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1.
Cell ; 174(2): 433-447.e19, 2018 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-29909985

RESUMO

Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these rearrangements include highly recurrent tandem duplications involving an upstream enhancer of AR in 70%-87% of cases compared with <2% of primary prostate cancers. A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered.


Assuntos
Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/genética , Sequenciamento Completo do Genoma , Idoso , Anilidas/uso terapêutico , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Elementos Facilitadores Genéticos/genética , Duplicação Gênica , Rearranjo Gênico , Genes myc , Loci Gênicos , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , PTEN Fosfo-Hidrolase/genética , Fenótipo , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico
2.
Int J Mol Sci ; 25(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38255999

RESUMO

Benzo[a]pyrene (B[a]P) is the most characterized polycyclic aromatic hydrocarbon associated with breast cancer. Our lab previously reported that the organosulfur compound (OSC), diallyl trisulfide (DATS), chemoprevention mechanism works through the induction of cell cycle arrest and a reduction in oxidative stress and DNA damage in normal breast epithelial cells. We hypothesize that DATS will inhibit B[a]P-induced cancer initiation in premalignant breast epithelial (MCF-10AT1) cells. In this study, we evaluated the ability of DATS to attenuate B[a]P-induced neoplastic transformation in MCF-10AT1 cells by measuring biological endpoints such as proliferation, clonogenicity, reactive oxygen species (ROS) formation, and 8-hydroxy-2-deoxyguanosine (8-OHdG) DNA damage levels, as well as DNA repair and antioxidant proteins. The results indicate that B[a]P induced proliferation, clonogenic formation, ROS formation, and 8-OHdG levels, as well as increasing AhR, ARNT/HIF-1ß, and CYP1A1 protein expression compared with the control in MCF-10AT1 cells. B[a]P/DATS's co-treatment (CoTx) inhibited cell proliferation, clonogenic formation, ROS formation, AhR protein expression, and 8-OHdG levels compared with B[a]P alone and attenuated all the above-mentioned B[a]P-induced changes in protein expression, causing a chemopreventive effect. This study demonstrates, for the first time, that DATS prevents premalignant breast cells from undergoing B[a]P-induced neoplastic transformation, thus providing more evidence for its chemopreventive effects in breast cancer.


Assuntos
Compostos Alílicos , Neoplasias da Mama , Alho , Lesões Pré-Cancerosas , Sulfetos , Humanos , Feminino , Antioxidantes , Espécies Reativas de Oxigênio , Dano ao DNA , Lesões Pré-Cancerosas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Estresse Oxidativo
3.
Health Soc Work ; 49(3): 147-156, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822677

RESUMO

Food insecurity (FI) is a modifiable social determinant of health that impacts approximately 10 percent of the U.S. population. FI has been linked to poorer health outcomes and higher healthcare costs. Given the prevalence of chronic health conditions in the United States, including serious mental illness (SMI), the current study aims to better understand the relationship between FI and chronic conditions, including SMI, in a nationally representative sample. Authors analyzed data from the 2016 Medical Expenditure Panel Survey household component and food security supplement. Findings indicate the prevalence of FI among those with diabetes, lung disease, stroke, and SMI is higher than among the general population, with the prevalence for those with SMI being particularly high (43 percent of the sample). Logistic regression models indicate strong, statistically significant relationships between FI and chronic conditions, including SMI, as well as FI and two or more chronic illnesses, even when controlling for sociodemographic and health factors. There are likely bidirectional relationships between FI and chronic conditions. Findings have implications for social workers, in relation to prevention and treatment of SMI and FI through direct care, advocacy, and integrated services in health, mental health, and social services.


