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991.
Anne Esther Njom Nlend Annie Nga Motazé Suzie Moyo Tetang Cécile Zeudja Marcus Ngantcha Mathurin Tejiokem 《PloS one》2016,11(3)
Background
Effects of antiretroviral therapy (ART) on birth outcomes remain controversial.Objective
To assess the impact of antenatal exposure to ART on the occurrence of preterm birth (PTB) and low birth weight (LBW).Methods
A cross-sectional study conducted at the Essos Hospital Center in Yaounde from 2008 to 2011 among HIV vertically exposed infants with two distinct maternal antiretroviral experiences: monotherapy group (Zidovudine, ZDV) and the combination ART group (cART). Mothers already receiving cART before pregnancy were ineligible. In both groups, events of PTB (<37 weeks) and LBW (<2,500g) were analyzed using univariate and multivariate logistic regression; with p<0.05 considered statistically significant.Results
Of the 760 infants, 481 were born from cART-exposed mothers against 279 from maternal-ZDV. Median maternal CD4 count was 378 [interquartile range (IQR): 253–535] cells/mm3. Median duration of ART at onset of delivery was 13 [IQR: 10–17] weeks. In the cART-group, 64.9% (312/481) of mothers were exposed to Zidovudine/Lamuvidine/Nevirapine and only 2% (9/481) were on protease inhibitor-based regimens. Events of PTB were not significantly higher in the cART-group compared to the ZDV-group (10.2% vs. 6.4% respectively, p = 0.08), while onsets of LBW were significantly found in the cART-group compared to ZDV-group (11.6% vs. 7.2% respectively, p = 0.05). Other factors (parity, maternal age at delivery or CD4 cell count) were not associated with PTB.Conclusion
cART, initiated during pregnancy, would be an independent factor of LBW. In the era of option B+ (lifelong ART to all HIV-pregnant women), further studies would guide towards measures limiting onsets of LBW. 相似文献992.
993.
994.
dHb9 expressing larval motor neurons persist through metamorphosis to innervate adult‐specific muscle targets and function in Drosophila eclosion 下载免费PDF全文
Soumya Banerjee Marcus Toral Matthew Siefert David Conway Meredith Dorr Joyce Fernandes 《Developmental neurobiology》2016,76(12):1387-1416
The Drosophila larval nervous system is radically restructured during metamorphosis to produce adult specific neural circuits and behaviors. Genesis of new neurons, death of larval neurons and remodeling of those neurons that persistent collectively act to shape the adult nervous system. Here, we examine the fate of a subset of larval motor neurons during this restructuring process. We used a dHb9 reporter, in combination with the FLP/FRT system to individually identify abdominal motor neurons in the larval to adult transition using a combination of relative cell body location, axonal position, and muscle targets. We found that segment specific cell death of some dHb9 expressing motor neurons occurs throughout the metamorphosis period and continues into the post‐eclosion period. Many dHb9 > GFP expressing neurons however persist in the two anterior hemisegments, A1 and A2, which have segment specific muscles required for eclosion while a smaller proportion also persist in A2–A5. Consistent with a functional requirement for these neurons, ablating them during the pupal period produces defects in adult eclosion. In adults, subsequent to the execution of eclosion behaviors, the NMJs of some of these neurons were found to be dismantled and their muscle targets degenerate. Our studies demonstrate a critical continuity of some larval motor neurons into adults and reveal that multiple aspects of motor neuron remodeling and plasticity that are essential for adult motor behaviors. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1387–1416, 2016 相似文献
995.
996.
Ammon Handisurya Corinna Kerscher Andrea Tura Harald Herkner Berit Anna Payer Mattias Mandorfer Johannes Werzowa Wolfgang Winnicki Thomas Reiberger Alexandra Kautzky-Willer Giovanni Pacini Marcus S?emann Alice Schmidt 《PloS one》2016,11(1)
Background
Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients.Methods
In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR).Results
After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82–441.92) vs. 468.80 (414.27–488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032–0.106) vs. 0.083 (0.054–0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression.Conclusions
HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant recipients may benefit from a cyclosporine A-based immunosuppressive regimen.Trial Registration
ClinicalTrials.gov NCT02108301相似文献997.
Thomas A. Dewland Kirsten Bibbins-Domingo Feng Lin Eric Vittinghoff Elyse Foster Kofo O. Ogunyankin Joao A. Lima David R. Jacobs Donglei Hu Esteban G. Burchard Gregory M. Marcus 《PloS one》2016,11(3)
Whites have an increased risk of atrial fibrillation (AF) compared to Blacks. The mechanism underlying this association is unknown. Left atrial (LA) size is an important AF risk factor, and studies in older adults suggest Whites have larger LA diameters. However, because AF itself causes LA dilation, LA size differences may be due to greater subclinical AF among older Whites. We therefore assessed for racial differences in LA size among young adults at low AF risk. The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled White and Black participants between 18 and 30 years of age. LA diameter was measured in a subset of participants using echocardiography at Year 5 (n = 4,201) and Year 25 (n = 3,373) of follow up. LA volume was also assessed at Year 5 (n = 2,489). Multivariate linear regression models were used to determine the adjusted association between race and LA size. In unadjusted analyses, mean LA diameter was significantly larger among Blacks compared to Whites both at Year 5 (35.5 ± 4.8 mm versus 35.1 ± 4.5 mm, p = 0.01) and Year 25 (37.4 ± 5.1 mm versus 36.8 ± 4.9 mm, p = 0.002). After adjusting for demographics, comorbidities, and echocardiographic parameters, Whites demonstrated an increased LA diameter (0.7 mm larger at Year 5, 95% CI 0.3–1.1, p<0.001; 0.6 mm larger at Year 25, 95% CI 0.3–1.0, p<0.001). There was no significant association between race and adjusted Year 5 LA volume. In conclusion, in a young, well-characterized cohort, the larger adjusted LA diameter among White participants suggests inherent differences in atrial structure may partially explain the higher risk of AF in Whites. The incongruent associations between race, LA diameter, and LA volume suggest that LA geometry, rather than size alone, may have implications for AF risk. 相似文献
998.
