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1.
Proc Natl Acad Sci U S A ; 121(36): e2400085121, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39186643

RESUMO

As climate change shifts crop exposure to dry and wet extremes, a better understanding of factors governing crop response is needed. Recent studies identified shallow groundwater-groundwater within or near the crop rooting zone-as influential, yet existing evidence is largely based on theoretical crop model simulations, indirect or static groundwater data, or small-scale field studies. Here, we use observational satellite yield data and dynamic water table simulations from 1999 to 2018 to provide field-scale evidence for shallow groundwater effects on maize yields across the United States Corn Belt. We identify three lines of evidence supporting groundwater influence: 1) crop model simulations better match observed yields after improvements in groundwater representation; 2) machine learning analysis of observed yields and modeled groundwater levels reveals a subsidy zone between 1.1 and 2.5 m depths, with yield penalties at shallower depths and no effect at deeper depths; and 3) locations with groundwater typically in the subsidy zone display higher yield stability across time. We estimate an average 3.4% yield increase when groundwater levels are at optimum depth, and this effect roughly doubles in dry conditions. Groundwater yield subsidies occur ~35% of years on average across locations, with 75% of the region benefitting in at least 10% of years. Overall, we estimate that groundwater-yield interactions had a net monetary contribution of approximately $10 billion from 1999 to 2018. This study provides empirical evidence for region-wide groundwater yield impacts and further underlines the need for better quantification of groundwater levels and their dynamic responses to short- and long-term weather conditions.

2.
EMBO Rep ; 25(3): 1106-1129, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38308064

RESUMO

Herpesviruses modulate immune control to secure lifelong infection. The mechanisms Human Cytomegalovirus (HCMV) employs in this regard can reveal unanticipated aspects of cellular signaling involved in antiviral immunity. Here, we describe a novel relationship between the TGF-ß family cytokine BMP9 and HCMV infection. We identify a cross-talk between BMP9-induced and IFN receptor-mediated signaling, showing that BMP9 boosts the transcriptional response to and antiviral activity of IFNß, thereby enhancing viral restriction. We also show that BMP9 is secreted by human fibroblasts upon HCMV infection. However, HCMV infection impairs BMP9-induced enhancement of the IFNß response, indicating that this signaling role of BMP9 is actively targeted by HCMV. Indeed, transmembrane proteins US18 and US20, which downregulate type I BMP receptors, are necessary and sufficient to cause inhibition of BMP9-mediated boosting of the antiviral response to IFNß. HCMV lacking US18 and US20 is more sensitive to IFNß. Thus, HCMV has a mutually antagonistic relationship with BMP9, which extends the growing body of evidence that BMP signaling is an underappreciated modulator of innate immunity in response to viral infection.


Assuntos
Fator 2 de Diferenciação de Crescimento , Imunidade Inata , Humanos , Citocinas/metabolismo , Citomegalovirus/metabolismo , Fator 2 de Diferenciação de Crescimento/metabolismo , Transdução de Sinais
3.
Proc Natl Acad Sci U S A ; 120(8): e2218605120, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36800385

RESUMO

A reconstruction attack on a private dataset D takes as input some publicly accessible information about the dataset and produces a list of candidate elements of D. We introduce a class of data reconstruction attacks based on randomized methods for nonconvex optimization. We empirically demonstrate that our attacks can not only reconstruct full rows of D from aggregate query statistics Q(D)∈ℝm but can do so in a way that reliably ranks reconstructed rows by their odds of appearing in the private data, providing a signature that could be used for prioritizing reconstructed rows for further actions such as identity theft or hate crime. We also design a sequence of baselines for evaluating reconstruction attacks. Our attacks significantly outperform those that are based only on access to a public distribution or population from which the private dataset D was sampled, demonstrating that they are exploiting information in the aggregate statistics Q(D) and not simply the overall structure of the distribution. In other words, the queries Q(D) are permitting reconstruction of elements of this dataset, not the distribution from which D was drawn. These findings are established both on 2010 US decennial Census data and queries and Census-derived American Community Survey datasets. Taken together, our methods and experiments illustrate the risks in releasing numerically precise aggregate statistics of a large dataset and provide further motivation for the careful application of provably private techniques such as differential privacy.

