Analysis of genetic copy number changes in cervical disease progression

<p>Abstract</p> <p>Background</p> <p>Cervical dysplasia and tumorigenesis have been linked with numerous chromosomal aberrations. The goal of this study was to evaluate 35 genomic regions associated with cervical disease and to select those which were found to have the highest frequency of aberration for use as probes in fluorescent in-situ hybridization.</p> <p>Methods</p> <p>The frequency of gains and losses using fluorescence in-situ hybridization were assessed in these 35 regions on 30 paraffin-embedded cervical biopsy specimens. Based on this assessment, 6 candidate fluorescently labeled probes (8q24, Xp22, 20q13, 3p14, 3q26, CEP15) were selected for additional testing on a set of 106 cervical biopsy specimens diagnosed as Normal, CIN1, CIN2, CIN3, and SCC. The data were analyzed on the basis of signal mean, % change of signal mean between histological categories, and % positivity.</p> <p>Results</p> <p>The study revealed that the chromosomal regions with the highest frequency of copy number gains and highest combined sensitivity and specificity in high-grade cervical disease were 8q24 and 3q26. The cytological application of these two probes was then evaluated on 118 ThinPrep™ samples diagnosed as Normal, ASCUS, LSIL, HSIL and Cancer to determine utility as a tool for less invasive screening. Using gains of either 8q24 or 3q26 as a positivity criterion yielded specificity (Normal +LSIL+ASCUS) of 81.0% and sensitivity (HSIL+Cancer) of 92.3% based on a threshold of 4 positive cells.</p> <p>Conclusions</p> <p>The application of a FISH assay comprised of chromosomal probes 8q24 and 3q26 to cervical cytology specimens confirms the positive correlation between increasing dysplasia and copy gains and shows promise as a marker in cervical disease progression.</p

Is Wounding Aggression in Zoo-housed Chimpanzees and Ring-tailed Lemurs related to Zoo Visitor Numbers?

Chimpanzees in laboratory colonies experience more wounds on week days than on weekends, which has been attributed to the increased number of people present during the week; thus the presence of more people was interpreted as stressful. If this were also true for primates in zoos, where high human presence is a regular feature, this would clearly be of concern. Here we examine wounding rates in two primate species (chimpanzees Pan troglodytes and ring-tailed lemurs Lemur catta) at three different zoos, to determine whether they correlate with mean number of visitors to the zoo. Wounding data were obtained from zoo electronic record keeping system (ZIMS™). The pattern of wounds did not correlate with mean gate numbers for those days for either species in any group. We conclude that there is no evidence that high visitor numbers result in increased woundings in these two species when housed in zoos

Evaluating the effects of giraffe skin disease and wire snare wounds on the gaits of free-ranging Nubian giraffe

Abstract Giraffe skin disease (GSD), a condition that results in superficial lesions in certain giraffe (Giraffa spp.) populations, has emerged as a potential conservation threat. Preliminary findings suggested that individuals with GSD lesions move with greater difficulty which may in turn reduce their foraging efficiency or make them more vulnerable to predation. A current known threat to some giraffe populations is their mortality associated with entrapment in wire snares, and the morbidity and potential locomotor deficiencies associated with wounds acquired from snares. The goal of our study was to quantify the locomotor kinematics of free-ranging Nubian giraffe (G. camelopardalis camelopardalis) in Murchison Falls National Park (MFNP), Uganda, and compare spatiotemporal limb and neck angle kinematics of healthy giraffe to those of giraffe with GSD lesions, snare wounds, and both GSD lesions and snare wounds. The presence of GSD lesions did not significantly affect spatiotemporal limb kinematic parameters. This finding is potentially because lesions were located primarily on the necks of Nubian giraffe in MFNP. The kinematic parameters of individuals with snare wounds differed from those of healthy individuals, resulting in significantly shorter stride lengths, reduced speed, lower limb phase values, and increased gait asymmetry. Neck angle kinematic parameters did not differ among giraffe categories, which suggests that GSD neck lesions do not impair normal neck movements and range of motion during walking. Overall, MFNP giraffe locomotor patterns are largely conservative between healthy individuals and those with GSD, while individuals with snare wounds showed more discernible kinematic adjustments consistent with unilateral limb injuries. Additional studies are recommended to assess spatiotemporal limb kinematics of giraffe at sites where lesions are found predominantly on the limbs to better assess the potential significance of GSD on their locomotion

