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1.
Artigo em Inglês | MEDLINE | ID: mdl-38959160

RESUMO

Introduction: Surgical site infection (SSI) is a substantial cause of peri-operative morbidity among patients undergoing radical cystectomy (RC). The purpose of this study was to identify the risk factors of SSI after RC and to classify and characterize treatment of SSIs. Methods: We retrospectively analyzed peri-operative characteristics and SSI, for patients undergoing RC from 2007 to 2022. Patients were stratified by SSI versus no SSI and differences were assessed. Uni-variable/multi-variable logistic regression analyses were performed to identify factors associated with SSI. SSIs were categorized by the Centers for Disease Control and Prevention (CDC) type: Superficial incisional, deep incisional, and organ/space confined. Results: Three hundred and ninety-eight patients had RC, 279 open, and 119 robotic; 78 (19.6%) developed SSI. Cohorts were similar demographically. Length of stay (LOS) was longer in the SSI cohort (8.8 d versus 12.4 d, p < 0.001), and body mass index (BMI) was greater in patients with SSI (24.34 vs. 25.39, p = 0.0003). On uni-variable analysis, age, gender, Charlson Comorbidity Index, diabetes mellitus, diversion, odds ratio (OR) time, blood loss, and open versus robotic technique were not substantial SSI predictors. BMI was an independent risk factor for SSI on both uni-variable (OR: 1.07, 95% confidence interval [CI]: 1.018-1.115, p = 0.0061) and multi-variable analysis (OR: 1.06, 95% CI: 1.009-1.109, p = 0.02) for 10 (12.8%) and 24 (30.8%) superficial and deep-incisional SSIs, respectively. Superficial wound SSI was treated conservatively with 60% receiving antibiotic agents and no procedural intervention. Deep SSIs received antibiotic agents and 50% required surgical intervention. There were 44 (56.4%) organ/space SSIs, and the most common treatment was antibiotic agents (100%) and IR drain placement (30, 68.2%). Conclusion: In patients undergoing RC, BMI was an independent risk factor for SSI. Type of the surgical procedure, robotic versus open, was not predictive of SSI. LOS was longer for patients with SSI. SSI was managed differently depending on CDC classification.

2.
Sci Rep ; 13(1): 17213, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821522

RESUMO

Longitudinal data sets for population abundance are essential for studies of imperiled organisms with long life spans or migratory movements, such as marine turtles. Population status trends are crucial for conservation managers to assess recovery effectiveness. A direct assessment of population growth is the enumeration of nesting numbers and quantifying nesting attempts (successful nests/unsuccessful attempts) and emergence success (number of hatchlings leaving the nest) because of the substantial annual variations due to nest placement, predation, and storm activity. We documented over 133,000 sea turtle crawls for 50.9 km of Florida Gulf of Mexico coastline from 1982 to 2021 for a large loggerhead turtle nesting aggregation and a recovering remnant population of green sea turtles. Over time both species have emerged to nest significantly earlier in the year and green sea turtle nesting seasons have extended. Nest counts and hatchling production for both species have significantly increased, but the rate of emergence success of hatchlings leaving nests has not changed for loggerheads and has declined for green sea turtles. Sea level rise and coastal developments undoubtedly influence coastal habitats in the long-term, impacting nest site selection and potential recruitment from the loss of emerged hatchlings. However, the present indications for steady Gulf of Mexico recovery of loggerhead and green sea turtles counter findings of the Florida Atlantic coasts. This study indicates that effective conservation practices can be detected within time scales of 1-2 turtle generations.


Assuntos
Tartarugas , Animais , Golfo do México , Crescimento Demográfico , Florida , Comportamento de Nidação
3.
Front Cell Neurosci ; 17: 1130816, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187610

