Using Geospatial Data and Random Forest To Predict PFAS Contamination in Fish Tissue in the Columbia River Basin, United States.

Decision makers in the Columbia River Basin (CRB) are currently challenged with identifying and characterizing the extent of per- and polyfluoroalkyl substances (PFAS) contamination and human exposure to PFAS. This work aims to develop and pilot a methodology to help decision makers target and prioritize sampling investigations and identify contaminated natural resources. Here we use random forest models to predict ∑PFAS in fish tissue; understanding PFAS levels in fish is particularly important in the CRB because fish can be a major component of tribal and indigenous people diet. Geospatial data, including land cover and distances to known or potential PFAS sources and industries, were leveraged as predictors for modeling. Models were developed and evaluated for Washington state and Oregon using limited available empirical data. Mapped predictions show several areas where detectable concentrations of PFAS in fish tissue are predicted to occur, but prior sampling has not yet confirmed. Variable importance is analyzed to identify potentially important sources of PFAS in fish in this region. The cost-effective methodologies demonstrated here can help address sparsity of existing PFAS occurrence data in environmental media in this and other regions while also giving insights into potentially important drivers and sources of PFAS in fish.

Mobility of Molecular Motors Regulates Contractile Behaviors of Actin Networks.

Cells generate mechanical forces primarily from interactions between F-actin, cross-linking proteins, myosin motors, and other actin-binding proteins in the cytoskeleton. To understand how molecular interactions between the cytoskeletal elements generate forces, a number of in vitro experiments have been performed but are limited in their ability to accurately reproduce the diversity of motor mobility. In myosin motility assays, myosin heads are fixed on a surface and glide F-actin. By contrast, in reconstituted gels, the motion of both myosin and F-actin is unrestricted. Because only these two extreme conditions have been used, the importance of mobility of motors for network behaviors has remained unclear. In this study, to illuminate the impacts of motor mobility on the contractile behaviors of the actin cytoskeleton, we employed an agent-based computational model based on Brownian dynamics. We find that if motors can bind to only one F-actin like myosin I, networks are most contractile at intermediate mobility. In this case, less motor mobility helps motors stably pull F-actins to generate tensile forces, whereas higher motor mobility allows F-actins to aggregate into larger clustering structures. The optimal intermediate motor mobility depends on the stall force and affinity of motors that are regulated by mechanochemical rates. In addition, we find that the role of motor mobility can vary drastically if motors can bind to a pair of F-actins. A network can exhibit large contraction with high motor mobility because motors bound to antiparallel pairs of F-actins can exert similar forces regardless of their mobility. Results from this study imply that the mobility of molecular motors may critically regulate contractile behaviors of actin networks in cells.

Population Density Modulates Drug Inhibition and Gives Rise to Potential Bistability of Treatment Outcomes for Bacterial Infections.

The inoculum effect (IE) is an increase in the minimum inhibitory concentration (MIC) of an antibiotic as a function of the initial size of a microbial population. The IE has been observed in a wide range of bacteria, implying that antibiotic efficacy may depend on population density. Such density dependence could have dramatic effects on bacterial population dynamics and potential treatment strategies, but explicit measures of per capita growth as a function of density are generally not available. Instead, the IE measures MIC as a function of initial population size, and population density changes by many orders of magnitude on the timescale of the experiment. Therefore, the functional relationship between population density and antibiotic inhibition is generally not known, leaving many questions about the impact of the IE on different treatment strategies unanswered. To address these questions, here we directly measured real-time per capita growth of Enterococcus faecalis populations exposed to antibiotic at fixed population densities using multiplexed computer-automated culture devices. We show that density-dependent growth inhibition is pervasive for commonly used antibiotics, with some drugs showing increased inhibition and others decreased inhibition at high densities. For several drugs, the density dependence is mediated by changes in extracellular pH, a community-level phenomenon not previously linked with the IE. Using a simple mathematical model, we demonstrate how this density dependence can modulate population dynamics in constant drug environments. Then, we illustrate how time-dependent dosing strategies can mitigate the negative effects of density-dependence. Finally, we show that these density effects lead to bistable treatment outcomes for a wide range of antibiotic concentrations in a pharmacological model of antibiotic treatment. As a result, infections exceeding a critical density often survive otherwise effective treatments.

