Fish responses to underwater sounds depend on auditory adaptations: An experimental test of the effect of motorboat sounds on the fish community of a large fluvial lake.

Freshwater fishes exhibit a wide range of auditory adaptations and capabilities, which are assumed to help them navigate their environment, avoid predators, and find potential mates. Yet, we know very little about how freshwater environments sound to fish, or how fish with different auditory adaptations respond to different soundscapes. We first compiled data on fish hearing acuity and adaptations and provided a portrait of how anthropogenic sounds compare to natural sounds in different freshwater soundscapes. We then conducted a sound-enrichment field experiment at Lake Saint Pierre, a large fluvial lake in Canada, to evaluate the effect of motorboat sound exposure on the fish community by looking at the extent to which changes in species abundances were linked to auditory adaptations. Data compilation showed that the hearing acuity of most species overlaps with a wide range of ambient and anthropogenic underwater sounds while the field experiment showed that species with more specialized auditory structures were captured less often in sound-enriched traps, indicating avoidance behavior. Our findings highlight the importance of considering species' sensorial adaptations when evaluating the community-scale effects of anthropogenic sounds on the fish community, especially at low levels of anthropogenic activity.

Bioengineered in vitro three-dimensional tumor models in endocrine cancers.

Abstract: Endocrine tumors are a heterogeneous cluster of malignancies that originate from cells that can secrete hormones. Examples include, but are not limited to, thyroid cancer, adrenocortical carcinoma, and neuroendocrine tumors. Many endocrine tumors are relatively slow to proliferate, and as such, they often do not respond well to common antiproliferative chemotherapies. Therefore, increasing attention has been given to targeted therapies and immunotherapies in these diseases. However, in contrast to other cancers, many endocrine tumors are relatively rare, and as a result, less is understood about their biology, including specific targets for intervention. Our limited understanding of such tumors is in part due to a limitation in model systems that accurately recapitulate and enable mechanistic exploration of these tumors. While mouse models and 2D cell cultures exist for some endocrine tumors, these models often may not accurately model nuances of human endocrine tumors. Mice differ from human endocrine physiology and 2D cell cultures fail to recapitulate the heterogeneity and 3D architectures of in vivo tumors. To complement these traditional cancer models, bioengineered 3D tumor models, such as organoids and tumor-on-a-chip systems, have advanced rapidly in the past decade. However, these technologies have only recently been applied to most endocrine tumors. In this review we provide descriptions of these platforms, focusing on thyroid, adrenal, and neuroendocrine tumors and how they have been and are being applied in the context of endocrine tumors.

A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity.

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture. Organoids and other small 3D in vitro models of tissues or tumors can model certain complexities of human in vivo biology; however, this technology has largely yet to be applied to ACC. In this study, we describe the generation of 3D tumor constructs from an established ACC cell line, NCI-H295R. NCI-H295R cells were encapsulated to generate 3D ACC constructs. Tumor constructs were assessed for biomarker expression, viability, proliferation, and cortisol production. In addition, matrix metalloproteinase (MMP) functionality was assessed directly using fluorogenic MMP-sensitive biosensors and through infusion of NCI-H295R cells into a metastasis-on-a-chip microfluidic device platform. ACC tumor constructs showed expression of biomarkers associated with ACC, including SF-1, Melan A, and inhibin α. Treatment of ACC tumor constructs with chemotherapeutics demonstrated decreased drug sensitivity compared to 2D cell culture. Since most tumor cells migrate through tissue using MMPs to break down extracellular matrix, we validated the utility of ACC tumor constructs by integrating fluorogenic MMP-sensitive peptide biosensors within the tumor constructs. Lastly, in our metastasis-on-a-chip device, NCI-H295R cells successfully engrafted in a downstream lung cell line-based construct, but invasion distance into the lung construct was decreased by MMP inhibition. These studies, which would not be possible using 2D cell cultures, demonstrated that NCI-H295R cells secreted active MMPs that are used for invasion in 3D. This work represents the first evidence of a 3D tumor constructs platform for ACC that can be deployed for future mechanistic studies as well as development of new targets for intervention and therapies.

Surgical Treatment of a Supratentorial Extraventricular Ependymoma: A Case Report.

Supratentorial extraventricular ependymomas (STEE) are very rare primary tumors of the central nervous system (CNS). A 19-year-old man complained of headache, hemiparesis and seizures and was admitted to our hospital. Magnetic resonance imaging (MRI) revealed a right frontal intra-axial lesion. The patient underwent surgical treatment, and the tumor was resected successfully. A diagnosis of World Health Organization (WHO) grade 3 STEE was based on microscopic examination and immunohistochemical analysis. The patient was discharged without a neurological deficit.

