The role of the fibreoptic bronchoscope in otorhinolaryngological practice

Flexible fibreoptic bronchoscope has been employed in the examination of the nasopharynx, pharynx, larynx, trachea, bronchus and intrathoracic oesophagus under local anaesthesia. It is used either for diagnostic or therapeutic purposes. A total of 1690 procedures have been performed with no complication. The indications and findings in these procedures are listed. The advantages and limitations of the use of flexible fibreoptic bronchoscope as a 'panendoscopic examination' instrument are discussed.published_or_final_versio

Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.

The current knowledge on how transcription factors (TFs), the ultimate targets and executors of cellular signalling pathways, are regulated by protein-protein interactions remains limited. Here, we performed proteomics analyses of soluble and chromatin-associated complexes of 56 TFs, including the targets of many signalling pathways involved in development and cancer, and 37 members of the Forkhead box (FOX) TF family. Using tandem affinity purification followed by mass spectrometry (TAP/MS), we performed 214 purifications and identified 2,156 high-confident protein-protein interactions. We found that most TFs form very distinct protein complexes on and off chromatin. Using this data set, we categorized the transcription-related or unrelated regulators for general or specific TFs. Our study offers a valuable resource of protein-protein interaction networks for a large number of TFs and underscores the general principle that TFs form distinct location-specific protein complexes that are associated with the different regulation and diverse functions of these TFs

Optical properties of dense self-assembled gold nanoparticle layers with organic linker molecules

Films consisting of self-assembled gold nanoparticles cross-linked with alkane-dithiols were prepared by a filtration method and studied with scanning electron microscopy to determine the structure of the films and spectrophotometry and ellipsometry to ascertain their optical properties. The structural characterization showed the existence of nanometer-sized voids within the films. This previously unmentioned feature is responsible for the previous difficulties in modelling the optical properties with effective medium models. This can be remedied, using a two-tiered hierarchical effective medium model, which takes into account the existence of the voids. Using this model we were able to fit the experimental data, with only the void volume fraction to be determined by the overall fit, while the gold volume fraction in the linker medium is fixed by the wavelength of the resonance peak. Our model should be applicable to all such films, when the deposition method, which determines the microstructure, is properly taken into account

Gestational Exposure to Antidepressants and Risk of Seizure in Offspring: A systematic review and meta-analysis

In spite of the preliminary evidence suggesting a link between gestational use of antidepressant and neurodevelopmental disorders in their offspring, the association between maternal use of antidepressants during pregnancy and the risk of neurologically-related adverse outcomes such as neonatal seizure is still unclear. This study summarises the available evidence on the association between gestational exposure to any antidepressants and the risk of seizure in neonates and children. We found that gestational antidepressant exposure is associated with a 2.3-fold higher incidence of seizure in offspring. Although a causal relationship cannot be confirmed in view of other potential confounders, our findings warrant future research on related clinical aspects, and possibly more careful monitoring of foetal neurodevelopment in pregnant women taking antidepressants during pregnancy. However, this does not suggest the abrupt withdrawal of antidepressants during pregnancy for all cases at risk of seizure in offspring as this must be balanced with the risk of negative consequences caused by untreated maternal depression, and decision-making should be individualised for each patient

Increasing Risk of Dementia Among Patients with Subsequent Epilepsy Within 2 Years Post-Traumatic Brain Injury: A Population‐Based Case-Control Study

Shu-Fen Chu,1 Kuo-Hsing Liao,2– 5 Li Wei2,6 1College of Nursing and Health Management, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 2Division of Neurosurgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Division of Critical Medicine, Department of Emergency and Critical Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 4Department of Neurotraumatology and Intensive Care, Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan; 5Division of Neurosurgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, TaiwanCorrespondence: Li Wei, Graduate Institute of Injury Prevention and Control, Taipei Medical University, 250 Wu-Hsing Street, Taipei City, Taiwan 110, Taiwan, Email [email protected]: Although the association between neurodegenerative diseases, such as dementia, and traumatic brain injury (TBI) has long been known, the association between dementia and TBI with epilepsy has been controversial.Aim: This data-driven population-based study is designed to investigate the association between dementia and epilepsy after TBI within a 2-year period.Methods: This case-control cohort study was conducted using the Longitudinal Health Insurance Database 2000 (LHID2000). We included 784 individuals ambulatory or hospitalized for TBI with epilepsy from 2001 to 2011, compared with 2992 patients with TBI without epilepsy who were matched for characteristics including sex, age, and healthcare resource use index date. Every participant was followed up for 5 years to ascertain any dementia development. Data were stratified and analyzed using the Cox proportional hazards regression.Results: Through the 5-year follow-up period, 39 patients (5.21%) with TBI with epilepsy and 55 (1.53%) with TBI without epilepsy developed dementia. TBI with epilepsy was independently associated with a > 3.03 times risk of dementia after correcting for age, sex, and comorbidities.Conclusion: These findings suggest an increased risk of dementia in patients with TBI with epilepsy. Our research recommends that individuals with TBI and epilepsy be monitored more intensively.Keywords: neurodegenerative diseases, dementia, epilepsy, traumatic brain injury, data-driven, population-based stud

