ABSTRACT
Mercury (Hg) concentrations and their associated toxicological effects in terrestrial ecosystems of the Gulf of Mexico are largely unknown. Compounding this uncertainty, a large input of organic matter from the 2010 Deepwater Horizon oil spill may have altered Hg cycling and bioaccumulation dynamics. To test this idea, we quantified blood concentrations of total mercury (THg) in Seaside Sparrows (Ammospiza maritima) and Marsh Rice Rats (Oryzomys palustris) in marshes west and east of the Mississippi River in 2015 and 2016. We also tested for a difference in THg concentrations between oiled and non-oiled sites. To address the potential confounding effect of diet variation on Hg transfer, we used stable nitrogen (δ15N) and carbon (δ13C) isotope values as proxies of trophic position and the source of primary production, respectively. Our results revealed that five to six years after the spill, THg concentrations were not higher in sites oiled by the spill compared to non-oiled sites. In both species, THg was higher at sites east of the Mississippi River compared to control and oiled sites, located west. In Seaside Sparrows but not in Marsh Rice Rats, THg increased with δ15N values, suggesting Hg trophic biomagnification. Overall, even in sites with the most elevated THg, concentrations were generally low. In Seaside Sparrows, THg concentrations were also lower than previously reported in this and other closely related passerines, with only 7% of tested birds exceeding the lowest observed effect concentration associated with toxic effects across bird species (0.2 µg/g ww). The factors associated with geographic heterogeneity in Hg exposure remain uncertain. Clarification could inform risk assessment and future restoration and management actions in a region facing vast anthropogenic changes.
ABSTRACT
The increasing frequency and severity of wildfires are among the most visible impacts of climate change. However, the effects of wildfires on mercury (Hg) transformations and bioaccumulation in stream ecosystems are poorly understood. We sampled soils, water, sediment, in-stream leaf litter, periphyton, and aquatic invertebrates in 36 burned (one-year post fire) and 21 reference headwater streams across the northwestern U.S. to evaluate the effects of wildfire occurrence and severity on total Hg (THg) and methylmercury (MeHg) transport and bioaccumulation. Suspended particulate THg and MeHg concentrations were 89 and 178% greater in burned watersheds compared to unburned watersheds and increased with burn severity, likely associated with increased soil erosion. Concentrations of filter-passing THg were similar in burned and unburned watersheds, but filter-passing MeHg was 51% greater in burned watersheds, and suspended particles in burned watersheds were enriched in MeHg but not THg, suggesting higher MeHg production in burned watersheds. Among invertebrates, MeHg in grazers, filter-feeders, and collectors was 33, 48, and 251% greater in burned watersheds, respectively, but did not differ in shredders or predators. Thus, increasing wildfire frequency and severity may yield increased MeHg production, mobilization, and bioaccumulation in headwaters and increased transport of particulate THg and MeHg to downstream environments.
Subject(s)
Bioaccumulation , Mercury , Methylmercury Compounds , Rivers , Water Pollutants, Chemical , Wildfires , Mercury/metabolism , Water Pollutants, Chemical/metabolism , Methylmercury Compounds/metabolism , Rivers/chemistry , Northwestern United States , Methylation , Animals , Invertebrates/metabolism , Environmental Monitoring , EcosystemABSTRACT
Atmospheric mercury (Hg) emissions and subsequent transport and deposition are major concerns within protected lands, including national parks, where Hg can bioaccumulate to levels detrimental to human and wildlife health. Despite this risk to biological resources, there is limited understanding of the relative importance of different Hg sources and delivery pathways within the protected regions. Here, we used Hg stable isotope measurements within a single aquatic bioindicator, dragonfly larvae, to determine if these tracers can resolve spatial patterns in Hg sources, delivery mechanisms, and aquatic cycling at a national scale. Mercury isotope values in dragonfly tissues varied among habitat types (e.g., lentic, lotic, and wetland) and geographic location. Photochemical-derived isotope fractionation was habitat-dependent and influenced by factors that impact light penetration directly or indirectly, including dissolved organic matter, canopy cover, and total phosphorus. Strong patterns for Δ200Hg emerged in the western United States, highlighting the relative importance of wet deposition sources in arid regions in contrast to dry deposition delivery in forested regions. This work demonstrates the efficacy of dragonfly larvae as biosentinels for Hg isotope studies due to their ubiquity across freshwater ecosystems and ability to track variation in Hg sources and processing attributed to small-scale habitat and large-scale regional patterns.
