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The dependency on hibernacula for extended periods presents terrestrial reptiles with the challenge of locating thermally adequate hibernacula each winter. Defining the habitat characteristics of hibernacula is crucial for understanding the overwintering requirements and distributions of hibernacula-dependent reptiles, alongside identifying habitats which warrant special conservation concern. Our objectives were to identify the overwintering habitat characteristics of the imperiled timber rattlesnake Crotalus horridus in Illinois, USA, and to determine the distribution of likely hibernacula habitats throughout the state. Due to the initial sparsity of hibernacula records in Illinois, we adopted an iterative habitat suitability modeling process consisting of 3 distinct rounds of Maxent construction and revision. Each round was informed with updated information from model-guided surveys or by building rapport with in-state naturalists and researchers who knew of additional hibernacula locations. We created our final model using 36 hibernacula and identified slope angle (indicative of rock outcrops and shallow soils), topographical position index, forest patch area, and aspect (decomposed into 2 linearized variables: southness and eastness) as important drivers of C. horridus hibernacula habitat in Illinois. Together, the 5 variables and site surveys suggest the suitable overwintering habitat for C. horridus in Illinois is located on south- to southwest-facing outcrops on upper slopes and ridges of larger forest patches. Such habitat is distributed primarily in southern Illinois and throughout the Mississippi River and Illinois River border counties. Our study adds to the current understanding of the species’ overwintering requirements and provides a foundation for future ecological studies, management, and survey efforts throughout Illinois.

Ice-associated seals rely on sea ice for a variety of activities, including pupping, breeding, molting, and resting. In the Arctic, many of these activities occur in spring (April through June) as sea ice begins to melt and retreat northward. Rapid acceleration of climate change in Arctic ecosystems is therefore of concern as the quantity and quality of suitable habitat is forecast to decrease. Robust estimates of seal population abundance are needed to properly monitor the impacts of these changes over time. Aerial surveys of seals on ice are an efficient method for counting seals but must be paired with estimates of the proportion of seals out of the water to derive population abundance. In this paper, we use hourly percent-dry data from satellite-linked bio-loggers deployed between 2005 and 2021 to quantify the proportion of seals hauled out on ice. This information is needed to accurately estimate abundance from aerial survey counts of ice-associated seals ( i.e. , to correct for the proportion of animals that are in the water, and so are not counted, while surveys are conducted). In addition to providing essential data for survey 'availability' calculations, our analysis also provides insights into the seasonal timing and environmental factors affecting haul-out behavior by ice-associated seals. We specifically focused on bearded ( Erignathus barbatus ), ribbon ( Histriophoca fasciata ), and spotted seals ( Phoca largha ) in the Bering and Chukchi seas. Because ringed seals ( Phoca (pusa) hispida ) can be out of the water but hidden from view in snow lairs analysis of their 'availability' to surveys requires special consideration; therefore, they were not included in this analysis. Using generalized linear mixed pseudo-models to properly account for temporal autocorrelation, we fit models with covariates of interest ( e.g. , day-of-year, solar hour, age and sex class, wind speed, barometric pressure, temperature, precipitation) to examine their ability to explain variation in haul-out probability. We found evidence for strong diel and within-season patterns in haul-out behavior, as well as strong weather effects (particularly wind and temperature). In general, seals were more likely to haul out on ice in the middle of the day and when wind speed was low and temperatures were higher. Haul-out probability increased through March and April, peaking in May and early June before declining again. The timing and frequency of haul-out events also varied based on species and age-sex class. For ribbon and spotted seals, models with year effects were highly supported, indicating that the timing and magnitude of haul-out behavior varied among years. However, we did not find broad evidence that haul-out timing was linked to annual sea-ice extent. Our analysis emphasizes the importance of accounting for seasonal and temporal variation in haul-out behavior, as well as associated environmental covariates, when interpreting the number of seals counted in aerial surveys., Competing Interests: The authors declare there are no competing interests. Josh M. London, Paul B. Conn, Stacie M. Koslovsky, Erin L. Richmond, Jay M. Ver Hoef, Michael F. Cameron and Peter L. Boveng are employed by National Marine Fisheries Service. Justin A. Crawford and Lori Quakenbush are employed by Alaska Department of Fish and Game. Andrew L. Von Duyke is employed by the North Slope Borough’s Department of Wildlife Management., (©2024 London et al.)

Staphylococcus aureus causes the majority of skin and soft tissue infections, but this pathogen only transiently colonizes healthy skin. However, this transient skin exposure enables S. aureus to transition to infection. The initial adhesion of S. aureus to skin corneocytes is mediated by surface protein G (SasG). Here, phylogenetic analyses reveal the presence of two major divergent SasG alleles in S. aureus: SasG-I and SasG-II. Structural analyses of SasG-II identify a nonaromatic arginine in the binding pocket of the lectin subdomain that mediates adhesion to corneocytes. Atomic force microscopy and corneocyte adhesion assays indicate that SasG-II can bind to a broader variety of ligands than SasG-I. Glycosidase treatment results in different binding profiles between SasG-I and SasG-II on skin cells. In addition, SasG-mediated adhesion is recapitulated using differentiated N/TERT keratinocytes. Our findings indicate that SasG-II has evolved to adhere to multiple ligands, conferring a distinct advantage to S. aureus during skin colonization., Competing Interests: Declaration of interests A.B.H. has served as a scientific advisory board member for Hoth Therapeutics, holds equity in Hoth Therapeutics and Chelexa BioSciences, and was a co-inventor on seven patents broadly related to the subject matter of this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The influence of intraspecific trait variation on species interactions makes trait-based approaches critical to understanding eco-evolutionary processes. Because species occupy habitats that are patchily distributed in space, species interactions are influenced not just by the degree of intraspecific trait variation but also the relative proportion of trait variation that occurs within- versus between-patches. Advancement in trait-based ecology hinges on understanding how trait variation is distributed within and between habitat patches across the landscape. We sampled larval spotted salamanders (Ambystoma maculatum) across six spatially discrete ponds to quantify within- and between-pond variation in mass, length, and various metrics associated with their relationship (scaling, body condition, shape). Across all traits, within-pond variation contributed more to total observed morphological variation than between-pond variation. Between-pond variation was not negligible, however, and explained 20-41% of total observed variation in measured traits. Between-pond variation was more pronounced in salamander tail morphology compared to head or body morphology, suggesting that pond-level factors more strongly influence tails than other body parts. We also observed differences in mass-length relationships across ponds, both in terms of scaling slopes and intercepts, though differences in the intercepts were much stronger. Preliminary evidence hinted that newly constructed ponds were a driver of the observed differences in mass-length relationships and morphometrics. General pond-level difference in salamander trait covariation suggest that allometric scaling of morphological traits is context dependent in patchy landscapes. Effects of pond age offer the hypothesis that habitat restoration through pond construction is a driver of variation in trait scaling, which managers may leverage to bolster trait diversity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Green et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: With increasing reports of accelerated and acute silicosis, PMF, and autoimmune disease among coal miners and silica-exposed countertop workers, we present previously incompletely-described pulmonary pathology of accelerated silicosis and correlations with mineralogy, radiography, and disease progression in 46 Texas oilfield pipe sandblasters who were biopsied between 1988 and 1995., Methods: Worker examinations included pulmonary function tests, chest X-ray (CXR), high-resolution computed tomography (HRCT), and Gallium-67 scans. Quantitative mineralogic analysis of pulmonary parenchymal burden of silica, silicates, and metal particles used scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM EDS)., Results: Workers had clinical deterioration after <10 years exposure in dusty workplaces. Although initial CXR was normal in 54%, Gallium-67 scans were positive in 68% of those with normal CXR, indicating pulmonary inflammation. The histology of accelerated silicosis is diffuse interstitial infiltration of macrophages filled with weakly birefringent particles with or without silicotic nodules or alveolar proteinosis. Lung silica concentrations were among the highest in our database, showing a dose-response relationship with CXR, HRCT, and pathologic changes (macrophages, fibrosis, and silicotic nodules). Radiographic scores and diffusing capacity worsened during observation. Silica exposure was intensified, patients presented younger, with shorter exposure, more severe clinical abnormalities, higher lung particle burdens, and more rapid progression in a subset of patients exposed to recycled blasting sand., Conclusions: Accelerated silicosis may present with a normal CXR despite significant histopathology. Multivariable analyses showed silica, and not other particles, is the driver of observed radiologic, physiologic, and histologic outcomes. Eliminating this preventable disease requires higher physician, public health, and societal awareness., (© 2024 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

