171 research outputs found
Etiological spectrum and treatment outcome of Obstructive jaundice at a University teaching Hospital in northwestern Tanzania: A diagnostic and therapeutic challenges
Obstructive jaundice poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was undertaken to highlight the etiological spectrum, treatment outcome of obstructive jaundice in our setting and to identify prognostic factors for morbidity and mortality. This was a descriptive prospective study which was conducted at Bugando Medical Centre between July 2006 and June 2010. All patients with a clinical diagnosis of obstructive jaundice were, after informed consent for the study, consecutively enrolled into the study. Data were collected using a pre-tested structured questionnaire and analyzed using SPSS computer software version 11.5. A total of 116 patients were studied. Females outnumbered males by a ratio of 1.3:1. Patients with malignant obstructive jaundice were older than those of benign type. Ca head of pancreas was the commonest malignant cause of jaundice where as choledocholithiasis was the commonest benign cause. Abdominal ultrasound was the only diagnostic imaging done in all patients and revealed dilated intra and extra-hepatic ducts, common bile stones and abdominal masses in 56.2%, 78.9%, 58.1% and 72.4% of the cases respectively. A total of 110 (94.8%) patients underwent surgical treatment and the remaining 6 (5.2%) patients were unfit for surgery. The complication rate was 22.4% mainly surgical site infections. The mean hospital stay and mortality rate were 14.54 days and 15.5% respectively. A low haematocrit and presence of postoperative sepsis were the main predictors of the hospital stay (P < 0.001), whereas age > 60 years, prolonged duration of jaundice, malignant causes and presence of postoperative complications mainly sepsis significantly predicted mortality (P < 0.001). Obstructive jaundice in our setting is more prevalent in females and the cause is mostly malignant. The result of this study suggests that early diagnosis and treatment plays an important role in the prognosis of patients with obstructive jaundice
Activation of BMP-Smad1/5/8 Signaling Promotes Survival of Retinal Ganglion Cells after Damage In Vivo
While the essential role of bone morphogenetic protein (BMP) signaling in nervous system development is well established, its function in the adult CNS is poorly understood. We investigated the role of BMP signaling in the adult mouse retina following damage in vivo. Intravitreal injection of N-Methyl-D-aspartic acid (NMDA) induced extensive retinal ganglion cell death by 2 days. During this period, BMP2, -4 and -7 were upregulated, leading to phosphorylation of the downstream effector, Smad1/5/8 in the inner retina, including in retinal ganglion cells. Expression of Inhibitor of differentiation 1 (Id1; a known BMP-Smad1/5/8 target) was also upregulated in the retina. This activation of BMP-Smad1/5/8 signaling was also observed following light damage, suggesting that it is a general response to retinal injuries. Co-injection of BMP inhibitors with NMDA effectively blocked the damage-induced BMP-Smad1/5/8 activation and led to further cell death of retinal ganglion cells, when compared with NMDA injection alone. Moreover, treatment of the retina with exogenous BMP4 along with NMDA damage led to a significant rescue of retinal ganglion cells. These data demonstrate that BMP-Smad1/5/8 signaling is neuroprotective for retinal ganglion cells after damage, and suggest that stimulation of this pathway can serve as a potential target for neuroprotective therapies in retinal ganglion cell diseases, such as glaucoma
Anti-cancer drug validation: the contribution of tissue engineered models
Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio
High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model
Copyright: Copyright 2014 Elsevier B.V., All rights reserved.Background: The combination of virotherapy and chemotherapy may enable efficient tumor regression that would be unachievable using either therapy alone. In this study, we investigated the efficiency of transgene delivery and the cytotoxic effects of alphaviral vector in combination with 5-fluorouracil (5-FU) in a mouse mammary tumor model (4 T1).Methods: Replication-deficient Semliki Forest virus (SFV) vectors carrying genes encoding fluorescent proteins were used to infect 4 T1 cell cultures treated with different doses of 5-FU. The efficiency of infection was monitored via fluorescence microscopy and quantified by fluorometry. The cytotoxicity of the combined treatment with 5-FU and alphaviral vector was measured using an MTT-based cell viability assay. In vivo experiments were performed in a subcutaneous 4 T1 mouse mammary tumor model with different 5-FU doses and an SFV vector encoding firefly luciferase.Results: Infection of 4 T1 cells with SFV prior to 