ABSTRACT
Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms resulting from exposure to trauma. Women are twice as likely to be diagnosed with anxiety and PTSD compared to men; however, the reason for this vulnerability remains unknown. We conducted four experiments where we first demonstrated a female vulnerability to stress-enhanced fear learning (SEFL) with a moderate, acute early life stress (aELS) exposure (4 footshocks in a single session), compared to a more intense aELS exposure (15 footshocks in a single session) where males and females demonstrated comparable SEFL. Next, we demonstrated that this female vulnerability does not result from differences in footshock reactivity or contextual fear conditioning during the aELS exposure. Finally, using gonadectomy or sham surgeries in adult male and female rats, we showed that circulating levels of gonadal steroid hormones at the time of adult fear conditioning do not explain the female vulnerability to SEFL. Additional research is needed to determine whether this vulnerability can be explained by organizational effects of gonadal steroid hormones or differences in sex chromosome gene expression. Doing so is critical for a better understanding of increased female vulnerability to certain psychiatric diseases.
Subject(s)
Fear , Sex Characteristics , Stress, Psychological , Animals , Fear/physiology , Male , Female , Rats , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Behavior, Animal/physiology , Conditioning, Classical/physiology , Rats, Sprague-Dawley , Gonadal Steroid Hormones/metabolism , Learning/physiologyABSTRACT
INTRODUCTION: Pregnancy has a profound impact on physical fitness, and delivery does not allow for rapid return to peak performance levels as physiologic changes can persist for greater than 1 year postpartum. Multiple studies across all military services have documented decrements in physical performance with pregnancy among women. The purpose of this study was to determine the impact of serial pregnancies on physical fitness and body composition in a cohort of Army women. We hypothesized that a second pregnancy would be associated with increasing decrements in physical fitness in active duty soldiers beyond that seen following a first delivery. MATERIALS AND METHODS: This retrospective cohort study screened all active duty soldiers who had delivered a singleton pregnancy of ≥32 weeks gestation between January 1, 2011 and March 31, 2017 at a single military medical center. This roster of eligible women was used to extract Army Physical Fitness Test (APFT) and height/weight data from the U.S. Army Digital Training Management System. Soldiers who delivered their first 2 pregnancies over this period were included. Select antepartum, intrapartum, and postpartum data were collected from the electronic medical record. The primary outcome variables were raw scores for push-ups, sit-ups, and run events as well as weight measures across the 2 pregnancies. The secondary outcomes were the failure rates on both the APFT events and body mass index measurements. Data were analyzed using paired t-tests to compare the means of APFT scores across the 2 pregnancies. The subjects served as their own controls. This study was approved by Regional Health Command-Pacific. RESULTS: A total of 2,103 active duty soldiers delivered singleton pregnancies at Tripler Army Medical Center between January 2011 and March 2017. Among these, 16 women delivered both their first- and second-term pregnancies and had APFT data available for analysis. Average age at time of first and second delivery was 26.1 and 28.1 years, respectively. Mean time separating the first postpartum APFT from the delivery was 8.8 months for the first pregnancy and 7.3 months following the second.A significant decrease in mean sit-up score was found comparing APFT-1 with APFT-2 (72.1 vs 65.7, P = .043) and comparing APFT-1 to APFT-3 (72.1 vs 60.9, P = .002). A significant increase in mean run time was found comparing APFT-1 to APFT-3 (16.9 minutes vs 17.9 minutes, P = .010) and APFT-2 to APFT-3 (17.5 minutes vs 17.9 minutes, P = .027). Comparing APFT-1 to APFT-3 showed a significant decrease in sit-up raw scores (P = .002), run times (P = .010), and total APFT scores (P = .01). Overall, the data show a trend of decreasing performance in all APFT events across the 3 APFTs and a trend toward higher failure rates. This cohort of soldiers did not experience weight gain following the pregnancies. CONCLUSIONS: The present study is the first to analyze the association of serial pregnancies on physical fitness utilizing a validated physical fitness test, and the results suggest that a second pregnancy is associated with progressive worsening of performance. This study is limited by the small sample size, and future studies could further elucidate the degree to which serial pregnancies affect physical fitness.