A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity.

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture. Organoids and other small 3D in vitro models of tissues or tumors can model certain complexities of human in vivo biology; however, this technology has largely yet to be applied to ACC. In this study, we describe the generation of 3D tumor constructs from an established ACC cell line, NCI-H295R. NCI-H295R cells were encapsulated to generate 3D ACC constructs. Tumor constructs were assessed for biomarker expression, viability, proliferation, and cortisol production. In addition, matrix metalloproteinase (MMP) functionality was assessed directly using fluorogenic MMP-sensitive biosensors and through infusion of NCI-H295R cells into a metastasis-on-a-chip microfluidic device platform. ACC tumor constructs showed expression of biomarkers associated with ACC, including SF-1, Melan A, and inhibin alpha. Treatment of ACC tumor constructs with chemotherapeutics demonstrated decreased drug sensitivity compared to 2D cell culture. Since most tumor cells migrate through tissue using MMPs to break down extracellular matrix, we validated the utility of ACC tumor constructs by integrating fluorogenic MMP-sensitive peptide biosensors within the tumor constructs. Lastly, in our metastasis-on-a-chip device, NCI-H295R cells successfully engrafted in a downstream lung cell line-based construct, but invasion distance into the lung construct was decreased by MMP inhibition. These studies, which would not be possible using 2D cell cultures, demonstrated that NCI-H295R cells secreted active MMPs that are used for invasion in 3D. This work represents the first evidence of a 3D tumor constructs platform for ACC that can be deployed for future mechanistic studies as well as development of new targets for intervention and therapies.

Design, assembly and validation of a low-cost, high-fidelity simulator for heart exploration.

INTRODUCTION: Heart exploration is an essential clinical competence that requires continuous training and exposure. Low availability and accessibility to patients with heart disease constitutes a barrier to acquiring this competence. Inadequate cardiac auscultation skills in medical students, residents, and graduate physicians have been documented. OBJECTIVE: To develop and validate a low-cost, high-fidelity simulator for heart exploration. METHODS: A low-cost, high-fidelity heart examination simulator capable of reproducing normal cardiac sounds was designed and developed. Subsequently, the simulator was validated by a group of experts who gave their opinion according to a Likert scale. RESULTS: Ninety-four percent agreed that the simulator motivates the learning of heart exploration, and 92 % considered it to be a realistic model; 91 % considered that the simulator is an attractive tool to reinforce learning and 98 % recommended its further use. CONCLUSIONS: The use of the simulator facilitates the acquisition of skills and stimulates learning in the student, which can be attributed to repeated practice, longer exposure time and cognitive interaction.

INTRODUCCIÓN: La exploración cardiaca es una competencia clínica fundamental que requiere exposición o entrenamiento continuo. La baja disponibilidad y accesibilidad de pacientes con patología cardiaca constituye una barrera para adquirir esta competencia. Se han documentado inadecuadas habilidades de auscultación cardiaca en estudiantes de medicina, residentes y médicos graduados. OBJETIVO: Elaborar y validar un simulador de alta fidelidad y bajo costo para exploración cardiaca. MÉTODOS: Se diseñó y elaboró un simulador para exploración cardiaca, realista y de bajo costo capaz de reproducir ruidos cardiacos normales. Posteriormente se realizó la validación del simulador por un grupo de expertos que emitieron su opinión de acuerdo con una escala tipo Likert. RESULTADOS: El 94 % afirmó que el simulador motiva el aprendizaje de la exploración cardiaca y 92 % lo consideró un modelo realista; 91 % consideró que el simulador es una herramienta atractiva para fortalecer el aprendizaje y 98 % recomendó seguir utilizándolo. CONCLUSIONES: El uso del simulador facilita la adquisición de competencias y estimula el aprendizaje en el estudiante, lo cual puede ser atribuido a la práctica deliberada, a un mayor tiempo de exposición y a la interacción cognitiva.

Saliva is a reliable and accessible source for the detection of SARS-CoV-2.

OBJECTIVES: The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated. METHODS: A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components. RESULTS: The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C. CONCLUSIONS: The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction.