4.
Genet Epidemiol ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39315597

RESUMO

Colorectal cancer (CRC) is a complex disease with monogenic, polygenic and environmental risk factors. Polygenic risk scores (PRSs) aim to identify high polygenic risk individuals. Due to differences in genetic background, PRS distributions vary by ancestry, necessitating standardization. We compared four post-hoc methods using the All of Us Research Program Whole Genome Sequence data for a transancestry CRC PRS. We contrasted results from linear models trained on A. the entire data or an ancestrally diverse subset AND B. covariates including principal components of ancestry or admixture. Standardization with the training subset also adjusted the variance. All methods performed similarly within ancestry, OR (95% C.I.) per s.d. change in PRS: African 1.5 (1.02, 2.08), Admixed American 2.2 (1.27, 3.85), European 1.6 (1.43, 1.89), and Middle Eastern 1.1 (0.71, 1.63). Using admixture and an ancestrally diverse training set provided distributions closest to standard Normal. Training a model on ancestrally diverse participants, adjusting both the mean and variance using admixture as covariates, created standard Normal z-scores, which can be used to identify patients at high polygenic risk. These scores can be incorporated into comprehensive risk calculation including other known risk factors, allowing for more precise risk estimates.

5.
Proc Natl Acad Sci U S A ; 119(47): e2212183119, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36375070

RESUMO

About one in six Asian Americans have fallen victim to anti-Asian racism during the COVID-19 pandemic [J. Lee, K. Ramakrishnan, aapidata.com/blog/discrimination-survey-2022/]. By examining anti-Asian racism in the United States primarily as a domestic issue, most prior studies have overlooked the connections between shifting US-China relations and Americans' prejudices against the Chinese in China and, by extension, East Asian Americans. This study investigates the patterns and perceptual bases of nationality-based prejudices against Chinese amid the COVID-19 pandemic in the United States. Our nationally representative online survey experiment reveals that Americans assess a hypothetical Chinese person in China as inferior in multiple social and psychological characteristics to an otherwise identical Japanese person in Japan or East Asian American. Furthermore, subjects who perceive China as more threatening to America's national interests assess Chinese more negatively, especially in terms of trustworthiness and morality, suggesting that perceived China threats propel Americans' negative stereotypes about Chinese. A contextual analysis further indicates that counties with a higher share of Trump voters in 2016 tend to perceive all East Asian-origin groups similarly as a racial outgroup. By contrast, residents in predominantly Democrat-voting counties tend to perceive Chinese in China more negatively relative to Asian Americans, despite broadly viewing East Asians more favorably. Overall, this study underscores the often-overlooked relationships between the prevailing anti-Asian sentiments in the United States and the US-China geopolitical tensions and America's domestic political polarization.


Assuntos
COVID-19 , Racismo , Humanos , Estados Unidos/epidemiologia , COVID-19/epidemiologia , Pandemias , Preconceito , Racismo/psicologia , Asiático/psicologia , Princípios Morais , China
6.
Eur Heart J ; 45(40): 4318-4332, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39132911

