Practical pathology of aging mice

Background: Treatment of invasive breast cancer has an alarmingly high rate of failure because effective targets have not been identified. One potential target is mitochondrial generated reactive oxygen species (ROS) because ROS production has been associated with changes in substrate metabolism and lower concentration of anti-oxidant enzymes in tumor and stromal cells and increased metastatic potential. Methods: Transgenic mice expressing a human catalase gene (mCAT) were crossed with MMTV-PyMT transgenic mice that develop metastatic breast cancer. All mice (33 mCAT positive and 23 mCAT negative) were terminated at 110 days of age, when tumors were well advanced. Tumors were histologically assessed for invasiveness, proliferation and metastatic foci in the lungs. ROS levels and activation status of p38 MAPK were determined. Results: PyMT mice expressing mCAT had a 12.5 per cent incidence of high histological grade primary tumor invasiveness compared to a 62.5 per cent incidence in PyMT mice without mCAT. The histological grade correlated with incidence of metastasis with 56 per cent of PyMT mice positive for mCAT showing evidence of pulmonary metastasis compared to 85.4 per cent of PyMT mice negative for mCAT with pulmonary metastasis (p ≤ 0.05). PyMT tumor cells expressing mCAT had lower ROS levels and were more resistant to hydrogen peroxide-induced oxidative stress than wild type tumor cells, suggesting that mCAT has the potential of quenching intracellular ROS and subsequent invasive behavior. The metastatic tumor burden in PyMT mice expressing mCAT was 0.1 mm²/cm² of lung tissue compared with 1.3 mm²/cm² of lung tissue in PyMT mice expressing the wild type allele (p ≤ 0.01), indicating that mCAT could play a role in mitigating metastatic tumor progression at a distant organ site. Expression of mCAT in the lungs increased resistance to hydrogen peroxide-induced oxidative stress that was associated with decreased activation of p38MAPK suggesting ROS signaling is dependent on p38MAPK for at least some of its downstream effects. Conclusion: Targeting catalase within mitochondria of tumor cells and tumor stromal cells suppresses ROS-driven tumor progression and metastasis. Therefore, increasing the antioxidant capacity of the mitochondrial compartment could be a rational therapeutic approach for invasive breast cancer. Please see related commentary article: http://www.biomedcentral.com/1741-7015/9/62

Professionals throughout the world have been working to assess the interdisciplinary interaction and interdependence between health and wellbeing in a constantly changing environment. The One Health concept was developed to encourage sustainable collaborative partnerships and to promote optimal health for people, animals, plants, the environment, and the whole planet. The dissemination of scientific discoveries and policies, by working directly with diverse communities, has been one of the main goals for Global One Health. The One Health concept has also been referred or related to as “One Medicine, One Medicine-One Health, One World-One Health, EcoHealth,” and Planetary Health,” depending on each fundamental view and approach. In Latin America, despite the concept still being discussed among health professionals and educators, several One Health initiatives have been used daily for more than decades. One Health action has been applied especially in rural and underserved urban areas where low socioeconomic status, lack of health professionals, and scarcity of medical resources may require professionals to work together. Local communities from diverse social and economic statuses, including indigenous populations have been working with institutions and social organizations for many years, accomplishing results through grassroots movements. These “bottom-up” socio-community approaches have also been tools for the prevention and control of diseases, such practice has preceded the One Health concepts in Latin American countries. It is strongly believed that collaborative, multidisciplinary, political, and economic initiatives with prosocial focus may become investments toward obtaining significant results in the face of global, economic and health challenges; working for a healthier world with inclusivity, equity, and equality. In this study, it is briefly presented how the One Health approach has been initiated and developed in Latin America, highlighting the events and actions taken in Brazil, Chile, and Colombia.

This short communication is an effort to describe and elucidate the trajectory of the modern historical concept of “One Health.” It is dedicated to the many integrated approaches of health closely related to One Health, while also recognizing the contribution and origination of One Health perspectives/notions from those that have led the way and spearheaded this movement while considering Indigenous cultures across the world. The effects of synergies of those involved in building these integrative approaches are potentially bigger and better lasting than the sum of the individual players. It is only through collaboration, cooperation and diplomacy that we can achieve impactful transformation to benefit health. In this commentary, we aim to appropriately and accurately describe how the current use of “One Health” came to be and who were the main players.

Reliable detection of unwanted microbial agents is essential for meaningful health monitoring in laboratory animal facilities. Most rodents at our institution are housed in IVC rack systems to minimize aerogenic transmission of infectious agents between cages. The most commonly used rodent health monitoring systems expose live sentinel rodents to soiled bedding collected from other rodent cages on IVC racks and subsequently test these soiled-bedding sentinels for evidence of infection with excluded agents. However, infectious agents might go undetected when using this health surveillance method, due to inefficient organism shedding or transmission failure. In 2016, our institution switched the health monitoring methodology for the majority of our SPF rodent colonies to real-time PCR testing of environmental samples collected from the exhaust plenums of IVC racks. Here we describe our rationale for this conversion, describe some interesting health monitoring cases that arose soon after the conversion, and discuss a potential problem with the conversion—residual nucleic acids. We compared cost and implementation effort associated with 2 sampling methods, sticky swabs and in-line collection media. We also compared the ability of these 2 sampling methods to detect 2 prevalent microbes in our facilities, Helicobacter and murine norovirus. Our institution-wide switch to health monitoring by real-time PCR assay of exhaust air dust samples thus far has provided a sensitive, simple, and reliable approach for maintenance of SPF conditions in laboratory rodents and has dramatically reduced the use of live sentinel animals.

Brazil presents one of the highest COVID-19 death tolls in the world. The initial SARS-CoV-2 epicenter was São Paulo city. As of 2019, the homeless population of São Paulo city was estimated at 24,344 individuals, the largest national homeless population. The present study aimed to concomitantly assess the molecular and serological prevalence and associated risk factors of SARS-CoV-2 infection in a homeless population and related shelter workers from a day-shelter. Serum samples, nasopharyngeal and oropharyngeal swabs of persons who are homeless and shelter workers collected from August 25^th to 27^th, 2020 were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies by ELISA and SARS-CoV-2 RNA by RT-qPCR, respectively. All swab samples tested negative by RT-qPCR. Seropositivity of IgM and IgG was 5/203 (2.5%) and 111/203 (54.7%) in persons who are homeless, and 5/87 (5.7%) and 41/87 (47.1%) in shelter workers, respectively, with no statistical differences between groups. The high seroprevalence found herein indicates early environmental and urban spreading of SARS-CoV-2, associated with sociodemographic and economic vulnerability.