Diseño, elaboración y validación de un simulador realista y de bajo costo para exploración cardiaca / Design, assembly and validation of a low-cost, high-fidelity simulator for heart exploration

Resumen Introducción: La exploración cardiaca es una competencia clínica fundamental que requiere exposición o entrenamiento continuo. La baja disponibilidad y accesibilidad de pacientes con patología cardiaca constituye una barrera para adquirir esta competencia. Se han documentado inadecuadas habilidades de auscultación cardiaca en estudiantes de medicina, residentes y médicos graduados. Objetivo: Elaborar y validar un simulador de alta fidelidad y bajo costo para exploración cardiaca. Métodos: Se diseñó y elaboró un simulador para exploración cardiaca, realista y de bajo costo capaz de reproducir ruidos cardiacos normales. Posteriormente se realizó la validación del simulador por un grupo de expertos que emitieron su opinión de acuerdo con una escala tipo Likert. Resultados: El 94 % afirmó que el simulador motiva el aprendizaje de la exploración cardiaca y 92 % lo consideró un modelo realista; 91 % consideró que el simulador es una herramienta atractiva para fortalecer el aprendizaje y 98 % recomendó seguir utilizándolo. Conclusiones: El uso del simulador facilita la adquisición de competencias y estimula el aprendizaje en el estudiante, lo cual puede ser atribuido a la práctica deliberada, a un mayor tiempo de exposición y a la interacción cognitiva.

Abstract Introduction: Heart exploration is an essential clinical competence that requires continuous training and exposure. Low availability and accessibility to patients with heart disease constitutes a barrier to acquiring this competence. Inadequate cardiac auscultation skills in medical students, residents, and graduate physicians have been documented. Objective: To develop and validate a low-cost, high-fidelity simulator for heart exploration. Methods: A low-cost, high-fidelity heart examination simulator capable of reproducing normal cardiac sounds was designed and developed. Subsequently, the simulator was validated by a group of experts who gave their opinion according to a Likert scale. Results: Ninety-four percent agreed that the simulator motivates the learning of heart exploration, and 92 % considered it to be a realistic model; 91 % considered that the simulator is an attractive tool to reinforce learning and 98 % recommended its further use. Conclusions: The use of the simulator facilitates the acquisition of skills and stimulates learning in the student, which can be attributed to repeated practice, longer exposure time and cognitive interaction.

Eight-and-a-half syndrome: video evidence and updated literature review.

The eight-and-a-half syndrome (EHS)-defined by the combination of a seventh cranial nerve palsy and an ipsilateral one-and-a-half syndrome-is a rare brainstem syndrome, which localises to the caudal tegmental region of the pons. We present a case of the EHS secondary to an inflammatory lesion on a previously healthy 26-year-old woman, with a literature review emphasising the relevance of aetiological assessment.

Novel coronavirus, novel faculty development programs: rapid transition to eLearning during the pandemic.

The novel coronavirus disease 2019 (COVID-19) has caused a rapid and massive transition to online education. We describe the response of our Office of Faculty Development at Texas Tech University Health Sciences Center El Paso (TTUHSC EP) to this unprecedented challenge during and after this post-pandemic crisis. The initiatives for emergency transition to eLearning and faculty development described in this paper may serve as a model for other academic health centers, schools, colleges and universities.

Predicting cyanobacterial biovolume from water temperature and conductivity using a Bayesian compound Poisson-Gamma model.

Eutrophication and climate change scenarios engender the need to develop good predictive models for harmful cyanobacterial blooms (CyanoHABs). Nevertheless, modeling cyanobacterial biomass is a challenging task due to strongly skewed distributions that include many absences as well as extreme values (dense blooms). Most modeling approaches alter the natural distribution of the data by splitting them into zeros (absences) and positive values, assuming that different processes underlie these two components. Our objectives were (1) to develop a probabilistic model relating cyanobacterial biovolume to environmental variables in the Río de la Plata Estuary (35°S, 56°W, n = 205 observations) considering all biovolume values (zeros and positive biomass) as part of the same process; and (2) to use the model to predict cyanobacterial biovolume under different risk level scenarios using water temperature and conductivity as explanatory variables. We developed a compound Poisson-Gamma (CPG) regression model, an approach that has not previously been used for modeling phytoplankton biovolume, within a Bayesian hierarchical framework. Posterior predictive checks showed that the fitted model had a good overall fit to the observed cyanobacterial biovolume and to more specific features of the data, such as the proportion of samples crossing three threshold risk levels (0.2, 1 and 2 mm³ L-1) at different water temperatures and conductivities. The CPG model highlights the strong control of cyanobacterial biovolume by nonlinear and interactive effects of water temperature and conductivity. The highest probability of crossing the three biovolume levels occurred at 22.2 °C and at the lowest observed conductivity (∼0.1 mS cm-1). Cross-validation of the fitted model using out-of-sample observations (n = 72) showed the model's potential to be used in situ, as it enabled prediction of cyanobacterial biomass based on two readily measured variables (temperature and conductivity), making it an interesting tool for early alert systems and management strategies. Furthermore, this novel application demonstrates the potential of the Bayesian CPG approach for predicting cyanobacterial dynamics in response to environmental change.

