Estrogen Receptor-α Mediates Diethylstilbestrol-Induced Feminization of the Seminal Vesicle in Male Mice

Background: Studies have shown that perinatal exposure to the synthetic estrogen diethylstilbestrol (DES) leads to feminization of the seminal vesicle (SV) in male mice, as illustrated by tissue hyperplasia, ectopic expression of the major estrogen-inducible uterine secretory protein lactoferrin (LF), and reduced expression of SV secretory protein IV (SVS IV)

Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO)

Male mice with a knockout of the estrogen receptor (ER)-α gene, a ligand-activated transcription factor, showed reduced levels of intromissions and no ejaculations whereas simple mounting behavior was not affected. In contrast, all components of sexual behaviors were intact in male mice lacking the novel ER-β gene. Here we measure the extent of phenotype in mice that lack both ER-α and ER-β genes (αβERKO). αβERKO male mice did not show any components of sexual behaviors, including simple mounting behavior. Nor did they show ultrasonic vocalizations during behavioral tests with receptive female mice. On the other hand, reduced aggressive behaviors of αβERKO mice mimicked those of single knockout mice of ER-α gene (αERKO). They showed reduced levels of lunge and bite aggression, but rarely showed offensive attacks. Thus, either one of the ERs is sufficient for the expression of simple mounting in male mice, indicating a redundancy in function. Offensive attacks, on the other hand, depend specifically on the ER-α gene. Different patterns of natural behaviors require different patterns of functions by ER genes

Developing a database of systematic reviews of animal studies

Systematic reviews (SRs) are common practice in clinical and public health research, but less common in non-human animal research. Systematic reviews of animal studies can be valuable to inform clinical research, to evaluate the need for further animal experiments on a given topic, and to assess the hazard of an environmental exposure in the evaluation of toxicological studies. In the last 10 years, there has been an increase in the number of SRs of animal research, as well as several publications with detailed guidance on how to perform high-quality systematic reviews of experimental animal studies. In order to evaluate current analytical approaches used in SRs of animal studies, easily identify all systematic reviews on a specific topic, and subsequently the original animal studies and their results and promote awareness and understanding of these emerging approaches, we compiled a database of SRs of animal studies. The database was developed using a rigorous, systematic approach and covers a broad range of research fields: preclinical research, toxicology, environmental health, and veterinary medicine. The database currently includes 3113 SRs of animal studies (search date June 2019). In addition to bibliographical information, data on whether or not a risk of bias assessment and meta-analysis were conducted were extracted. For future users, the search features of the database provide users with a platform to identify and select SRs with a particular characteristic for export to Microsoft Word or Microsoft Excel. From there, users may perform additional data extraction to meet their research needs. The database is freely available at www.Mendeley.com (link). The database provides methodologists a comprehensive source that can be used to explore and advance the current methodology applied to SRs of animal studies, and can help researchers to easily identify all systematic reviews on a specific topic, and subsequently the original animal studies and their results and avoid duplication and unnecessary animal research

Becoming aWARE: The Development of a Web-Based Tool for Autism Research and the Environment

A sharp rise in autism spectrum disorder (ASD) prevalence estimates, beginning in the 1990s, suggested factors additional to genetics were at play. This stimulated increased research investment in nongenetic factors, including the study of environmental chemical exposures, diet, nutrition, lifestyle, social factors, and maternal medical conditions. Consequently, both peer- and non-peer-reviewed bodies of evidence investigating environmental contributors to ASD etiology have grown significantly. The heterogeneity in the design and conduct of this research results in an inconclusive and unwieldy ‘virtual stack’ of publications. We propose to develop a Web-based tool for Autism Research and the Environment (aWARE) to comprehensively aggregate and assess these highly variable and often conflicting data. The interactive aWARE tool will use an approach for the development of systematic evidence maps (SEMs) to identify and display all available relevant published evidence, enabling users to explore multiple research questions within the scope of the SEM. Throughout tool development, listening sessions and workshops will be used to seek perspectives from the broader autism community. New evidence will be indexed in the tool annually, which will serve as a living resource to investigate the association between environmental factors and ASD

Identifying environmental factors that influence immune response to SARS-CoV-2: Systematic evidence map protocol.

