Ear, nose and throat injuries at Bugando Medical Centre in northwestern Tanzania: a five-year prospective review of 456 cases.

Injuries to the ear, nose and throat (ENT) regions are not uncommon in clinical practice and constitute a significant cause of morbidity and mortality in our setting. There is dearth of literature on this subject in our environment. This study was conducted to describe the causes, injury pattern and outcome of these injuries in our setting and proffer possible preventive measures. This was a descriptive prospective study of patients with ear, nose and throat injuries managed at Bugando Medical Centre between May 2007 and April 2012. Ethical approval to conduct the study was sought from relevant authorities. Statistical data analysis was performed using SPSS computer software version 17.0. A total of 456 patients were studied. The median age of patients at presentation was 18 years (range 1 to 72 years). The male to female ratio was 2:1. The commonest cause of injury was foreign bodies (61.8%) followed by road traffic accidents (22.4%). The ear was the most common body region injured accounting for 59.0% of cases. The majority of patients (324, 71.1%) were treated as an outpatient and only 132(28.9%) patients required admission to the ENT wards after definitive treatment. Foreign body removal and surgical wound debridement were the most common treatment modalities performed in 61.9% and 16.2% of cases respectively. Complication rate was 14.9%. Suppurative otitis media (30.9%) was the commonest complication in the ear while traumatic epistaxis (26.5%) and hoarseness of voice (11.8%) in the aero-digestive tract were commonest in the nose and throat. The overall median length of hospital stay for in-patients was 8 days (range 1 to 22 days). Patients who developed complications and those who had associated injuries stayed longer in the hospital (P < 0.001).Mortality rate related to isolated ENT injuries was 1.3% (6 deaths). The majority of patients (96.9%) were treated successfully and only 3.1% of cases were discharged with permanent disabilities. Injuries to the ENT regions are not uncommon in our environment and foreign bodies constitute a significant cause of injury. Majority of these injuries can be prevented through public enlightenment campaigns

Variation in flavonoids in a collection of peppers (Capsicum sp.) under organic and conventional cultivation: effect of the genotype, ripening stage, and growing system

This is the peer reviewed version of the following article: Ribes-Moya, A.M., Adalid, A.M., Raigón, M.D., Hellín, P., Fita, A. and Rodríguez-Burruezo, A. (2020), Variation in flavonoids in a collection of peppers (Capsicum sp.) under organic and conventional cultivation: effect of the genotype, ripening stage, and growing system. J Sci Food Agric, 100: 2208-2223, which has been published in final form at https://doi.org/10.1002/jsfa.10245. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] BACKGROUND In recent years, the acreage used for organic agriculture and the demand for organic fruit and vegetables have increased considerably. Given this scenario, landraces, such as Capsicum landraces, can provide valuable germplasm. Capsicum peppers are very interesting because of their high phenolic content, and particularly their flavonoid content, which provides a high added value. Moreover, the broad genetic diversity in local varieties expands the opportunities for adaptation to organic production and for exploiting genotype x environment interactions to select peppers with the highest phenolic content. RESULTS In this work, the main flavonoids of peppers were exhaustively evaluated over 2 years in a wide collection of heirlooms, both unripe and fully ripe, under organic and conventional cultivation. The genotype and ripening stage contributed to a high degree to the variation in flavonoids. The growing system influenced this variation to a lesser extent. Luteolin and quercetin showed the highest contributions to total phenolic content (70% and > 20%, respectively) at both ripening stages, while myricetin, apigenin, and kaempferol showed lower contributrions. The average flavonoid content was higher in ripe fruits, and organic management significantly increased the accumulation of total flavonoids and luteolin. Positive correlations between flavonoids were found at both ripening stages, especially between main flavonoids luteolin and quercetin and between kaempferol and quercetin (rho > 0.7). CONCLUSION Genotype x environment interaction enabled the identification of accessions with high flavonoid content grown under organic conditions at both ripening stages, particularly total flavonoids and luteolin at the fully ripe stage. Our results reinforce the importance of a wide genetic variation and of considering different ripening stages and growing conditions for breeding high-quality peppers.This work has been funded by the Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (INIA) project RTA2014-00041-C02-02, Fondo Europeo de Desarrollo Regional (FEDER) funds. A.M. Ribes-Moya expresses her gratitude to the Universitat Politecnica de Valencia (UPV) for her scholarship FPI-UPV-2017 (PAID-01-17). The authors also thank the farmers' association Unio de Llauradors i Ramaders (LA UNI) for the arrangement and management of fields - specifically Manuel Figueroa, Rafael Hurtado, Ricard Ballester, and Antonio Munoz, and seed providers P.W. Bosland, S. Lanteri, Francois Jourdan, Santiago Larregla, and the Regulatory Boards of the PDOs and PGIs included in this work. The authors are also grateful for the support of Professor Jaime Prohens with statistical methods.Ribes Moya, AM.; Adalid-Martinez, AM.; Raigón Jiménez, MD.; Hellín, P.; Fita, A.; Rodríguez Burruezo, A. (2020). Variation in flavonoids in a collection of peppers (Capsicum sp.) under organic and conventional cultivation: effect of the genotype, ripening stage, and growing system. Journal of the Science of Food and Agriculture. 100(5):2208-2223. https://doi.org/10.1002/jsfa.10245S220822231005WillerH European organic market grew by double digits and organic area reached 13.5 million hectares in2016 [Online]. 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Probing Shadowed Nuclear Sea with Massive Gauge Bosons in the Future Heavy-Ion Collisions