Assuntos
Insegurança Alimentar , Transtornos Mentais , Serviço Social , Humanos , Doença Crônica/epidemiologia , Estados Unidos/epidemiologia , Feminino , Transtornos Mentais/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto , Prevalência , Idoso , Determinantes Sociais da Saúde , Inquéritos e Questionários , Fatores Socioeconômicos
4.
Eur Respir J ; 61(3)2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36396144

RESUMO

RATIONALE: Severe viral respiratory infections are often characterised by extensive myeloid cell infiltration and activation and persistent lung tissue injury. However, the immunological mechanisms driving excessive inflammation in the lung remain poorly understood. OBJECTIVES: To identify the mechanisms that drive immune cell recruitment in the lung during viral respiratory infections and identify novel drug targets to reduce inflammation and disease severity. METHODS: Preclinical murine models of influenza A virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: Oxidised cholesterols and the oxysterol-sensing receptor GPR183 were identified as drivers of monocyte/macrophage infiltration to the lung during influenza A virus (IAV) and SARS-CoV-2 infection. Both IAV and SARS-CoV-2 infection upregulated the enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily member B1 (CYP7B1) in the lung, resulting in local production of the oxidised cholesterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC). Loss-of-function mutation of Gpr183 or treatment with a GPR183 antagonist reduced macrophage infiltration and inflammatory cytokine production in the lungs of IAV- or SARS-CoV-2-infected mice. The GPR183 antagonist significantly attenuated the severity of SARS-CoV-2 infection and viral loads. Analysis of single-cell RNA-sequencing data on bronchoalveolar lavage samples from healthy controls and COVID-19 patients with moderate and severe disease revealed that CH25H, CYP7B1 and GPR183 are significantly upregulated in macrophages during COVID-19. CONCLUSION: This study demonstrates that oxysterols drive inflammation in the lung via GPR183 and provides the first preclinical evidence for the therapeutic benefit of targeting GPR183 during severe viral respiratory infections.


Assuntos
COVID-19 , Influenza Humana , Animais , Camundongos , Humanos , SARS-CoV-2 , Macrófagos , Inflamação , Colesterol , Pulmão , Receptores Acoplados a Proteínas G
5.
Reproduction ; 166(5): 311-322, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37647207

RESUMO

In brief: Inadequate maternal nutrition during gestation can have immediate and lifelong effects on offspring. This study shows that maternal restricted - and over- nutrition during gestation do not affect semen characteristics in F1 male offspring but alters offspring sperm sncRNA profiles and DNA methylome in sheep. Abstract: There is a growing body of evidence that inadequate maternal nutrition during gestation can have immediate and lifelong effects on offspring. However, little is known about the effects of maternal nutrition during gestation on male offspring reproduction. Here, using a sheep model of maternal restricted - and over - nutrition (60 or 140% of the National Research Council requirements) during gestation, we found that maternal restricted - and over - nutrition do not affect semen characteristics (i.e. volume, sperm concentration, pH, sperm motility, sperm morphology) or scrotal circumference in male F1 offspring. However, using small RNA sequencing analysis, we demonstrated that both restricted - and over - nutrition during gestation induced marked changes in composition and expression of sperm small noncoding RNAs (sncRNAs) subpopulations including in male F1 offspring. Whole-genome bisulfite sequencing analysis further identified specific genomic loci where poor maternal nutrition resulted in alterations in DNA methylation. These findings indicate that maternal restricted - and over - nutrition during gestation induce epigenetic modifications in sperm of F1 offspring sperm in sheep, which may contribute to environmentally influenced phenotypes in ruminants.


Assuntos
Epigenoma , Desnutrição , Feminino , Gravidez , Animais , Masculino , Ovinos , Sêmen , Motilidade dos Espermatozoides , Reprodução , Espermatozoides/metabolismo , Desnutrição/metabolismo
6.
J Community Health ; 48(6): 919-925, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37284916

RESUMO

High costs make many medications inaccessible to patients in the United States. Uninsured and underinsured patients are disproportionately affected. Pharmaceutical companies offer patient assistance programs (PAPs) to lower the cost-sharing burden of expensive prescription medications for uninsured patients. PAPs are used by various clinics, particularly oncology clinics and those caring for underserved communities, to expand patients' access to medications. Prior studies describing the implementation of PAPs in student-run free clinics have demonstrated cost-savings during the first few years of using PAPs. However, there is a lack of data regarding the efficacy and cost savings of longitudinal use of PAPs across several years. This study describes the growth of PAP use at a student-run free clinic in Nashville, Tennessee over ten years, demonstrating that PAPs can be used reliably and sustainably to expand patients' access to expensive medications. From 2012 to 2021, we increased the number of medications available through PAPs from 8 to 59 and the number of patient enrollments from 20 to 232. In 2021, our PAP enrollments demonstrated potential cost savings of over $1.2 million. Strategies, limitations, and future directions of PAP use are also discussed, highlighting that PAPs can be a powerful tool for free clinics in serving underserved communities.


