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Quantitative adverse outcome pathways (qAOPs) describe the response-response relationships that link the magnitude and/or duration of chemical interaction with a specific molecular target to the probability and/or severity of the resulting apical-level toxicity of regulatory relevance. The present study developed the first qAOP for latent toxicities showing that early life exposure adversely affects health at adulthood. Specifically, a qAOP for embryonic activation of the aryl hydrocarbon receptor 2 (AHR2) of fishes by polycyclic aromatic hydrocarbons (PAHs) leading to decreased fecundity of females at adulthood was developed by building on existing qAOPs for (1) activation of the AHR leading to early life mortality in birds and fishes, and (2) inhibition of cytochrome P450 aromatase activity leading to decreased fecundity in fishes. Using zebrafish (Danio rerio) as a model species and benzo[a]pyrene as a model PAH, three linked quantitative relationships were developed: (1) plasma estrogen in adult females as a function of embryonic exposure, (2) plasma vitellogenin in adult females as a function of plasma estrogen, and (3) fecundity of adult females as a function of plasma vitellogenin. A fourth quantitative relationship was developed for early life mortality as a function of sensitivity to activation of the AHR2 in a standardized in vitro AHR transactivation assay to integrate toxic equivalence calculations that would allow prediction of effects of exposure to untested PAHs. The accuracy of the predictions from the resulting qAOP were evaluated using experimental data from zebrafish exposed as embryos to another PAH, benzo[k]fluoranthene. The qAOP developed in the present study demonstrates the potential of the AOP framework in enabling consideration of latent toxicities in quantitative ecological risk assessments and regulatory decision-making. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.
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Background: Native American communities suffered disproportionately negative effects during the COVID-19 pandemic, yet no research has explored the experiences of rural Eastern Region Native Americans. Methods: Informed by the Native Reliance Model and Indigenous Standpoint Theory, we conducted a qualitative descriptive project in the Spring and Summer of 2022; data included semi-structured interviews and focus groups with 24 individuals representing five South Carolina tribal groups. Findings: Thematic analysis yielded four emergent themes: 1) "Let's just finish the Indians off": Pandemic distrust rooted in historical and contemporary Native American experiences; 2) "We have been misled": Making sense of conflicting public health information; 3) "I'm not giving it to some innocent person": COVID-19 mitigation behaviors as Native American cultural practice; and 4) "We put the plan in place": Self-advocacy and action as a source of Native American pride and responsibility. Interpretation: These participants demonstrated resiliency grounded in family and tribal ties, even in the face of personal losses, economic struggles, and healthcare barriers. To strike a balance between cultural traditions and public health recommendations, public health practitioners should 1) build partnerships with community leaders, elders, and tribal health authorities to facilitate the development of culturally respectful interventions that address specific health concerns in the context of historical traumas; and 2) implement alternative methods of communication and engagement to ensure equitable access to healthcare services in rural locations, such as collaborating with community organizations, deploying mobile health units, and utilizing traditional channels of communication within these communities.
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BACKGROUND/AIM: Uveal melanoma is an ocular malignancy whose prognosis severely worsens following metastasis. In order to improve the understanding of molecular physiology of metastatic uveal melanoma, we identified genes and pathways implicated in metastatic vs non-metastatic uveal melanoma. PATIENTS AND METHODS: A previously published dataset from Gene Expression Omnibus (GEO) was used to identify differentially expressed genes between metastatic and non-metastatic samples as well as to conduct pathway and perturbagen analyses using Gene Set Enrichment Analysis (GSEA), EnrichR, and iLINCS. RESULTS: In male metastatic uveal melanoma samples, the gene LOC401052 is significantly down-regulated and FHDC1 is significantly up-regulated compared to non-metastatic male samples. In female samples, no significant differently expressed genes were found. Additionally, we identified many significant up-regulated immune response pathways in male metastatic uveal melanoma, including "T cell activation in immune response". In contrast, many top up-regulated female pathways involve iron metabolism, including "heme biosynthetic process". iLINCS perturbagen analysis identified that both male and female samples have similar discordant activity with growth factor receptors, but only female samples have discordant activity with progesterone receptor agonists. CONCLUSION: Our results from analyzing genes, pathways, and perturbagens demonstrate differences in metastatic processes between sexes.