Influence of Boron Additions and Heat Treatments on the Fatigue Resistance of CoCrMo Alloys.

Cobalt-based alloys are widely used in the manufacture of joint prostheses. In this study, the effect of boron additions and heat treatment on the ASTM F75 was evaluated by rotating bending fatigue. The boron ranged from 0.06⁻1 wt %. The alloys were tested in as-cast and heat-treated conditions. In the as-cast condition, the infinite life was observed at 380 MPa, improving to 433⁻615 MPa according to the amount of boron added. In the heat treatment condition, the fatigue resistance was improved only in the base alloy. The addition of 0.06 wt % boron and heat treatment led to the same resistance as in the as-cast condition. Adding large amounts of boron combined with heat treatment diminished the fatigue limit. The fracture analysis revealed primarily brittle behaviour with some ductile features even on the same sample; only the heat-treated alloy with 0.06 wt % boron was clearly ductile. This alloy also exhibited notably better toughness to crack propagation.

Microdamage distribution in fatigue fractures of bone allografts following gamma-ray exposure.

PURPOSE: Although significant differences in bone properties have been extensively studied, results vary when bones are exported to gamma radiation of a range usually used for sterilization purposes (25-35 kGy). Hence, the aim of this work was the study of the mechanical properties and microdamage development of human bones used as allografts following gamma-ray exposure, followed by an extensive statistical analysis of microdamage effects in fatigue behaviour. METHODS: Specimens of the cortical region of human femurs were exposed to 15-25 kGy and 26-30 kGy radiation levels, then they were subjected to compression fatigue tests until fracture. The fatigue life was determined in relation to the radiation level, and the evolution of microdamage was assessed using fluorescence microscopy in order to calculate characteristic lengths of microcracks. RESULTS: Significant differences in fatigue life were detected (p < 0.05) between non-radiated (control) and radiated specimens, resulting in a drastic 89.2% fatigue life reduction of the 15-25 kGy group, and 95.3% in the 26-30 kGy group, compared to the reference. Microdamage analysis showed a considerable increase in microcrack lengths when bone was exposed to gamma radiation, which may indicate that bones used as allografts could fracture at some point when subjected to loading conditions in vivo. CONCLUSIONS: The results of our research indicate that even if a range of 15-25 kGy is suggested to sterilize bone allografts, such practice needs to be reconsidered. In addition, using Weibull distribution, this work describes the conditions in which microcracks grow towards the fracture of bones in relation to the decrease in their mechanical properties.

Satisfaction and perceived effectiveness in patients on subcutaneous immunotherapy with a high-dose hypoallergenic pollen extract.

This study was designed to determine the level of satisfaction, tolerance and perceived effectiveness by patients in the first pollen season after starting treatment with Alergovit(®). For this purpose, a nationwide, retrospective, multicentre and cross-sectional observational study was carried on 256 patients. Perceived effectiveness by the patients was measured using a visual analogue scale and was clinically significant in 92.4% of the patients. The satisfaction level was evaluated with a specific questionnaire. 32.5% of the patients were totally satisfied with Allergovit(®) and 48.8% reported a high degree of satisfaction. The treatment was well tolerated by 99.2% of the patients. Our results demonstrate that subcutaneous immunotherapy with Allergovit(®) is effective and well-tolerated in routine clinical practice.

Testing the influence of environmental heterogeneity on fish species richness in two biogeographic provinces.

Environmental homogenization in coastal ecosystems impacted by human activities may be an important factor explaining the observed decline in fish species richness. We used fish community data (>200 species) from extensive surveys conducted in two biogeographic provinces (extent >1,000 km) in North America to quantify the relationship between fish species richness and local (grain <10 km(2)) environmental heterogeneity. Our analyses are based on samples collected at nearly 800 stations over a period of five years. We demonstrate that fish species richness in coastal ecosystems is associated locally with the spatial heterogeneity of environmental variables but not with their magnitude. The observed effect of heterogeneity on species richness was substantially greater than that generated by simulations from a random placement model of community assembly, indicating that the observed relationship is unlikely to arise from veil or sampling effects. Our results suggest that restoring or actively protecting areas of high habitat heterogeneity may be of great importance for slowing current trends of decreasing biodiversity in coastal ecosystems.

Aerosol species concentrations and source apportionment of ammonia at Rocky Mountain National Park.

