A comparison of methods to assess cell mechanical properties.

The mechanical properties of cells influence their cellular and subcellular functions, including cell adhesion, migration, polarization, and differentiation, as well as organelle organization and trafficking inside the cytoplasm. Yet reported values of cell stiffness and viscosity vary substantially, which suggests differences in how the results of different methods are obtained or analyzed by different groups. To address this issue and illustrate the complementarity of certain approaches, here we present, analyze, and critically compare measurements obtained by means of some of the most widely used methods for cell mechanics: atomic force microscopy, magnetic twisting cytometry, particle-tracking microrheology, parallel-plate rheometry, cell monolayer rheology, and optical stretching. These measurements highlight how elastic and viscous moduli of MCF-7 breast cancer cells can vary 1,000-fold and 100-fold, respectively. We discuss the sources of these variations, including the level of applied mechanical stress, the rate of deformation, the geometry of the probe, the location probed in the cell, and the extracellular microenvironment.

Antarctic Penguins as Reservoirs of Diversity for Avian Avulaviruses.

Wild birds harbor a huge diversity of avian avulaviruses (formerly avian paramyxoviruses). Antarctic penguin species have been screened for avian avulaviruses since the 1980s and, as such, are known hosts of these viruses. In this study, we screened three penguin species from the South Shetland Islands and the Antarctic Peninsula for avian avulaviruses. We show that Adelie penguins (Pygoscelis adeliae) are hosts for four different avian avulavirus species, the recently described avian avulaviruses 17 to 19 and avian avulavirus 10-like, never before isolated in Antarctica. A total of 24 viruses were isolated and sequenced; avian avulavirus 17 was the most common, and phylogenetic analysis demonstrated patterns of occurrence, with different genetic clusters corresponding to penguin age and location. Following infection in specific-pathogen-free (SPF) chickens, all four avian avulavirus species were shed from the oral cavity for up to 7 days postinfection. There was limited shedding from the cloaca in a proportion of infected chickens, and all but one bird seroconverted by day 21. No clinical signs were observed. Taken together, we propose that penguin species, including Antarctic penguins, may be the central reservoir for a diversity of avian avulavirus species and that these viruses have the potential to infect other avian hosts.IMPORTANCE Approximately 99% of all viruses are still to be described, and in our changing world, any one of these unknown viruses could potentially expand their host range and cause epidemic disease in wildlife, agricultural animals, or humans. Avian avulavirus 1 causes outbreaks in wild birds and poultry and is thus well described. However, for many avulavirus species, only a single specimen has been described, and their viral ecology and epidemiology are unknown. Through the detection of avian avulaviruses in penguins from Antarctica, we have been able to expand upon our understanding of three avian avulavirus species (avian avulaviruses 17 to 19) and report a potentially novel avulavirus species. Importantly, we show that penguins appear to play a key role in the epidemiology of avian avulaviruses, and we encourage additional sampling of this avian group.

The Intersection of the "Opioid Crisis" with Changes in US Immigration Policy: Contextual Barriers to Substance Abuse Research with Latinx Communities.

One of the 12 Grand Challenges facing contemporary social work is to close the health gap experienced by those in historically marginalized communities (Uehara et al., 2013). As social workers, we seek to understand the individual, interpersonal, social, and environmental factors along with the structural inequities leading to initiation and continuation of substance misuse. We are constantly contextualizing the circumstances under which substance misuse occurs, as well as contextualizing our approaches to addressing this issue from both a public health and social justice perspective. In order to adequately meet this challenge, considerably more research-based knowledge on the substance use treatment needs and preferences of America's largest ethnic/cultural group, Latinx, is needed. This brief report outlines current challenges associated with substance use research focusing on active Latinx heroin users living in a border state in a time of rapidly evolving social policy related to immigration, substance regulation, and public health.

Survivorship issues in older breast cancer survivors.