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Perfilação da Expressão Gênica , Melanoma , Neoplasias Uveais , Humanos , Neoplasias Uveais/genética , Neoplasias Uveais/patologia , Neoplasias Uveais/metabolismo , Melanoma/genética , Melanoma/patologia , Melanoma/metabolismo , Feminino , Masculino , Metástase Neoplásica , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Fatores SexuaisRESUMO
Working with aquatic organisms often requires handling multiple individuals in a single session, potentially resulting in cross-contamination by live pathogens or DNA. Most researchers address this problem by disposing of gloves between animals. However, this generates excessive waste and may be impractical for processing very slippery animals that might be easier to handle with cotton gloves. We tested methods to decontaminate cotton or nitrile gloves after contamination with cultured Batrachochytrium dendrobatidis (Bd) or after handling heavily Bd-infected Xenopus laevis with layered cotton and nitrile gloves. Bleach eliminated detectable Bd DNA from culture-contaminated nitrile gloves, but gloves retained detectable Bd DNA following ethanol disinfection. After handling a Bd-infected frog, Bd DNA contamination was greatly reduced by removal of the outer cotton glove, after which either bleach decontamination or ethanol decontamination followed by drying hands with a paper towel lowered Bd DNA below the detection threshold of our assay. These results provide new options to prevent pathogen or DNA cross-contamination, especially when handling slippery aquatic organisms. However, tradeoffs should be considered when selecting an animal handling procedure, such as the potential for cotton gloves to abrade amphibian skin or disrupt skin mucus. Disposing of gloves between animals should remain the gold standard for maintaining biosecurity in sensitive situations.
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Descontaminação , Luvas Protetoras , Animais , Descontaminação/métodos , Luvas Protetoras/microbiologia , Batrachochytrium , DNA Fúngico , Micoses/veterinária , Micoses/prevenção & controle , Micoses/microbiologiaRESUMO
Rubisco is the primary CO2 fixing enzyme of the biosphere yet has slow kinetics. The roles of evolution and chemical mechanism in constraining the sequence landscape of rubisco remain debated. In order to map sequence to function, we developed a massively parallel assay for rubisco using an engineered E. coli where enzyme function is coupled to growth. By assaying >99% of single amino acid mutants across CO2 concentrations, we inferred enzyme velocity and CO2 affinity for thousands of substitutions. We identified many highly conserved positions that tolerate mutation and rare mutations that improve CO2 affinity. These data suggest that non-trivial kinetic improvements are readily accessible and provide a comprehensive sequence-to-function mapping for enzyme engineering efforts.
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We estimated COVID-19 transmission potential and case burden by variant type in Alberta, British Columbia, and Ontario, Canada, during January 23, 2020-January 27, 2022; we also estimated the effectiveness of public health interventions to reduce transmission. We estimated time-varying reproduction number (Rt) over 7-day sliding windows and nonoverlapping time-windows determined by timing of policy changes. We calculated incidence rate ratios (IRRs) for each variant and compared rates to determine differences in burden among provinces. Rt corresponding with emergence of the Delta variant increased in all 3 provinces; British Columbia had the largest increase, 43.85% (95% credible interval [CrI] 40.71%-46.84%). Across the study period, IRR was highest for Omicron (8.74 [95% CrI 8.71-8.77]) and burden highest in Alberta (IRR 1.80 [95% CrI 1.79-1.81]). Initiating public health interventions was associated with lower Rt and relaxing restrictions and emergence of new variants associated with increases in Rt.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/transmissão , Ontário/epidemiologia , Colúmbia Britânica/epidemiologia , Alberta/epidemiologia , Incidência , Número Básico de Reprodução , Saúde PúblicaRESUMO
Benzotriazole ultraviolet stabilizers (BUVSs) are chemicals used to mitigate UV-induced damage to manufactured goods. Their presence in aquatic environments and biota raises concerns, as certain BUVSs activate the aryl hydrocarbon receptor (AhR), which is linked to adverse effects in fish. However, potencies of BUVSs as AhR agonists and species sensitivities to AhR activation are poorly understood. This study evaluated the toxicity of three BUVSs using embryotoxicity assays. Zebrafish (Danio rerio) embryos exposed to BUVSs by microinjection suffered dose-dependent increases in mortality, with LD50 values of 4772, 11â¯608, and 56â¯292 ng/g-egg for UV-P, UV-9, and UV-090, respectively. The potencies and species sensitivities to AhR2 activation by BUVSs were assessed using a luciferase reporter gene assay with COS-7 cells transfected with the AhR2 of zebrafish and eight other fishes. The rank order of potency for activation of the AhR2 from all nine species was UV-P > UV-9 > UV-090. However, AhR2s among species differed in sensitivities to activation by up to 100-fold. An approximate reversed rank order of species sensitivity was observed compared to the rank order of sensitivity to 2,3,7,8-tetrachlorodibenzo[p]dioxin, the prototypical AhR agonist. Despite this, a pre-existing quantitative adverse outcome pathway linking AhR activation to embryo lethality could predict embryotoxicities of BUVSs in zebrafish.