Exposure to aluminum compounds is clearly associated with pulmonary function decrements, and several animal models document possible mechanisms of aluminum- compound-induced pulmonary toxicity. Nevertheless, disagreements remain about the precise mechanism by which exposures lead to damage. We present a strong case for attributing a case of interstitial pulmonary disease to occupational exposure to aluminum trihydrate. This report follows a 2014 publication of another case of interstitial pulmonary disease following a similar exposure. Our patient eventually underwent double lung transplantation nearly 5 years postexposure. Detailed pulmonary particulate elemental analysis suggested that aluminum metal, including aluminum trihydrate, was the most likely cause. A detailed assessment of the worker's relevant occupational exposures accompanies this case report., (© 2024 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals LLC.)

Chaperone-mediated autophagy (CMA) is a lysosome-dependent degradation pathway that eliminates proteins that are damaged, partially unfolded, or targeted for selective proteome remodeling. CMA contributes to several cellular processes, including stress response and proteostasis. Age-associated increase in cellular stressors and decrease in CMA contribute to pathologies associated with aging in various tissues. CMA contributes to bone homeostasis in young mice. An age-associated reduction in CMA was reported in osteoblast lineage cells; however, whether declining CMA contributes to skeletal aging is unknown. Herein we show that cellular stressors stimulate CMA in UAMS-32 osteoblastic cells. Moreover, the knockdown of an essential component of the CMA pathway, LAMP2A, sensitizes osteoblasts to cell death caused by DNA damage, ER stress, and oxidative stress. As elevations in these stressors are thought to contribute to age-related bone loss, we hypothesized that declining CMA contributes to the age-associated decline in bone formation by sensitizing osteoblast lineage cells to elevated stressors. To test this, we aged male CMA-deficient mice and controls up to 24 months of age and examined age-associated changes in bone mass and architecture. We showed that lack of CMA did not alter age-associated decline in bone mineral density as measured by dual x-ray absorptiometry (DXA). Moreover, microCT analysis performed at 24 months of age showed that vertebral cancellous bone volume, cortical thickness, and porosity of CMA-deficient and control mice were similar. Taken together, these results suggest that reduction of CMA does not contribute to age-related bone loss., (©2024 The Authors FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.)

Staphylococcus aureus causes the majority of skin and soft tissue infections, but this pathogen only transiently colonizes healthy skin. However, this transient skin exposure enables S. aureus to transition to infection. Initial adhesion of S. aureus to skin corneocytes is mediated by surface protein G (SasG). Here, phylogenetic analyses reveal the presence of two major divergent SasG alleles in S. aureus , SasG-I and SasG-II. Structural analyses of SasG-II identified a unique non-aromatic arginine in the binding pocket of the lectin subdomain that mediates adhesion to corneocytes. Atomic force microscopy and corneocyte adhesion assays indicated SasG-II can bind to a broader variety of ligands than SasG-I. Glycosidase treatment resulted in different binding profiles between SasG-I and SasG-II on skin cells. Additionally, SasG-mediated adhesion was recapitulated using differentiated N/TERT keratinocytes. Our findings indicate that SasG-II has evolved to adhere to multiple ligands, conferring a distinct advantage to S. aureus during skin colonization., Competing Interests: Declaration of interests A.B.H. has served as a Scientific Advisory Board member for Hoth Therapeutics, Inc., holds equity in Hoth Therapeutics and Chelexa BioSciences, LLC, and was a co-inventor on seven patents broadly related to the subject matter of this work.

Cre-mediated recombination is frequently used for cell type-specific loss of function (LOF) studies. A major limitation of this system is recombination in unwanted cell types. CRISPR interference (CRISPRi) has been used effectively for global LOF in mice. However, cell type-specific CRISPRi, independent of recombination-based systems, has not been reported. To test the feasibility of cell type-specific CRISPRi, we produced two novel knock-in mouse models that achieve gene suppression when used together: one expressing dCas9::KRAB under the control of a cell type-specific promoter and the other expressing a single guide RNA from a safe harbor locus. We then compared the phenotypes of mice in which the same gene was targeted by either CRISPRi or the Cre-loxP system, with cell specificity conferred by Dmp1 regulatory elements in both cases. We demonstrate that CRISPRi is effective for cell type-specific LOF and that it provides improved cell type-specificity compared to the Cre-loxP system., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Resistance-nodulation-division (RND) superfamily efflux pumps promote antibiotic resistance in Gram-negative pathogens, but their role in Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) is undocumented. However, recent in vitro selections for resistance of S. aureus to an antimicrobial fatty acid, linoleic acid, and an antibiotic, rhodomyrtone, identified H121Y and C116R substitution variants, respectively, in a TetR family regulator, FarR, promoting increased expression of the RND pump FarE. Hypothesizing that in vivo selection pressures have also promoted the emergence of FarR variants, we searched available genome data and found that strains with FarR H121Y from human and bovine hosts have emerged sporadically in clonal complexes (CCs) CC1, CC30, CC8, CC22, and CC97, whereas multiple FarR variants have occurred within CC5 hospital-associated (HA)-MRSA. Of these, FarR E160G and FarR E93EE were exclusive to CC5, while FarR C116Y , FarR P165L , and FarR G166D also occurred in nonrelated CCs, primarily from bovine hosts. Within CC5, FarR C116Y and FarR G166D strains were polyphyletic, each exhibiting two emergence events. FarR C116Y and FarR E160G were individually sufficient to confer increased expression of FarE and enhanced resistance to linoleic acid (LA). Isolates with FarR E93EE were most closely related to S. aureus N315 MRSA and exhibited increased resistance independently of FarR E93EE . Accumulation of pseudogenes and additional polymorphisms in FarR E93EE strains contributed to a multiresistance phenotype which included fosfomycin and fusidic acid resistance in addition to increased linoleic acid resistance. These findings underscore the remarkable adaptive capacity of CC5 MRSA, which includes the polyphyletic USA100 lineage of HA-MRSA that is endemic in the Western hemisphere and known for the acquisition of multiple resistance phenotypes.