RESUMO

Introduction: There is a lack of robust metabolic imaging techniques that can be routinely applied to characterize lesions in patients with brain tumors. Here we explore in an animal model of glioblastoma the feasibility to detect uptake and metabolism of deuterated choline and describe the tumor-to-brain image contrast. Methods: RG2 cells were incubated with choline and the level of intracellular choline and its metabolites measured in cell extracts using high resolution 1H NMR. In rats with orthotopically implanted RG2 tumors deuterium metabolic imaging (DMI) was applied in vivo during, as well as 1 day after, intravenous infusion of 2H9-choline. In parallel experiments, RG2-bearing rats were infused with [1,1',2,2'-2H4]-choline and tissue metabolite extracts analyzed with high resolution 2H NMR to identify molecule-specific 2H-labeling in choline and its metabolites. Results: In vitro experiments indicated high uptake and fast phosphorylation of exogenous choline in RG2 cells. In vivo DMI studies revealed a high signal from the 2H-labeled pool of choline + metabolites (total choline, 2H-tCho) in the tumor lesion but not in normal brain. Quantitative DMI-based metabolic maps of 2H-tCho showed high tumor-to-brain image contrast in maps acquired both during, and 24 h after deuterated choline infusion. High resolution 2H NMR revealed that DMI data acquired during 2H-choline infusion consists of free choline and phosphocholine, while the data acquired 24 h later represent phosphocholine and glycerophosphocholine. Discussion: Uptake and metabolism of exogenous choline was high in RG2 tumors compared to normal brain, resulting in high tumor-to-brain image contrast on DMI-based metabolic maps. By varying the timing of DMI data acquisition relative to the start of the deuterated choline infusion, the metabolic maps can be weighted toward detection of choline uptake or choline metabolism. These proof-of-principle experiments highlight the potential of using deuterated choline combined with DMI to metabolically characterize brain tumors.

4.
Cancers (Basel) ; 15(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37173972

RESUMO

We provide a comprehensive review of current approved systemic treatment strategies for advanced hepatocellular carcinoma (HCC), starting with the phase III clinical trial of sorafenib which was the first to definitively show a survival benefit. After this trial, there was an initial period of little progress. However, in recent years, an explosion of new agents and combinations of agents has resulted in a markedly improved outlook for patients. We then provide the authors' current approach to therapy, i.e., "How We Treat HCC". Promising future directions and important gaps in therapy that persist are finally reviewed. HCC is a highly prevalent cancer worldwide and the incidence is growing due not only to alcoholism, hepatitis B and C, but also to steatohepatitis. HCC, like renal cell carcinoma and melanoma, is a cancer largely resistant to chemotherapy but the advent of anti-angiogenic, targeted and immune therapies have improved survival for all of these cancers. We hope this review will heighten interest in the field of HCC therapies, provide a clear outline of the current data and strategy for treatment, and sensitize readers to new developments that are likely to emerge in the near future.

5.
mBio ; 13(2): e0298321, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35285699

RESUMO

Individuals with metabolic dysregulation of cellular glycosylation often experience severe influenza disease, with a poor immune response to the virus and low vaccine efficacy. Here, we investigate the consequences of aberrant cellular glycosylation for the glycome and the biology of influenza virus. We transiently induced aberrant N-linked glycosylation in cultured cells with an oligosaccharyltransferase inhibitor, NGI-1. Cells treated with NGI-1 produced morphologically unaltered viable influenza virus with sequence-neutral glycosylation changes (primarily reduced site occupancy) in the hemagglutinin and neuraminidase proteins. Hemagglutinin with reduced glycan occupancy required a higher concentration of surfactant protein D (an important innate immunity respiratory tract collectin) for inhibition compared to that with normal glycan occupancy. Immunization of mice with NGI-1-treated virus significantly reduced antihemagglutinin and antineuraminidase titers of total serum antibody and reduced hemagglutinin protective antibody responses. Our data suggest that aberrant cellular glycosylation may increase the risk of severe influenza as a result of the increased ability of glycome-modified influenza viruses to evade the immune response. IMPORTANCE People with disorders such as cancer, autoimmune disease, diabetes, or obesity often have metabolic dysregulation of cellular glycosylation and also have more severe influenza disease, a reduced immune response to the virus, and reduced vaccine efficacy. Since influenza viruses that infect such people do not show consistent genomic variations, it is generally assumed that the altered biology is mainly related to host factors. However, since host cells are responsible for glycosylation of influenza virus hemagglutinin and neuraminidase, and glycosylation is important for interactions of these proteins with the immune system, the viruses may have functional differences that are not reflected by their genomic sequence. Here, we show that imbalanced cellular glycosylation can modify the viral glycome without genomic changes, leading to reduced innate and adaptive host immune responses to infection. Our findings link metabolic dysregulation of host glycosylation to increased risk of severe influenza and reduced influenza virus vaccine efficacy.