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshift stimulatory element (FSE) is necessary for programmed -1 ribosomal frameshifting (-1 PRF) and optimized viral efficacy. The FSE has an abundance of context-dependent alternate conformations, but two of the structures most crucial to -1 PRF are an attenuator hairpin and a three-stem H-type pseudoknot structure. A crystal structure of the pseudoknot alone features three RNA stems in a helically stacked linear structure, whereas a 6.9 Å cryo-EM structure including the upstream heptameric slippery site resulted in a bend between two stems. Our previous research alluded to an extended upstream multibranch loop that includes both the attenuator hairpin and the slippery site-a conformation not previously modeled. We aim to provide further context to the SARS-CoV-2 FSE via computational and medium resolution cryo-EM approaches, by presenting a 6.1 Å cryo-EM structure featuring a linear pseudoknot structure and a dynamic upstream multibranch loop.
Subject(s)
Cryoelectron Microscopy , Frameshifting, Ribosomal , Nucleic Acid Conformation , RNA, Viral , SARS-CoV-2 , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , RNA, Viral/chemistry , RNA, Viral/genetics , RNA, Viral/metabolism , Humans , Models, Molecular , COVID-19/virologyABSTRACT
INTRODUCTION: Physical activity (PA) promotion among school-aged youth is a global health priority. Recommendations for such promotion include implementing whole-of-school approaches that maximize resources across the school environment. This study examined schools' participation in an annual, government-led, and emirate-wide initiative in Dubai, called the Dubai Fitness Challenge, in which the goal is to accrue 30 minutes of PA every day for 30 days (as such, the initiative is colloquially referred to as "Dubai 30x30"). METHODS: A mixed-methods design was employed for this study. Three schools were recruited using convenience sampling. Participants were 18 physical education teachers, 20 classroom teachers, 2 principals and 45 students. Data sources included surveys, focus groups, and interviews. Data were analyzed using descriptive statistics, multinomial logistic regression, and open and axial coding to develop themes. RESULTS: School staff reported that most Dubai 30x30 activities were provided in physical education, at break times during school, and before and after school. Students reported that they mainly participated in Dubai 30x30 activities during physical education and occasionally participated in activities after school and on weekends. During school, students were more likely to reach higher PA intensity levels when they were in contexts other than the regular classroom setting. Among school staff, physical education teachers were most involved and classroom teachers were least involved in promoting Dubai 30x30. Parent engagement was high. Staff perceived that Dubai 30x30 brought the community together, but physical education teachers also indicated there was a lack of implementation guidance and they felt burdened. Participants believed Dubai 30x30 increased PA participation and helped to promote their schools. DISCUSSION: This study provides an initial glimpse into schools' participation in Dubai 30x30 and suggests that a whole-of-school PA lens is useful in gleaning information that could help to increase and optimize PA opportunities for students.
Subject(s)
Exercise , Schools , Adolescent , Humans , Child , Students , Motivation , Population Groups , School Health Services , Health Promotion/methodsABSTRACT
PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. CONCLUSIONS: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.