Chaperone-mediated autophagy (CMA) is a protein degradation pathway that eliminates soluble cytoplasmic proteins that are damaged, incorrectly folded, or targeted for selective proteome remodeling. However, the role of CMA in skeletal homeostasis under physiological and pathophysiological conditions is unknown. To address the role of CMA for skeletal homeostasis, we deleted an essential component of the CMA process, namely Lamp2a, from the mouse genome. CRISPR-Cas9-based genome editing led to the deletion of both Lamp2a and Lamp2c, another Lamp2 isoform, producing Lamp2AC global knockout (L2ACgKO) mice. At 5 weeks of age female L2ACgKO mice had lower vertebral cancellous bone mass compared to wild-type (WT) controls, whereas there was no difference between genotypes in male mice at this age. The low bone mass of L2ACgKO mice was associated with elevated RANKL expression and the osteoclast marker genes Trap and Cathepsin K. At 18 weeks of age, both male and female L2ACgKO mice had lower vertebral cancellous bone mass compared to WT controls. The low bone mass of L2ACgKO mice was associated with increased osteoclastogenesis and decreased mineral deposition in cultured cells. Consistent with these findings, specific knockdown of Lamp2a in an osteoblastic cell line increased RANKL expression and decreased mineral deposition. Moreover, similar to what has been observed in other cell types, macroautophagy and proteasomal degradation were upregulated in CMA-deficient osteoblasts in culture. Thus, an increase in other protein degradation pathways may partially compensate for the loss of CMA in osteoblasts. Taken together, our results suggest that CMA plays a role in vertebral cancellous bone mass accrual in young adult mice and that this may be due to an inhibitory role of CMA on osteoclastogenesis or a positive role of CMA in osteoblast formation or function., (© 2022. The Author(s).)

The Advisory Committee on Immunization Practices (ACIP) was created out of the need to formalize vaccine recommendations for the United States. Annually, ACIP delivers recommendations to the CDC director for guidance about United States vaccine use and publishes the Adult Immunization Schedule. Updated schedules feature changes to vaccine recommendations as well as changes to the schedule's usability for physicians. The objective of this study was to determine physicians' attitudes about the Adult Immunization Schedule. Surveys were administered to a sentinel physician network from October 2019 through January 2020. Physicians that responded were comfortable using the Adult Immunization Schedule, but reported confusion about some medical condition-based indications. Physicians reported a lack engagement with mobile applications, CDC Vaccine Schedules and Shots by STFM (the Society for Teachers of Family Medicine). Future work should focus on increasing clarity regarding the recommendations with medical condition-based indications and increasing knowledge of mobile applications for physicians., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Polar bears (Ursus maritimus) are experiencing loss of sea ice habitats used to access their marine mammal prey. Simultaneously, ocean warming is changing ecosystems that support marine mammal populations. The interactive effects of sea ice and prey are not well understood yet may explain spatial-temporal variation in the response of polar bears to sea ice loss. Here, we examined the potential combined effects of sea ice, seal body condition, and atmospheric circulation patterns on the body condition, recruitment, diet, and feeding probability of 469 polar bears captured in the Chukchi Sea, 2008-2017. The body condition of ringed seals (Pusa hispida), the primary prey of females and subadults, was related to dietary proportions of ringed seal, feeding probability, and the body condition of females and cubs. In contrast, adult males consumed more bearded seals (Erignathus barbatus) and exhibited better condition when bearded seal body condition was higher. The litter size, number of yearlings per adult female, and the condition of dependent young were higher following winters characterized by low Arctic Oscillation conditions, consistent with a growing number of studies. Body condition, recruitment, and feeding probability were either not associated or negatively associated with sea ice conditions, suggesting that, unlike some subpopulations, Chukchi Sea bears are not currently limited by sea ice availability. However, spring sea ice cover declined 2% per year during our study reaching levels not previously observed in the satellite record and resulting in the loss of polar bear hunting and seal pupping habitat. Our study suggests that the status of ice seal populations is likely an important factor that can either compound or mitigate the response of polar bears to sea ice loss over the short term. In the long term, neither polar bears nor their prey are likely robust to limitless loss of their sea ice habitat., (© 2021 John Wiley & Sons Ltd.)

Background: Human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) continues to increase in incidence. Patients are younger, non-smokers and most commonly present with a neck mass often with no other symptoms. This altered presentation compared with non-HPV OPSCC may not be recognized by medical practitioners, leading to delayed diagnosis., Methods: Patients with histopathological confirmation of OPSCC and known HPV and/or P16 status who presented to our institution between 2012-2017 inclusive were included in the study. Demographic data, tumour characteristics and presenting symptoms were retrospectivxely obtained from both electronic- and paper-based records. Descriptive statistics were used to report demographic data and the two sample t-test and Fisher's exact test were used to compare groups based on HPV status. Time to diagnosis was also reported., Results: A total of 184 patients were included in the study. The majority of patients were male (85.4%) and HPV + (85.3%). The tonsillar complex (53.8%) and tongue base (42.4%) were the most common primary sites. HPV+ patients were less likely to smoke (17.8%) and they commonly presented with a neck mass (39.5% alone or with other symptoms 61.2%). Time to diagnosis in the HPV+ group was longer (15 weeks)., Conclusion: Our review has highlighted the altered presentation of OPSCC due to the increased incidence of HPV infection. We showed a delayed time to diagnosis in HPV+ OPSCC compared with non-HPV disease. This confirms the importance of focusing our efforts on educating medical practitioners and creating further awareness to facilitate early detection and treatment., (© 2021 Royal Australasian College of Surgeons.)

Drought imposes stress on plants and associated soil microbes, inducing coordinated adaptive responses, which can involve plant-soil signalling via phytohormones. However, we know little about how microbial communities respond to phytohormones, or how these responses are shaped by chronic (long-term) drought. Here, we added three phytohormones (abscisic acid, 1-aminocyclopropane-1-carboxylic acid, and jasmonic acid) to soils from long-term (25-year), field-based climate treatments to test the hypothesis that chronic drought alters soil microbial community responses to plant stress signalling. Phytohormone addition increased soil respiration, but this effect was stronger in irrigated than in droughted soils and increased soil respiration at low phytohormone concentrations could not be explained by their use as substrate. Thus, we show that drought adaptation within soil microbial communities modifies their responses to phytohormone inputs. Furthermore, distinct phytohormone-induced shifts in microbial functional groups in droughted vs. irrigated soils might suggest that drought-adapted soil microorganisms perceive phytohormones as stress-signals, allowing them to anticipate impending drought.