Assuntos
Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Orthomyxoviridae , Animais , Glicosilação , Hemaglutininas/genética , Humanos , Imunidade Inata , Camundongos , Neuraminidase/genética , Polissacarídeos
6.
Front Microbiol ; 12: 774711, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956139

RESUMO

Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV strains are largely resistant to these lectins, likely contributing to increased spread and worse outcomes. In this paper, we evaluated the inhibition of IAV by mannose-binding lectins of human, bacterial, and fungal origin to understand and possibly increase activity vs. the pandemic IAV. A modified version of the human surfactant protein D (SP-D) neck and carbohydrate recognition domain (NCRD) with combinatorial substitutions at the 325 and 343 positions, previously shown to inhibit pandemic H3N2 IAV in vitro and in vivo, and to inhibit pandemic H1N1 in vitro, failed to protect mice from pandemic H1N1 in vivo in the current study. We attempted a variety of maneuvers to improve the activity of the mutant NCRDs vs. the 2009 pandemic H1N1, including the formation of full-length SP-D molecules containing the mutant NCRD, cross-linking of NCRDs through the use of antibodies, combining SP-D or NCRDs with alpha-2-macroglobulin, and introducing an additional mutation to the double mutant NCRD. None of these substantially increased the antiviral activity for the pandemic H1N1. We also tested the activity of bacterial and algal mannose-binding lectins, cyanovirin, and griffithsin, against IAV. These had strong activity against seasonal IAV, which was largely retained against pandemic H1N1. We propose mechanisms to account for differences in activity of SP-D constructs against pandemic H3N2 and H1N1, and for differences in activity of cyanovirin vs. SP-D constructs.

7.
Cancer ; 127(20): 3847-3855, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34237147

RESUMO

BACKGROUND: The purpose of this study was to examine the health-related quality of life of sexual minority survivors in comparison with heterosexual survivors. METHODS: Four hundred eighty eligible survivors participated in a telephone survey that measured survivors' outcomes, which consisted of physical and mental quality of life and self-rated fair or poor health. These survivors were diagnosed with stage I, II, or III colorectal cancer an average of 3 years before the survey and were recruited from 4 cancer registries. Using forward selection with generalized linear models or logistic regression models, the authors considered 4 domains-personal factors, environmental factors, health condition characteristics, and body function and structure-as correlates for each survivorship outcome. RESULTS: The authors found that unadjusted physical quality of life and self-rated fair/poor health were similar for all survivors. Sexual minority survivors had poorer unadjusted mental quality of life in comparison with heterosexual survivors. After adjustments for covariates, this difference was no longer statistically significant. Three domains (personal factors, health condition characteristics, and body function and structure) explained colorectal cancer survivors' fair/poor health and 46% of the variance in physical quality of life, whereas 56% of the variance in mental quality of life was explained by personal factors, body function and structure, and environmental factors. CONCLUSIONS: This study has identified modifiable factors that can be used to improve cancer survivors' quality of life and are, therefore, relevant to ongoing efforts to improve the survivorship experience.


Assuntos
Sobreviventes de Câncer , Neoplasias Colorretais , Feminino , Humanos , Masculino , Qualidade de Vida , Comportamento Sexual , Sobreviventes
8.
J Robot Surg ; 15(5): 773-780, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33226567