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Dibenzodioxinas Policloradas , Peixe-Zebra , Animais , Receptores de Hidrocarboneto Arílico/genética , Triazóis/toxicidade , Triazóis/metabolismo , Dibenzodioxinas Policloradas/toxicidadeRESUMO
BACKGROUND: Pediatric renal trauma is rare and lacks sufficient population-specific data to generate evidence-based management guidelines. A non-operative approach is preferred and has been shown to be safe. However, bleeding risk assessment and management of collecting system injury is not well understood. We introduce the Multi-institutional Pediatric Acute Renal Trauma Study (Mi-PARTS), a retrospective cohort study designed to address these questions. This manuscript describes the demographics and contemporary management of pediatric renal trauma at Level I trauma centers in the United States. METHODS: Retrospective data were collected at 13 participating Level I trauma centers on pediatric patients presenting with renal trauma between 2010-2019. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Descriptive statistics were used to report on demographics, acute management and outcomes. RESULTS: In total 1216 cases were included in this study. 67.2% were male, and 93.8% had a blunt injury mechanism. 29.3% had isolated renal injuries. 65.6% were high-grade (AAST Grade III-V) injuries. The mean Injury Severity Score (ISS) was 20.5. Most patients were managed non-operatively (86.4%) 3.9% had an open surgical intervention, including 2.7% having nephrectomy. Angioembolization was performed in 0.9%. Collecting system intervention was performed in 7.9%. Overall mortality was 3.3% and was only observed in polytrauma. The rate of avoidable transfer was 28.2%. CONCLUSION: The management and outcomes of pediatric renal trauma lacks data to inform evidence-based guidelines. Non-operative management of bleeding following renal injury is a well-established practice. Intervention for renal trauma is rare. Our findings reinforce differences from the adult population, and highlights opportunities for further investigation. With data made available through Mi-PARTS we aim to answer pediatric specific questions, including a pediatric-specific bleeding risk nomogram, and better understanding indications for interventions for collecting system injuries. LEVEL OF EVIDENCE: IV, Epidemiological (prognostic/epidemiological, therapeutic/care management, diagnostic test/criteria, economic/value-based evaluations, and Systematic Review and Meta-Analysis).
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Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) present similarly with bradykinesia, tremor, rigidity, and cognitive impairments. Neuroimaging studies have found differential changes in the nigrostriatal pathway in these disorders, however whether the volume and shape of specific regions within this pathway can distinguish between atypical Parkinsonian disorders remains to be determined. This paper investigates striatal and thalamic volume and morphology as distinguishing biomarkers, and their relationship to neuropsychiatric symptoms. Automatic segmentation to calculate volume and shape analysis of the caudate nucleus, putamen, and thalamus were performed in 18 PD patients, 12 MSA, 15 PSP, and 20 healthy controls, then correlated with clinical measures. PSP bilateral thalami and right putamen were significantly smaller than controls, but not MSA or PD. The left caudate and putamen significantly correlated with the Neuropsychiatric Inventory total score. Bilateral thalamus, caudate, and left putamen had significantly different morphology between groups, driven by differences between PSP and healthy controls. This study demonstrated that PSP patient striatal and thalamic volume and shape are significantly different when compared with controls. Parkinsonian disorders could not be differentiated on volumetry or morphology, however there are trends for volumetric and morphological changes associated with PD, MSA, and PSP.
