Feasibility of intraoperative neuromonitoring during thyroid surgery using transcartilage surface recording electrodes

Background: Intraoperative neural monitoring (IONM) has gained widespread acceptance as an adjunct to the gold standard of visual identification of the recurrent laryngeal nerve (RLN) during thyroid surgery. Currently, laryngeal electromyography (EMG) recording during IONM is almost always performed using endotracheal tube (ETT) surface electrodes placed adjacent to vocal folds originating from the inner surface of the thyroid cartilage (TC). Therefore, we hypothesized that surface recording electrodes placed on the outer surface of the TC should enable access to the EMG response of the vocal folds during IONM. The aims of this experimental study were to evaluate the feasibility of the transcartilage approach for laryngeal EMG recording during IONM. Methods: A porcine model (12 pigs and 24 RLN sides) with well-established applicability in IONM research was used for the experiments. Both ETT electrodes adjacent to vocal folds and adhesive pre-gelled electrodes on the TC were used for EMG recording during IONM. Electrically evoked EMG signals detected by both electrode types were recorded and analyzed. EMG changes during tracheal displacement and RLN traction injury were compared. Results: Both the ETT and TC electrodes recorded typical laryngeal EMG waveforms evoked by a 1 mA stimulus current applied on both sides of the RLNs and vagus nerves (VNs). Under RLN stimulation, the mean EMG amplitudes recorded with the ETT and TC electrodes were 973μV (±179) and 695μV (±150), respectively. Under VN stimulation, the mean amplitudes were 841μV (± 163) and 607μV (± 162), respectively. When upward displacement of the trachea was experimentally induced, the TC electrodes showed less variation in recorded EMG signals compared to ETT electrodes. When RLN traction stress was experimentally induced, both the ETT and TC electrodes accurately recorded the typical EMG pattern of progressively degrading amplitude and gradual recovery after release of traction. Conclusions: This study confirmed the feasibility of using transcartilage surface electrodes for recording of laryngeal EMG signals evoked during IONM in an animal model. Before practical application of this approach in clinical thyroid surgery, however, further studies are needed to improve electrode designs by optimizing their shapes and sizes, and increasing their adhesive stability and sensitivity

Improving Voice Outcomes After Thyroid Surgery – Review of Safety Parameters for Using Energy-Based Devices Near the Recurrent Laryngeal Nerve

Technological advances in thyroid surgery have rapidly increased in recent decades. Specifically, recently developed energy-based devices (EBDs) enable simultaneous dissection and sealing tissue. EBDs have many advantages in thyroid surgery, such as reduced blood loss, lower rate of post-operative hypocalcemia, and shorter operation time. However, the rate of recurrent laryngeal nerve (RLN) injury during EBD use has shown statistically inconsistent. EBDs generate high temperature that can cause iatrogenic thermal injury to the RLN by direct or indirect thermal spread. This article reviews relevant medical literatures of conventional electrocauteries and different mechanisms of current EBDs, and compares two safety parameters: safe distance and cooling time. In general, conventional electrocautery generates higher temperature and wider thermal spread range, but when applying EBDs near the RLN adequate activation distance and cooling time are still required to avoid inadvertent thermal injury. To improve voice outcomes in the quality-of-life era, surgeons should observe safety parameters and follow the standard procedures when using EBDs near the RLN in thyroid surgery

The Identification of FN1 as an Early Diagnostic Marker for Recurrent Abortion by Single-Exosome Profiling