BackgroundWidespread environmental contamination can directly interact with human immune system functions. Environmental effects on the immune system may influence human susceptibility to respiratory infections as well as the severity of infectious diseases, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, the efficacy of vaccines to respiratory diseases may be impacted by environmental exposures through immune perturbations. Given the quick pace of research about COVID-19 and associated risk factors, it is critical to identify and curate the streams of evidence quickly and effectively.ObjectiveWe developed this systematic evidence map protocol to identify and organize existing human and animal literature on high-priority environmental chemical classes (Per- and polyfluoroalkyl substances, pesticides, phthalates, quaternary ammonium compounds, and air pollutants) and their potential to influence three key outcomes: (1) susceptibility to respiratory infection, including SARS-CoV-2 (2) severity of the resultant disease progression, and (3) impact on vaccine efficacy. The result of this project will be an online, interactive database which will show what evidence is currently available between involuntary exposures to select environmental chemicals and immune health effects, data gaps that require further research, and data rich areas that may support further analysis.Search and study eligibilityWe will search PubMed for epidemiological or toxicological literature on select toxicants from each of the chemical classes and each of the three outcomes listed above.Study appraisal and synthesis of methodsFor each study, two independent reviewers will conduct title and abstract screening as well as full text review for data extraction of study characteristics. Study quality will not be evaluated in this evidence mapping. The main findings from the systematic evidence map will be visualized using a publicly available and interactive database hosted on Tableau Public

Using Machine-Learning to Facilitate Data Extraction for Human Health Chemical Assessments: Protocol for a case application

<p>Artificial intelligence (AI) methods including natural language processing, active learning, and large language models are expected to provide workflow advances to reduce risk assessors' time and effort while maintaining the accuracy necessary to meet demand for chemical assessments. A growing suite of modular software applications that integrate AI methods and leverage human-in-the-loop workflows are making operationalization of these advancements feasible. The case application in this protocol supports development of a Provisional Peer-Reviewed Toxicity Value (PPRTV) assessment for 1,3-dinitrobenzene (1,3-DNB). The protocol describes methods to develop a literature inventory and systematic evidence map (SEM) for 1,3-DNB. Along with typical systematic review methods, the protocol applies an active learning approach to screen records at the title and abstract level using AI methods. While active learning has been a routine method used to reduce the resources required to screen records at the title and abstract level, automated processes for data extraction with user verification have evolved slowly. The slow evolution of AI for data extraction continues to be a challenge primarily because the resources required to develop appropriate training datasets for model development are limited, leading to immature models with poor performance, or the lack of models for many domain-specific data extraction fields. This protocol showcases how software applications like Dextr can be used to address both challenges with the potential to make progress toward a modern workflow stack including data extraction.</p&gt

Femoral bone density changes after total hip arthroplasty with uncemented taper-design stem: a five year follow-up study

We measured bone density (BD) changes to assess adaptive bone remodelling five years after uncemented total hip arthroplasty with taper-design femoral component using quantitative computed-tomography-assisted osteodensitometry (qCT). Nineteen consecutive patients (21 hips) with degenerative joint disease were enrolled in the study. A press-fit cup and a tapered uncemented stem ceramic−ceramic pairing were used in all patients. Serial clinical, radiological and qCT osteodensitometry assessments were performed after the index operation and at the one, two and five year follow-ups. At the latest follow-up, the clinical outcome was rated satisfactory in all hips. The radiological assessment showed signs of osteointegration with stable fixation of all cups and stems. Overall, there was evidence of a BD loss at year five (p = 0.004). We estimate that BD loss was between 2.2% and 12.1% in comparison with baseline postoperative values. Progressive loss of BD in the metaphyseal region was observed in all hips. We found unremarkable BD changes of diaphyseal cortical BD throughout the five year follow-up period. qCT osteodensitometry technology allows differentiation of cortical and cancellous BD changes over time. Periprosthetic BD changes at the five year follow-up are suggestive of stable stem osteointegration with proximal femoral diaphysis load transfer and metaphyseal stress shielding