PURPOSE: Almost half of breast cancer survivors are aged ≥ 65 years and the proportion is likely to increase due to the aging of the population. The objectives of this article were to review studies of health outcomes among older breast cancer survivors ≥ 65 years to identify gaps in the published literature and offer suggestions for future research. METHODS: The present review is based upon bibliographic searches in PubMed and CINAHL and relevant search terms. Articles published in English from January 1, 1970 through October 1, 2018 were identified using the following MeSH search terms and Boolean algebra commands. RESULTS: This review has revealed that older breast cancer survivors cope with health issues related to cancer treatment and the aging process, including comorbidities, osteoporosis, symptoms, physical functioning, cognitive functioning, nutrition, and physical activity. CONCLUSIONS: Additional research is needed to examine therapeutic interventions to address the health conditions older breast cancer survivors are coping with. Particular focus of further research should be on the nutritional status and physical activity levels of older breast cancer survivors. Individualized nutrition plans and tailored physical activity programs for older survivors are needed that meet people where they are and that form habits.

Prevalence of pathogenic and likely pathogenic variants in the RASopathy genes in patients who have had panel testing for cardiomyopathy.

RASopathies are a group of developmental disorders caused by pathogenic variants in the RAS-MAPK pathway. Cardiomyopathy is a major feature of this group of disorders, specifically hypertrophic cardiomyopathy (HCM). HCM can be the first presenting feature in individuals with RASopathies. We conducted a retrospective study of all individuals who have had a cardiomyopathy gene panel ordered through our institution to determine the prevalence of pathogenic or likely pathogenic variants in RAS pathway genes in individuals with cardiomyopathy. We evaluated variants in the following genes: BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NF1, NRAS, PTPN11, RAF1, SHOC2, and SOS1. We reviewed 74 cases with cardiomyopathy, including 32 with HCM, 24 with dilated cardiomyopathy (DCM), nine with both left ventricular noncompaction (LVNC) and DCM, four with LVNC only, two with arrhythmogenic right ventricular cardiomyopathy (ARVC) and three with unspecified cardiomyopathy. We identified four patients (5.41%) with pathogenic or likely pathogenic variants in HRAS, PTPN11 and RAF1 (two individuals). Indication for testing for all four individuals was HCM. The prevalence of pathogenic or likely pathogenic variants in RASopathy genes in our HCM patient cohort is 12.5% (4/32). We conclude that the RASopathy genes should be included on multi-gene panels for cardiomyopathy to increase diagnostic yield for individuals with HCM.

Developmental differences in stress responding after repeated underwater trauma exposures in rats.

Adolescence is a distinct developmental period characterized by behavioral and physiological maturation. Rapid ongoing changes during neurodevelopment in particular present potential opportunities for stress to have lasting effects on longitudinal outcomes of behavioral and neuroendocrine function. While adult stress effects on outcomes during adulthood have been characterized, little is known about the lasting effects of adolescent repeated stressor exposure on outcomes during adolescence. We have previously reported different stress responses in adolescent rats relative to adult rats, including a blunted fear response outcome in adulthood in rats stressed during adolescence. The present study characterized the ontogeny of behavioral and neuroendocrine responses to eight underwater trauma (UWT) exposures in rats over a two week poststress time period during adolescence (P34) or adulthood (P83) relative to age-matched control groups that underwent eight swimming episodes without UWT. Repeated UWT exposures starting in adolescence, but not adulthood, resulted in adverse behavioral responses on the elevated plus maze 1 day post-stress. Corticosterone responses did not differ between UWT-exposed and controls for either age group at 1 day or at 7 days poststress, although there was an effect of age on corticosterone levels. We conclude that repeated UWT stress events have a lasting, negative behavioral effect on adolescent rats that is not observed in adult rats after the two-week exposure window. These results suggest that neurophysiological mechanisms underlying recovery from a repeated stressor are immature in adolescence relative to adulthood in rats.

