Sensorineural hearing loss after concurrent chemoradiotherapy in nasopharyngeal cancer patients

<p>Abstract</p> <p>Background</p> <p>Sensorineural hearing loss (SNHL) is one of the major long term side effects from radiation therapy (RT) in nasopharyngeal cancer (NPC) patients. This study aims to review the incidences of SNHL when treating with different radiation techniques. The additional objective is to determine the relationship of the SNHL with the radiation doses delivered to the inner ear.</p> <p>Methods</p> <p>A retrospective cohort study of 134 individual ears from 68 NPC patients, treated with conventional RT and IMRT in combination with chemotherapy from 2004-2008 was performed. Dosimetric data of the cochlea were analyzed. Significant SNHL was defined as > 15 dB increase in bone conduction threshold at 4 kHz and PTA (pure tone average of 0.5, 1, 2 kHz). Relative risk (RR) was used to determine the associated factors with the hearing threshold changes at 4 kHz and PTA.</p> <p>Results</p> <p>Median audiological follow up time was 14 months. The incidence of high frequency (4 kHz) SNHL was 44% for the whole group (48.75% in the conventional RT, 37% with IMRT). Internal auditory canal mean dose of > 50 Gy had shown a trend to increase the risk of high frequency SNHL (RR 2.02 with 95% CI 1.01-4.03, p = 0.047).</p> <p>Conclusion</p> <p>IMRT and radiation dose limitation to the inner ear appeared to decrease SNHL.</p

A Factorization Law for Entanglement Decay

We present a simple and general factorization law for quantum systems shared by two parties, which describes the time evolution of entanglement upon passage of either component through an arbitrary noisy channel. The robustness of entanglement-based quantum information processing protocols is thus easily and fully characterized by a single quantity.Comment: 4 pages, 5 figure

El Niño adversely affected childhood stature and lean mass in northern Peru

El Niño is responsible for natural disasters and infectious disease outbreaks worldwide. During the 1997–1998 El Niño, northern Peru endured extreme rainfall and flooding. Since short stature may occur as a result of undernutrition or repeated infections during childhood, both of which are highly prevalent during natural disasters, we sought to determine if the 1997–1998 El Niño had an adverse effect on stature and body composition a decade later. In 2008–2009, we measured height, weight, and bioimpedance in a random sample of 2,095 children born between 1991 and 2001 in Tumbes, Peru

Clinical, Virological and Immunological Features from Patients Infected with Re-Emergent Avian-Origin Human H7N9 Influenza Disease of Varying Severity in Guangdong Province

The second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region.Background The second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region. Methods Five patients with H7N9 virus infection admitted to our hospital during August 2013 to February 2014 were intensively investigated. Viral load in the respiratory tract was determined by quantitative polymerase chain reaction (Q-PCR) and cytokine levels were measured by bead-based flow cytometery. Results Four patients survived and one died. Viral load in different clinical specimens was correlated with cytokine levels in plasma and broncho-alveolar fluid (BALF), therapeutic modalities used and clinical outcome. Intravenous zanamivir appeared to be better than peramivir as salvage therapy in patients who failed to respond to oseltamivir. Higher and more prolonged viral load was found in the sputum or endotracheal aspirates compared to throat swabs. Upregulation of proinflammatory cytokines IP-10, MCP-1, MIG, MIP-1α/β, IL-1β and IL-8 was found in the plasma and BALF samples. The levels of cytokines in the plasma and viral load were correlated with disease severity. Reactivation of herpes simplex virus type 1(HSV-1) was found in three out of five patients (60%). Conclusion Expectorated sputum or endotracheal aspirate specimens are preferable to throat swabs for detecting and monitoring H7N9 virus. Severity of the disease was correlated to the viral load in the respiratory tract as well as the extents of cytokinemia. Reactivation of HSV-1 may contribute to clinical outcome.published_or_final_versio

Targeting canine bladder transitional cell carcinoma with a human bladder cancer-specific ligand