ABSTRACT
The androgen receptor (AR) is a ligand-dependent nuclear transcription factor belonging to the steroid hormone nuclear receptor family. Due to its roles in regulating cell proliferation and differentiation, AR is tightly regulated to maintain proper levels of itself and the many genes it controls. AR dysregulation is a driver of many human diseases including prostate cancer. Though this dysregulation often occurs at the RNA level, there are many unknowns surrounding post-transcriptional regulation of AR mRNA, particularly the role that RNA secondary structure plays. Thus, a comprehensive analysis of AR transcript secondary structure is needed. We address this through the computational and experimental analyses of two key isoforms, full length (AR-FL) and truncated (AR-V7). Here, a combination of in-cell RNA secondary structure probing experiments (targeted DMS-MaPseq) and computational predictions were used to characterize the static structural landscape and conformational dynamics of both isoforms. Additionally, in-cell assays were used to identify functionally relevant structures in the 5' and 3' UTRs of AR-FL. A notable example is a conserved stem loop structure in the 5'UTR of AR-FL that can bind to Poly(RC) Binding Protein 2 (PCBP2). Taken together, our results reveal novel features that regulate AR expression.
Subject(s)
Nucleic Acid Conformation , Receptors, Androgen , Receptors, Androgen/metabolism , Receptors, Androgen/genetics , Receptors, Androgen/chemistry , Humans , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Isoforms/chemistry , RNA, Messenger/metabolism , RNA, Messenger/genetics , RNA, Messenger/chemistry , 3' Untranslated Regions , 5' Untranslated Regions , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , MaleABSTRACT
BACKGROUND: Regular participation in physical activity (PA) benefits children's health and well-being and protects against the development of unhealthy body weight. A key factor in children's PA participation is their motor competence (MC). The comprehensive school physical activity program (CSPAP) framework offers a way to classify existing PA interventions that have included children's MC development and understand the potential avenues for supporting children's MC. However, there have been no systematic reviews or meta-analyses of PA interventions and their effects on the MC of elementary school children (aged 5-12 years) from a CSPAP perspective. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We searched seven electronic databases (PubMed/Medline, Embase, ERIC, SPORTDiscus, CINAHL, Web of Science, and PsycINFO) for articles on 29 November 2021. The CSPAP framework was used to categorize the different intervention approaches. This review was registered with PROSPERO (CRD42020179866). RESULTS: Twenty-seven studies were included in the review, and twenty-six studies were included in the meta-analysis. A wide range of PA intervention approaches (e.g., single component or multicomponent) within the context of the CSPAP framework appear to be promising pathways in enhancing children's MC. The results of the aggregate meta-analysis presented that effect sizes for the development of MC from pre-and post- intervention ranged from moderate to large (Hedges' g = 0.41-0.79). The analysis revealed that the predicted moderators, including study length, delivery agent, and study design, did not result in statistically significant moderate variations in MC outcomes. There was, however, considerable heterogeneity in study design, instruments, and study context, and studies were implemented in over 11 countries across diverse settings. CONCLUSIONS: This study uniquely contributes to the literature through its primary focus on the effectiveness of PA interventions on elementary children's MC. This review emphasizes the importance of customizing CSPAP to fit the specific characteristics of each school setting, including its environmental, demographic, and resource attributes. The effectiveness of CSPAP, particularly its physical education (PE) component, is significantly enhanced when these programs are adapted to address the unique needs of each school. This adaptation can be effectively achieved through targeted professional teacher training, ensuring that PE programs are not only contextually relevant but also optimized for maximum impact in diverse educational environments. Researchers and practitioners should pursue how to effectively translate the evidence into practice to better conceptualize CSPAPs designed for children's MC development.
Subject(s)
Exercise , Humans , Child , Child, Preschool , School Health Services , Health Promotion/methods , Motor Skills/physiology , SchoolsABSTRACT
PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.