Climate change is expected to systematically alter the distribution and population dynamics of species around the world. The effects are expected to be particularly strong at high latitudes and elevations, and for ectothermic species with small ranges and limited movement potential, such as salamanders in the southern Appalachian Mountains. In this study, we sought to establish baseline abundance estimates for plethodontid salamanders (family: Plethodontidae) over an elevational gradient in Great Smoky Mountains National Park. In addition to generating these baseline data for multiple species, we describe methods for surveying salamanders that allow for meaningful comparisons over time by separating observation and ecological processes generating the data. We found that Plethodon jordani had a mid-elevation peak (1,500 m) in abundance and Desmognathus wrighti increased in abundance with elevation up to the highest areas of the park (2025 m), whereas Eurycea wilderae increased in abundance up to 1,600 m and then plateaued with increasing uncertainty. Litter depth, herbaceous ground cover, and proximity to stream were also important predictors of abundance (dependent upon species), whereas daily temperature, precipitation, ground cover, and humidity influenced detection rates. Our data provide some of the first minimally biased information for future studies to assess changes in the abundance and distribution of salamanders in this region. Understanding abundance patterns along with detailed baseline distributions will be critical for comparisons with future surveys to understand the population and community-level effects of climate change on montane salamanders., Competing Interests: The authors do not have any competing interest., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Rationale: Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease. Objectives: As part of a public health investigation of a manufacturing facility, we performed a cross-sectional study using paired environmental and human sampling to evaluate the cross-pollination of microbes between the environment and the host and possible effects on lung pathology present among workers. Methods: Workplace environmental microbiota were evaluated in air and MWF samples. Human microbiota were evaluated in lung tissue samples from workers with respiratory symptoms found to have lymphocytic bronchiolitis and alveolar ductitis with B-cell follicles and emphysema, in lung tissue samples from control subjects, and in skin, nasal, and oral samples from 302 workers from different areas of the facility. In vitro effects of MWF exposure on murine B cells were assessed. Measurements and Main Results: An increased similarity of microbial composition was found between MWF samples and lung tissue samples of case workers compared with control subjects. Among workers in different locations within the facility, those that worked in the machine shop area had skin, nasal, and oral microbiota more closely related to the microbiota present in the MWF samples. Lung samples from four index cases and skin and nasal samples from workers in the machine shop area were enriched with Pseudomonas , the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation in vitro , a hallmark cell subtype found in the pathology of index cases. Conclusions: Evaluation of a manufacturing facility with a cluster of workers with respiratory disease supports cross-pollination of microbes from MWF to humans and suggests the potential for exposure to these microbes to be a health hazard.

Wildlife are faced with numerous threats to survival, none more pressing than that of climate change. Understanding how species will respond behaviorally, physiologically, and demographically to a changing climate is a cornerstone of many contemporary ecological studies, especially for organisms, such as amphibians, whose persistence is closely tied to abiotic conditions. Activity is a useful parameter for understanding the effects of climate change because activity is directly linked to fitness as it dictates foraging times, energy budgets, and mating opportunities. However, activity can be challenging to measure directly, especially for secretive organisms like plethodontid salamanders, which only become surface active when conditions are cool and moist because of their anatomical and physiological restrictions. We estimated abiotic predictors of surface activity for the seven species of the Plethodon jordani complex. Five independent data sets collected from 2004 to 2017 were used to determine the parameters driving salamander surface activity in the present day, which were then used to predict potential activity changes over the next 80 yrs. Average active seasonal temperature and vapor pressure deficit were the strongest predictors of salamander surface activity and, without physiological or behavioral modifications, salamanders were predicted to exhibit a higher probability of surface activity during peak active season under future climate conditions. Temperatures during the active season likely do not exceed salamander thermal maxima to cause activity suppression and, until physiological limits are reached, future conditions may continue to increase activity. Our model is the first comprehensive field-based study to assess current and future surface activity probability. Our study provides insights into how a key behavior driving fitness may be affected by climate change., (© 2020 by the Ecological Society of America.)

Introduction: Approximately 4% of NSCLC harbor BRAF mutations, and approximately 50% of these are non-V600 mutations. Treatment of tumors harboring non-V600 mutations is challenging because of functional heterogeneity and lack of knowledge regarding their clinical significance and response to targeted agents., Methods: We conducted an integrative analysis of BRAF non-V600 mutations using genomic profiles of BRAF-mutant NSCLC from the Guardant360 database. BRAF mutations were categorized by clonality and class (1 and 2: RAS-independent; 3: RAS-dependent). Cell viability assays were performed in Ba/F3 models. Drug screens were performed in NSCLC cell lines., Results: A total of 305 unique BRAF mutations were identified. Missense mutations were most common (276, 90%), and 45% were variants of unknown significance. F468S and N581Y were identified as novel activating mutations. Class 1 to 3 mutations had higher clonality than mutations of unknown class (p < 0.01). Three patients were treated with MEK with or without BRAF inhibitors. Patients harboring G469V and D594G mutations did not respond, whereas a patient with the L597R mutation had a durable response. Trametinib with or without dabrafenib, LXH254, and lifirafenib had more potent inhibition of BRAF non-V600-mutant NSCLC cell lines than other MEK, BRAF, and ERK inhibitors, comparable with the inhibition of BRAF V600E cell line., Conclusions: In BRAF-mutant NSCLC, clonality is higher in known functional mutations and may allow identification of variants of unknown significance that are more likely to be oncogenic drivers. Our data indicate that certain non-V600 mutations are responsive to MEK and BRAF inhibitors. This integration of genomic profiling and drug sensitivity may guide the treatment for BRAF-mutant NSCLC., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Continued Arctic warming and sea-ice loss will have important implications for the conservation of ringed seals, a highly ice-dependent species. A better understanding of their spatial ecology will help characterize emerging ecological trends and inform management decisions. We deployed satellite transmitters on ringed seals in the summers of 2011, 2014, and 2016 near Utqiaġvik (formerly Barrow), Alaska, to monitor their movements, diving, and haul-out behavior. We present analyses of tracking and dive data provided by 17 seals that were tracked until at least January of the following year. Seals mostly ranged north of Utqiaġvik in the Beaufort and Chukchi Seas during summer before moving into the southern Chukchi and Bering Seas during winter. In all seasons, ringed seals occupied a diversity of habitats and spatial distributions, from near shore and localized, to far offshore and wide-ranging in drifting sea ice. Continental shelf waters were occupied for >96% of tracking days, during which repetitive diving (suggestive of foraging) primarily to the seafloor was the most frequent activity. From mid-summer to early fall, 12 seals made ~1-week forays off-shelf to the deep Arctic Basin, most reaching the retreating pack-ice, where they spent most of their time hauled out. Diel activity patterns suggested greater allocation of foraging efforts to midday hours. Haul-out patterns were complementary, occurring mostly at night until April-May when midday hours were preferred. Ringed seals captured in 2011-concurrent with an unusual mortality event that affected all ice-seal species-differed morphologically and behaviorally from seals captured in other years. Speculations about the physiology of molting and its role in energetics, habitat use, and behavior are discussed; along with possible evidence of purported ringed seal ecotypes., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Ichthyosporean parasites (order Dermocystida) can cause morbidity and mortality in amphibians, but their ecology and epidemiology remain understudied. We investigated the prevalence, gross and histologic appearance, and molecular phylogeny of a novel dermocystid in the state-endangered silvery salamander (Ambystoma platineum) and the co-occurring, non-threatened small-mouthed salamander (Ambystoma texanum) from Illinois. Silvery salamanders (N = 610) were sampled at six ephemeral wetlands from 2016 to 2018. Beginning in 2017, 1-3 mm raised, white skin nodules were identified in 24 silvery salamanders and two small-mouthed salamanders from five wetlands (prevalence = 0-11.1%). Skin biopsy histology (N = 4) was consistent with dermocystid sporangia, and necropsies (N = 3) identified infrequent hepatic sporangia. Parasitic 18S rRNA sequences (N = 5) from both salamander species were identical, and phylogenetic analysis revealed a close relationship to Dermotheca viridescens. Dermocystids were not identified in museum specimens from the same wetlands (N = 125) dating back to 1973. This is the first report of Dermotheca sp. affecting caudates in the Midwestern United States. Future research is needed to determine the effects of this pathogen on individual and population health, and to assess whether this organism poses a threat to the conservation of ambystomatid salamanders.