RESUMO

To compare the outcomes of robotic-assisted (RARC) vs. open radical cystectomy (ORC) at a single academic institution. We retrospectively identified patients undergoing radical cystectomy for urothelial carcinoma of the bladder at our institution from 2007 to 2017. Data collected included age, sex, Body Mass Index (BMI), Charlson Age-Adjusted Comorbidity Index (CCI), final pathologic stage, surgical margins, lymph-node yield, estimated blood loss (EBL), 90-day complication rate, and length of stay (LOS). We evaluated overall survival (OS) and recurrence-free survival (RFS). Multivariable Cox proportional hazard models were used to adjust for covariates. We identified 232 patients (73 RARC, 159 ORC) who underwent radical cystectomy. Patients who underwent RARC were older (71.8 vs. 67.5, p < 0.05) and had higher CCI scores (6.2 vs. 5.3, p < 0.05). In comparing perioperative outcomes, RARC patients had lower EBL (500 vs. 850, p < 0.01), lower blood transfusion rate (p < 0.01), and lower lymph-node yield (12 vs. 20, p < 0.01), and higher ICU admission rate (29% vs. 16% p < 0.01). There was no difference in BMI (p = 0.93), sex (p = 0.28), final pathological stage (p = 0.35), positive surgical margins (p = 0.47), complications (p = 0.58), or LOS (p = 0.34). Kaplan-Meier analysis showed no difference in OS (p = 0.26) or RFS (p = 0.86). There was no difference in restricted mean survival time for OS (53 vs. 56 months, p = 0.81) or for RFS (65 vs. 64 months, p = 0.90). Cox multivariate regression models showed that surgical approach does not have a significant impact on OS (p = 0.46) or RFS (p = 0.35). Our study indicates that in our 10-year experience, patients undergoing there was no difference between RARC and ORC patients with respect to OS and RFS despite being older and having more comorbidities. Our work supports the importance of patient selection to optimize outcomes.


Assuntos
Carcinoma de Células de Transição , Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária , Cistectomia/efeitos adversos , Humanos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia
9.
J Leukoc Biol ; 110(1): 155-166, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33205458

RESUMO

Innate immunity is vital for the early control of influenza A virus (IAV) infection. Serum amyloid A (SAA1) is an acute phase reactant produced in the liver and lung that rises dramatically during IAV infection. The potential role of SAA1 in host defense against IAV is unknown. SAA1 has been reported to directly activate neutrophils and to recruit them to the lung during infectious and inflammatory processes. Neutrophils are the most abundant cell recruited to the lung in the early phase of IAV infection. There are different forms and preparations of SAA1 that have found to have different effects on phagocyte responses, through various receptors. In this paper, we test the direct effects of various preparations of serum derived or recombinant SAA on IAV and how it modulates the interactions of IAV with neutrophils. All SAA preparations bound to IAV in vitro but caused minimal hemagglutination inhibition or viral aggregation. The human serum-derived SAA1 or the complex of SAA1 with HDL did have IAV neutralizing activity in vitro, whereas the recombinant SAA1 preparations did not. We found that different SAA preparations also had markedly different effects on neutrophil functions, with E. coli-derived SAA1 triggering some responses in neutrophils on its own or in presence of IAV whereas mammalian cell-derived SAA1 did not. This discrepancy could be explained by the reported contamination of the former preparation with bacterial components. Of interest, however, serum SAA alone, serum SAA complexed with HDL, or HDL alone potentiated some neutrophil responses to IAV. Our results suggest that SAA may play some role in host response to IAV, but further work needs to be done to clarify the role of different variants of SAA alone or complexed with HDL.


Assuntos
Interações Hospedeiro-Patógeno , Vírus da Influenza A/fisiologia , Influenza Humana/metabolismo , Influenza Humana/virologia , Neutrófilos/metabolismo , Proteína Amiloide A Sérica/metabolismo , Replicação Viral , Cálcio/metabolismo , Citocinas/metabolismo , Testes de Hemaglutinação , Humanos , Peróxido de Hidrogênio/metabolismo , Imunidade Inata , Ligação Proteica
10.
J Leukoc Biol ; 109(4): 763-775, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32803840

RESUMO

Extracellular histones have been implicated as a cause of tissue inflammatory injury in a variety of disorders including sepsis, lung, and liver diseases. However, little is known about their interactions with neutrophils and how this might contribute to injury. Here, it is shown that histone H4 acts as neutrophil activator by inducing hydrogen peroxide production, degranulation, cell adhesion, and IL-8 generation. Histone H4 caused permeabilization of the neutrophil membrane (a phenomenon described in other cell types) leading to accelerated cell death. H4 caused sustained rise in neutrophil intracellular calcium that is necessary for respiratory burst activation and degranulation. Convincing evidence was not found for TLRs or ATP receptors in H4 mediated activation. However, pertussis toxin and wortmannin (inhibitors of G protein and PI3K) inhibited H4-induced hydrogen peroxide production and degranulation. These studies suggest that release of histone H4 in sites of infection or inflammation may potentiate neutrophil activation and promote additional inflammatory responses. These studies may provide a better basis for developing novel therapeutic strategies to block neutrophil extracellular trap (NET) and H4-related pathology in sepsis and various forms of lung injury including that induced by viruses like influenza or SAR-CoV2.