Assuntos
Medicamentos sob Prescrição , Clínica Dirigida por Estudantes , Humanos , Estados Unidos , Instituições de Assistência Ambulatorial , Custos de Medicamentos , Pessoas sem Cobertura de Seguro de Saúde , Redução de Custos
7.
J Cancer Educ ; 38(3): 963-970, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36001237

RESUMO

To determine the impact of a letter-based advance care planning (ACP) healthcare improvement (HI) initiative on rates of ACP conversations and documentation among gynecologic oncology (GO) inpatients. An HI initiative was implemented from January to December 2020 to improve ACP documentation among GO inpatients. Patients admitted to the GO service were given ACP packets with a letter-based ACP worksheet. GO inpatients who were interested in learning more about ACP were visited by medical students trained to lead ACP conversations. ACP documentation rates in the EMR (electronic medical record) pre- and post-intervention were evaluated. Descriptive statistics were calculated. Associations between sociodemographic characteristics and ACP documentation were analyzed using logistic regression. There were 172 patients admitted in 2019 (pre-implementation cohort). Of these, 45/172 patients (26%) had an advance directive (AD) documented in their electronic medical record (EMR). Following the implementation of the ACP HI in 2020, 55/168 patients (33%) had an AD documented in their EMR. This was a 7% absolute increase and 27% relative increase from pre-intervention AD documentation rates. Increasing age was associated with an increased likelihood of having an AD in the chart (p = 0.004). Married women were less likely to have an AD in their chart (p = 0.05). An HI utilizing a letter-based ACP packet given to GO inpatients improved AD documentation in the EMR. This HI offers a unique method for introducing ACP to patients. More work is needed to improve the occurrence and documentation of ACP conversations.


Assuntos
Planejamento Antecipado de Cuidados , Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/terapia , Diretivas Antecipadas , Pacientes , Comunicação , Documentação/métodos
8.
Matern Child Nutr ; 19(3): e13509, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37002655

RESUMO

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.


Assuntos
Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer , Suplementos Nutricionais , Ácido Fólico , Idade Gestacional , Ferro , Micronutrientes , Resultado da Gravidez , Nascimento Prematuro/prevenção & controle , Estudos Prospectivos
9.
J Infect Dis ; 225(12): 2219-2228, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35303091

RESUMO

BACKGROUND: We previously reported that reduced GPR183 expression in blood from tuberculosis (TB) patients with diabetes is associated with more severe TB. METHODS: To further elucidate the role of GPR183 and its oxysterol ligands in the lung, we studied dysglycemic mice infected with Mycobacterium tuberculosis (Mtb). RESULTS: We found upregulation of the oxysterol-producing enzymes CH25H and CYP7B1 and increased concentrations of 25-hydroxycholesterol upon Mtb infection in the lungs of mice. This was associated with increased expression of GPR183 indicative of oxysterol-mediated recruitment of GPR183-expressing immune cells to the lung. CYP7B1 was predominantly expressed by macrophages in TB granulomas. CYP7B1 expression was significantly blunted in lungs from dysglycemic animals, which coincided with delayed macrophage infiltration. GPR183-deficient mice similarly had reduced macrophage recruitment during early infection. CONCLUSIONS: Taken together, we demonstrate a requirement of the GPR183/oxysterol axis for positioning of macrophages to the site of infection and add an explanation to more severe TB in diabetes patients.