Soil organic carbon (SOC) dynamics represent a persisting uncertainty in our understanding of the global carbon cycle. SOC storage is strongly linked to plant inputs via the formation of soil organic matter, but soil geochemistry also plays a critical role. In tropical soils with rapid SOC turnover, the association of organic matter with soil minerals is particularly important for stabilising SOC but projected increases in tropical forest productivity could trigger feedbacks that stimulate the release of stored SOC. Here, we demonstrate limited additional SOC storage after 13-15 years of experimentally doubled aboveground litter inputs in a lowland tropical forest. We combined biological, physical, and chemical methods to characterise SOC along a gradient of bioavailability. After 13 years of monthly litter addition treatments, most of the additional SOC was readily bioavailable and we observed no increase in mineral-associated SOC. Importantly, SOC with weak association to soil minerals declined in response to long-term litter addition, suggesting that increased plant inputs could modify the formation of organo-mineral complexes in tropical soils. Hence, we demonstrate the limited capacity of tropical soils to sequester additional C inputs and provide insights into potential underlying mechanisms.

Background: A cluster of severe lung disease occurred at a manufacturing facility making industrial machines. We aimed to describe disease features and workplace exposures., Methods: Clinical, functional, radiologic, and histopathologic features were characterized. Airborne concentrations of thoracic aerosol, metalworking fluid, endotoxin, metals, and volatile organic compounds were measured. Facility airflow was assessed using tracer gas. Process fluids were examined using culture, polymerase chain reaction, and 16S ribosomal RNA sequencing., Results: Five previously healthy male never-smokers, ages 27 to 50, developed chest symptoms from 1995 to 2012 while working in the facility's production areas. Patients had an insidious onset of cough, wheeze, and exertional dyspnea; airflow obstruction (mean FEV 1  = 44% predicted) and reduced diffusing capacity (mean = 53% predicted); and radiologic centrilobular emphysema. Lung tissue demonstrated a unique pattern of bronchiolitis and alveolar ductitis with B-cell follicles lacking germinal centers, and significant emphysema for never-smokers. All had chronic dyspnea, three had a progressive functional decline, and one underwent lung transplantation. Patients reported no unusual nonoccupational exposures. No cases were identified among nonproduction workers or in the community. Endotoxin concentrations were elevated in two air samples; otherwise, exposures were below occupational limits. Air flowed from areas where machining occurred to other production areas. Metalworking fluid primarily grew Pseudomonas pseudoalcaligenes and lacked mycobacterial DNA, but 16S analysis revealed more complex bacterial communities., Conclusion: This cluster indicates a previously unrecognized occupational lung disease of yet uncertain etiology that should be considered in manufacturing workers (particularly never-smokers) with airflow obstruction and centrilobular emphysema. Investigation of additional cases in other settings could clarify the cause and guide prevention., (© 2019 Wiley Periodicals, Inc.)

The term sarcopenia was introduced in 1988. The original definition was a "muscle loss" of the appendicular muscle mass in the older people as measured by dual energy x-ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC-F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease-related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age-related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age-related and disease-related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life-long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Introduction: The pathophysiology of normal-pressure hydrocephalus and the correlation with its symptomatology is not well understood., Objective: To monitor and evaluate the enlargement patterns of the ventricular system for each ventricle and its correlation with the presenting symptoms., Methods: Bilateral kaolin injection into the subarachnoid space overlying the cranial convexities was done in 18 adult rats. Magnetic resonance imaging was performed on an 11.7-T scanner 15, 60, 90, and 120 days after injection. Volumes of the ventricular system were measured for each ventricle and correlated with biweekly behavioral findings., Results: There was a progressive increase in the ventricular volume for the lateral ventricles since day 15 in the kaolin-injected animals. There was a nonsignificant trend in volume growth for the third ventricle, but its enlargement was synchronous with the lateral ventricles. No significant change for the fourth ventricle. No symptoms were detected in the first 60 days. Association was found between the ventricular volume and locomotor changes. In addition, the odds of locomotor symptoms increased by 3% for every additional cubic millimeter of volume in the left (P < 0.001) and right (P = 0.023) ventricles, and for the total magnetic resonance imaging volume by 1% (P = 0.013)., Conclusions: Expansion of the lateral ventricles maintained similar proportions over time, accompanied by a synchronous third ventricular expansion with less proportion and a nonsignificant fourth enlargement. Lateral ventricles enlarged most in those animals that were to develop late locomotor deterioration. Further research using this animal model combined with different radiologic imaging techniques, such as diffusion tensor imaging and perfusion studies, is recommended., (Copyright © 2018 Elsevier Inc. All rights reserved.)

GATA4 is a transcription factor that is responsible for tissue-specific gene regulation in many tissues, and more recent studies showed that it is necessary for osteoblast differentiation. Previously, we showed that in vivo deletion of Gata4 using Cre-recombinase under the control of the Col1a1 2.3 kb promoter, showed significantly reduced trabecular bone properties. To understand the role of GATA4 in more differentiated cells, GATA4 fl/fl mice were crossed with mice expressing Cre-recombinase under the control of the osteocalcin promoter. MicroCT analysis of trabecular bone properties of the femur and tibia from 14-week-old female osteocalcin-Cre/GATA4 fl/fl (OCN-cKO) mice showed a significant reduction in percentage bone volume, a decrease in trabecular number and an increase in trabecular spacing. In vivo, histomorphometric analysis revealed a decrease in the number of osteoblasts and an increase in the number of osteoclasts in the tibiae of OCN-cKO mice. In vivo and in vitro systems correlated a decrease in Gata4 mRNA with increased RANKL gene expression. To determine if RANKL is a direct target of GATA4, chromatin immunoprecipitation (ChIP)-sequencing was performed, and it demonstrated that GATA4 is recruited to seven enhancers near RANKL. Furthermore, when Gata4 is knocked down, the chromatin at the RANKL region is further opened, as detected by a reduction in histone 3 lysine 27 trimethylation (H3K27me3) and an increase in histone 3 lysine 4 dimethylation (H3K4me2) in the RANKL locus. In vitro, TRAP staining of cells from bone marrow cultures from Gata4 knockout cells show that the increased levels of RANKL are sufficient for osteoclast formation. Together, the data suggest that GATA4 directly represses RANKL expression via seven cis-regulatory regions and plays an important role in maintaining proper bone development and osteoclast formation., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

