General Medical Emergencies in Athletes.

This article focuses on the management of the most common on-field medical emergencies. As with any discipline in medicine, a well-defined plan and systematic approach is the cornerstone of quality health care delivery. In addition, the team-based collaboration is necessary for the safety of the athlete and the success of the treatment plan.

Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material.

Nighttime NO loss and ClNO formation in the residual layer of a polluted region: Insights from field measurements and an iterative box model.

The heterogeneous reaction of dinitrogen pentoxide (NO) on aerosols is an important sink of nitrogen oxides (NO) in the polluted boundary layer, and the production of nitryl chloride (ClNO) can have significant effects on the atmospheric oxidative capacity. However, the heterogeneous loss of NO and the formation of ClNO are still not well quantified, especially in China. In a previous study, we measured ClNO and NO concentrations in several air masses at a high-elevation site in Hong Kong, and found the highest levels ever reported at one night.

Using Patient Feedback to Optimize the Design of a Certolizumab Pegol Electromechanical Self-Injection Device: Insights from Human Factors Studies.

Introduction: We incorporated patient feedback from human factors studies (HFS) in the patient-centric design and validation of ava, an electromechanical device (e-Device) for self-injecting the anti-tumor necrosis factor certolizumab pegol (CZP).

Methods: Healthcare professionals, caregivers, healthy volunteers, and patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or Crohn's disease participated in 11 formative HFS to optimize the e-Device design through intended user feedback; nine studies involved simulated injections. Formative participant questionnaire feedback was collected following e-Device prototype handling.

Telomere attrition in beta and alpha cells with age.

We have reported telomere attrition in β and α cells of the pancreas in elderly patients with type 2 diabetes, but it has not been explored how the telomere lengths of these islet cells change according to age in normal subjects. To examine the telomere lengths of β and α cells in individuals without diabetes across a wide range of ages, we conducted measurement of the telomere lengths of human pancreatic β and α cells obtained from 104 autopsied subjects without diabetes ranging in age from 0 to 100 years. As an index of telomere lengths, the normalized telomere-centromere ratio (NTCR) was determined for β (NTCRβ) and α (NTCRα) cells by quantitative fluorescence in situ hybridization (Q-FISH).

Combined Use of Gene Expression Modeling and siRNA Screening Identifies Genes and Pathways Which Enhance the Activity of Cisplatin When Added at No Effect Levels to Non-Small Cell Lung Cancer Cells In Vitro.

Platinum-based combination chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). While cisplatin is effective, its use is not curative and resistance often emerges. As a consequence of microenvironmental heterogeneity, many tumour cells are exposed to sub-lethal doses of cisplatin.

Death by homicide in National Collegiate Athletic Association athletes between 2003 and 2013.

Background: The incidence of homicide-related death among individuals of college age in the United States population is estimated at 15.5/100,000. The incidence of homicide among National Collegiate Athletic Association (NCAA) athletes is unknown.

A co-culture genome-wide RNAi screen with mammary epithelial cells reveals transmembrane signals required for growth and differentiation.

Introduction: The extracellular signals regulating mammary epithelial cell growth are of relevance to understanding the pathophysiology of mammary epithelia, yet they remain poorly characterized. In this study, we applied an unbiased approach to understanding the functional role of signalling molecules in several models of normal physiological growth and translated these results to the biological understanding of breast cancer subtypes.

Methods: We developed and utilized a cytogenetically normal clonal line of hTERT immortalized human mammary epithelial cells in a fibroblast-enhanced co-culture assay to conduct a genome-wide small interfering RNA (siRNA) screen for evaluation of the functional effect of silencing each gene.

Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

Along with the increasing need for living-donor liver transplantation (LDLT), the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved.

Quantitative fluorescence in situ hybridization measurement of telomere length in skin with/without sun exposure or actinic keratosis.