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Atrofia de Múltiplos Sistemas , Doença de Parkinson , Transtornos Parkinsonianos , Paralisia Supranuclear Progressiva , Humanos , Doença de Parkinson/diagnóstico por imagem , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Tálamo/metabolismoRESUMO
Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood. Here, we investigate the mechanisms of loss using an environmental enrichment removal (ER) paradigm in male rats. The basolateral amygdala (BLA) was identified as a region of interest, demonstrating differential Fos responsivity to ER and having an established role in stress processing and adaptation. A comprehensive multi-omics investigation of the BLA, spanning multiple cohorts, platforms, and analyses, revealed alterations in microglia and the extracellular matrix (ECM). Follow-up studies indicated that ER decreased microglia size, complexity, and phagocytosis, suggesting reduced immune surveillance. Loss also substantially increased ECM coverage, specifically targeting perineuronal nets surrounding parvalbumin interneurons, suggesting decreased plasticity and increased inhibition within the BLA following loss. Behavioral analyses suggest that these molecular effects are linked to impaired BLA salience evaluation, leading to a mismatch between stimulus and reaction intensity. These loss-like behaviors could be rescued by depleting BLA ECM during the removal period, helping us understand the mechanisms underlying loss and revealing novel molecular targets to ameliorate its impact.
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Complexo Nuclear Basolateral da Amígdala , Ratos , Animais , Masculino , Complexo Nuclear Basolateral da Amígdala/fisiologia , Neurobiologia , Qualidade de Vida , Interneurônios , Matriz ExtracelularRESUMO
While there is substantial public health literature that documents the negative impacts of living in "food deserts" (e.g., obesity and diabetes), little is known regarding whether living in a food desert is associated with increased criminal victimization. With the block group as the unit of analysis, the present study examines whether there is a relationship between food deserts and elevated crime counts, and whether this relationship varies by racial composition. Results from multiple count models suggest that living in a food desert is not associated with higher levels of violent or property crime. But multiplicative models interacting percent Black with food deserts revealed statistically significant associations with violent crime but not property crime. Alternatively, multiplicative models interacting percent White with food deserts revealed statistically significant associational reductions in violent crimes. Several policy and research implications are discussed.
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Vítimas de Crime , Desertos Alimentares , Humanos , Violência , Crime , AgressãoRESUMO
There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD). In 3671 participants aged 46-70 years at baseline, ∆lean mass was a stronger determinant than ∆fat mass of ∆BMD over 6 years. Maintained or increased lean mass may slow down age-related bone loss. PURPOSE: There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD) with ageing. We examined these in the Busselton Healthy Ageing Study. METHODS: We studied 3671 participants (2019 females) aged 46-70 years at baseline with body composition and BMD assessments by dual-energy x-ray absorptiometry at baseline and after ~6 years. Relationships between changes in total body mass (∆TM), lean mass (∆LM) and fat mass (∆FM) with ∆BMD at total hip, femoral neck and lumbar spine were evaluated using restricted cubic spline modelling (accounting for baseline covariates) and mid-quartile least square means were compared. RESULTS: ∆TM was positively associated with ∆BMD of total hip and femoral neck in both sexes, and spine in females; in females but not males, associations plateaued at ∆TM above ~5kg for all sites. In females, ∆LM was positively associated with ∆BMD of all three sites with plateauing of the relationship at ∆LM above ~1kg. Women in the highest quartile of ∆LM (Q4, mid-quartile value +1.6 kg) had 0.019-0.028 g/cm2 less reduction in BMD than those in the lowest quartile (Q1, -2.1 kg). In males, ∆LM was positively associated with ∆BMD of total hip and femoral neck; men in Q4 (+1.6 kg) had 0.015 and 0.011 g/cm2 less bone loss, respectively, compared with Q1 (-2.7 kg). ∆FM was positively associated with ∆BMD of total hip only in both sexes. CONCLUSION: ∆LM is a stronger determinant than ∆FM of ∆BMD. Maintained or increased LM is associated with less age-related bone loss.
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Densidade Óssea , Osteoporose , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Austrália/epidemiologia , Composição Corporal , Osteoporose/epidemiologia , Absorciometria de Fóton , Vértebras LombaresRESUMO
Remote sensing (RS), satellite imaging (SI), and geospatial analysis have established themselves as extremely useful and very diverse domains for research associated with space, spatio-temporal components, and geography. We evaluated in this review the existing evidence on the application of those geospatial techniques, tools, and methods in the coronavirus pandemic. We reviewed and retrieved nine research studies that directly used geospatial techniques, remote sensing, or satellite imaging as part of their research analysis. Articles included studies from Europe, Somalia, the USA, Indonesia, Iran, Ecuador, China, and India. Two papers used only satellite imaging data, three papers used remote sensing, three papers used a combination of both satellite imaging and remote sensing. One paper mentioned the use of spatiotemporal data. Many studies used reports from healthcare facilities and geospatial agencies to collect the type of data. The aim of this review was to show the use of remote sensing, satellite imaging, and geospatial data in defining features and relationships that are related to the spread and mortality rate of COVID-19 around the world. This review should ensure that these innovations and technologies are instantly available to assist decision-making and robust scientific research that will improve the population health diseases outcomes around the globe.