This study showcases the potential of unnatural amino acids to enable non-natural functions when incorporated in the protein scaffold of heme metalloproteins. For this purpose, a genetically-engineered myoglobin (Mb) mutant was created by incorporating redox-active 3-amino-l-tyrosine (NH 2 Tyr) into its active site, replacing the distal histidine (H64) with NH 2 Tyr. In peroxide-shunt assays, this variant exhibits an increased rate of turnover for thioanisole and benzaldehyde oxidation as compared to the wild-type (WT) Mb. Indeed, in the presence of excess hydrogen peroxide (H 2 O 2 ), a 9-fold and 81-fold increase in activity was observed over multiple turnovers for thioanisole sulfoxidation and benzoic acid formation, respectively. The increased oxidation activity in the H64NH 2 Tyr Mb mutant underlined the role of NH 2 Tyr in the distal active-site scaffold in peroxide activation. Kinetic, electrochemical, and EPR spectroscopic experiments were performed. On the basis of these studies, it is argued that the single NH 2 Tyr residue within the Mb variant simultaneously serves the role of the conserved His/Arg-pair within the distal pocket of horseradish peroxidase., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to evaluate efficacy of maintenance sunitinib after first-line chemotherapy for stage IIIB/IV NSCLC., Methods: Cancer and Leukemia Group B 30607 trial was a randomized, double-blind, placebo-controlled, phase III study that enrolled patients without progression after four cycles of first-line platinum-based doublet chemotherapy with or without bevacizumab. Bevacizumab was allowed only during the four cycles of chemotherapy. Patients were randomized to receive sunitinib, 37.5 mg/d, or placebo and were treated until unacceptable adverse event(s), progression, or death. The primary end point was progression-free survival (PFS)., Results: A total of 210 patients were enrolled, randomized, and included in the intent-to-treat analysis. Ten patients did not receive maintenance therapy (four who received placebo and six who received sunitinib). Grade 3/4 adverse events affecting more than 5% of the patients were fatigue (25%), thrombocytopenia (12%), hypertension (12%), rash (11%), mucositis (11%), neutropenia (7%), and anemia (6%) for sunitinib and none for placebo. There were three grade 5 events in patients receiving sunitinib (one pulmonary hemorrhage, one other pulmonary event, and one death not associated with a Common Terminology Criteria for Adverse Events term) and two grade 5 events in patients receiving placebo (one other pulmonary event and one thromboembolism). Median PFS was 4.3 months for sunitinib and 2.6 months for placebo (hazard ratio = 0.62, 95% confidence interval: 0.47-0.82, p = 0.0006). Median overall survival was 11.7 months for sunitinib versus 12.1 months for placebo (hazard ratio = 0.98, 95% confidence interval: 0.73-1.31, p = 0.89)., Conclusions: Maintenance sunitinib was safe and improved PFS as maintenance therapy in stage IIIB/IV NSCLC but had no impact on overall survival. There is no room for future investigations of sunitinib in this setting., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Single-site experiments have demonstrated detritus quality in wetlands can have strongly negative, neutral, and even positive influences on wildlife. However, an examination of the influence of detritus quality across several regions is lacking and can provide information on whether impacts from variation in detritus quality are consistent across species with wide ranges. To address this gap in regional studies we examined effects of emergent and allochthonous detritus of different nutrient qualities on amphibians and assessed a mechanism that may contribute to potential impacts. We used aquatic mesocosms to raise wood frogs (Rana sylvatica) from two regions of the United States with whole plants from purple loosestrife (Lythrum salicaria), leaf litter from native hardwood trees, and a mixture of both. We examined several metrics of amphibian fitness and life history, including survival, number of days to metamorphosis, and size at metamorphosis. Further, we quantified whether the effects of detritus type could translate to variation in anuran biomass or standing stock of nitrogen or phosphorus export. Our results show detritus with high nutrient quality (purple loosestrife) negatively influenced survival of wood frogs, but increased size of metamorphic individuals in two different regions of the United States. Despite the decrease in survival, the increase in size of post-metamorphic anurans raised with high quality detritus resulted in anuran biomass and standing stock of N and P export being similar across treatments at both locations. These results further demonstrate the role of plant quality in shaping wetland ecosystem dynamics, and represent the first demonstration that effects are consistent within species across ecoregional boundaries., Competing Interests: The authors have declared that no competing interests exist.

Background: The pathogenesis of adult chronic hydrocephalus is not fully understood, and the temporal relationship between development of the radiological changes and neurological deterioration is unknown., Objective: To clarify the progression of radiological-histological changes and subsequent clinical manifestations of adult chronic hydrocephalus., Methods: Kaolin was injected bilaterally into the subarachnoid space overlying the cranial convexities in 20 adult rats. Magnetic resonance imaging (MRI) was obtained by using an 11.7 T scanner at 14, 60, 90, and 120 days after kaolin injection. Locomotor, gait, and cognitive evaluations were performed independently. Kaolin distribution and the associated inflammatory and fibrotic responses were histologically analyzed., Results: Evans index of ventriculomegaly showed significant progressive growth in ventricular size over all time points examined. The greatest enlargement occurred within the first 2 months. Evans index also correlated with the extent of kaolin distribution by MRI and by pathological examination at all time points. First gait changes occurred at 69 days, anxiety at 80, cognitive impairment at 81, and locomotor difficulties after 120 days. Only locomotor deterioration was associated with Evans index or the radiological evaluation of kaolin extension. Inflammatory/fibrotic response was histologically confirmed over the cranial convexities in all rats, and its extension was associated with ventricular size and with the rate of ventricular enlargement., Conclusion: Kaolin injected into the subarachnoid space over the cerebral hemispheres of adult rats produces an inflammatory/fibrotic response leading in a slow-onset communicating hydrocephalus that is initially asymptomatic. Increased ventricular size eventually leads to gait, memory, and locomotor impairment closely resembling the course of human adult chronic hydrocephalus., Abbreviation: NPH, normal pressure hydrocephalus.