Respiratory therapy faculty perspectives on interprofessional education: Findings from a cross-sectional online survey.

Interprofessional education (IPE) improves collaboration and patient care through joint education between health professions. Respiratory therapy (RT) has not been previously evaluated as participants in IPE. A cross-sectional online survey was distributed to evaluate the opportunities and barriers towards IPE of 874 respiratory therapy faculty with both quantitative measures and open-ended questions. Responses (n = 187) to open-ended questions about the opportunities and barriers to IPE inclusion included only one significant difference between Associate's (n = 121, 64.7%) and Bachelor's faculty (n = 66, 35.3%). Open-ended questions were analyzed using directed content analysis. Two trained independent reviewers examined responses for common categories. Reviewers then collated initial categories into broader categories. Faculty responses indicate the importance of IPE, barriers related to schedule and faculty attitudes, and perceived opportunities for IPE with nursing programs and through increasing simulation training opportunities. The most common barriers identified were faculty attitudes, scheduling and logistics, curriculum requirements, administration, and time. All faculty seemed to perceive similar opportunities and barriers regardless of programme type and are supportive of IPE inclusion within their curriculums.

Adulthood stress responses in rats are variably altered as a factor of adolescent stress exposure.

Stress exposure during development may influence adulthood stress response severity. The present study investigates persisting effects of two adolescent stressors upon adulthood response to predator exposure (PE). Rats were exposed to underwater trauma (UWT) or PE during adolescence, then to PE after reaching adulthood. Rats were then exposed to predator odor (PO) to test responses to predator cues alone. Behavioral and neuroendocrine assessments were conducted to determine acute effects of each stress experience. Adolescent stress altered behavioral response to adulthood PE. Acoustic startle response was blunted. Bidirectional changes in plus maze exploration were revealed as a factor of adolescent stress type. Neuroendocrine response magnitude did not predict severity of adolescent or adult stress response, suggesting that different adolescent stress events may differentially alter developmental outcomes regardless of acute behavioral or neuroendocrine response. We report that exposure to two different stressors in adolescence may differentially affect stress response outcomes in adulthood. Acute response to an adolescent stressor may not be consistent across all stressors or all dependent measures, and may not predict alterations in developmental outcomes pertaining to adulthood stress exposure. Further studies are needed to characterize factors underlying long-term effects of a developmental stressor.

Discovery and complete genome sequence of a novel circovirus-like virus in the endangered rowi kiwi, Apteryx rowi.

Circoviruses are circular, non-enveloped, single-stranded DNA viruses around 2000 nucleotides (nt) in length and include the pathogenic species, Porcine circovirus 1 and Beak and feather disease virus, capable of causing significant morbidity and mortality. This group of viruses may be robust to degradation by external environments, and avian circoviruses are known to move between closely related hosts. Using a de novo metagenomic approach, followed by confirmatory PCR, we identify for the first time a circular Rep-encoding single-stranded (CRESS) DNA virus in New Zealand kiwi, Apteryx spp., derived from faecal matter of the rowi kiwi (A. rowi) showing signs of verminous dermatitis. The entire 2085 nt genome was cloned and sequenced and contains both capsid and replicase genes, as well as a conserved 9 nt motif. Phylogenetic analyses place it within Circoviridae, adjacent to other environmental CRESS-DNA viruses, and most closely related to badger circovirus-like virus (Meles meles circovirus-like virus). As the rowi is the most critically endangered kiwi, it is vital to understand the role of rowi kiwi circovirus-like virus as a possible pathogen and also any potential cross-species transmission.

Mie scattering of highly focused, scalar fields: an analytic approach.

We present a method for modeling the scattering of a focused scalar field incident on a spherical particle. This approach involves the expansion of the incident field in an orthonormal basis of closed-form solutions of the Helmholtz equation which are nonparaxial counterparts of Laguerre-Gaussian beams. This method also allows for the analytic calculation of the forces and torques exerted on a particle at any position with respect to the beam's focus.