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COVID-19 , Tecnologia de Sensoriamento Remoto , Humanos , Tecnologia de Sensoriamento Remoto/métodos , Índia , China , EquadorRESUMO
INTRODUCTION: Venous leg ulcers (VLUs) are the final stage of chronic venous insufficiency. This study aims to characterize the association between cardiovascular diseases and VLU. METHODS: A multicentric case-control study analyzed 17,788 patients between 2015 and 2020. Cases were matched (1:2) by age and sex, and odds ratios (OR) were analyzed with conditional logistic regressions adjusted by risk factors. RESULTS: The prevalence of VLU was 15.2%. 2390 cases were analyzed. Diseases found to be associated with VLU were atrial fibrillation (OR, 1.21; 95% CI: 1.03-1.42), pulmonary hypertension (OR, 1.45; 95% CI: 1.06-2.00), right heart failure (OR, 1.27; 95% CI: 1.13-1.43), peripheral artery disease (OR, 2.21; 95% CI: 1.90-2.56), and history of pulmonary embolism (OR, 1.45; 95% CI: 1.06-2.00). CONCLUSIONS: Certain cardiovascular conditions showed an association with VLU. Further studies are warranted to evaluate the effect that treating concomitant cardiovascular diseases might exert on the natural history of venous leg ulcers.
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Doenças Cardiovasculares , Úlcera da Perna , Úlcera Varicosa , Insuficiência Venosa , Humanos , Estudos de Casos e Controles , Úlcera Varicosa/terapia , Insuficiência Venosa/epidemiologia , Fatores de Risco , Úlcera da Perna/epidemiologiaRESUMO
To date, little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, on the upper respiratory tract (URT) microbiota over time. To fill this knowledge gap, we used 16S ribosomal RNA gene sequencing to characterize the URT microbiota in 48 adults, including (1) 24 participants with mild-to-moderate COVID-19 who had serial mid-turbinate swabs collected up to 21 days after enrolment and (2) 24 asymptomatic, uninfected controls who had mid-turbinate swabs collected at enrolment only. To compare the URT microbiota between groups in a comprehensive manner, different types of statistical analyses that are frequently employed in microbial ecology were used, including âº-diversity, ß-diversity and differential abundance analyses. Final statistical models included age, sex and the presence of at least one comorbidity as covariates. The median age of all participants was 34.00 (interquartile range=28.75-46.50) years. In comparison to samples from controls, those from participants with COVID-19 had a lower observed species index at day 21 (linear regression coefficient=-13.30; 95â% CI=-21.72 to -4.88; q=0.02). In addition, the Jaccard index was significantly different between samples from participants with COVID-19 and those from controls at all study time points (PERMANOVA q<0.05 for all comparisons). The abundance of three amplicon sequence variants (ASVs) (one Corynebacterium ASV, Frederiksenia canicola, and one Lactobacillus ASV) were decreased in samples from participants with COVID-19 at all seven study time points, whereas the abundance of one ASV (from the family Neisseriaceae) was increased in samples from participants with COVID-19 at five (71.43â%) of the seven study time points. Our results suggest that mild-to-moderate COVID-19 can lead to alterations of the URT microbiota that persist for several weeks after the initial infection.
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COVID-19 , Microbiota , Humanos , Adulto , Pessoa de Meia-Idade , SARS-CoV-2 , Sistema RespiratórioRESUMO
Little is known about the relationships between symptomatic early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate coronavirus disease 19 (COVID-19). We measured SARS-CoV-2 viral load using reverse transcription-quantitative PCR (RT-qPCR). We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 95% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited codetection of other respiratory viruses, with the human Rhinovirus C being identified in 4 (6%) samples. This limited codetection of other respiratory viral pathogens may be due to the implementation of public health measures, like social distancing and masking practices. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusting for age, sex, and race. Interestingly, the expression levels of most of these genes plateaued at a cycle threshold (CT) value of ~25. Overall, our data show that the early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, potentially modifying COVID-19 outcomes. IMPORTANCE Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load, airway mucosal gene expression, and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load, interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load dependent and may modify COVID-19 outcomes.