5-FU treatment did not produce a synergistic anti-proliferative effect. An alternative treatment strategy, in which 5-FU was used prior to virus infection, strongly inhibited SFV expression. Nevertheless, in vivo experiments showed a significant enhancement in SFV-driven transgene (luciferase) expression upon intratumoral and intraperitoneal vector administration in 4 T1 tumor-bearing mice pretreated with 5-FU: here, we observed a positive correlation between 5-FU dose and the level of luciferase expression.Conclusions: Although 5-FU inhibited SFV-mediated transgene expression in 4 T1 cells in vitro, application of the drug in a mouse model revealed a significant enhancement of intratumoral transgene synthesis compared with 5-FU untreated mice. These results may have implications for efficient transgene delivery and the development of potent cancer treatment strategies using alphaviral vectors and 5-FU.publishersversionPeer reviewe
From Poverty to Disaster and Back: a Review of the Literature
Poor people are disproportionally affected by natural hazards and disasters. This paper provides a review of the multiple factors that explain why this is the case. It explores the role of exposure (often, but not always, poor people are more likely to be affected by hazards), vulnerability (when they are affected, poor people tend to lose a larger fraction of their wealth), and socio-economic resilience (poor people have a lower ability to cope with and recover from disaster impacts). Finally, the paper highlights the vicious circle between poverty and disaster losses: poverty is a major driver of people’s vulnerability to natural disasters, which in turn increase poverty in a measurable and significant way. The main policy implication is that poverty reduction can be considered as disaster risk management, and disaster risk management can be considered as poverty reduction
Search for an invisible in a final state with two muons and missing energy at Belle II
The extension of the standard model predicts the existence
of a lepton-flavor-universality-violating boson that couples only
to the heavier lepton families. We search for such a through its
invisible decay in the process . We use a
sample of electron-positron collisions at a center-of-mass energy of 10.58GeV
collected by the Belle II experiment in 2019-2020, corresponding to an
integrated luminosity of 79.7fb. We find no excess over the expected
standard-model background. We set 90-confidence-level upper limits on the
cross section for this process as well as on the coupling of the model, which
ranges from at low masses to 1 at
masses of 8
Tests of light-lepton universality in angular asymmetries of decays
We present the first comprehensive tests of light-lepton universality in the
angular distributions of semileptonic \Bz-meson decays to charged spin-1
charmed mesons. We measure five angular-asymmetry observables as functions of
the decay recoil that are sensitive to lepton-universality-violating
contributions. We use events where one neutral \B is fully reconstructed in
\PUpsilonFourS{} \to\B\overline{B} decays in data corresponding to \lumion
integrated luminosity from electron-positron collisions collected with the
\belletwo detector. We find no significant deviation from the standard model
expectations
Precise measurement of the lifetime at Belle II
We measure the lifetime of the meson using a data sample of 207
fb collected by the Belle II experiment running at the SuperKEKB
asymmetric-energy collider. The lifetime is determined by fitting the
decay-time distribution of a sample of
decays. Our result is \tau^{}_{D^+_s} = (498.7\pm
1.7\,^{+1.1}_{-0.8}) fs, where the first uncertainty is statistical and the
second is systematic. This result is significantly more precise than previous
measurements.Comment: 7 pages, 4 figures, to be submitted to Physical Review Letter
Measurement of the branching fraction and asymmetry of decays using pairs in Belle II data
We report measurements of the branching fraction and asymmetry in
decays reconstructed at Belle II in an
electron-positron collision sample containing
pairs. We measure a branching fraction \mathcal{B}(\Bpipi) =
(1.38 \pm 0.27 \pm 0.22) \times 10^{-6} and a asymmetry \Acp(\Bpipi)
= 0.14 \pm 0.46 \pm 0.07, where the first uncertainty is statistical and the
second is systematic
Measurement of asymmetries and branching-fraction ratios for and with using Belle and Belle II data
We measure asymmetries and branching-fraction ratios for and decays with , where
is a superposition of and . We use the full data set of the
Belle experiment, containing pairs, and data from the
Belle~II experiment, containing pairs, both collected
in electron-positron collisions at the resonance. Our results
provide model-independent information on the unitarity triangle angle .Comment: 26 pages, 8 figure
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