The production of the massive bosons $Z^0$ and $W^{\pm}$ could provide an excellent tool to study cold nuclear matter effects and the modifications of nuclear parton distribution functions (nPDFs) relative to parton distribution functions (PDFs) of a free proton in high energy nuclear reactions at the LHC as well as in heavy-ion collisions (HIC) with much higher center-of mass energies available in the future colliders. In this paper we calculate the rapidity and transverse momentum distributions of the vector boson and their nuclear modification factors in p+Pb collisions at $\sqrt{s_{NN}}=63$TeV and in Pb+Pb collisions at $\sqrt{s_{NN}}=39$TeV in the framework of perturbative QCD by utilizing three parametrization sets of nPDFs: EPS09, DSSZ and nCTEQ. It is found that in heavy-ion collisions at such high colliding energies, both the rapidity distribution and the transverse momentum spectrum of vector bosons are considerably suppressed in wide kinematic regions with respect to p+p reactions due to large nuclear shadowing effect. We demonstrate that in the massive vector boson productions processes with sea quarks in the initial-state may give more contributions than those with valence quarks in the initial-state, therefore in future heavy-ion collisions the isospin effect is less pronounced and the charge asymmetry of W boson will be reduced significantly as compared to that at the LHC. Large difference between results with nCTEQ and results with EPS09 and DSSZ is observed in nuclear modifications of both rapidity and $p_T$ distributions of $Z^0$ and $W$ in the future HIC.Comment: 13 pages, 21 figures, version accepted for publication in Eur. Phys. J.

In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB

A mathematical model for the adenylosuccinate synthetase reaction involved in purine biosynthesis

BACKGROUND: Development of the mathematical models that adequately describe biochemical reactions and molecular-genetic mechanisms is one of the most important tasks in modern bioinformatics. Because the enzyme adenylosuccinate synthetase (AdSS) has long been extensively studied, a wealth of kinetic data has been accumulated. RESULTS: We describe a mathematical model for the reaction catalyzed by AdSS. The model's parameters were fitted to experimental data obtained from published literature. The advantage of our model is that it includes relationships between the reaction rate, the concentrations of three substrates (GTP, IMP and ASP), the effects of five inhibitors (GMP, GDP, AMP, ASUC and SUCC), and the influence of Mg(2+ )ions. CONCLUSION: Our model describes the reaction catalyzed by AdSS as a fully random process. The model structure implies that each of the inhibitors included in it is only competitive to one of the substrates. The model was tested for adequacy using experimental data published elsewhere. The values obtained for the parameters are as follows: V(max )= 1.35·10(-3 )mM/min, Km(GTP )= 0.023 mM, Km(IMP )= 0.02 mM, Km(ASP )= 0.3 mM, Ki(GMP )= 0.024 mM, Ki(GDP )= 8·10(-3 )mM, Ki(AMP )= 0.01 mM, Ki(ASUC )= 7.5·10(-3 )mM, Ki(SUCC )= 8 mM, Km(Mg )= 0.08 mM

IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury.

Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury

Z' Bosons at Colliders: a Bayesian Viewpoint

We revisit the CDF data on di-muon production to impose constraints on a large class of Z' bosons occurring in a variety of E_6 GUT based models. We analyze the dependence of these limits on various factors contributing to the production cross-section, showing that currently systematic and theoretical uncertainties play a relatively minor role. Driven by this observation, we emphasize the use of the Bayesian statistical method, which allows us to straightforwardly (i) vary the gauge coupling strength, g', of the underlying U(1)'; (ii) include interference effects with the Z' amplitude (which are especially important for large g'); (iii) smoothly vary the U(1)' charges; (iv) combine these data with the electroweak precision constraints as well as with other observables obtained from colliders such as LEP 2 and the LHC; and (v) find preferred regions in parameter space once an excess is seen. We adopt this method as a complementary approach for a couple of sample models and find limits on the Z' mass, generally differing by only a few percent from the corresponding CDF ones when we follow their approach. Another general result is that the interference effects are quite relevant if one aims at discriminating between models. Finally, the Bayesian approach frees us of any ad hoc assumptions about the number of events needed to constitute a signal or exclusion limit for various actual and hypothetical reference energies and luminosities at the Tevatron and the LHC.Comment: PDFLaTeX, 24 pages, 7 figures. Version with improved tables and figure

Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

Inhaled nitric oxide alleviates hyperoxia suppressed phosphatidylcholine synthesis in endotoxin-induced injury in mature rat lungs

BACKGROUND: We investigated efficacy of inhaled nitric oxide (NO) in modulation of metabolism of phosphatidylcholine (PC) of pulmonary surfactant and in anti-inflammatory mechanism of mature lungs with inflammatory injury. METHODS: Healthy adult rats were divided into a group of lung inflammation induced by i.v. lipopolysaccharides (LPS) or a normal control (C) for 24 h, and then exposed to: room air (Air), 95% oxygen (O), NO (20 parts per million, NO), both O and NO (ONO) as subgroups, whereas [(3)H]-choline was injected i.v. for incorporation into PC of the lungs which were processed subsequently at 10 min, 4, 8, 12 and 24 h, respectively, for measurement of PC synthesis and proinflammatory cytokine production. RESULTS: LPS-NO subgroup had the lowest level of labeled PC in total phospholipids and disaturated PC in bronchoalveolar lavage fluid and lung tissue (decreased by 46–59%), along with the lowest activity of cytidine triphosphate: phosphocholine cytidylyltransferase (-14–18%) in the lungs, compared to all other subgroups at 4 h (p < 0.01), but not at 8 and 12 h. After 24-h, all LPS-subgroups had lower labeled PC than the corresponding C-subgroups (p < 0.05). LPS-ONO had higher labeled PC in total phospholipids and disaturated PC, activity of cytidylyltransferase, and lower activity of nuclear transcription factor-κB and expression of proinflammatory cytokine mRNA, than that in the LPS-O subgroup (p < 0.05). CONCLUSION: In LPS-induced lung inflammation in association with hyperoxia, depressed PC synthesis and enhanced proinflammatory cytokine production may be alleviated by iNO. NO alone only transiently suppressed the PC synthesis as a result of lower activity of cytidylyltransferase