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COVID-19 , Expressão Gênica , Mucosa Respiratória , SARS-CoV-2 , Carga Viral , Adulto , Humanos , Quimiocinas/fisiologia , COVID-19/imunologia , COVID-19/virologia , Expressão Gênica/imunologia , Imunidade nas Mucosas/imunologia , Interferons/fisiologia , SARS-CoV-2/genética , Mucosa Respiratória/imunologia , Mucosa Respiratória/virologiaRESUMO
Pharmacokinetic modelling suggests that sugammadex may interact with endogenous progesterone and reduce levels by 34% in patients taking hormonal contraception. Due to this potential interaction that may be equivalent to missing one dose of an oral contraceptive pill, both the manufacturer and professional anaesthesia organisations recommend counselling patients to use additional non-hormonal contraception after administration of sugammadex. We performed a prospective observational study examining the changes in serum oestrogen and progesterone concentrations in premenopausal adult women undergoing an operative procedure. Sixty participants who were on hormonal contraception received sugammadex. Two additional control groups were recruited, consisting of 30 participants who were not on hormonal contraception and did not receive sugammadex, and 32 who were not on hormonal contraception and did receive sugammadex. Three blood samples were taken: before sugammadex; 15 min post-sugammadex; and 240 min post-sugammadex or end of operating theatre time. Median oestrogen levels decreased from baseline by around 40% at 240 min in all three groups (p ≤ 0.001). Progesterone levels rose significantly at 15 min (p = 0.002) in patients on contraception then decreased non-significantly to 20% below baseline at 240 min. The decrease in oestrogen and the rise in progesterone could both act to minimise the risk of ovulation and thus protect contraception in this population. We found no evidence of a change in hormone levels that might threaten contraceptive efficacy in women on hormonal contraception receiving sugammadex.
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Anticoncepção , Progesterona , Adulto , Humanos , Feminino , Sugammadex/farmacologia , Anticoncepção/métodos , Estrogênios , Estudos ProspectivosRESUMO
Little is known about the relationships between symptomatic early-time SARS-CoV-2 viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate COVID-19. We measured SARS-CoV-2 viral load using qRT-PCR. We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 85% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited co-detection of common respiratory viruses i.e., only the human Rhinovirus (HRV) being identified in 6% of the samples. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusted for age, sex and race. Interestingly, the expression levels of most of these genes plateaued at a CT value of ~25. Overall, our data shows that early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, which potentially could modify COVID-19 outcomes. AUTHOR SUMMARY: Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load and airway mucosal gene expression and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during Spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load with interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load-dependent and may modify COVID-19 outcomes.
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BACKGROUND: Ulnar collateral ligament (UCL) surgery continues to demonstrate excellent clinical outcomes and a high return-to-play (RTP) rate with a low complication rate. Recent studies have demonstrated similar clinical outcomes for baseball players who have undergone either UCL reconstruction or UCL repair. In comparison, few studies have assessed the clinical outcomes of UCL surgery for nonthrowing athletes. PURPOSE/HYPOTHESIS: The primary objective of this study is to provide clinical outcomes of UCL surgery performed in nonthrowing athletes at a single institution with a minimum 2-year follow-up. Our hypothesis was that these patients would have similar clinical outcomes, complication rates, and RTP rates when compared with throwing athletes. LEVEL OF EVIDENCE: Case series; Level of evidence, 4. METHODS: From our longitudinal elbow registry, 40 nonthrowing athletes were identified who underwent UCL surgery (repair or reconstruction) between 2011 and 2019. Participant characteristics were recorded: age, sex, laterality, arm dominance, sport, level of competition, and type of surgery (UCL repair or reconstruction). Outcomes included RTP rate and average time, American Shoulder and Elbow Surgeons (ASES) scores, and complications. RESULTS: From the 40 patients eligible for inclusion in this study with a minimum 2-year follow-up, 37 (93%) were successfully contacted: 16 male (43%) and 21 female (57%). Mean ± standard deviation age at the time of surgery was 18.0 ± 3.7 years. From the 37 technical procedures, 28 (76%) were UCL repairs and 9 (24%) were UCL reconstructions. For these patients, 15 (41%) had partial tears, 20 (54%) had complete tears, 1 (3%) had a medial epicondyle avulsion, and 1 (3%) had an unspecified pathology. Sports included football (n = 11), gymnastics (11), cheerleading (7), wrestling (4), volleyball (2), basketball (1), and acrobatics (1). Quarterbacks were excluded from the football patients, as quarterbacks are throwing athletes. Level of competition included high school (n = 26), college (8), professional (2), and youth sports (1). The RTP rate was 93% (26/28) at a mean 7.4 months for UCL repair and 100% (9/9) at a mean 10.0 months for UCL reconstruction. Mean ASES scores were 94.4 and 98.7 for UCL repair and reconstruction, respectively. Complications were low, with 2 patients in the UCL repair group requiring ulnar nerve transposition for ulnar nerve paresthesia. CONCLUSION: In nonthrowing athletes, patients undergoing UCL repair and UCL reconstruction show favorable outcomes at minimum 2-year follow-up. RTP and clinical outcomes are consistent with previous studies in baseball players as well as a parallel ongoing study conducted on non-baseball throwing athletes.