Assuntos
Mycobacterium tuberculosis , Oxisteróis , Receptores Acoplados a Proteínas G , Tuberculose , Animais , Humanos , Pulmão/microbiologia , Macrófagos , Camundongos , Mycobacterium tuberculosis/fisiologia , Oxisteróis/metabolismo , Receptores Acoplados a Proteínas G/metabolismo
10.
AIDS Behav ; 26(4): 1260-1269, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34648131

RESUMO

Long-acting injectable (LAI) modalities have been developed for ART and PrEP. Women face unique barriers to LAI use yet little research has examined women's perceptions of potential LAI HIV therapy candidates. We conducted 89 in-depth interviews at six Women's Interagency HIV Study (WIHS) sites with women living with HIV (n = 59) and HIV-negative women (n = 30) from 2017 to 2018. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Participants identified specific sub-populations who could most benefit from LAI over daily pills: (1) young people; (2) women with childcare responsibilities; (3) people with adherence-related psychological distress; (4) individuals with multiple sex partners; and (5) people facing structural insecurities such as homelessness. Women are underserved by current HIV care options and their perspectives are imperative to ensure a successful scale-up of LAI PrEP and LAI ART that prioritizes equitable access and benefit for all individuals.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Adolescente , Fármacos Anti-HIV/uso terapêutico , Cidades , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Estados Unidos/epidemiologia
11.
Curr Issues Mol Biol ; 43(2): 749-757, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34294671

RESUMO

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is routinely used for bacterial identification. It would be highly beneficial to also be able to use the technology as a fast way to detect clinically relevant clones of bacterial species. However, studies to this aim have often had limited success. The methods used for data acquisition, processing and data interpretation are highly diverse amongst studies on MALDI-TOF MS sub-species typing. In addition to this, feasibility may depend on the bacterial species and strains investigated, making it difficult to determine what methods may or may not work. In our paper, we have reviewed recent research on MALDI-TOF MS typing of bacterial strains. Although we found a lot of variation amongst the methods used, there were approaches shared by multiple research groups. Multiple spectra of the same isolate were often combined before further analysis for strain distinction. Many groups used a protein extraction step to increase resolution in their MALDI-TOF MS results. Peaks at a high mass range were often excluded for data interpretation. Three groups have found ways to determine feasibility of MALDI-TOF MS typing for their set of strains at an early stage of their project.


Assuntos
Bactérias/classificação , Proteínas de Bactérias/metabolismo , Técnicas de Tipagem Bacteriana/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Bactérias/isolamento & purificação , Bactérias/metabolismo , Humanos
12.
Expert Rev Proteomics ; 18(8): 719-735, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34551655

RESUMO

BACKGROUND: The present study investigates the proteomic content of milk-derived exosomes. A detailed description of the content of milk exosomes is essential to improve our understanding of the various components of milk and their role in nutrition. METHODS: The exosomes used in this study were isolated as previously described and characterized by their morphology, particle concentration, and the presence of exosomal markers. Human and bovine milk exosomes were evaluated using Information-Dependent Acquisition (IDA) Mass Spectrometry. A direct comparison is made between their proteomic profiles. RESULTS: IDA analyses revealed similarities and differences in protein content. About 229 and 239 proteins were identified in the human and bovine milk exosome proteome, respectively, of which 176 and 186 were unique to each species. Fifty-three proteins were common in both groups. These included proteins associated with specific biological processes and molecular functions. Most notably, the 4 abundant milk proteins lactadherin, butyrophilin, perilipin-2, and xanthine dehydrogenase/oxidase were present in the top 20 list for both human and bovine milk exosomes. CONCLUSION: The milk exosome protein profiles we have provided are crucial new information for the field of infant nutrition. They provide new insight into the components of milk from both humans and bovines.


Assuntos
Exossomos , Animais , Cromatografia Líquida , Humanos , Espectrometria de Massas , Leite , Proteômica
13.
AIDS Behav ; 25(3): 667-678, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32910351

RESUMO

Long-acting injectable (LAI) pre-exposure prophylaxis (PrEP) has the potential to facilitate adherence and transform HIV prevention. However, little LAI PrEP research has occurred among women, who face unique barriers. We conducted 30 in-depth interviews with HIV-negative women from 2017-2018 across six sites (New York; Chicago; San Francisco; Atlanta; Washington, DC; Chapel Hill) of the Women's Interagency HIV Study. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Few women expressed interest in PrEP and when prompted to choose a regimen, 55% would prefer LAI, 10% daily pills, and 33% said they would not take PrEP regardless of formulation. Perceived barriers included: (1) the fear of new-and perceived untested-injectable products and (2) potential side effects (e.g., injection-site pain, nausea). Facilitators included: (1) believing shots were more effective than pills; (2) ease and convenience; and (3) confidentiality. Future studies should incorporate women's LAI PrEP-related experiences to facilitate uptake.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Profilaxia Pré-Exposição/métodos , Adulto , Idoso , Cidades , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Preferência do Paciente , Pesquisa Qualitativa , Estados Unidos
14.
BMC Pregnancy Childbirth ; 21(Suppl 1): 236, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33765957