<p>Abstract</p> <p>Objective</p> <p>To determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells.</p> <p>Experimental Design</p> <p>The binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC) cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. <it>In vivo </it>tumor-specific homing/targeting property and biodistribution of PLZ4 was performed in a mouse xenograft model via tail vein injection and was confirmed with <it>ex vivo </it>imaging.</p> <p>Results</p> <p>PLZ4 exhibited high affinity and specific dose-dependent binding to canine bladder TCC cell lines, but not to normal canine urothelial cells. No significant changes in cell viability or proliferation were observed upon incubation with PLZ4. The <it>in vivo </it>and <it>ex vivo </it>optical imaging study showed that, when linked with the near-infrared fluorescent dye Cy5.5, PLZ4 substantially accumulated at the canine bladder cancer foci in the mouse xenograft model as compared to the control.</p> <p>Conclusions and Clinical Relevance</p> <p>PLZ4 can specifically bind to canine bladder cancer cells. This suggests that the preclinical studies of PLZ4 as a potential diagnostic and therapeutic agent can be performed in dogs with naturally occurring bladder cancer, and that PLZ4 can possibly be developed in the management of canine bladder cancer.</p

Childhood deaths from external causes in Estonia, 2001–2005

<p>Abstract</p> <p>Background</p> <p>In 2000, the overall rate of injury deaths in children aged 0–14 was 28.7 per 100000 in Estonia, which is more than 5 times higher than the corresponding rate in neighbouring Finland. This paper describes childhood injury mortality in Estonia by cause and age groups, and validates registration of these deaths in the Statistical Office of Estonia against the autopsy data.</p> <p>Methods</p> <p>The data on causes of all child deaths in Estonia in 2001–2005 were abstracted from the autopsy protocols at the Estonian Bureau of Forensic Medicine. Average annual mortality rates per 100,000 were calculated. Coverage (proportion of the reported injury deaths from the total number of injury deaths) and accuracy (proportion of correctly classified injury deaths) of the registration of causes of death in Statistical Office of Estonia were assessed by comparing the Statistical Office of Estonia data with the data from Estonian Bureau of Forensic Medicine.</p> <p>Results</p> <p>Average annual mortality from external causes in 0–14 years-old children in Estonia was 19.1 per 100,000. Asphyxia and transport accidents were the major killers followed by poisoning and suicides. Relative contribution of these causes varied greatly between age groups. Intent of death was unknown for more than 10% of injury deaths. Coverage and accuracy of registration of injury deaths by Statistical Office of Estonia were 91.5% and 95.3%, respectively.</p> <p>Conclusion</p> <p>Childhood mortality from injuries in Estonia is among the highest in the EU. The number of injury deaths in Statistical Office of Estonia is slightly underestimated mostly due to misclassification for deaths from diseases. Accuracy of the Statistical Office of Estonia data was high with some underestimation of intentional deaths. Moreover, high proportion of death with unknown intent suggests underestimation of intentional deaths.</p> <p>Reduction of injury deaths should be given a high priority in Estonia. More information on circumstances around death is needed to enable establishing the intent of death.</p

The Role of Response Elements Organization in Transcription Factor Selectivity: The IFN-β Enhanceosome Example

What is the mechanism through which transcription factors (TFs) assemble specifically along the enhancer DNA? The IFN-β enhanceosome provides a good model system: it is small; its components' crystal structures are available; and there are biochemical and cellular data. In the IFN-β enhanceosome, there are few protein-protein interactions even though consecutive DNA response elements (REs) overlap. Our molecular dynamics (MD) simulations on different motif combinations from the enhanceosome illustrate that cooperativity is achieved via unique organization of the REs: specific binding of one TF can enhance the binding of another TF to a neighboring RE and restrict others, through overlap of REs; the order of the REs can determine which complexes will form; and the alternation of consensus and non-consensus REs can regulate binding specificity by optimizing the interactions among partners. Our observations offer an explanation of how specificity and cooperativity can be attained despite the limited interactions between neighboring TFs on the enhancer DNA. To date, when addressing selective TF binding, attention has largely focused on RE sequences. Yet, the order of the REs on the DNA and the length of the spacers between them can be a key factor in specific combinatorial assembly of the TFs on the enhancer and thus in function. Our results emphasize cooperativity via RE binding sites organization