RESUMO

BACKGROUND AND AIMS: This study assessed whether a model incorporating clinical features and a polygenic score for ascending aortic diameter would improve diameter estimation and prediction of adverse thoracic aortic events over clinical features alone. METHODS: Aortic diameter estimation models were built with a 1.1 million-variant polygenic score (AORTA Gene) and without it. Models were validated internally in 4394 UK Biobank participants and externally in 5469 individuals from Mass General Brigham (MGB) Biobank, 1298 from the Framingham Heart Study (FHS), and 610 from All of Us. Model fit for adverse thoracic aortic events was compared in 401 453 UK Biobank and 164 789 All of Us participants. RESULTS: AORTA Gene explained more of the variance in thoracic aortic diameter compared to clinical factors alone: 39.5% (95% confidence interval 37.3%-41.8%) vs. 29.3% (27.0%-31.5%) in UK Biobank, 36.5% (34.4%-38.5%) vs. 32.5% (30.4%-34.5%) in MGB, 41.8% (37.7%-45.9%) vs. 33.0% (28.9%-37.2%) in FHS, and 34.9% (28.8%-41.0%) vs. 28.9% (22.9%-35.0%) in All of Us. AORTA Gene had a greater area under the receiver operating characteristic curve for identifying diameter ≥ 4 cm: 0.836 vs. 0.776 (P < .0001) in UK Biobank, 0.808 vs. 0.767 in MGB (P < .0001), 0.856 vs. 0.818 in FHS (P < .0001), and 0.827 vs. 0.791 (P = .0078) in All of Us. AORTA Gene was more informative for adverse thoracic aortic events in UK Biobank (P = .0042) and All of Us (P = .049). CONCLUSIONS: A comprehensive model incorporating polygenic information and clinical risk factors explained 34.9%-41.8% of the variation in ascending aortic diameter, improving the identification of ascending aortic dilation and adverse thoracic aortic events compared to clinical risk factors.


Assuntos
Aorta , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Medição de Risco/métodos , Idoso , Dilatação Patológica/genética , Aorta/patologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Adulto
7.
J Allergy Clin Immunol ; 153(6): 1510-1517, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599291

RESUMO

The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the United States. Through the depletion of circulating IgE and the subsequent reduction of FcεR1 on key effector cells, patients increase their tolerance to food allergens. However, omalizumab does not permit patients to eat foods that they are allergic to with impunity. Rather, it protects them from most accidental exposures. In addition, omalizumab does not cure food allergy and has not demonstrated true immunomodulation. Thus, omalizumab might be a lifelong therapy for some patients. Furthermore, there are many important questions and issues surrounding the appropriate administration of omalizumab to treat food allergy, which we discuss. Managing treatment of patients with disease that falls outside the dosing range, assessing treatment response or nonresponse, addressing its appropriateness for patients older than 55, and determining whether immunotherapy plus omalizumab provides any advantage over omalizumab alone all need to be examined. Identifying appropriate patients for this therapy is critical given the cost of biologics. Indeed, not all food allergy patients are good candidates for this therapy. Also, when and how to stop omalizumab therapy in patients who may have outgrown their food allergy needs to be elucidated. Thus, although this therapy provides a good option for patients with food allergies, much information is needed to determine how best to use this therapy. Despite many unanswered questions and issues, we provide clinicians with some practical guidance on implementing this therapy in their patients.


Assuntos
Antialérgicos , Hipersensibilidade Alimentar , Omalizumab , Humanos , Anafilaxia/tratamento farmacológico , Anafilaxia/imunologia , Análise Custo-Benefício , Aprovação de Drogas , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/imunologia , Acessibilidade aos Serviços de Saúde , Imunoglobulina E/imunologia , Imunoterapia , Omalizumab/administração & dosagem , Omalizumab/imunologia , Omalizumab/farmacologia , Omalizumab/uso terapêutico , Resultado do Tratamento , Guias de Prática Clínica como Assunto , Antialérgicos/administração & dosagem , Antialérgicos/imunologia , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico
8.
J Proteome Res ; 23(6): 2041-2053, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38782401

RESUMO

Extracellular chemical cues constitute much of the language of life among marine organisms, from microbes to mammals. Changes in this chemical pool serve as invisible signals of overall ecosystem health and disruption to this finely tuned equilibrium. In coral reefs, the scope and magnitude of the chemicals involved in maintaining reef equilibria are largely unknown. Processes involving small, polar molecules, which form the majority components of labile dissolved organic carbon, are often poorly captured using traditional techniques. We employed chemical derivatization with mass spectrometry-based targeted exometabolomics to quantify polar dissolved phase metabolites on five coral reefs in the U.S. Virgin Islands. We quantified 45 polar exometabolites, demonstrated their spatial variability, and contextualized these findings in terms of geographic and benthic cover differences. By comparing our results to previously published coral reef exometabolomes, we show the novel quantification of 23 metabolites, including central carbon metabolism compounds (e.g., glutamate) and novel metabolites such as homoserine betaine. We highlight the immense potential of chemical derivatization-based exometabolomics for quantifying labile chemical cues on coral reefs and measuring molecular level responses to environmental stressors. Overall, improving our understanding of the composition and dynamics of reef exometabolites is vital for effective ecosystem monitoring and management strategies.