RESUMO

BACKGROUND: Birth registration marks a child's right to identity and is the first step to establishing citizenship and access to services. At the population level, birth registration data can inform effective programming and planning. In Tanzania, almost two-thirds of births are in health facilities, yet only 26% of children under 5 years have their births registered. Our mixed-methods research explores the gap between hospital birth and birth registration in Dar es Salaam, Tanzania. METHODS: The study was conducted in the two Tanzanian hospital sites of the Every Newborn-Birth Indicators Research Tracking in Hospitals (EN-BIRTH) multi-country study (July 2017-2018). We described the business processes for birth notification and registration and collected quantitative data from women's exit surveys after giving birth (n = 8038). We conducted in-depth interviews (n = 21) to identify barriers and enablers to birth registration among four groups of participants: women who recently gave birth, women waiting for a birth certificate at Temeke Hospital, hospital employees, and stakeholders involved in the national birth registration process. We synthesized findings to identify opportunities to improve birth registration. RESULTS: Standard national birth registration procedures were followed at Muhimbili Hospital; families received birth notification and were advised to obtain a birth certificate from the Registration, Insolvency, and Trusteeship Agency (RITA) after 2 months, for a fee. A pilot programme to improve birth registration coverage included Temeke Hospital; hand-written birth certificates were issued free of charge on a return hospital visit after 42 days. Among 2500 women exit-surveyed at Muhimbili Hospital, 96.3% reported receiving a birth notification form and nearly half misunderstood this to be a birth certificate. Of the 5538 women interviewed at Temeke Hospital, 33.0% reported receiving any documentation confirming the birth of their child. In-depth interview respondents perceived birth registration to be important but considered both the standard and pilot processes in Tanzania complex, burdensome and costly to both families and health workers. CONCLUSION: Birth registration coverage in Tanzania could be improved by further streamlining between health facilities, where most babies are born, and the civil registry. Families and health workers need support to navigate processes to register every child.


Assuntos
Declaração de Nascimento , Hospitais/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Idade Materna , Gravidez , Inquéritos e Questionários , Tanzânia , Adulto Jovem
15.
Nucleic Acids Res ; 47(22): e147, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31598677

RESUMO

DNA target enrichment via hybridization capture is a commonly adopted approach which remains expensive due in-part to using biotinylated-probe panels. Here we provide a novel isothermal amplification reaction to amplify rapidly existing probe panels without knowledge of the sequences involved, thereby decreasing a major portion of the overall sample preparation cost. The reaction employs two thermostable enzymes, BST-polymerase and duplex-specific nuclease DSN. DSN initiates random 'nicks' on double-stranded-DNA which enable BST to polymerize DNA by displacing the nicked-strand. Displaced strands re-hybridize and the process leads to an exponential chain-reaction generating biotinylated DNA fragments within minutes. When starting from single-stranded-DNA, DNA is first converted to double-stranded-DNA via terminal-deoxynucleotidyl-transferase (TdT) prior to initiation of BST-DSN reaction. Biotinylated probes generated by TdT-BST-DSN (TBD) reactions using panels of 33, 190 or 7186 DNA targets are used for hybrid-capture-based target enrichment from amplified circulating-DNA, followed by targeted re-sequencing. Polymerase-nuclease isothermal-chain-reactions generate random amplified probes with no apparent sequence dependence. One round of target-capture using TBD probes generates a modest on-target sequencing ratio, while two successive rounds of capture generate >80% on-target reads with good sequencing uniformity. TBD-reactions generate enough capture-probes to increase by approximately two to three orders-of-magnitude the target-enrichment experiments possible from an initial set of probes.