Chenlu Wang,1,* Zhaojin Lu,1,* Guangpeng She,2 Kaining Chen,1 Huazhong Zhou,1 Xueli Zhan,3 Hongyan Yu,1 Lei Pi,1 Liandong Zuo,4 Di Che1 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510620, People’s Republic of China; 2Department of Laboratory Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 3Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510620, People’s Republic of China; 4Department of Andrology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510620, People’s Republic of China*These authors contributed equally to this workCorrespondence: Di Che, Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Guangzhou, Guangdong, 510620, People’s Republic of China, Email [email protected] Liandong Zuo, Department of Andrology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong, 510620, People’s Republic of China, Email [email protected]: Recurrent abortion(RA) is a prevalent adverse pregnancy event. Exosomes, secreted by various body fluids, are known to play a role in disease diagnosis and serve as biomarkers through intercellular communication. This study aims to analyze single exosomes in patients with recurrent abortion to identify new biomarkers that may significantly contribute to recurrent abortion, providing new directions for its treatment.Patients and Methods: A total of 244 serum exosomes were collected, including 216 patients with recurrent abortion of varying outcomes and 28 normal pregnancies. We performed the proximity barcoding assay (PBA) to analyze single exosome surface proteins, which allowed us to identify individual exosomes related to the development of RA as well as the major subpopulations of exosomes. After PBA treatment, samples were analyzed for single exosomes, and exosomes from each group were compared using volcano plots, dot plots, and ROC curves.Results: By intersecting all significantly differentially expressed genes obtained from comparisons between the normal pregnancy control group and the recurrent abortion group, including the RA before abortion, RA after abortion, and RA non-pregnancy groups, we identified seven shared differential genes: FN1, APIPOQ, CDH13, DSG1, CLDN4, CD36, and ULBP3. Among these, FN1 was the most significantly differentially expressed gene in exosomes, with FN1 | log2 (fold change) |> 1.5 and an AUC of 0.7414. In addition, exosome subpopulation analyses showed that cluster 11 accounted for the largest proportion of the total 16 subpopulations, and FN1 was the marker with the highest concentration of cluster 11.Conclusion: Single-exosome profiling and exosome subpopulations of RA by PBA yielded significant differential gene FN1, which provides new possibilities for diagnostic screening of RA.Keywords: recurrent abortion, exosomes, FN1, PB

Distinct DNA methylation epigenotypes in bladder cancer from different Chinese sub-populations and its implication in cancer detection using voided urine

<p>Abstract</p> <p>Background</p> <p>Bladder cancer is the sixth most common cancer in the world and the incidence is particularly high in southwestern Taiwan. Previous studies have identified several tumor-related genes that are hypermethylated in bladder cancer; however the DNA methylation profile of bladder cancer in Taiwan is not fully understood.</p> <p>Methods</p> <p>In this study, we compared the DNA methylation profile of multiple tumor suppressor genes (<it>APC</it>, <it>DAPK</it>, <it>E-cadherin</it>, <it>hMLH1</it>, <it>IRF8</it>, <it>p14</it>, <it>p15</it>, <it>RASSF1A</it>, <it>SFRP1 </it>and <it>SOCS-1</it>) in bladder cancer patients from different Chinese sub-populations including Taiwan (104 cases), Hong Kong (82 cases) and China (24 cases) by MSP. Two normal human urothelium were also included as control. To investigate the diagnostic potential of using DNA methylation in non-invasive detection of bladder cancer, degree of methylation of <it>DAPK</it>, <it>IRF8</it>, <it>p14</it>, <it>RASSF1A </it>and <it>SFRP1 </it>was also accessed by quantitative MSP in urine samples from thirty bladder cancer patients and nineteen non-cancer controls.</p> <p>Results</p> <p>There were distinct DNA methylation epigenotypes among the different sub-populations. Further, samples from Taiwan and China demonstrated a bimodal distribution suggesting that CpG island methylator phentotype (CIMP) is presented in bladder cancer. Moreover, the number of methylated genes in samples from Taiwan and Hong Kong were significantly correlated with histological grade (P < 0.01) and pathological stage (P < 0.01). Regarding the samples from Taiwan, methylation of <it>SFRP1</it>, <it>IRF8</it>, <it>APC </it>and <it>RASSF1A </it>were significantly associated with increased tumor grade, stage. Methylation of <it>RASSF1A </it>was associated with tumor recurrence. Patients with methylation of <it>APC </it>or <it>RASSF1A </it>were also significantly associated with shorter recurrence-free survival. For methylation detection in voided urine samples of cancer patients, the sensitivity and specificity of using any of the methylated genes (<it>IRF8</it>, <it>p14 </it>or <it>sFRP1</it>) by qMSP was 86.7% and 94.7%.</p> <p>Conclusions</p> <p>Our results indicate that there are distinct methylation epigenotypes among different Chinese sub-populations. These profiles demonstrate gradual increases with cancer progression. Finally, detection of gene methylation in voided urine with these distinct DNA methylation markers is more sensitive than urine cytology.</p