Assuntos
Recifes de Corais , Metabolômica , Animais , Metabolômica/métodos , Metaboloma , Ilhas Virgens Americanas , Antozoários/metabolismo , Antozoários/química , Espectrometria de Massas/métodos , Ecossistema , Carbono/metabolismo , Carbono/química
9.
Am J Physiol Lung Cell Mol Physiol ; 326(4): L482-L495, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38318664

RESUMO

Chlorine gas (Cl2) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl2 exposures frequently occur in domestic and occupational environments, and in transportation accidents. Modeling the human etiology of Cl2-induced acute lung injury (ALI), forensic biomarkers, and targeted countermeasures development have been hampered by inadequate large animal models. The objective of this study was to develop a translational model of Cl2-induced ALI in swine to understand toxico-pathophysiology and evaluate whether it is suitable for screening potential medical countermeasures and to identify biomarkers useful for forensic analysis. Specific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl2 (≤240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation. Exposure to Cl2 resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Cl2 exposure resulted in increased total leucocyte and neutrophil counts in bronchoalveolar lavage fluid, vascular leakage, and pulmonary edema compared with the air-exposed group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-l-tyrosine and 3,5-dichloro-l-tyrosine) were detected in plasma and lung tissue after Cl2 exposure. In this study, we developed a translational swine model that recapitulates key features of human Cl2 inhalation injury and is suitable for testing medical countermeasures, and validated chlorinated fatty acids and protein adducts as biomarkers of Cl2 inhalation.NEW & NOTEWORTHY We established a swine model of chlorine gas-induced acute lung injury that exhibits several features of human acute lung injury and is suitable for screening potential medical countermeasures. We validated chlorinated fatty acids and protein adducts in plasma and lung samples as forensic biomarkers of chlorine inhalation.


Assuntos
Lesão Pulmonar Aguda , Cloro , Humanos , Animais , Suínos , Cloro/toxicidade , Cloro/metabolismo , Pulmão/metabolismo , Líquido da Lavagem Broncoalveolar , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Biomarcadores/metabolismo , Ácidos Graxos/metabolismo
10.
Emerg Infect Dis ; 30(11): 2227-2230, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39447134

RESUMO

The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.


Assuntos
Antibacterianos , Desenvolvimento de Medicamentos , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Estados Unidos , United States Food and Drug Administration , Farmacorresistência Bacteriana , Acinetobacter baumannii/efeitos dos fármacos
11.
Am J Epidemiol ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39136389

RESUMO

Understanding disability trends is critical for health care and social policy. Although trends in disability and limitations have been studied extensively among older and middle-aged adults, little is known about trends in younger Americans, despite their importance for current and future population health. We present the first comprehensive evidence on disability trends among U.S. adults age 18-44. We analyze 20 measures of disability and limitations collected in the nationally representative National Health Interview Survey 2000-2018 (N=261,505). Robust Poisson models estimate age- and sex-adjusted trends and their covariates. Over one quarter (27.4%) reported at least one disability or limitation; the age-adjusted prevalence increased by 5% from 2000 to 2018. However, trends for specific disabilities and limitations varied tremendously. ADL and IADL limitations, cognitive, and social disabilities increased steeply (by 65-89% over the study period). Mobility limitations were generally unchanged or increased modestly. Hearing and 'other' limitations decreased significantly (25-48% decrease). The trends are only partly explained by education, health behaviors, chronic conditions, and other covariates. Disability trends research must not be limited to older adults. Researchers and policy makers interested in health care policy, planning, and caregiving should pay attention to disability trends among young adults in the United States.