Assuntos
Sondas de DNA/química , DNA/química , Sondas de Oligonucleotídeos/química , Reação em Cadeia da Polimerase/métodos , Biotinilação/métodos , Ácidos Nucleicos Livres/genética , DNA/genética , Sondas de DNA/genética , Voluntários Saudáveis , Humanos , Técnicas de Diagnóstico Molecular/métodos , Neoplasias/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Sondas de Oligonucleotídeos/genética
16.
Community Ment Health J ; 57(8): 1537-1546, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33475886

RESUMO

The stigma of young children with mental health and/or neurodevelopmental disorders is experienced by their parents in at least two ways: self-stigma and vicarious stigma. Secrecy may diminish stigma through impression management or strategic disclosure. The present study explores the relationship between vicarious stigma, self-stigma, secrecy coping, depression, and quality of life. Additionally, we examine the structure of a novel measure of vicarious stigma. Fifty parents of children with mental health and/or neurodevelopmental disorders completed measures. Self-stigma and sadness due to vicarious stigma were significantly associated with greater depression and diminished quality of life. Higher secrecy coping was also associated with higher depression and lower quality of life, supporting the benefits of disclosure. This research meaningfully adds to our understanding of stigma in general, and as experienced by parents of children with mental health and/or neurodevelopmental disorders. Implications for ongoing stigma change development and evaluation are discussed.


Assuntos
Transtornos Mentais , Transtornos do Neurodesenvolvimento , Criança , Pré-Escolar , Humanos , Saúde Mental , Pais , Qualidade de Vida , Estigma Social
17.
Ann Surg Oncol ; 27(13): 5086-5095, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32779054

RESUMO

BACKGROUND: Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment strategy for patients with unresectable liver-only or liver-dominant colorectal liver metastases (CRLM). Although HAI has previously been performed in only a few centers, this study aimed to describe patient selection and initial perioperative outcomes during implementation of a new HAI program. METHODS: The study enrolled patients with CRLM selected for HAI after multi-disciplinary review November 2018-January 2020. Demographics, prior treatment, and perioperative outcomes were assessed. Objective hepatic response was calculated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. RESULTS: During a 14-month period, 21 patients with CRLM underwent HAI pump placement. Of these 21 patients, 20 (95%) had unresectable disease. Most of the patients had synchronous disease (n = 18, 86%) and had received prior chemotherapy (n = 20, 95%) with extended treatment cycles (median 16; interquartile range, 8-22; range, 0-66). The median number of CRLMs was 7 (range, 2-40). Operations often were performed with combined hepatectomy (n = 4, 19%) and/or colectomy/proctectomy (n = 11, 52%). The study had no 90-day mortality. The overall surgical morbidity was 19%. The HAI-specific complications included pump pocket seroma (n = 2), hematoma (n = 1), surgical-site infection (n = 1), and extrahepatic perfusion (n = 1). HAI was initiated in 20 patients (95%). The hepatic response rates at 3 months included partial response (n = 4, 24%), stable disease (n = 9, 53%), and progression of disease (n = 4, 24%), yielding a 3-month hepatic disease control rate (DCR) of 76%. CONCLUSION: Implementation of a new HAI program is feasible, and HAI can be delivered safely to selected patients with CRLM. The initial response and DCR are promising, even for patients heavily pretreated with chemotherapy.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Seleção de Pacientes , Resultado do Tratamento
18.
J Psychosoc Oncol ; 38(2): 125-142, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31510882

RESUMO

Purpose: To describe the prevalence of fear of cancer recurrence (FCR) and test its associations with validated mental health status measures.Design: Cross-sectional survey using the Medical Expenditure Panel Survey Experiences with Cancer Survivorship Supplement.Sample: Post-treatment cancer survivors (n = 1032).Methods: Survey-weighted U.S. population-based estimates describe the prevalence of sociodemographic, health and mental health characteristics of cancer survivors by their level of FCR. Multinomial logistic regression was used to test associations of validated measures of mental health status and individual characteristics on levels of FCR in unadjusted models and those controlling for sociodemographic and health characteristics.Findings: Overall, 34.3% of cancer survivors reported no FCR, 54.4% reported low FCR, and 11.3% reported high FCR. Cancer survivors were at increased risk of reporting high FCR relative to no FCR if they had a low 12-item Short Form Health Survey Mental Component Summary score (≤48) compared to high scores (odds ratio = 2.88; 95% confidence interval = 1.57, 5.29). Reporting depressive symptoms or psychological distress did not significantly increase the risk of reporting high or low FCR relative to no FCR.Conclusions: To our knowledge, this study is the first to provide U.S. population-based estimates of associations between FCR and individual and health characteristics.Implications for Psychosocial Providers or Policy: Our results provide valuable information about which survivors are most at-risk for FCR. Future research is needed to more clearly differentiate FCR from other constructs.