Chromosomal and genomic instability due to telomere dysfunction is known to play an important role in carcinogenesis. To study telomere shortening in the epidermis surrounding actinic keratosis, we measured telomere lengths of basal, parabasal, and suprabasal cells in epidermis with actinic keratosis (actinic keratosis group, n = 18) and without actinic keratosis (sun-protected, n = 15, and sun-exposed, n = 13 groups) and in actinic keratosis itself as well as in dermal fibroblasts in the 3 groups, using quantitative fluorescence in situ hybridization. Among the 3 cell types, telomeres of basal cells were not always the longest, suggesting that tissue stem cells are not necessarily located among basal cells.

Atmospheric peroxides in a polluted subtropical environment: seasonal variation, sources and sinks, and importance of heterogeneous processes.

Hydrogen peroxide (H2O2) and organic peroxides play an important role in atmospheric chemistry, but knowledge of their abundances, sources, and sinks from heterogeneous processes remains incomplete. Here we report the measurement results obtained in four seasons during 2011-2012 at a suburban site and a background site in Hong Kong. Organic peroxides were found to be more abundant than H2O2, which is in contrast to most previous observations.

Telomere lengths at birth in trisomies 18 and 21 measured by Q-FISH.

Trisomies 18 and 21 are genetic disorders in which cells possess an extra copy of each of the relevant chromosomes. Individuals with these disorders who survive birth generally have a shortened life expectancy. As telomeres are known to play an important role in the maintenance of genomic integrity by protecting the chromosomal ends, we conducted a study to determine whether there are differences in telomere length at birth between individuals with trisomy and diploidy, and between trisomic chromosomes and normal chromosomes.

Investigation of telomere length dynamics in induced pluripotent stem cells using quantitative fluorescence in situ hybridization.

Here we attempted to clarify telomere metabolism in parental cells and their derived clonal human induced pluripotent stem cells (iPSCs) at different passages using quantitative fluorescence in situ hybridization (Q-FISH). Our methodology involved estimation of the individual telomere lengths of chromosomal arms in individual cells within each clone in relation to telomere fluorescence units (TFUs) determined by Q-FISH. TFUs were very variable within the same metaphase spread and within the same cell.

Telomere shortening in the esophagus of Japanese alcoholics: relationships with chromoendoscopic findings, ALDH2 and ADH1B genotypes and smoking history.

Chromoendoscopy with Lugol iodine staining provides important information on the development of squamous cell carcinoma (SCC). In particular, distinct iodine-unstained lesions (DIULs) larger than 10 mm show a high prevalence in high-grade intraepithelial neoplasia. It has also been reported that inactive ALDH2*1/*2 and less-active ADH1B*1/*1, and smoking, are risk factors for esophageal SCC.

Short telomeres and chromosome instability prior to histologic malignant progression and cytogenetic aneuploidy in papillary urothelial neoplasms.

Purpose: Evaluation of the relationships existing among 3 histologic types of urothelial tumors, chromosomal instability, and telomere length.

Patients And Methods: We examined 37 consecutive cases of papillary urothelial neoplasm, from which 26 (70.3%) were suitable for karyotype analysis, comprising 7 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 10 low-grade papillary urothelial carcinomas (PUCs), and 9 high-grade PUCs.

Amplification of the human epidermal growth factor receptor 2 gene in differentiated thyroid cancer correlates with telomere shortening.

The human epidermal growth factor receptor 2 (HER2) proto-oncogene plays an important role in the development and progression of breast and gastric cancer. Monitoring of the HER2 status and treatment with trastuzumab was performed initially in breast cancer, and subsequently in gastric cancer. However, the HER2 status of thyroid cancer remains unexplored.

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution.

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it possible to map SCEs at orders-of-magnitude greater resolution than was previously possible. On average, murine embryonic stem (mES) cells exhibit eight SCEs, which are detected at a resolution of up to 23 bp.

Collapse of telomere homeostasis in hematopoietic cells caused by heterozygous mutations in telomerase genes.