Changes in ecosystem function at Rocky Mountain National Park (RMNP) are occurring because of emissions of nitrogen and sulfate species along the Front Range of the Colorado Rocky Mountains, as well as sources farther east and west. The nitrogen compounds include both oxidized and reduced nitrogen. A year-long monitoring program of various oxidized and reduced nitrogen species was initiated to better understand their origins as well as the complex chemistry occurring during transport from source to receptor. Specifically the goals of the study were to characterize the atmospheric concentrations of nitrogen species in gaseous, particulate, and aqueous phases (precipitation and clouds) along the east and west sides of the Continental Divide; identify the relative contributions to atmospheric nitrogen species in RMNP from within and outside of the state of Colorado; identify the relative contributions to atmospheric nitrogen species in RMNP from emission sources along the Colorado Front Range versus other areas within Colorado; and identify the relative contributions to atmospheric nitrogen species from mobile sources, agricultural activities, and large and small point sources within the state of Colorado. Measured ammonia concentrations are combined with modeled releases of conservative tracers from ammonia source regions around the United States to apportion ammonia to its respective sources, using receptor modeling tools.

Fish dispersal in fragmented landscapes: a modeling framework for quantifying the permeability of structural barriers.

Dispersal is a key determinant of the spatial distribution and abundance of populations, but human-made fragmentation can create barriers that hinder dispersal and reduce population viability. This study presents a modeling framework based on dispersal kernels (modified Laplace distributions) that describe stream fish dispersal in the presence of obstacles to passage. We used mark-recapture trials to quantify summer dispersal of brook trout (Salvelinus fontinalis) in four streams crossed by a highway. The analysis identified population heterogeneity in dispersal behavior, as revealed by the presence of a dominant sedentary component (48-72% of all individuals) characterized by short mean dispersal distance (<10 m), and a secondary mobile component characterized by longer mean dispersal distance (56-1086 m). We did not detect evidence of barrier effects on dispersal through highway crossings. Simulation of various plausible scenarios indicated that detectability of barrier effects was strongly dependent on features of sampling design, such as spatial configuration of the sampling area, barrier extent, and sample size. The proposed modeling framework extends conventional dispersal kernels by incorporating structural barriers. A major strength of the approach is that ecological process (dispersal model) and sampling design (observation model) are incorporated simultaneously into the analysis. This feature can facilitate the use of prior knowledge to improve sampling efficiency of mark-recapture trials in movement studies. Model-based estimation of barrier permeability and its associated uncertainty provides a rigorous approach for quantifying the effect of barriers on stream fish dispersal and assessing population dynamics of stream fish in fragmented landscapes.

Incorporating temporally dynamic baselines in isotopic mixing models.

Stable isotopes (particularly C and N) are widely used to make inferences regarding food web structure and the phenology of consumer diet shifts, applications that require accurate isotopic characterization of trophic resources to avoid biased inferences of feeding relationships. For example, most isotope mixing models require that endmembers be adequately represented by a single probability distribution; yet, there is mounting evidence that the isotopic composition of aquatic organisms often used as mixing model endmembers can change over periods of weeks to months. A review of the literature indicated that the delta13C values of five aquatic primary consumer taxa, commonly used as proxies of carbon production sources (i.e., trophic baselines), express seasonally dynamic cycles characterized by an oscillation between summer maxima and winter minima. Based on these results, we built a dynamic baseline mixing model that allows a growing consumer to track temporal gradients in the isotopic baselines of a food web. Simulations showed that the ability of a consumer to maintain or approach isotopic equilibrium with its diet over a realistic growth season was strongly affected by both the rate of change of the isotopic baseline and equilibration rate of the consumer. In an empirical application, mixing models of varying complexity were used to estimate the relative contribution of benthic vs. pelagic carbon sources to nine species of juvenile fish in a fluvial lake of the St. Lawrence River system (Québec, Canada). Estimates of p (proportion of carbon derived from benthic sources) derived from a static mixing model indicated broad interspecific variation in trophic niche, ranging from complete benthivory to > 95% reliance on pelagic food webs. Output from the more realistic dynamic baseline mixing model increased estimated benthivory by an average of 36% among species. Taken together, our results demonstrate that failing to identify dynamic baselines when present, and (or) matching consumers with baseline taxa that possess substantially different equilibration rates can seriously bias interpretation of stable isotope data. Additionally, by providing a formalized framework that allows both resources and consumers to shift their isotopic value through time, our model demonstrates a feasible approach for incorporating temporally dynamic isotope conditions in trophic studies of higher consumers.