rb</it>-null hepatocytes, cMYC activity decreased slightly but P16<sup>INK4A </sup>was not activated and the great majority of cells continued cycling. <it>Rb </it>is therefore central to TGFβ-induced cell cycle arrest in hepatocytes. However some <it>Rb</it>-null hepatocytes remained sensitive to TGFβ-induced cell cycle arrest. As these hepatocytes expressed very high levels of P21<sup>Cip1 </sup>and P53 we investigated whether these proteins regulate pRb-independent signaling to cell cycle arrest by evaluating the consequences of disruption of <it>p53 </it>and <it>p21</it><sup><it>Cip1</it></sup>. Hepatocytes deficient in <it>p53 or p21</it><sup><it>Cip1 </it></sup>showed diminished growth inhibition by TGFβ. Double deficiency had a similar impact showing that in cells containing functional pRb; P21<sup>Cip </sup>and P53 work through the same pathway to regulate G1/S in response to TGFβ. In <it>Rb</it>-deficient cells however, <it>p53 </it>but not <it>p21</it><sup><it>Cip </it></sup>deficiency had an additive effect highlighting a pRb-independent-P53-dependent effector pathway of inhibition of E2F activity.</p> <p>Conclusion</p> <p>The present results show that otherwise genetically normal hepatocytes with disabled <it>p53</it>, <it>p21</it><sup><it>Cip1 </it></sup>or <it>Rb </it>genes respond less well to the antiproliferative effects of TGFβ. As the function of these critical cellular proteins can be impaired by common causes of chronic liver disease and HCC, including viral hepatitis B and C proteins, we suggest that disruption of pRb function, and to a lesser extend P21<sup>Cip1 </sup>and P53 in hepatocytes may represent an additional new mechanism of escape from TGFβ-growth-inhibition in the inflammatory milieu of chronic liver disease and contribute to cancer development.</p
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