Discovery of novel virus sequences in an isolated and threatened bat species, the New Zealand lesser short-tailed bat (Mystacina tuberculata).

Bats harbour a diverse array of viruses, including significant human pathogens. Extensive metagenomic studies of material from bats, in particular guano, have revealed a large number of novel or divergent viral taxa that were previously unknown. New Zealand has only two extant indigenous terrestrial mammals, which are both bats, Mystacina tuberculata (the lesser short-tailed bat) and Chalinolobus tuberculatus (the long-tailed bat). Until the human introduction of exotic mammals, these species had been isolated from all other terrestrial mammals for over 1 million years (potentially over 16 million years for M. tuberculata). Four bat guano samples were collected from M. tuberculata roosts on the isolated offshore island of Whenua hou (Codfish Island) in New Zealand. Metagenomic analysis revealed that this species still hosts a plethora of divergent viruses. Whilst the majority of viruses detected were likely to be of dietary origin, some putative vertebrate virus sequences were identified. Papillomavirus, polyomavirus, calicivirus and hepevirus were found in the metagenomic data and subsequently confirmed using independent PCR assays and sequencing. The new hepevirus and calicivirus sequences may represent new genera within these viral families. Our findings may provide an insight into the origins of viral families, given their detection in an isolated host species.

Metagenomic analysis of viruses in feces from unsolved outbreaks of gastroenteritis in humans.

The etiology of an outbreak of gastroenteritis in humans cannot always be determined, and ∼25% of outbreaks remain unsolved in New Zealand. It is hypothesized that novel viruses may account for a proportion of unsolved cases, and new unbiased high-throughput sequencing methods hold promise for their detection. Analysis of the fecal metagenome can reveal the presence of viruses, bacteria, and parasites which may have evaded routine diagnostic testing. Thirty-one fecal samples from 26 gastroenteritis outbreaks of unknown etiology occurring in New Zealand between 2011 and 2012 were selected for de novo metagenomic analysis. A total data set of 193 million sequence reads of 150 bp in length was produced on an Illumina MiSeq. The metagenomic data set was searched for virus and parasite sequences, with no evidence of novel pathogens found. Eight viruses and one parasite were detected, each already known to be associated with gastroenteritis, including adenovirus, rotavirus, sapovirus, and Dientamoeba fragilis. In addition, we also describe the first detection of human parechovirus 3 (HPeV3) in Australasia. Metagenomics may thus provide a useful audit tool when applied retrospectively to determine where routine diagnostic processes may have failed to detect a pathogen.

Invasive ants carry novel viruses in their new range and form reservoirs for a honeybee pathogen.

When exotic animal species invade new environments they also bring an often unknown microbial diversity, including pathogens. We describe a novel and widely distributed virus in one of the most globally widespread, abundant and damaging invasive ants (Argentine ants, Linepithema humile). The Linepithema humile virus 1 is a dicistrovirus, a viral family including species known to cause widespread arthropod disease. It was detected in samples from Argentina, Australia and New Zealand. Argentine ants in New Zealand were also infected with a strain of Deformed wing virus common to local hymenopteran species, which is a major pathogen widely associated with honeybee mortality. Evidence for active replication of viral RNA was apparent for both viruses. Our results suggest co-introduction and exchange of pathogens within local hymenopteran communities. These viral species may contribute to the collapse of Argentine ant populations and offer new options for the control of a globally widespread invader.

Physical biology in cancer. 1. Cellular physics of cancer metastasis.