Telomerase activity is readily detectable in extracts from human hematopoietic stem and progenitor cells, but appears unable to maintain telomere length with proliferation in vitro and with age in vivo. We performed a detailed study of the telomere length by flow FISH analysis in leukocytes from 835 healthy individuals and 60 individuals with reduced telomerase activity. Healthy individuals showed a broad range in average telomere length in granulocytes and lymphocytes at any given age.

Hepatocellular telomere length in biliary atresia measured by Q-FISH.

Background: Liver transplantation for biliary atresia is indicated whenever a Kasai portoenterostomy is considered unfeasible. However, the timing of liver transplantation in biliary atresia has not been precisely defined. Excessive shortening of hepatocellular telomeres may occur in patients with biliary atresia, and therefore, telomere length could be a predictor of hepatocellular reserve capacity.

Short telomeres in an oral precancerous lesion: Q-FISH analysis of leukoplakia.

Objectives: A precancerous condition is a lesion that, if left untreated, leads to cancer or can be induced to become malignant. In the oral region, leukoplakia is a lesion that has been regarded as precancerous. In cases of oral carcinoma, we have frequently noticed that a type of leukoplakia histologically demonstrating hyper-orthokeratosis and mild atypia (ortho-keratotic dysplasia; OKD) is often associated with carcinoma, either synchronously or metachronously.

Retinoblastoma-binding proteins 4 and 9 are important for human pluripotent stem cell maintenance.

Objective: The molecular mechanisms that maintain human pluripotent stem (PS) cells are not completely understood. Here we sought to identify new candidate PS cell regulators to facilitate future improvements in their generation, expansion, and differentiation.

Materials And Methods: We used bioinformatic analyses of multiple serial-analysis-of-gene-expression libraries (generated from human PS cells and their differentiated derivatives), together with small interfering RNA (siRNA) screening to identify candidate pluripotency regulators.

The testosterone-dependent and independent transcriptional networks in the hypothalamus of Gpr54 and Kiss1 knockout male mice are not fully equivalent.

Background: Humans and mice with loss of function mutations in GPR54 (KISS1R) or kisspeptin do not progress through puberty, caused by a failure to release GnRH. The transcriptional networks regulated by these proteins in the hypothalamus have yet to be explored by genome-wide methods.

Results: We show here, using 1 million exon mouse arrays (Exon 1.

Alcoholics show reduced telomere length in the oesophagus.

Telomeres are repetitive G-rich DNA sequences located at the ends of chromosomes. Chromosomal and genomic instability due to telomere dysfunction plays an important role in carcinogenesis. To study telomere shortening in the oesophageal epithelium of alcoholics, we measured the telomere lengths of basal and parabasal cells in comparison with those of non-alcoholics using Q-FISH and our original software, Tissue Telo, and also assessed histological inflammation.

Chromosomal instability and telomere lengths of each chromosomal arm measured by Q-FISH in human fibroblast strains prior to replicative senescence.

We monitored the telomere lengths and chromosomal instability characteristics of fibroblasts at different population doubling levels (PDLs) to gain further insight into the role of telomere shortening in chromosomal instability. We used 7 normal diploid human fibroblast strains (TIG-1, 3, 7, 103, 104, 112, and 114) and a quantitative fluorescence in situ hybridization method to measure telomere lengths of the p- and q-arms of individual chromosomes. We also enumerated morphologic signs of chromosomal instability, including fusion or loss of chromosomes, and anaphase bridges.

Q-FISH analysis of telomere and chromosome instability in the oesophagus with and without squamous cell carcinoma in situ.

Chromosomal and genomic instability due to telomere dysfunction is known to play an important role in carcinogenesis. To study telomere dysfunction in the surrounding background epithelium of squamous cell carcinoma in situ (CIS) of the oesophagus, we measured telomere lengths of basal and parabasal cells of epithelia with and without CIS using quantitative fluorescence in situ hybridization (Q-FISH) and our original software, Tissue Telo. Additionally, we assessed histological inflammation and the anaphase bridge index.