Assuntos
Ansiedade/epidemiologia , Sobreviventes de Câncer/psicologia , Depressão/epidemiologia , Medo/psicologia , Recidiva Local de Neoplasia/psicologia , Adolescente , Adulto , Idoso , Sobreviventes de Câncer/estatística & dados numéricos , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Estados Unidos/epidemiologia , Adulto Jovem
19.
J Cancer Educ ; 35(4): 669-677, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-30879181

RESUMO

We examine the relationships between fear of cancer recurrence (FCR), physical activity, smoking status, and engagement in healthier habits in a US population-based sample of post-treatment cancer survivors. We used data from the 2011 Medical Expenditure Panel Survey (MEPS) Experience with Cancer Survivorship Supplement. Multivariable logistic regression was used to test the relationship of FCR to physical activity, smoking status, and engagement in healthier habits. In all analyses, MEPS survey weights were applied to account for the survey design. Compared with those reporting no FCR, survivors reporting high FCR had significantly lower odds of reporting that they were not currently smokers (odds ratio [OR] = 0.46; 95% CI 0.24, 0.91) and those with any level of FCR had significantly higher odds of reporting healthier habits since diagnosis relative to those with no FCR (low FCR OR = 1.97; 95% CI 1.36, 2.85; high FCR OR = 2.40; 95% CI 1.33, 4.32). FCR was not associated with the odds of reporting physical activity. Findings from this large population-based survey suggest that some of survivors' lifestyle factors may be related to their level of FCR. Understanding the effects of FCR on lifestyle factors may help survivors, survivorship care providers, and policy makers better understand important differences among cancer survivors and personalize interventions in clinical care.


Assuntos
Sobreviventes de Câncer/psicologia , Medo/psicologia , Estilo de Vida , Recidiva Local de Neoplasia/psicologia , Neoplasias/psicologia , Adolescente , Adulto , Idoso , California/epidemiologia , Sobreviventes de Câncer/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias/terapia , Inquéritos e Questionários , Adulto Jovem
20.
Environ Sci Technol ; 53(12): 7075-7082, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31125216

RESUMO

Microplastic debris is a pervasive environmental contaminant that has the potential to impact the health of biota, although its modes of action remain somewhat unclear. The current study tested the hypothesis that exposure to fibrous and particulate microplastics would alter feeding, impacting on lipid accumulation, and normal development (e.g., growth, moulting) in an ecologically important coldwater copepod Calanus finmarchicus. Preadult copepods were incubated in seawater containing a mixed assemblage of cultured microalgae (control), with the addition of ∼50 microplastics mL-1 of nylon microplastic granules (10-30 µm) or fibers (10 × 30 µm), which are similar in shape and size to the microalgal prey. The additive chemical profiles showed the presence of stabilizers, lubricants, monomer residues, and byproducts. Prey selectivity was significantly altered in copepods exposed to nylon fibers (ANOVA, P < 0.01) resulting in a nonsignificant 40% decrease in algal ingestion rates (ANOVA, P = 0.07), and copepods exposed to nylon granules showed nonsignificant lipid accumulation (ANOVA, P = 0.62). Both microplastics triggered premature moulting in juvenile copepods (Bernoulli GLM, P < 0.01). Our results emphasize that the shape and chemical profile of a microplastic can influence its bioavailability and toxicity, drawing attention to the importance of using environmentally relevant microplastics and chemically profiling plastics used in toxicity testing.


Assuntos
Copépodes , Poluentes Químicos da Água , Animais , Monitoramento Ambiental , Lipídeos , Muda , Nylons , Plásticos , Zooplâncton
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