12.
Biochem Biophys Res Commun ; 700: 149584, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38295647

RESUMO

The pseudouridine (ψ) synthase, RluD is responsible for three ψ modifications in the helix 69 (H69) of bacterial 23S rRNA. While normally dispensable, rluD becomes critical for rapid cell growth in bacteria that are defective in translation-termination. In slow-growing rluD- bacteria, suppressors affecting termination factors RF2 and RF3 arise frequently and restore normal termination and rapid cell growth. Here we describe two weaker suppressors, affecting rpsG, encoding ribosomal protein uS7 and ssrA, encoding tmRNA. In K-12 strains of E. coli, rpsG terminates at a TGA codon. In the suppressor strain, alteration of an upstream CAG to a TAG stop codon results in a shortened uS7 and partial alleviation of slow growth, likely by replacing an inefficient TGA stop codon with the more efficient TAG. Inefficient termination events, such as occurs in some rluD- strains, are targeted by trans-translation. Inactivation of the ssrA gene in slow-growing, termination-defective mutants lacking RluD and RF3, also partially restores robust growth, most probably by preventing destruction of completed polypeptides on ribosomes at slow-terminating stop codons. Finally, an additional role for RluD has been proposed, independent of its pseudouridine synthase activity. This is based on the observation that plasmids expressing catalytically dead (D139N or D139T) RluD proteins could nonetheless restore robust growth to an E. coli K-12 rluD- mutant. However, newly constructed D139N and D139T rluD plasmids do not have any growth-restoring activity and the original observations were likely due to the appearance of suppressors.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Proteínas de Escherichia coli/metabolismo , Códon de Terminação/genética , Biossíntese de Proteínas , Hidroliases/metabolismo
13.
Small ; 20(33): e2401670, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38586925

RESUMO

Atomically thin two-dimensional (2D) semiconductors have high potential in optoelectronics and magneto-optics appliances due to their tunable band structures and physicochemical stability. The work demonstrates that Gd3+ incorporated 2D-g-C3N4 nanosheet (Gd3+/2D-g-C3N4 NS) is synthesized through chemisorption methodology for defect enrichment. The material characterizations reveal that the ion decoration enhances the surface area and defect concentration of the 2D sheet. The experimental observations have been further corroborated with the help of density functional theory (DFT) simulation. Spin asymmetry polarizations near the Fermi level, obtained through the partial density of states (PDOS) analyses, reveal the magnetic nature of the synthesized material, validating the room temperature ferromagnetism obtained through a vibrating-sample magnetometer (VSM). Gd3+/2D-g-C3N4 NS shows significant enhancement in saturation magnetization (Ms) experimentally and computationally compared to the pristine one. The magnetic catalyst shows 98% remediation efficiency for ultrasound-assisted visible-light-driven photodegradation of methyl orange (MO). The synergistic approach of liquid chromatography-mass spectrometry (LC-MS) analyses and DFT studies elucidates reaction intermediates and unveils the degradation mechanism. Post-characterization studies assure the stability of the magnetic catalyst through optical, chemical, magnetic, and microscopic analyses. So, the synthesized material can be proficiently used as a magnetic nanocatalyst in wastewater treatments and spin-electronics applications.