Quantum-Dot Light-Emitting Diodes with Nitrogen-Doped Carbon Nanodot Hole Transport and Electronic Energy Transfer Layer

Electroluminescence efficiency is crucial for the application of quantum-dot light-emitting diodes (QD-LEDs) in practical devices. We demonstrate that nitrogen-doped carbon nanodot (N-CD) interlayer improves electrical and luminescent properties of QD-LEDs. The N-CDs were prepared by solution-based bottom up synthesis and were inserted as a hole transport layer (HTL) between other multilayer HTL heterojunction and the red-QD layer. The QD-LEDs with N-CD interlayer represented superior electrical rectification and electroluminescent efficiency than those without the N-CD interlayer. The insertion of N-CD layer was found to provoke the Forster resonance energy transfer (FRET) from N-CD to QD layer, as confirmed by time-integrated and - resolved photoluminescence spectroscopy. Moreover, hole-only devices (HODs) with N-CD interlayer presented high hole transport capability, and ultraviolet photoelectron spectroscopy also revealed that the N-CD interlayer reduced the highest hole barrier height. Thus, more balanced carrier injection with sufficient hole carrier transport feasibly lead to the superior electrical and electroluminescent properties of the QD-LEDs with N-CD interlayer. We further studied effect of N-CD interlayer thickness on electrical and luminescent performances for high-brightness QD-LEDs. The ability of the N-CD interlayer to improve both the electrical and luminescent characteristics of the QD-LEDs would be readily exploited as an emerging photoactive material for high-efficiency optoelectronic devices.ope

Post-Transcriptional Regulation of 5-Lipoxygenase mRNA Expression via Alternative Splicing and Nonsense-Mediated mRNA Decay

5-Lipoxygenase (5-LO) catalyzes the two initial steps in the biosynthesis of leukotrienes (LT), a group of inflammatory lipid mediators derived from arachidonic acid. Here, we investigated the regulation of 5-LO mRNA expression by alternative splicing and nonsense-mediated mRNA decay (NMD). In the present study, we report the identification of 2 truncated transcripts and 4 novel 5-LO splice variants containing premature termination codons (PTC). The characterization of one of the splice variants, 5-LOΔ3, revealed that it is a target for NMD since knockdown of the NMD factors UPF1, UPF2 and UPF3b in the human monocytic cell line Mono Mac 6 (MM6) altered the expression of 5-LOΔ3 mRNA up to 2-fold in a cell differentiation-dependent manner suggesting that cell differentiation alters the composition or function of the NMD complex. In contrast, the mature 5-LO mRNA transcript was not affected by UPF knockdown. Thus, the data suggest that the coupling of alternative splicing and NMD is involved in the regulation of 5-LO gene expression

Reverse Engineering a Signaling Network Using Alternative Inputs

One of the goals of systems biology is to reverse engineer in a comprehensive fashion the arrow diagrams of signal transduction systems. An important tool for ordering pathway components is genetic epistasis analysis, and here we present a strategy termed Alternative Inputs (AIs) to perform systematic epistasis analysis. An alternative input is defined as any genetic manipulation that can activate the signaling pathway instead of the natural input. We introduced the concept of an “AIs-Deletions matrix” that summarizes the outputs of all combinations of alternative inputs and deletions. We developed the theory and algorithms to construct a pairwise relationship graph from the AIs-Deletions matrix capturing both functional ordering (upstream, downstream) and logical relationships (AND, OR), and then interpreting these relationships into a standard arrow diagram. As a proof-of-principle, we applied this methodology to a subset of genes involved in yeast mating signaling. This experimental pilot study highlights the robustness of the approach and important technical challenges. In summary, this research formalizes and extends classical epistasis analysis from linear pathways to more complex networks, facilitating computational analysis and reconstruction of signaling arrow diagrams