Assuntos
Permeabilidade da Membrana Celular , Histonas/metabolismo , Ativação de Neutrófilo , Cálcio/metabolismo , Adesão Celular/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Integrinas/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/fisiologia , Peroxidase/metabolismo , Toxina Pertussis/farmacologia , Explosão Respiratória/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Wortmanina/farmacologia
11.
Biomed Opt Express ; 11(11): 6211-6230, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33282485

RESUMO

The presence of circulating tumor cells (CTCs) in a patient's bloodstream is a hallmark of metastatic cancer. The detection and analysis of CTCs is a promising diagnostic and prognostic strategy as they may carry useful genetic information from their derived primary tumor, and the enumeration of CTCs in the bloodstream has been known to scale with disease progression. However, the detection of CTCs is a highly challenging task owing to their sparse numbers in a background of billions of background blood cells. To effectively utilize CTCs, there is a need for an assay that can detect CTCs with high specificity and can locally enrich CTCs from a liquid biopsy. We demonstrate a versatile methodology that addresses these needs by utilizing a combination of nanoparticles. Enrichment is achieved using targeted magnetic nanoparticles and high specificity detection is achieved using a ratiometric detection approach utilizing multiplexed targeted and non-targeted surface-enhanced Raman Scattering Nanoparticles (SERS-NPs). We demonstrate this approach with model prostate and cervical circulating tumor cells and show the ex vivo utility of our methodology for the detection of PSMA or folate receptor over-expressing CTCs. Our approach allows for the mitigation of interference caused by the non-specific uptake of nanoparticles by other cells present in the bloodstream and our results from magnetically trapped CTCs reveal over a 2000% increase in targeted SERS-NP signal over non-specifically bound SERS-NPs.

12.
Front Cell Infect Microbiol ; 10: 563850, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194802

RESUMO

There is abundant evidence that the innate immune response to influenza A virus (IAV) is highly complex and plays a key role in protection against IAV induced infection and illness. Unfortunately it also clear that aspects of innate immunity can lead to severe morbidity or mortality from IAV, including inflammatory lung injury, bacterial superinfection, and exacerbation of reactive airways disease. We review broadly the virus and host factors that result in adverse outcomes from IAV and show evidence that inflammatory responses can become damaging even apart from changes in viral replication per se, with special focus on the positive and adverse effects of neutrophils and monocytes. We then evaluate in detail the role of soluble innate inhibitors including surfactant protein D and antimicrobial peptides that have a potential dual capacity for down-regulating viral replication and also inhibiting excessive inflammatory responses and how these innate host factors could possibly be harnessed to treat IAV infection. Where appropriate we draw comparisons and contrasts the SARS-CoV viruses and IAV in an effort to point out where the extensive knowledge existing regarding severe IAV infection could help guide research into severe COVID 19 illness or vice versa.


Assuntos
COVID-19/imunologia , Imunidade Inata , Vírus da Influenza A/fisiologia , Influenza Humana/imunologia , SARS-CoV-2/fisiologia , Animais , COVID-19/patologia , COVID-19/virologia , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Influenza Humana/patologia , Influenza Humana/virologia , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Replicação Viral
13.
J Virol ; 94(5)2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31826991

RESUMO

Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D). Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes. These can pose a pandemic threat through reassortment and emergence in human populations. Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value. Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype. Using mass spectrometry, we determined the glycan subclasses and heterogeneities at each head glycosylation site. Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8. Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data. We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs. SP-D was not active on LPAIV but was on H3 HAs. Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes. Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype. Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s). While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks. Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Vírus da Influenza A/metabolismo , Polissacarídeos/metabolismo , Proteína D Associada a Surfactante Pulmonar/metabolismo , Sequência de Aminoácidos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Humanos , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza A Subtipo H3N8 , Virus da Influenza A Subtipo H5N1 , Modelos Moleculares , Polissacarídeos/química , Conformação Proteica , Análise de Sequência de Proteína , Virulência
14.
Health Equity ; 3(1): 619-627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31872167