14.
J Virol ; 97(3): e0154522, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36786600

RESUMO

Pseudorabies virus (PRV) infection causes enormous economic losses to the pork industry and severe health consequences in many hosts. Annexin A2 (ANXA2) is a membrane-associated protein with various intracellular functions associated with many viral infections. However, the role of ANXA2 in alphaherpesvirus replication is still not explored. In the present study, we identified the interaction between ANXA2 and PRV US3. The deficiency of ANXA2 significantly restricted PRV proliferation. PRV infection or US3 overexpression led to ANXA2 extracellular translocation. Furthermore, we confirmed that PRV or US3 could lead to the phosphorylation of the Tyr23 ANXA2 and Tyr419 Src kinase, which was associated with the ANXA2 cell surface transposition. US3 can also bind to Src in an ANXA2-independent manner and enhance the interaction between Src and ANXA2. Additionally, inhibitors targeting ANXA2 (A2ti-1) or Src (PP2) could remarkably inhibit PRV propagation in vitro and protect mice from PRV infection in vivo. Collectively, our findings broaden our understanding of the molecular mechanisms of ANXA2 in alphaherpesvirus pathogenicity and suggest that ANXA2 is a potential therapeutic target for treating alphaherpesvirus-induced infectious diseases. IMPORTANCE PRV belongs to the alphaherpesvirus and has recently re-emerged in China, causing severe economic losses. Recent studies also indicate that PRV may pose a potential public health challenge. ANXA2 is a multifunctional calcium- and lipid-binding protein implicated in immune function, multiple human diseases, and viral infection. Herein, we found that ANXA2 was essential to PRV efficient proliferation. PRV infection resulted in the extracellular translocation of ANXA2 through phosphorylation of ANXA2 and Src. ANXA2 and Src formed a complex with PRV US3. Importantly, inhibitors targeting ANXA2 or Src prevented PRV infection in vitro and in vivo. Therefore, our studies reveal a novel strategy by which alphaherpesvirus modifies ANXA2 to promote its replication and highlight ANXA2 as a target in developing novel promising antivirus agents in viral therapy.


Assuntos
Anexina A2 , Herpesvirus Suídeo 1 , Pseudorraiva , Replicação Viral , Animais , Humanos , Camundongos , Anexina A2/genética , Anexina A2/metabolismo , Herpesvirus Suídeo 1/metabolismo , Herpesvirus Suídeo 1/patogenicidade , Fosforilação , Pseudorraiva/virologia , Transporte Proteico
15.
Artigo em Inglês | MEDLINE | ID: mdl-39152278

RESUMO

PURPOSE: Cervical screening is used to detect and treat precancers to prevent invasive cancers. However, successful prevention also requires adequate follow-up and treatment of individuals with abnormal screening results. The aim was to investigate demographics, clinical characteristics, and follow-up status for individuals needing colposcopy after an abnormal screening result. METHODS: The STRIDES (Studying Risk to Improve DisparitiES) cohort comprises individuals undergoing cervical cancer screening and management at a Mississippi Health Department or University of Mississippi clinic. Follow-up status, demographics, and clinical data were assessed from electronic health records and, if necessary, patient navigation on individuals identified as needing a colposcopy after an abnormal screening. RESULTS: Of the 1,458 individuals requiring colposcopy, 43.0% had the procedure within 4 months, 16.4% had a delayed procedure, and 39.5% had no documented colposcopy follow-up, with significant predictors of follow-up identified as age and cytology diagnosis. Individuals 30 + were more likely to have follow up with a colposcopy compared to individuals < 30 years (49% and 38.7%, respectively; p < .001). Individuals with cytology diagnoses of LSIL (52.9%), ASC-H (51.4%), and HSIL (62.3%) had higher percentages of adherence to follow-up guidelines (p < .001). In total, we found that 78% of individuals had some type of follow-up, including a repeat screening visit. CONCLUSION: Despite high cervical cancer screening rates among Mississippians, a substantial proportion did not have adequate next-step intervention. However, it is encouraging that highest risk individuals were more likely to have a colposcopy. Regardless, continuing to understand the underlying causes for incomplete follow-up is crucial for timely secondary targeted interventions to reduce cervical cancer burden, promote awareness, and improve health outcomes.