One of the major challenges in cancer research today is developing new therapeutic strategies to control metastatic disease, the spread of cancer cells from a primary tumor to seed in a distant site. Advances in diagnosis and treatment options have increased the survival rate for most patients with local tumors; however, less progress has been made in treatment of disseminated disease. According to the SEER Cancer Statistics Review, 1975-2010, in the case of breast and prostate cancers, only one in four patients diagnosed with distant metastatic disease will survive more than five years. Current research efforts largely focus on identifying biological targets, such as specific genes and signaling pathways that drive two key steps of metastasis, invasion from the primary tumor and growth in the secondary site. On the other hand, there are phenotypic traits and dynamics in the metastatic process that are not encoded by single genes or signaling pathways but, rather, a larger system of events and biophysical characteristics. Connecting genomic and pathway investigations with quantitative physical phenotypic characteristics of cells, the physical microenvironment, and the physical spatiotemporal interactions of the metastatic process provides a stronger complementary understanding of the disease.

New alphacoronavirus in Mystacina tuberculata bats, New Zealand.

Because of recent interest in bats as reservoirs of emerging diseases, we investigated the presence of viruses in Mystacina tuberculata bats in New Zealand. A novel alphacoronavirus sequence was detected in guano from roosts of M. tuberculata bats in pristine indigenous forest on a remote offshore island (Codfish Island).

Translating motivational interviewing for the HPV vaccine into a computable ontology model for automated AI conversational interaction.

Human papillomavirus (HPV) vaccinations are lower than expected. To protect the onset of head and neck cancers, innovative strategies to improve the rates are needed. Artificial intelligence may offer some solutions, specifically conversational agents to perform counseling methods. We present our efforts in developing a dialogue model for automating motivational interviewing (MI) to encourage HPV vaccination. We developed a formalized dialogue model for MI using an existing ontology-based framework to manifest a computable representation using OWL2. New utterance classifications were identified along with the ontology that encodes the dialogue model. Our work is available on GitHub under the GPL v.3. We discuss how an ontology-based model of MI can help standardize/formalize MI counseling for HPV vaccine uptake. Our future steps will involve assessing MI fidelity of the ontology model, operationalization, and testing the dialogue model in a simulation with live participants.

Development of an in vitro biofilm model of the human supra-gingival microbiome for Oral microbiome transplantation.

The high prevalence of dental caries and periodontal disease place a significant burden on society, both socially and economically. Recent advances in genomic technologies have linked both diseases to shifts in the oral microbiota - a community of >700 bacterial species that live within the mouth. The development of oral microbiome transplantation draws on the success of fecal microbiome transplantation for the treatment of gut pathologies associated with disease. Many current in vitro oral biofilm models have been developed but do not fully capture the complexity of the oral microbiome which is required for successful OMT. To address this, we developed an in vitro biofilm system that maintained an oral microbiome with 252 species on average over 14 days. Six human plaque samples were grown in 3D printed flow cells on hydroxyapatite discs using artificial saliva medium (ASM). Biofilm composition and growth were monitored by high throughput sequencing and confocal microscopy/SEM, respectively. While a significant drop in bacterial diversity occurred, up to 291 species were maintained in some flow cells over 14 days with 70% viability grown with ASM. This novel in vitro biofilm model represents a marked improvement on existing oral biofilm systems and provides new opportunities to develop oral microbiome transplant therapies.

Those who opt to leave: Comparison by triage acuity of emergency patients who leave prior to seeing a medical practitioner.

BACKGROUND: People who present to an emergency department but leave before seeing a medical practitioner (LWBS) pose a potential risk, especially those triaged with higher acuity care needs. OBJECTIVE: To describe and compare characteristics of emergency patients who LWBS by triage acuity. METHOD: Retrospective review of administrative data for a 1-year period. Chi-square and logistic regression analyses conducted to investigate differences in characteristics specific to individual and the timing of presentation between patients who LWBS and were triaged as higher acuity compared to those who left but were triaged as less- or non-urgent. RESULTS: During study period, 12.6 % of patients LWBS with 30.0 % of these cases triaged as higher acuity. Number triaged as higher acuity who LWBS tended to be higher during days with a higher volume of higher acuity cases. The likelihood of LWBS for those triaged as higher acuity was higher among older age groups and those with a primary care provider who presented on weekdays, during evening and night shifts, and in the winter months. CONCLUSIONS: Findings highlight differences in LWBS cases by triage acuity and raise questions about emergency nurses' professional responsibility to follow-up with those who LWBS if they have been triaged as higher acuity based on an assessment of their presenting complaint and risk for complications or deterioration. While continuing to work to reduce wait times and improve patient flow, it is important to identify factors affecting patients' decision to LWBS, especially for those triaged with higher acuity healthcare needs.