RESUMO

Purpose: Quality cancer care entails receipt of a Survivorship Care Plan (SCP). The purpose of this study was to determine differences in SCP delivery by patient-level and neighborhood characteristics. Methods: We obtained California cancer registry data on individuals who were diagnosed with stage I, II, or III colorectal cancer (CRC) between 2012 and 2015 and resided in predetermined geographic areas. We then mailed them a questionnaire, which queried about receipt of a SCP and its content. SCP was defined by content, as summary of cancer treatment, cancer surveillance recommendations, and/or an individualized preventive care. Using logistic regression modeling, each measure of SCP, as well as the summary measure (none vs. any), was evaluated by person-level characteristics. Subsequently, neighborhood-level characteristics were added to the model to explore their additional value. Results: Overall 80% of CRC survivors received a SCP. Receipt of SCPs was associated with person-level characteristics, while neighborhood characteristics did not make an additional contribution. Young, male employed survivors and those with more recent diagnoses or later cancer stages had greater odds of receiving a SCP. Conclusion: When providing SCPs, health care providers prioritize patient groups who they may perceive as vulnerable or likely to benefit from SCPs.

15.
Front Immunol ; 10: 2476, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749796

RESUMO

Innate immunity is critical in the early containment of influenza A virus (IAV) infection and surfactant protein D (SP-D) plays a crucial role in innate defense against IAV in the lungs. Multivalent lectin-mediated interactions of SP-D with IAVs result in viral aggregation, reduced epithelial infection, and enhanced IAV clearance by phagocytic cells. Previous studies showed that porcine SP-D (pSP-D) exhibits distinct antiviral activity against IAV as compared to human SP-D (hSP-D), mainly due to key residues in the lectin domain of pSP-D that contribute to its profound neutralizing activity. These observations provided the basis for the design of a full-length recombinant mutant form of hSP-D, designated as "improved SP-D" (iSP-D). Inspired by pSP-D, the lectin domain of iSP-D has 5 amino acids replaced (Asp324Asn, Asp330Asn, Val251Glu, Lys287Gln, Glu289Lys) and 3 amino acids inserted (326Gly-Ser-Ser). Characterization of iSP-D revealed no major differences in protein assembly and saccharide binding selectivity as compared to hSP-D. However, hemagglutination inhibition measurements showed that iSP-D expressed strongly enhanced activity compared to hSP-D against 31 different IAV strains tested, including (pandemic) IAVs that were resistant for neutralization by hSP-D. Furthermore, iSP-D showed increased viral aggregation and enhanced protection of MDCK cells against infection by IAV. Importantly, prophylactic or therapeutic application of iSP-D decreased weight loss and reduced viral lung titers in a murine model of IAV infection using a clinical isolate of H1N1pdm09 virus. These studies demonstrate the potential of iSP-D as a novel human-based antiviral inhalation drug that may provide immediate protection against or recovery from respiratory (pandemic) IAV infections in humans.


Assuntos
Carboidratos , Engenharia de Proteínas , Domínios e Motivos de Interação entre Proteínas , Proteína D Associada a Surfactante Pulmonar/química , Proteína D Associada a Surfactante Pulmonar/metabolismo , Sítios de Ligação , Carboidratos/imunologia , Resistência à Doença/genética , Resistência à Doença/imunologia , Glicosilação , Humanos , Vírus da Influenza A/imunologia , Influenza Humana/genética , Influenza Humana/imunologia , Influenza Humana/virologia , Modelos Moleculares , Conformação Molecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas/genética , Proteína D Associada a Surfactante Pulmonar/genética , Proteína D Associada a Surfactante Pulmonar/imunologia , Proteínas Recombinantes , Relação Estrutura-Atividade
16.
Environ Sci Technol ; 53(24): 14734-14743, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31765146