16.
Cancer Causes Control ; 35(2): 203-214, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37679534

RESUMO

PURPOSE: We aimed to assess whether nativity differences in socioeconomic (SES) barriers and health literacy were associated with healthcare delays among US cancer survivors. METHODS: "All of Us" survey data were analyzed among adult participants ever diagnosed with cancer. A binary measure of healthcare delay (1+ delays versus no delays) was created. Health literacy was assessed using the Brief Health Literacy Screen. A composite measure of SES barriers (education, employment, housing, income, and insurance statuses) was created as 0, 1, 2, or 3+. Multivariable logistic regression model tested the associations of (1) SES barriers and health literacy with healthcare delays, and (2) whether nativity modified this relationship. RESULTS: Median participant age was 64 years (n = 10,020), with 8% foreign-born and 18% ethnic minorities. Compared to survivors with no SES barriers, those with 3+ had higher likelihood of experiencing healthcare delays (OR 2.18, 95% CI 1.84, 2.58). For every additional barrier, the odds of healthcare delays were greater among foreign-born (1.72, 1.43, 2.08) than US-born (1.27, 1.21, 1.34). For every 1-unit increase in health literacy among US-born, the odds of healthcare delay decreased by 9% (0.91, 0.89, 0.94). CONCLUSION: We found that SES barriers to healthcare delays have a greater impact among foreign-born than US-born cancer survivors. Higher health literacy may mitigate healthcare delays among US cancer survivors. Healthcare providers, systems and policymakers should assess and address social determinants of health and promote health literacy as a way to minimize healthcare delays among both foreign- and US-born cancer survivors.


Assuntos
Sobreviventes de Câncer , Neoplasias , Saúde da População , Adulto , Humanos , Pessoa de Meia-Idade , Promoção da Saúde , Escolaridade , Atenção à Saúde , Neoplasias/epidemiologia
17.
J Urol ; : 101097JU0000000000004222, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39226591

RESUMO

PURPOSE: Focal therapy aims to provide a durable oncologic treatment option for men with prostate cancer (PCa), while preserving their quality of life. Most focal therapy modalities rely on the direct tissue effect, resulting in a possible nontargeted approach to ablation. Here, we report the results of the first human feasibility trial utilizing nanoparticle-directed focal photothermal ablation for PCa. MATERIALS AND METHODS: A prospective, open-label, single-arm, multicenter study of men with localized PCa in Gleason Grade Group 1 to 3 was conducted. Men received a single infusion of gold nanoparticles (AuroShells), followed by magnetic resonance (MR)/ultrasound (US) fusion-guided laser excitation of the target tissue to induce photothermal ablation. MRI was used to assess the effectiveness of prostate tissue ablation at 48 to 96 hours, 3 months, and 12 months post treatment. At 3 months, a targeted fusion biopsy of the lesion(s) was conducted. At 12 months, a targeted fusion biopsy and standard templated biopsy were performed. Treatment success was determined based on a negative MR/US fusion biopsy outcome within the treated area. RESULTS: Forty-six men were enrolled in the study, and 44 men with 45 lesions completed nanoparticle infusion and laser treatment. The mean PSA level at baseline was 9.5 ng/mL, which decreased to 5.9 ng/mL at 3 months and to 4.7 ng/mL at 12 months (P < .0001). The oncologic success rates at 3 and 12 months resulted in 29 (66%) and 32 (73%) of 44 patients, respectively, being successfully treated, confirmed with negative MR/US fusion biopsies within the ablation zone. Among Gleason Grade Group, maximum lesion diameter on MRI, prostate volume, and Prostate Imaging Reporting and Data System scoring, the maximum lesion diameter was significantly associated with the odds of treatment failure at 12 months (P = .046). CONCLUSIONS: Nanoparticle-directed focal laser ablation of neoplastic prostate tissue resulted in 73% of patients with successful treatment at 12 months post treatment, confirmed by negative MR/US fusion biopsy of the treated lesion and a systematic biopsy. CLINICAL TRIAL REGISTRATION NO.: 02680535.

18.
Rheumatology (Oxford) ; 63(2): 498-505, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37225418

RESUMO

OBJECTIVES: To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment. METHODS: The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis. RESULTS: The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease). CONCLUSIONS: Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment.