Measuring the health-related Sustainable Development Goals in 188 countries: a baseline analysis from the Global Burden of Disease Study 2015

BACKGROUND: In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030 ..

Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0-65·6) in 1990, to 71·5 years (UI 71·0-71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8-48·2) to 54·9 million (UI 53·6-56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade. Funding Bill &amp; Melinda Gates Foundation

Search for excited electrons singly produced in proton–proton collisions at \sqrt{s} = 13 TeV with the ALAS experiment at the LHC

A search for excited electrons produced in pp collisions at s√ = 13 TeV via a contact interaction qq¯→ee∗ is presented. The search uses 36.1 fb −1 of data collected in 2015 and 2016 by the ATLAS experiment at the Large Hadron Collider. Decays of the excited electron into an electron and a pair of quarks ( eqq¯ ) are targeted in final states with two electrons and two hadronic jets, and decays via a gauge interaction into a neutrino and a W boson ( νW ) are probed in final states with an electron, missing transverse momentum, and a large-radius jet consistent with a hadronically decaying W boson. No significant excess is observed over the expected backgrounds. Upper limits are calculated for the pp→ee∗→eeqq¯ and pp→ee∗→eνW production cross sections as a function of the excited electron mass me∗ at 95% confidence level. The limits are translated into lower bounds on the compositeness scale parameter Λ of the model as a function of me∗ . For me∗<0.5 TeV , the lower bound for Λ is 11 TeV . In the special case of me∗=Λ , the values of me∗<4.8 TeV are excluded. The presented limits on Λ are more stringent than those obtained in previous searches

Identification of boosted Higgs bosons decaying into b-quark pairs with the ATLAS detector at 13 TeV

This paper describes a study of techniques for identifying Higgs bosons at high transverse momenta decaying into bottom-quark pairs, H→bb¯ , for proton–proton collision data collected by the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy s√=13 TeV . These decays are reconstructed from calorimeter jets found with the anti- kt R=1.0 jet algorithm. To tag Higgs bosons, a combination of requirements is used: b-tagging of R=0.2 track-jets matched to the large-R calorimeter jet, and requirements on the jet mass and other jet substructure variables. The Higgs boson tagging efficiency and corresponding multijet and hadronic top-quark background rejections are evaluated using Monte Carlo simulation. Several benchmark tagging selections are defined for different signal efficiency targets. The modelling of the relevant input distributions used to tag Higgs bosons is studied in 36 fb −1 of data collected in 2015 and 2016 using g→bb¯ and Z(→bb¯)γ event selections in data. Both processes are found to be well modelled within the statistical and systematic uncertainties

Measurement of the inclusive cross-section for the production of jets in association with a Z boson in proton-proton collisions at 8 TeV using the ATLAS detector

The inclusive cross-section for jet production in association with a Z boson decaying into an electron–positron pair is measured as a function of the transverse momentum and the absolute rapidity of jets using 19.9 fb −1 of s√=8 TeV proton–proton collision data collected with the ATLAS detector at the Large Hadron Collider. The measured Z + jets cross-section is unfolded to the particle level. The cross-section is compared with state-of-the-art Standard Model calculations, including the next-to-leading-order and next-to-next-to-leading-order perturbative QCD calculations, corrected for non-perturbative and QED radiation effects. The results of the measurements cover final-state jets with transverse momenta up to 1 TeV, and show good agreement with fixed-order calculations