The Milan System for Reporting Salivary Gland Cytopathology: Analysis and suggestions of initial survey

BACKGROUND: An international panel of experts in the field of salivary gland cytology (SGC), supported by the American Society of Cytopathology (ASC) and the International Academy of Cytology, conducted a survey to seek evidence and practice patterns regarding SGC. Results were used to provide focus for the proposed Milan System for Reporting Salivary Gland Cytopathology. METHODS: The study group, formed during the 2015 European Congress of Cytology held in Milan, Italy, generated a survey that included 49 specific questions related to the taxonomies, practices, and diagnostic entities of salivary cytology. Qualtrics software was used as the study platform. Software and server support were provided by the division of information technology at the University of Wisconsin. The survey was available online from November 2015 until February 2016. Participants were invited through the Web sites of the ASC, the International Academy of Cytology, and the Papanicolaou Society of Cytopathology as well as by the ASC e-mail \u201cListServe\u201d; responses were evaluated by the Milan System editors. RESULTS: Responses from a total of 515 participants were collected and reviewed. A total of 347 participants provided demographic data information. Responses revealed variations in diagnostic practice and subsequent management. Participants believed that the acceptable rate for nondiagnostic samples should not be higher than 10%. There were varied opinions regarding the approach to neoplastic lesions of uncertain malignant potential, those that may or may have not local invasion and distant spread. CONCLUSIONS: Results of the survey demonstrated strong support for the development of a unified system for reporting SGC. Cancer Cytopathol 2017;125:757-66. \ua9 2017 American Cancer Society

Chromosomal damage as prognosis marker in cervical carcinogenesis

Cancer of the uterine cervix is the third most common cancer in women worldwide and the most common cancer among Mexican and Latin American women. Risk factors that have been associated with the development of cervical intraepithelial neoplasia suggest that Human Papillomavirus (HPV) types 16, 18, 31, and 33 entail a high risk of developing a malignancy of this type. The accumulation of genetic alterations allows the growth of neoplastic cells; chromosomal instability is an event that occurs in the precancerous stages. The candidate cancer risk biomarkers include cytogenetic endpoints, such as chromosomal aberrations, sister chromatid exchange, micronuclei, and the outcomes of comet assay and DNA breakage detection-fluorescence in situ hybridization. The patterns identified in these cytogenetic studies indicate that chromosomal instability is a transient and chromosomally unstable intermediate in the development of cervical lesions. In this context, the mechanisms that may underlie the progressive increase in genetic instability in these patients seem to be related directly to HPV infection. The studies discussed in this paper show that chromosomal instability may serve as a biomarker by predicting the progression of cervical intraepithelial neoplasia. Nevertheless, these results should be validated in larger, prospective studies.Рак шейки матки является третьим по распространенности в мире типов рака у женщин и наиболее часто встречающимся у женщин Мексики и Латинской Америки. Факторы риска, связанные с развитием интраэпителиальной цервикальной неоплазии, предполагают, что папилломавирус человека (HPV) типов 16, 18, 31 и 33 влечет за собой высокий риск развития опухолей этого типа. Накопление генетических изменений делает возможным рост опухолевых клеток, хромосомная нестабильность является событием, которое предшествует предраковым стадиям. Возможные биомаркеры риска опухоли включают цитогенетические критерии, такие как хромосомные аберрации, обмен сестринских хроматид, микроядра, и заканчиваются Comet-анализом и детекцией поломок ДНК с помощью флюоресцентной гибридизации in situ. Образцы, идентифицированные в таких цитогенетических исследованиях, показывают, что хромосомная нестабильность является транзиентным промежуточным звеном в развитии цервикальных нарушений. В этой связи механизмы, которые могут лежать в основе прогрессирующей генетической нестабильности у таких пациентов, кажутся непосредственно связанными с инфекцией HPV. Настоящее исследование показывает, что хромосомная нестабильность может служить биомаркером для предсказания развития интраэпителиальной цервикальной неоплазии, тем не менее эти результаты должны быть оценены в более масштабных исследованиях