Background: Toxoplasma gondii is a pathogen implicated in psychiatric disorders. As elevated antibodies to T. gondii are also present in non-symptomatic individuals, we hypothesized that the age during first exposure to the pathogen may affect symptom manifestation. We tested this hypothesis by evaluating neurobehavioral abnormalities and the immune response in mice following adolescent or adult T. gondii infection., Methods: Mice were infected with T. gondii at postnatal day 33 (adolescent/juvenile) or 61 (adult). At 8weeks post-infection (wpi), pre-pulse inhibition of the acoustic startle (PPI) in mice administered MK-801 (0.1 and 0.3mg/kg) and amphetamine (5 and 10mg/kg) was assessed. Peripheral (anti-T. gondii, C1q-associated IgG and anti-GLUN2 antibodies) and central (C1q and Iba1) markers of the immune response were also evaluated. In addition, regional brain expression of N-methyl-d-aspartate receptor (NMDAR) subunits (GLUN1 and GLUN2A), glutamatergic (vGLUT1, PSD95) and GABAergic (GAD67) markers, and monoamines (DA, NE, 5-HT) and their metabolites were measured., Results: Juvenile and adult infected mice exhibited opposite effects of MK-801 on PPI, with decreased PPI in juveniles and increased PPI in adults. There was a significantly greater elevation of GLUN2 autoantibodies in juvenile-compared to adult-infected mice. In addition, age-dependent differences were found in regional expression of NMDAR subunits and markers of glutamatergic, GABAergic, and monoaminergic systems. Activated microglia and C1q elevations were found in both juvenile- and adult-T. gondii infected mice., Conclusions: Our study demonstrates that the age at first exposure to T. gondii is an important factor in shaping distinct behavioral and neurobiological abnormalities. Elevation in GLUN2 autoantibodies or complement protein C1q may be a potential underlying mechanism. A better understanding of these age-related differences may lead to more efficient treatments of behavioral disorders associated with T. gondii infection., (Copyright © 2016. Published by Elsevier Inc.)

Surgery with transoral robotic surgery (TORS) offers significant advantages compared with traditional open surgical approaches and potentially minimizes the long-term side effects of organ preservation therapy with chemoradiation. Angled telescopes and wristed instruments allow visualization and access to areas of the pharynx that are difficult to reach with line-of-sight instrumentation. Although the application of TORS in head and neck surgery has expanded considerably, there are still only limited data available on the postoperative complications and their management. As further data become available, it is likely that further risk factors and treatment strategies will become available., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The inositol hexakisphosphate kinases (IP6Ks) are the principal enzymes that generate inositol pyrophosphates. There are three IP6Ks (IP6K1, 2, and 3). Functions of IP6K1 and IP6K2 have been substantially delineated, but little is known of IP6K3's role in normal physiology, especially in the brain. To elucidate functions of IP6K3, we generated mice with targeted deletion of IP6K3. We demonstrate that IP6K3 is highly concentrated in the brain in cerebellar Purkinje cells. IP6K3 physiologically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are perturbed in IP6K3-null mutants. Consequently, IP6K3 knock-out cerebella manifest abnormalities in Purkinje cell structure and synapse number, and the mutant mice display deficits in motor learning and coordination. Thus, IP6K3 is a major determinant of cytoskeletal disposition and function of cerebellar Purkinje cells., Significance Statement: We identified and cloned a family of three inositol hexakisphosphate kinases (IP6Ks) that generate the inositol pyrophosphates, most notably 5-diphosphoinositol pentakisphosphate (IP7). Of these, IP6K3 has been least characterized. In the present study we generated IP6K3 knock-out mice and show that IP6K3 is highly expressed in cerebellar Purkinje cells. IP6K3-deleted mice display defects of motor learning and coordination. IP6K3-null mice manifest aberrations of Purkinje cells with a diminished number of synapses. IP6K3 interacts with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mice may mediate phenotypic features of the mutant mice. These findings afford molecular/cytoskeletal mechanisms by which the inositol polyphosphate system impacts brain function., (Copyright © 2015 the authors 0270-6474/15/3511056-12$15.00/0.)

An increasing number of studies have demonstrated relationships between climate trends and body size change of organisms. In many cases, climate might be expected to influence body size by altering thermoregulation, energetics or food availability. However, observed body size change can result from a variety of ecological processes (e.g. growth, selection, population dynamics) or imperfect observation of biological systems. We used two extensive datasets to evaluate alternative mechanisms for recently reported changes in the observed body size of plethodontid salamanders. We found that mean adult body size of salamanders can be highly sensitive to survey conditions, particularly rainfall. This systematic bias in the detection of larger or smaller individuals could result in a signature of body size change in relation to reported climate trends when it is simply observation error. We also identify considerable variability in body size distributions among years and find that individual growth rates can be strongly influenced by weather. Finally, our study demonstrates that measures of mean adult body size can be highly variable among surveys and that large sample sizes may be required to make reliable inferences. Identifying the effects of climate change is a critical area of research in ecology and conservation. Researchers should be aware that observed changes in certain organisms can result from multiple ecological processes or systematic bias due to nonrandom sampling of populations., (© 2015 John Wiley & Sons Ltd.)

Indoor fungal exposure can compromise respiratory health. Low-income urban areas are of concern because of high asthma and allergy rates and housing disrepair. Understanding the conditions that affect indoor fungal exposures is important for assessing health risks and for developing mitigation strategies. We examined the types and concentrations of airborne fungi inside and outside of homes in low-income areas of Syracuse, NY as well as the effect of snow cover on fungal levels. At 103 homes, air samples for viable fungi were collected, occupants were interviewed and homes were inspected for visible mold, musty odors, water problems and other factors. Multivariable logistic regression was used to relate high fungal levels to home conditions. Predominant indoor fungi included Cladosporium, Penicillium, Aspergillus, Alternaria and hyaline unknowns. Basidiomycetes and an uncommon genus Acrodontium were also found frequently due to analysis methods developed for this project. With snow cover, outdoor total fungal levels were depressed and indoor concentrations were three times higher than outdoor on average with a maximum of 29 times higher. Visible mold was related to elevated levels of Penicillium (OR 4.11 95% CI 1.37-14.0) and bacteria (OR 3.79 95% CI 1.41-11.2). Musty, moldy odors were associated with elevated concentrations of total fungi (OR 3.48 95% CI 1.13-11.6) and basidiomycetes. Cockroaches, an indicator of moisture, were associated with elevated levels of Penicillium (OR 3.66 95% CI 1.16-13.1) and Aspergillus (OR 4.36 95% CI 1.60-13.4). Increasing relative humidity was associated with higher concentrations of Penicillium, yeasts and basidiomycetes. Visible mold, musty odors, indoor humidity and cockroaches are modifiable factors that were important determinants of indoor fungal exposures. Indoor air investigators should interpret indoor:outdoor fungal ratios cautiously when snow cover is present., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Possible relationships between mold contamination, as described by the Environmental Relative Moldiness Index (ERMI), home characteristics, and the development of wheeze in the first year of life were evaluated among a cohort of urban infants (n = 103) in Syracuse, New York. Pregnant women with a history of asthma were recruited in 2001-2002 for the "Assessment of Urban Dwellings for Indoor Toxics" (AUDIT) study. When the infants were approximately 3 months of age, a home inspection was carried out and indoor environmental samples collected, including vacuumed house dust. ERMI levels in the Syracuse cohort homes were higher than the U.S. average, with an overall mean of 11.4. ERMI levels were significantly higher in homes with visible water problems (p = 0.023) and visible mold (p = 0.023). ERMI levels in apartments were significantly lower than the values measured in houses (p = 0.0003). While infants experiencing wheeze (38%) tended to live in homes with higher ERMI values than those without wheeze (ERMI values of 12.3 and 10.9, respectively), the differences did not reach statistical significance. A subset analysis limited to infants with living room samples who remained in the same home during the study (n = 25) was suggestive of an association between higher ERMI values and wheeze (p = 0.10). In summary, the ERMI is a standardized metric which allows for comparison of moldiness levels in homes across studies and regions in the United States. ERMI levels in Syracuse homes were skewed to the high end of the national scale. Higher ERMI levels were indicators of water problems, mold, and type of housing.