Assuntos
Artrite , Artropatias , Sinovite , Humanos , Atividades Cotidianas , Artrite/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Inflamação , Ultrassonografia/métodos , Índice de Gravidade de Doença
19.
Ann Surg Oncol ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277546

RESUMO

BACKGROUND: US News and World Report (USNWR) hospital rankings influence patient choice of hospital, but their association with surgical outcomes remains ill-defined. We sought to characterize clinical outcomes and costs of surgery for colon cancer among USNWR top ranked and unranked hospitals. METHODS: Using Medicare Standard Analytic Files, patients aged ≥65 years undergoing surgery for colon cancer were identified. Hospitals were categorized as 'ranked' or 'unranked' based on USNWR cancer hospital rankings. One-to-one matching was performed between patients treated at ranked and unranked hospitals, and clinical outcomes and costs of surgery were compared. RESULTS: Among 50 ranked and 2522 unranked hospitals, 13,650 patient pairs were compared. Overall, 30-day mortality was 2.13% in ranked hospitals versus 3.68% in unranked hospitals (p < 0.0001), and the overall paired cost difference was $8159 (p < 0.0001). As patient risk increased, 30-day mortality differences became larger, with the ranked hospitals having 30-day mortality of 7.59% versus 11.84% for unranked hospitals among the highest-risk patients (p < 0.0001). Overall paired cost differences also increased with increasing patient risk, with cost of care being $72,229 for ranked hospitals versus $56,512 for unranked hospitals among the highest-risk patients (difference = $14,394; p = 0.02). The difference in cost per 1% reduction in 30-day mortality was $9009 (95% confidence interval [CI] $6422-$11,597) for lowest-risk patients, which dropped to $3387 (95% CI $2656-$4119) for highest-risk patients (p < 0.0001). CONCLUSION: Treatment at USNWR-ranked hospitals, particularly for higher-risk patients, was associated with better outcomes but higher-cost care. The benefit of being treated at highly ranked USNWR hospitals was most pronounced among high-risk patients.

20.
Ophthalmology ; 131(4): 492-498, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37852418

RESUMO

PURPOSE: To compare population demographics with the geographic distribution of oculofacial plastic surgeons (OPSs) in the United States. DESIGN: A cross-sectional study design was used to investigate demographic differences between counties with 1 or more OPSs and counties with zero OPSs. PARTICIPANTS: The number of OPSs were identified in each US county using online public databases: American Society of Ophthalmic Plastic and Reconstructive Surgeons and American Academy of Ophthalmology. Counties were categorized into 2 groups: 1 or more OPSs and zero OPSs. Demographic characteristics at the county level were obtained from the 2021 US Census Bureau Population Estimates and the American Community Survey. Cost of living was collected from the 2022 Economic Policy Institute Family Budget Calculator. MAIN OUTCOME MEASURES: Socioeconomic demographics of the US population as related to geographic OPS distribution. RESULTS: A total of 1238 OPSs were identified. States with the most OPSs per million were Hawaii (6.2), D.C. (6.0), Connecticut (5.8), Utah (5.1), and Maryland (5.0). Among 3143 counties, 2725 (86.7%) had zero OPSs and 418 (13.3%) had 1 or more OPSs. Counties with 1 or more OPSs had a higher median (standard deviation) household income versus counties with zero OPSs ($72 471 [$19 152] vs. $56 152 [$13 675]; difference $16 319; 95% confidence interval [CI], $14 300-$18 338; P < 0.001). The annual cost of living per person (standard deviation) was higher in counties with 1 or more OPSs versus counties with zero OPSs ($39 238 [$6992] vs. $36 227 [$3516]; difference $3011; 95% CI, $2328-$3694; P < 0.001). Counties with zero OPSs versus counties with 1 or more OPSs had higher proportions of persons with only Medicaid (15.6% vs. 13.6%; difference 2.0%; 95% CI, 1.4%-2.5%; P < 0.001), no health insurance (9.9% vs. 8.0%; difference 1.9%; 95% CI, 1.5%-2.4%; P < 0.001), no household internet access (17.2% vs. 9.6%; difference 7.6%; 95% CI, 7.1%-8.0%; P < 0.001), and higher proportions of persons aged 65 years or older (20.0% vs. 17.0%; difference 3.0%; 95% CI, 2.5%-3.5%; P < 0.001). CONCLUSIONS: This cross-sectional analysis of all US counties revealed socioeconomic disparities associated with access to OPSs. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Assuntos
Oftalmologia , Cirurgiões , Humanos , Estados Unidos , Estudos Transversais , Disparidades Socioeconômicas em Saúde
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