Assuntos
Beisebol , Ligamento Colateral Ulnar , Ligamentos Colaterais , Articulação do Cotovelo , Reconstrução do Ligamento Colateral Ulnar , Adolescente , Adulto , Atletas , Ligamento Colateral Ulnar/cirurgia , Ligamentos Colaterais/cirurgia , Cotovelo/cirurgia , Articulação do Cotovelo/cirurgia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: Extremity venous aneurysms result in the risk of pulmonary embolism (PE) and chronic venous insufficiency. At present, owing to the rarity of these aneurysms, no consensus for their treatment has been established. The purpose of the present study was to review the presentation, natural history, and contemporary management of extremity venous aneurysms. METHODS: We performed a retrospective, multi-institutional review of all patients with extremity venous aneurysms treated from 2008 to 2018. A venous aneurysm was defined as saccular or fusiform with an aneurysm/vein ratio of >1.5. RESULTS: A total of 66 extremity aneurysms from 11 institutions were analyzed, 40 of which were in a popliteal location, 14 iliofemoral, and 12 in an upper extremity or a jugular location. The median follow-up was 27 months (range, 0-120 months). Of the 40 popliteal venous aneurysms, 8 (20%) had presented with deep vein thrombosis (DVT) or PE, 13 (33%) had presented with pain, and 19 had been discovered incidentally. The mean size of the popliteal venous aneurysms presenting with DVT or PE was larger than that of those presenting without thromboembolism (3.8 cm vs 2.5 cm; P = .003). Saccular aneurysm morphology in the lower extremity was associated with thromboembolism (30% vs 9%; P = .046) and fusiform aneurysm morphology with a thrombus burden >25% (45% vs 3%). Patients presenting with thromboembolism were more likely to have had a thrombus burden >25% in their lower extremity venous aneurysm compared with those who had presented without thromboembolism (70% vs 9%). Approximately half of all the patients underwent immediate intervention, and half were managed with observation or antithrombotic regimen. In the non-operative cohort, three patients subsequently developed a DVT. Eight patients in the medically managed cohort went on to require surgical intervention. Of the 12 upper extremity venous aneurysms, none had presented with DVT or PE, and only 2 (17%) had presented with pain. Of the 66 patients in the entire cohort, 41 underwent surgical intervention. The most common indication was the absolute aneurysm size. Nine patients had undergone surgery because of a DVT or PE, and 11 for pain or extremity swelling. The most common surgery was aneurysmorrhaphy in 21 patients (53%), followed by excision and ligation in 14 patients (35%). Five patients (12%) had undergone interposition bypass grafting. A postoperative hematoma requiring reintervention was the most common complication, occurring in three popliteal vein repairs and one iliofemoral vein repair. None of the patients, treated either surgically or medically, had reported post-thrombotic complications during the follow-up period. CONCLUSIONS: Large lower extremity venous aneurysms and saccular aneurysms with thrombus >25% of the lumen are more likely to present with thromboembolic complications. Surgical intervention for lower extremity venous aneurysms is indicated to reduce the risk of venous thromboembolism (VTE) and the need for continued anticoagulation. Popliteal aneurysms >2.5 cm and all iliofemoral aneurysms should be considered for repair. Upper extremity aneurysms do not have a significant risk of VTE and warrant treatment primarily for symptoms other than VTE.