Climate Change and Health: Challenges to the Local Government Environmental Health Workforce in South Australia.

Climate change is the most urgent and significant public health risk facing the globe. In Australia, it has been identified that Environmental Health Officers/Practitioners (EHOs/EHPs, hereafter EHOs) are a currently underutilized source of knowledge and skills that can contribute to climate change adaptation planning at the local government level. The ability of local government EHOs to utilize their local knowledge and skills in human health risk assessment during a public health emergency was demonstrated through their role in the response to COVID-19. This study used a survey and follow up interviews to examine the roles and responsibilities of EHOs during the COVID-19 pandemic and used the results to examine the potential of the workforce to tackle climate change and health related issues. What worked well, what regulatory tools were helpful, how interagency collaboration worked and what barriers or hindering factors existed were also explored. A workforce review of EHOs in South Australia was also undertaken to identify current and future challenges facing EHOs and their capacity to assist in climate change preparedness. The findings demonstrated that the workforce was used in the response to COVID-19 for varying roles by councils, including in education and communication (both internally and externally) as well as monitoring and reporting compliance with directions. Notably, half the workforce believed they could have been better utilized, and the other half thought they were well utilized. The South Australian Local Government Functional Support Group (LGFSG) was praised by the workforce for a successful approach in coordinating multiagency responses and communicating directions in a timely fashion. These lessons learnt from the COVID-19 pandemic should be incorporated into climate change adaptation planning. To ensure consistent messaging and a consolidated information repository, a centralized group should be used to coordinate local government climate change adaptation plans in relation to environmental health and be included in all future emergency management response plans. The surveyed EHOs identified environmental health issues associated with climate change as the most significant future challenge; however, concerningly, participants believe that a lack of adequate resourcing, leading to workforce shortages, increasing workloads and a lack of support, is negatively impacting the workforce's preparedness to deal with these emerging issues. It was suggested that the misperception of environmental health and a failure to recognize its value has resulted in a unique dilemma where EHOs and their councils find themselves caught between managing current workload demands and issues, and endeavouring to prepare, as a priority, for emerging environmental health issues associated with climate change and insufficient resources.

The role of RHAMM in cancer: Exposing novel therapeutic vulnerabilities.

Receptor for hyaluronic acid-mediated motility (RHAMM) is a cell surface receptor for hyaluronic acid that is critical for cell migration and a cell cycle protein involved in microtubule assembly and stability. These functions of RHAMM are required for cellular stress responses and cell cycle progression but are also exploited by tumor cells for malignant progression and metastasis. RHAMM is often overexpressed in tumors and is an independent adverse prognostic factor for a number of cancers such as breast and prostate. Interestingly, pharmacological or genetic inhibition of RHAMM in vitro and in vivo ablates tumor invasiveness and metastatic spread, implicating RHAMM as a potential therapeutic target to restrict tumor growth and improve patient survival. However, RHAMM's pro-tumor activity is dependent on its subcellular distribution, which complicates the design of RHAMM-directed therapies. An alternative approach is to identify downstream signaling pathways that mediate RHAMM-promoted tumor aggressiveness. Herein, we discuss the pro-tumoral roles of RHAMM and elucidate the corresponding regulators and signaling pathways mediating RHAMM downstream events, with a specific focus on strategies to target the RHAMM signaling network in cancer cells.