RESUMO

The Deepwater Horizon (DWH) blowout resulted in the deposition of toxic polycyclic aromatic hydrocarbons (PAHs), in the coastal sediments of the Gulf of Mexico. The immediate effects on an ecosystem from an oil spill are clearly recognizable, however the long-term chronic effects and recovery after a spill are still not well understood. Current methodologies for biomonitoring wild populations are invasive and mostly lethal. Here, two potential nonlethal biomonitoring tools for the assessment of PAH toxicity and induced biological alterations in the field, were identified using laboratory-validated methods. In this study, subadult southern flounder (Paralichthys lethostigma) were chronically exposed to DWH surrogate oiled sediments for 35 days; a subset of these exposed flounder were then provided a clean nonexposure period to ascertain the utility of selected biomarkers to monitor recovery post exposure. After chronic exposure, there was an increase in gene expression of cytochrome P450 1A but not glutathione S-transferase. There was also a notable imbalance of oxidants to antioxidants, measured as reduced glutathione, oxidized glutathione, and their ratio in the blood. Evidence of subsequent oxidative damage due to chronic exposure was found through lipid peroxidation and DNA damage assessments of liver, gill, and blood.


Assuntos
Linguado , Poluição por Petróleo , Petróleo , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Animais , Biomarcadores , Ecossistema , Monitoramento Ambiental , Golfo do México , Estresse Oxidativo
17.
Opt Lett ; 44(14): 3466-3469, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31305549

RESUMO

A fiber-tetherable non-contact photoacoustic remote sensing microscopy system capable of multiplex functional imaging is reported. By utilizing stimulated Raman scattering within an over-pumped polarization-maintaining single-mode optical fiber, rapid pulse-to-pulse switching (500 kHz) of excitation spectral content is demonstrated and utilized as a photoacoustic excitation source. These rapid acquisitions aim to reduce motion artifacts and facilitate high frame rates appropriate for real-time feedback to users. The system is characterized by estimating blood oxygen saturation in blood-flow phantoms and within a mouse ear in vivo.

18.
Opt Lett ; 44(14): 3586-3589, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31305578

RESUMO

Traditional histopathology involves fixing, sectioning, and staining protocols that are time consuming and subject to staining variability. In this Letter, we present ultraviolet photoacoustic remote sensing microscopy, capable of imaging cell nuclei without the need for exogenous stains or labelling. Our reflection mode approach is non-contact and has the potential to provide useful histological information without laborious sample preparation steps. Tumor cell cultures and excised tissue samples were imaged with the 0.7 µm resolution and signal-to-noise ratios as high as 53 dB, with close agreement to traditional hematoxylin and eosin staining.

19.
Data Brief ; 22: 934-939, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30766908

RESUMO

Red drum (Sciaenops ocellatus) is an estuarine Sciaenid with high commercial value and recreational demand. During the past 50 years, overfishing has caused declines in the population that resulted in the development of red drum commercial and stock enhancement aquaculture fisheries. Despite the potential high economic value in both wild and aquaculture commercial fisheries the availability of transcriptomic data for red drum in public databases is limited. The data here represents the transcriptome profiles of three tissues: liver, testis and head kidney from red drum. The data was generated using Illumina high-throughput RNA sequencing, Trinity for de novo assembly and Blast2GO for annotation. Six individual libraries were pooled for sequencing of the transcriptome and the raw fastq reads have been deposited in the NCBI-SRA database (accession number SRP11690).

20.
Opt Express ; 26(18): 23689-23704, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30184866

RESUMO

Photoacoustic remote sensing microscopy (PARS) represents a new paradigm within the optical imaging community by providing high sensitivity (>50 dB in vivo) non-contact optical absorption contrast in scattering media with a reflection-mode configuration. Unlike contact-based photoacoustic modalities which can acquire complete A-scans with a single excitation pulse due to slow acoustic propagation facilitating the use of time-gated collection of returning acoustic signals, PARS provides depth resolution only through optical sectioning. Here we introduce a new approach for providing coherence-gated depth-resolved PARS imaging using a difference between pulsed-interrogation optical coherence tomography scan-lines with and without excitation pulses. Proposed methods are validated using simulations which account for pulsed-laser induced initial-pressures and accompanying refractive index changes. The changes in refractive index are shown to be proportional to optical absorption. It is demonstrated that to achieve optimal image quality, several key parameters must be selected including interrogation pulse duration and delay. The proposed approach offers the promise of non-contact depth-resolved optical absorption contrast at optical-resolution scales and may complement the scattering contrast offered by optical coherence tomography.

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