Subject(s)
Black or African American , Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , White People , Humans , Female , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/ethnology , Uterine Cervical Neoplasms/mortality , White People/statistics & numerical data , Middle Aged , Black or African American/statistics & numerical data , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/ethnology , Carcinoma, Squamous Cell/mortality , Adult , Adenocarcinoma/pathology , Adenocarcinoma/ethnology , Adenocarcinoma/mortality , United States/epidemiology , Healthcare Disparities/ethnology , Healthcare Disparities/statistics & numerical data , Health Status Disparities , Socioeconomic Factors , Proportional Hazards Models , Neoplasm StagingABSTRACT
Terrestrial soils in forested landscapes represent some of the largest mercury (Hg) reserves globally. Wildfire can alter the storage and distribution of terrestrial-bound Hg via reemission to the atmosphere or mobilization in watersheds where it may become available for methylation and uptake into food webs. Using data associated with the 2007 Moonlight and Antelope Fires in California, we examined the long-term direct effects of wildfire burn severity on the distribution and magnitude of Hg concentrations in riparian food webs. Additionally, we quantified the cross-ecosystem transfer of Hg from aquatic invertebrate to riparian bird communities; and assessed the influence of biogeochemical, landscape variables, and ecological factors on Hg concentrations in aquatic and terrestrial food webs. Benthic macroinvertebrate methylmercury (MeHg) and riparian bird blood total mercury (THg) concentrations varied by 710- and 760-fold, respectively, and Hg concentrations were highest in predators. We found inconsistent relationships between Hg concentrations across and within taxa and guilds in response to stream chemical parameters and burn severity. Macroinvertebrate scraper MeHg concentrations were influenced by dissolved organic carbon (DOC); however, that relationship was moderated by burn severity (as burn severity increased the effect of DOC declined). Omnivorous bird Hg concentrations declined with increasing burn severity. Overall, taxa more linked to in situ energetic pathways may be more responsive to the biogeochemical processes that influence MeHg cycling. Remarkably, 8 years post-fire, we still observed evidence of burn severity influencing Hg concentrations within riparian food webs, illustrating its overarching role in altering the storage and redistribution of Hg and influencing biogeochemical processes.
Subject(s)
Burns , Mercury , Methylmercury Compounds , Water Pollutants, Chemical , Wildfires , Animals , Ecosystem , Rivers , Water Pollutants, Chemical/analysis , Invertebrates/metabolism , Mercury/analysis , Methylmercury Compounds/metabolism , Food Chain , Birds/metabolism , Environmental MonitoringABSTRACT
MYC pre-mRNA is spliced with high fidelity to produce the transcription factor known to regulate cellular differentiation, proliferation, apoptosis, and alternative splicing. The mechanisms underpinning the pre-mRNA splicing of MYC, however, remain mostly unexplored. In this study, we examined the interaction of heterogeneous nuclear ribonucleoprotein C (HNRNPC) with MYC intron 2. Building off published eCLIP studies, we confirmed this interaction with poly(U) regions in intron 2 of MYC and found that full binding is correlated with optimal protein production. The interaction appears to be compensatory, as mutational disruption of all three poly(U) regions was required to reduce both HNRNPC binding capacity and fidelity of either splicing or translation. Poly(U) sequences in MYC intron 2 were relatively conserved across sequences from several different species. Lastly, we identified a short sequence just upstream of an HNRNPC binding region that when removed enhances MYC translation.
Subject(s)
RNA Precursors , RNA Splicing , Introns/genetics , RNA Precursors/genetics , Alternative Splicing , MutationABSTRACT
Impoundment is among the most common hydrologic alterations with impacts on aquatic ecosystems that can include effects on mercury (Hg) cycling. However, landscape-scale differences in Hg bioaccumulation between reservoirs and other habitats are not well characterized nor are the processes driving these differences. We examined total Hg (THg) concentrations of Smallmouth Bass (Micropterus dolomieu) collected from reservoir, tailrace, and free-flowing reaches along an 863 km segment of the Snake River, USA, a semiarid river with 22 impoundments along its course. Across three size-classes (putative 1-year-old, first reproductive, and harvestable sized fish), THg concentrations in reservoirs and tailraces averaged 76% higher than those in free-flowing segments. Among reservoirs, THg concentrations were highest in reservoirs with inconsistent stratification patterns, 47% higher than annually stratified, and 144% higher than unstratified reservoirs. Fish THg concentrations in tailraces immediately downstream of stratified reservoirs were higher than those below unstratified (38-130%) or inconsistently stratified (32-79%) reservoirs. Stratification regimes influenced the exceedance of fish and human health benchmarks, with 52-80% of fish from stratifying reservoirs and downstream tailraces exceeding a human consumption benchmark, compared to 6-17% where stratification did not occur. These findings suggest that impoundment and stratification play important roles in determining the patterns of Hg exposure risk across the landscape.