Neutrino Masses and Lepton-flavor-violating τ\tau Decays in the Supersymmetric Left-right Model

In the supersymmetric left-right model, the light neutrino masses are given by the Type-II seesaw mechanism. A duality property about this mechanism indicates that there exist eight possible Higgs triplet Yukawa couplings which result in the same neutrino mass matrix. In this paper, We work out the one-loop renormalization group equations for the effective neutrino mass matrix in the supersymmetric left-right model. The stability of the Type-II seesaw scenario is briefly discussed. We also study the lepton-flavor-violating processes ($\tau\to \mu\gamma$ and $\tau\to e\gamma$) by using the reconstructed Higgs triplet Yukawa couplings

Expression and function of proton-sensing G-protein-coupled receptors in inflammatory pain

<p>Abstract</p> <p>Background</p> <p>Chronic inflammatory pain, when not effectively treated, is a costly health problem and has a harmful effect on all aspects of health-related quality of life. Despite the availability of pharmacologic treatments, chronic inflammatory pain remains inadequately treated. Understanding the nociceptive signaling pathways of such pain is therefore important in developing long-acting treatments with limited side effects. High local proton concentrations (tissue acidosis) causing direct excitation or modulation of nociceptive sensory neurons by proton-sensing receptors are responsible for pain in some inflammatory pain conditions. We previously found that all four proton-sensing G-protein-coupled receptors (GPCRs) are expressed in pain-relevant loci (dorsal root ganglia, DRG), which suggests their possible involvement in nociception, but their functions in pain remain unclear.</p> <p>Results</p> <p>In this study, we first demonstrated differential change in expression of proton-sensing GPCRs in peripheral inflammation induced by the inflammatory agents capsaicin, carrageenan, and complete Freund's adjuvant (CFA). In particular, the expression of TDAG8, one proton-sensing GPCR, was increased 24 hours after CFA injection because of increased number of DRG neurons expressing TDAG8. The number of DRG neurons expressing both TDAG8 and transient receptor potential vanilloid 1 (TRPV1) was increased as well. Further studies revealed that TDAG8 activation sensitized the TRPV1 response to capsaicin, suggesting that TDAG8 could be involved in CFA-induced chronic inflammatory pain through regulation of TRPV1 function.</p> <p>Conclusion</p> <p>Each subtype of the OGR1 family was expressed differently, which may reflect differences between models in duration and magnitude of hyperalgesia. Given that TDAG8 and TRPV1 expression increased after CFA-induced inflammation and that TDAG8 activation can lead to TRPV1 sensitization, it suggests that high concentrations of protons after inflammation may not only directly activate proton-sensing ion channels (such as TRPV1) to cause pain but also act on proton-sensing GPCRs to regulate the development of hyperalgesia.</p

Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53

Background: The availability of various "omics" datasets creates a prospect of performing the study of genome-wide genetic regulatory networks. However, one of the major challenges of using mathematical models to infer genetic regulation from microarray datasets is the lack of information for protein concentrations and activities. Most of the previous researches were based on an assumption that the mRNA levels of a gene are consistent with its protein activities, though it is not always the case. Therefore, a more sophisticated modelling framework together with the corresponding inference methods is needed to accurately estimate genetic regulation from "omics" datasets. Results: This work developed a novel approach, which is based on a nonlinear mathematical model, to infer genetic regulation from microarray gene expression data. By using the p53 network as a test system, we used the nonlinear model to estimate the activities of transcription factor (TF) p53 from the expression levels of its target genes, and to identify the activation/inhibition status of p53 to its target genes. The predicted top 317 putative p53 target genes were supported by DNA sequence analysis. A comparison between our prediction and the other published predictions of p53 targets suggests that most of putative p53 targets may share a common depleted or enriched sequence signal on their upstream non-coding region. Conclusions: The proposed quantitative model can not only be used to infer the regulatory relationship between TF and its down-stream genes, but also be applied to estimate the protein activities of TF from the expression levels of its target genes

Folate cycle enzyme MTHFD1L confers metabolic advantages in hepatocellular carcinoma

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Structural insights into RNA processing by the human RISC-loading complex.

Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and the RNA-binding protein TRBP to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs and miRNAs from Dicer to AGO2. Here, using single-particle EM analysis, we show that human Dicer has an L-shaped structure. The RLC Dicer's N-terminal DExH/D domain, located in a short 'base branch', interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2