Nocturnal upper airway collapse is often multi-level in nature but typically will involve some degree of obstruction at the level of the tongue-base. Several surgical procedures have been developed in recent years to address this area in patients resistant to continuous positive airway pressure. This article outlines a novel way to treat obstructive sleep apnea lingual obstruction using the da Vinci robotic surgical system. This technique offers significant potential advantages over other established approaches and it should be included in the surgical armamentarium of sleep surgeons., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Cysteine dioxygenase (CDO) is a non-heme mononuclear iron enzyme that catalyzes the O(2)-dependent oxidation of L-cysteine (Cys) to produce cysteine sulfinic acid (CSA). In this study we demonstrate that the catalytic cycle of CDO can be "primed" by one electron through chemical oxidation to produce CDO with ferric iron in the active site (Fe(III)-CDO, termed 2). While catalytically inactive, the substrate-bound form of Fe(III)-CDO (2a) is more amenable to interrogation by UV-vis and EPR spectroscopy than the 'as-isolated' Fe(II)-CDO enzyme (1). Chemical-rescue experiments were performed in which superoxide (O(2)(•-)) anions were introduced to 2a to explore the possibility that a Fe(III)-superoxide species represents the first intermediate within the catalytic pathway of CDO. In principle, O(2)(•-) can serve as a suitable acceptor for the remaining 3-electrons necessary for CSA formation and regeneration of the active Fe(II)-CDO enzyme (1). Indeed, addition of O(2)(•-) to 2a resulted in the rapid formation of a transient species (termed 3a) observable at 565 nm by UV-vis spectroscopy. The subsequent decay of 3a is kinetically matched to CSA formation. Moreover, a signal attributed to 3a was also identified using parallel mode X-band EPR spectroscopy (g ~ 11). Spectroscopic simulations, observed temperature dependence, and the microwave power saturation behavior of 3a are consistent with a ground state S = 3 from a ferromagnetically coupled (J ~ -8 cm(-1)) high-spin ferric iron (S(A) = 5/2) with a bound radical (S(B) = 1/2), presumably O(2)(•-). Following treatment with O(2)(•-), the specific activity of recovered CDO increased to ~60% relative to untreated enzyme.

The Syracuse, NY, AUDIT (Assessment of Urban Dwellings for Indoor Toxics) study was designed to quantify asthma agent levels in the inner-city homes of a birth cohort whose mothers had a diagnosis of asthma. Risk of exposure to particulate matter (PM), particle number and tobacco smoke was assessed in 103 infants' homes. Repeat measurements were made in 44% of the homes. Infants also were examined on a quarterly basis during the first year of life to monitor their respiratory health and urine cotinine levels. Overall geometric mean (GM) values for PM(2.5) of 21.2 μg/m(3) and for PM(10) of 31.8 μg/m(3) were recorded in homes at visit 1. GM values for PM(2.5) and PM(10) in smoking homes were higher at 26.3 and 37.7 μg/m(3), while values in non-smoking homes were 12.7 and 21.2 μg/m(3) respectively. Fifty-four percent of mothers (55/103) smoked at some point in pregnancy (39% smoked throughout pregnancy). Environmental tobacco smoke (ETS) exposure occurred in 68% of homes during the infants' first year. Significant to this study was the size- and time-resolved monitoring of PM at 140 home visits and the classification of PM count data. PM number counts ranged from continuously low levels (little indoor activity) to continuously high counts (constant indoor activity), and recorded apparent instances of prolonged repeated cigarette smoking. Wheezing in the first year of life was recorded for 38% of the infants (39/103). Adjusted logistic regression modeling demonstrated that elevated levels of indoor PM(2.5) (≥ 15 μg/m(3)) were a significant risk factor for infant wheezing after controlling for infant gender, mothers' age and education level, season of home visit and presence of carpeting (OR 4.21; 95% CI 1.36-13.03; p=0.013). An elevated level of the nicotine metabolite cotinine in infant urine also was associated with infant wheezing after adjusting for infant gender, mothers' age and education level (OR 5.10; 95% CI 0.96-27.24; p=0.057). ETS exposure was pervasive in the AUDIT cohort and a risk for developing infants in this urban population., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The synthesis, structure, and spectroscopic signatures of a series of four-coordinate iron(II) complexes of β-ketoiminates and their zinc(II) analogues are presented. An unusual five-coordinate iron(II) triflate with three oxygen bound protonated β-ketoimines is also synthesized and structurally characterized. Single-crystal X-ray crystallographic analysis reveals that the deprotonated bis(chelate)metal complexes are four-coordinate with various degrees of distortion depending on the degree of steric bulk and the electronics of the metal center. Each of the high-spin iron(II) centers exhibits multiple electronic transitions including ligand π to π*, metal-to-ligand charge transfer, and spin-forbidden d-d bands. The (1)H NMR spectra of the paramagnetic high-spin iron(II) centers are assigned on the basis of chemical shifts, longitudinal relaxation times (T(1)), relative integrations, and substitution of the ligands. The electrochemical studies support variations in the ligand strength. Parallel mode EPR measurements for the isopropyl substituted ligand complex of iron(II) show low-field resonances (g > 9.5) indicative of complex aggregation or crystallite formation. No suitable solvent system or glassing mixture was found to remedy this phenomenon. However, the bulkier diisopropylphenyl substituted ligand exhibits an integer spin signal consistent with an isolated iron(ii) center [S = 2; D = -7.1 ± 0.8 cm(-1); E/D = 0.1]. A tentative molecular orbital diagram is assembled.

Background: gadolinium (Gd)-containing MRI contrast agents (GdCA) are widely used in studies of brain tumors, and a number of reports suggest that under certain conditions, such as renal failure, Gd may be released from GdCA into patient's tissues. Whether this may happen in abnormal tissues in the absence of renal failure has not been studied., Purpose: to test the hypothesis that the local retention of GdCA resulting from brain tumor-associated alterations in the blood-brain barrier (BBB) may result in the deposition of Gd released from the GdCA, depending on stability., Material and Methods: in this retrospective study, 30 selected brain tumor biopsies from 28 patients (taken before and after an institutional switch from a less stable to an intermediate stable GdCA) were searched for Gd-containing deposits using scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS). Relevant histories and laboratory results were obtained through institutional electronic records. Associations between the presence of deposits and other variables were tested for statistical significance using the two-tailed Fisher's exact test., Results: insoluble deposits containing Gd associated with phosphorus and calcium were found in seven biopsies from five patients. These deposits were found in patients with estimated GFRs above 53 ml/min, and were detected more often in those receiving GdCA before the switch from a less stable to an intermediate stable GdCA (P = 0.04), and may be more frequent in patients receiving more than one contrast-enhanced MR scan (P = 0.15)., Conclusion: Gd-containing deposits are present in brain tumors following contrast-enhanced MR scans in patients without severe renal disease. Further studies are needed to assess the clinical importance of the deposits we observed and to determine whether they are also found in other conditions that alter the integrity of the BBB.