Marcus R. Streit Celine S. Weiss S?ren Meyer Marco M. Ochs Marco Hagenmueller Johannes H. Riffel Sebastian J. Buss Thomas Heger Hugo A. Katus Stefan E. Hardt 《PloS one》2016,11(1)
Aims
Inhibition of β-adrenergic signalling plays a key role in treatment of heart failure. Gsα is essential for β-adrenergic signal transduction. In order to reduce side-effects of beta-adrenergic inhibition diminishing β-adrenergic signalling in the heart at the level of Gsα is a promising option.Methods and Results
We analyzed the influence of Gsα on regulation of myocardial function and development of cardiac hypertrophy, using a transgenic mouse model (C57BL6/J mice) overexpressing a dominant negative Gsα-mutant under control of the α-MHC-promotor. Cardiac phenotype was characterized in vivo and in vitro and under acute and chronic β-adrenergic stimulation. At rest, Gsα-DN-mice showed bradycardia (602 ± 13 vs. 660 ± 17 bpm, p<0.05) and decreased dp/dtmax (5037 ± 546- vs. 6835 ± 505 mmHg/s, p = 0.02). No significant differences were found regarding ejection fraction, heart weight and cardiomyocyte size. β-blockade by propranolol revealed no baseline differences of hemodynamic parameters between wildtype and Gsα-DN-mice. Acute adrenergic stimulation resulted in decreased β-adrenergic responsiveness in Gsα-DN-mice. Under chronic adrenergic stimulation, wildtype mice developed myocardial hypertrophy associated with increase of LV/BW-ratio by 23% (4.4 ± 0.2 vs. 3.5 ± 0.1 mg/g, p<0.01) and cardiac myocyte size by 24% (14927 ± 442 px vs. 12013 ± 583 px, p<0.001). In contrast, both parameters were unchanged in Gsα-DN-mice after chronic isoproterenol stimulation.Conclusion
Overexpression of a dominant negative mutant of Gsα leads to decreased β-adrenergic responsiveness and is protective against isoproterenol-induced hypertrophy. Thus, Gsα-DN-mice provide novel insights into β-adrenergic signal transduction and its modulation in myocardial overload and failure. 相似文献999.
Jo?o Pedreira Duprat Eduard René Brechtbülh Bianca Costa de Sá Mauro Enokihara Jose Humberto Fregnani Gilles Landman Marcus Maia Felice Riccardi Francisco Alberto Belfort Alberto Wainstein Luciana F. Moredo Higino Steck Miguel Brand?o Marcelo Moreno Eduardo Miranda Ivan Dunshee de Oliveira Santos 《PloS one》2016,11(2)
Aims
The aim of this study is to confirm the function of tumor-infiltrating lymphocytes (TILs) in sentinel lymph node (SLN) metastasis.Materials and Methods
This retrospective study included 633 patients with invasive melanoma who underwent sentinel lymph node biopsy in 7 referral centers certified by the Brazilian Melanoma Group. Independent risk factors of sentinel node metastasis (SNL) were identified by multiple logistic regression.Results
SLN metastasis was detected in 101 of 633 cases (16.1%) and in 93 of 428 patients (21.7%) when melanomas ≤ 1mm were excluded. By multiple logistic regression, the absence of TILs was as an independent risk factor of SLN metastasis (OR = 1.8; 95%CI: 1.1–3.0), in addition to Breslow index (greater than 2.00 mm), lymph vascular invasion, and presence of mitosis.Conclusion
SLNB can identify patients who might benefit from immunotherapy, and the determination of predictors of SLNB positivity can help select the proper population for this type of therapy. The absence of TILs is a reproducible parameter that can predict SLNB positivity in melanoma patients, since this study was made with several centers with different dermatopathologists. 相似文献1000.
Denise Silva Nogueira Pedro Henrique Gazzinelli-Guimar?es Fernando Sérgio Barbosa Nathália Maria Resende Caroline Cavalcanti Silva Luciana Maria de Oliveira Chiara Cássia Oliveira Amorim Fabrício Marcus Silva Oliveira Matheus Silvério Mattos Lucas Rocha Kraemer Marcelo Vidigal Caliari Soraya Gaze Lilian Lacerda Bueno Remo Castro Russo Ricardo Toshio Fujiwara 《PLoS neglected tropical diseases》2016,10(1)
Ascaris spp. infection affects 800 million people worldwide, and half of the world population is currently at risk of infection. Recurrent reinfection in humans is mostly due to the simplicity of the parasite life cycle, but the impact of multiple exposures to the biology of the infection and the consequences to the host’s homeostasis are poorly understood. In this context, single and multiple exposures in mice were performed in order to characterize the parasitological, histopathological, tissue functional and immunological aspects of experimental larval ascariasis. The most important findings revealed that reinfected mice presented a significant reduction of parasite burden in the lung and an increase in the cellularity in the bronchoalveolar lavage (BAL) associated with a robust granulocytic pulmonary inflammation, leading to a severe impairment of respiratory function. Moreover, the multiple exposures to Ascaris elicited an increased number of circulating inflammatory cells as well as production of higher levels of systemic cytokines, mainly IL-4, IL-5, IL-6, IL-10, IL-17A and TNF-α when compared to single-infected animals. Taken together, our results suggest the intense pulmonary inflammation associated with a polarized systemic Th2/Th17 immune response are crucial to control larval migration after multiple exposures to Ascaris. 相似文献