Subject(s)
Bass , Mercury , Methylmercury Compounds , Water Pollutants, Chemical , Animals , Humans , Infant , Mercury/analysis , Ecosystem , Environmental Monitoring , Water Pollutants, Chemical/analysis , FishesABSTRACT
The orphan gene of SARS-CoV-2, ORF10, is the least studied gene in the virus responsible for the COVID-19 pandemic. Recent experimentation indicated ORF10 expression moderates innate immunity in vitro. However, whether ORF10 affects COVID-19 in humans remained unknown. We determine that the ORF10 sequence is identical to the Wuhan-Hu-1 ancestral haplotype in 95% of genomes across five variants of concern (VOC). Four ORF10 variants are associated with less virulent clinical outcomes in the human host: three of these affect ORF10 protein structure, one affects ORF10 RNA structural dynamics. RNA-Seq data from 2070 samples from diverse human cells and tissues reveals ORF10 accumulation is conditionally discordant from that of other SARS-CoV-2 transcripts. Expression of ORF10 in A549 and HEK293 cells perturbs immune-related gene expression networks, alters expression of the majority of mitochondrially-encoded genes of oxidative respiration, and leads to large shifts in levels of 14 newly-identified transcripts. We conclude ORF10 contributes to more severe COVID-19 clinical outcomes in the human host.
ABSTRACT
A 53-year-old patient was admitted to the emergency department, presenting with fever, generalized weakness, and various myalgias and arthralgias lasting over seven days. Based upon the patient's worsening symptoms, elevated white blood cell count with neutrophilia and overall presentation, she was initially treated for an infectious cause and prescribed various antibiotics and antipyretic medications. As the patient's condition continued to worsen throughout the initial days of her intake, she was tested for a variety of infections, including coronavirus disease 2019 (COVID-19), Streptococcus, and influenza, and was administered a viral respiratory panel, all of which resulted negative. Upon the development of an evanescent rash on hospital day 9, as well as other symptoms including sore throat, arthritis, and an elevated fever present for over a week, a rheumatology consult now expressed concern for a possible case of Adult-Onset Still's Disease (AOSD). In line with the current treatment used for AOSD and the absence of all other infectious causes, the patient discontinued antibiotic treatment and was started on 125 milligrams of intravenous methylprednisolone every six hours. The patient showed minor improvements in symptoms over the next 24 hours but soon became refractory to treatment, resulting from multiorgan damage, and expired on hospital day 13.
ABSTRACT
Normal thyroid hormone levels are crucial for the homeostasis of many metabolic cycles and processes throughout the human body. Thyroid dysfunction, such as thyrotoxicosis, can result from many different etiologies, including Graves' disease (GD), toxic multinodular goiter (MNG), and toxic adenoma. These hyperthyroid disease states can cause devastating complications and disease, including the disruption of the bone remodeling cycle and skeletal development, which can result in osteoporosis. Osteoporosis is characterized by a decrease in bone mineral density and a propensity for fragility fractures. In addition to patients with overt hyperthyroidism, studies have provided evidence of other high-risk patient demographics, such as individuals with subclinical hyperthyroidism and postmenopausal women, who may be at an increased risk for the development of secondary osteoporosis. The treatment of patients with hyperthyroid-induced osteoporosis often requires a multifaceted management plan that may be unique to each patient's situation. Antithyroid therapy is often the first step in treating this disease and may include thioamide medications. Radioactive iodine-131 therapy (RAI) and the surgical removal of the thyroid gland may also be reasonable approaches for restoring normal thyroid function. Following thyrotoxicosis mitigation, antiresorptive drugs such as bisphosphonates, calcitonin, and selective estrogen receptor modulators (SERMs) may be used to counteract decreased bone mineral density (BMD). Additionally, the implementation of vitamin D, calcium supplements, and weight-bearing exercise may also reduce bone loss. While the effects of thyroid stimulating hormone (TSH) and triiodothyronine (T3) on bone remodeling have been studied in the past, more research is needed to identify unknown mechanisms and develop future improved treatments for this condition.