Tumor carcinoide primario de ovario. Reporte de caso / Primary ovarian carcinoid tumor. Case report / Primary ovarian carcinoid tumor. Case report

RESUMEN Los tumores neuroendocrinos primarios del ovario son raros y consisten en un grupo de neoplasias heterogéneas que expresan marcadores inmunohistoquímicos similares. Los tumores carcinoides son las neoplasias neuroendocrinas más comunes, la mayoría surgen en el tracto gastrointestinal y broncopulmonar. Los tumores carcinoides primarios del ovario son entidades raras que representan aproximadamente 0,3% de todos los tumores carcinoides y menos del 0,1% de todas las neoplasias ováricas, con buen pronóstico y generalmente limitados al parénquima ovárico. Estos tumores surgen del sistema de células neuroendocrinas del estroma, epitelio superficial y teratomas ováricos. Las manifestaciones clínicas, en la mayoría de los casos, están asociadas con liberación de sustancias vasoactivas que causan síntomas, como enrojecimiento cutáneo, diarrea y broncoespasmo. Para realizar el diagnóstico es necesario el uso de imágenes radiológicas multimodales y análisis bioquímicos de marcadores tumorales neuroendocrinos. El tratamiento de primera línea es la resección del tumor siempre que sea posible. El pronóstico es generalmente favorable, excepto en algunos casos con metástasis. Se presenta un caso de tumor carcinoide primario de ovario.

ABSTRACT Primary neuroendocrine tumors are rare. They belong to a group of heterogeneous neoplasms that express similar immunohistochemical markers. Carcinoid tumors are the most common neuroendocrine neoplasms. Most of them arise in the gastrointestinal and bronchopulmonary tract. Primary carcinoid tumors of the ovary are rare entities that represent approximately 0.3% of all carcinoid tumors and less than 0.1% of all ovarian neoplasms, with good prognosis and generally limited to the ovarian parenchyma. These tumors arise from the ovarian stromal neuroendocrine cell system, superficial epithelium, and teratomas. In most cases, clinical manifestations are associated with the release of vasoactive substances that cause symptoms such as skin redness, diarrhea, and bronchospasm. For diagnosis it is necessary to use multimodal radiological images and biochemical analysis of neuroendocrine tumor markers. First-line treatment is tumor resection whenever possible. Prognosis is generally favorable, except in some cases with metastases. A case of primary ovarian carcinoid tumor is presented.

Adenoma paratiroideo mediastínico como causa de hiperparatiroidismo primario / Mediastinal parathyroid adenoma as a cause of primary hyperparathyroidism

Resumen Las glándulas paratiroides participan en la regulación de las concentraciones de calcio al producir parathormona como respuesta a la hipocalcemia. Los adenomas paratiroideos, que rara vez se encuentran en mediastino, son la causa más importante de hiperparatiroidismo primario, una enfermedad rara con manifestaciones clínicas graves y que se diagnostica por la com binación de concentraciones elevadas de calcio sérico y paratohormona. Se considera que el adenoma paratiroideo ectópico se deriva de la migra ción de las glándulas paratiroides al mediastino y se conoce como una causa importante del fracaso de la exploración primaria del hiperparatiroi dismo primario. Se presenta un caso de adenoma paratiroideo mediastíni co en una mujer de 48 años que llevó a la aparición de hiperparatiroidismo primario. El adenoma se extirpó mediante esternotomía media total.

Abstract Parathyroid glands participate in regulation of calcium concentrations by producing parathormone in response to hypocalcemia. Parathyroid adeno mas, which are rarely found in the mediastinum, are the most important cause of primary hyperparathyroidism, which is a rare disease with serious clinical manifestations and is diagnosed by combination of high concentrations of serum calcium and parathormone. It is considered that ectopic parathyroid adenoma is derived from the migration of the parathyroid glands to the mediastinum and is known as an important cause of the failure of primary exploration of primary hyperparathyroidism. We present a case of medias tinal parathyroid adenoma in a 48-year-old woman that led to appearance of primary hyperparathyroidism. Adenoma was removed by total median sternotomy.