Mapping the contribution of single muscles to facial movements in the rhesus macaque

The rhesus macaque (Macaca mulatta) is the most utilized primate model in the biomedical and psychological sciences. Expressive behavior is of interest to scientists studying these animals, both as a direct variable (modeling neuropsychiatric disease, where expressivity is a primary deficit), as an indirect measure of health and welfare, and also in order to understand the evolution of communication. Here, intramuscular electrical stimulation of facial muscles was conducted in the rhesus macaque in order to document the relative contribution of each muscle to the range of facial movements and to compare the expressive function of homologous muscles in humans, chimpanzees and macaques. Despite published accounts that monkeys possess less differentiated and less complex facial musculature, the majority of muscles previously identified in humans and chimpanzees were stimulated successfully in the rhesus macaque and caused similar appearance changes. These observations suggest that the facial muscular apparatus of the monkey has extensive homology to the human face. The muscles of the human face, therefore, do not represent a significant evolutionary departure from those of a monkey species. Thus, facial expressions can be compared between humans and rhesus macaques at the level of the facial musculature, facilitating the systematic investigation of comparative facial communication

Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials

Objective: Interobserver agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. Study Design: Two adjacent serial histologic sections of oral lesions from 846 patients were independently scored by 2 different pathologists from a pool of 4. In instances where the original 2 pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. Results: Individual pathologist pair κ values ranged from 0.251 to 0.706 (fair-good) before the 3-stage review process. During the initial review phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. Conclusions: The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis

‘Cytology-on-a-chip’ based sensors for monitoring of potentially malignant oral lesions

Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. Objective To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. Materials and methods Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new ‘cytology-on-a-chip’ approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. Results Binary “low-risk”/“high-risk” models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity + specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. Conclusions This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum

Concentrações de hormônio na carcaça de tilápias-do-nilo e maturação precoce após reversão sexual Hormone concentration in carcass of Nile tilapia submitted to early maturation after sexual reversion

Um total de 1.500 larvas de tilápia-do-nilo foi distribuído em 15 aquários de 20 L (100 larvas cada um) para comparação de dois métodos de masculinização: via oral, com dieta com hormônio (60 mg do 17 &#945;-metiltestosterona.kg-1); e via banho de imersão (6 mg do 17 &#945;-metiltestosterona.L-1), cada um com cinco repetições. As larvas e os juvenis foram amostrados no dia 1 (início do experimento) e aos 30 (final do período de alimentação com hormônio), 40, 45, 60 e 90 dias. Uma amostra de 0,5 g de peixe foi coletada em cada repetição para análise da testosterona corporal. Os peixes alimentados com a dieta com hormônio receberam ração experimental por 30 dias e ração comercial até o final do experimento, e banho de imersão receberam ração comercial e foram submetidos a banhos de imersão (6 mg da 17 &#945;-metiltestosterona.L-1), de 36 horas, nos dias 6 e 10 após início do experimento. Nos peixes que receberam a ração sem hormônio (controle), os valores de testosterona corporal se mantiveram praticamente estáveis ao longo do experimento, aumentando moderadamente a partir de 60 dias. As concentrações de testosterona corporal nos peixes que receberam a dieta com hormônio ou o banho de imersão foram mais altas aos 30 dias. Nos peixes submetidos ao banho de imersão, os valores reduziram aos 40 dias e aumentaram novamente até os 60 dias de observação, enquanto naqueles submetidos à dieta com hormônio, as concentrações de testosterona aumentaram gradativamente até 60 dias. A utilização de 17 &#945;-metiltestosterona por via oral ou banho de imersão das larvas estimula a maturação sexual dos peixes a partir dos 45 dias, especialmente naqueles alimentados com ração contendo hormônio. As concentrações desse hormônio na carcaça são inferiores ao preconizado pelo Codex Alimentarius do Brasil como seguras para consumo humano.<br>A total of 1,500 larvae of Nile tilapia was distributed in 15 20-L aquaria (100 larvae in each one) to compare two methods of masculinization: via oral application, using a diet with hormone (60 mg 17&#945;-methyltestosterone.kg-1); and through immersion bath (6 mg 17&#945;-metyltestosterone.L-1), each one with five replicates. Larvae and juvenile were sampled on day 1 (beginning of the experiment) and on days 30 (end of hormone feeding period), 40, 45, 60 and 90. One sample with 0.5 g of fish was collected from each replication for analysis of body testosterone. Fish fed diet with hormone were given experimental ration for 30 days and commercial ration until the end of the experiment, and fish in immersion bath received commercial ration and they were submitted to immersion bath (6 mg 17 &#945;-metyltestosterone.L-1) for 36 hours on days 6 and 10 after the beginning of the experiment. For fish given ration without hormone (control), values of body testosterone were almost totally steady over the experiment, moderately increasing from day 60. Concentrations of body testosterone in fish fed diet with hormone or immersion bath were the highest on day 30. For fish submitted to immersion bath, the values were reduced on day 40 and they increased again until 60 days of observation, while for those submitted to diet with hormone, concentrations of testosterone gradually increased until 60 days. The use of 17 &#945;-methyltestosterone through oral administration or immersion bath of larvae promotes sexual maturation of fish from day 45, especially on those fed diet with hormone. Concentrations of hormone in the carcass are lower than the recommended by Codex Alimentarius from Brazil as safe for human consumption