ABSTRACT
Mercury (Hg) is a toxic contaminant that has been mobilized and distributed worldwide and is a threat to many wildlife species. Amphibians are facing unprecedented global declines due to many threats including contaminants. While the biphasic life history of many amphibians creates a potential nexus for methylmercury (MeHg) exposure in aquatic habitats and subsequent health effects, the broad-scale distribution of MeHg exposure in amphibians remains unknown. We used nonlethal sampling to assess MeHg bioaccumulation in 3,241 juvenile and adult amphibians during 2017-2021. We sampled 26 populations (14 species) across 11 states in the United States, including several imperiled species that could not have been sampled by traditional lethal methods. We examined whether life history traits of species and whether the concentration of total mercury in sediment or dragonflies could be used as indicators of MeHg bioaccumulation in amphibians. Methylmercury contamination was widespread, with a 33-fold difference in concentrations across sites. Variation among years and clustered subsites was less than variation across sites. Life history characteristics such as size, sex, and whether the amphibian was a frog, toad, newt, or other salamander were the factors most strongly associated with bioaccumulation. Total Hg in dragonflies was a reliable indicator of bioaccumulation of MeHg in amphibians (R2 ≥ 0.67), whereas total Hg in sediment was not (R2 ≤ 0.04). Our study, the largest broad-scale assessment of MeHg bioaccumulation in amphibians, highlights methodological advances that allow for nonlethal sampling of rare species and reveals immense variation among species, life histories, and sites. Our findings can help identify sensitive populations and provide environmentally relevant concentrations for future studies to better quantify the potential threats of MeHg to amphibians.
Subject(s)
Mercury , Methylmercury Compounds , Odonata , Water Pollutants, Chemical , Animals , Water Pollutants, Chemical/analysis , Mercury/analysis , Amphibians , Environmental MonitoringABSTRACT
The transfer of aquatic contaminants, including mercury (Hg), to terrestrial food webs is an often-overlooked exposure pathway to terrestrial animals. While research has implemented the use of shoreline spiders to assess aquatic to terrestrial Hg transfer, it is unclear whether Hg sources, estimated from isotope ratios, can be successfully resolved to inform site assessments and remedy effectiveness. To examine aquatic to terrestrial Hg transfer, we collected shoreline spiders (Tetragnatha spp.) and aquatic insect larvae (suborder Anisoptera) across a mosaic of aquatic and shoreline habitats in the St. Louis River and Bad River, tributaries to Lake Superior. The fraction of industrial Hg in sediments was reflected in the δ202Hg values of aquatic dragonfly larvae and predatory fish, connecting benthic Hg sources to the aquatic food web. Shoreline spiders mirrored these aquatic Hg source signatures with highly positive correlations in δ202Hg between tetragnathids and dragonfly larvae (r2 = 0.90). Further assessment of different spider taxa (i.e., araneids and pisaurids) revealed that differences in prey consumption and foraging strategies resulted in isotope differences, highlighting the importance of spider taxa selection for Hg monitoring efforts.
ABSTRACT
Major advances in RNA secondary structural motif prediction have been achieved in the last few years; however, few methods harness the predictive power of multiple approaches to deliver in-depth characterizations of local RNA motifs and their potential functionality. Additionally, most available methods do not predict RNA pseudoknots. This work combines complementary bioinformatic systems into one robust discovery pipeline where: â¢RNA sequences are folded to search for thermodynamically favorable motifs utilizing ScanFold.â¢Motifs are expanded and refolded into alternate pseudoknot conformations by Knotty/Iterative HFold.â¢All conformations are evaluated for covariance via the cm-builder pipeline (Infernal and R-scape).