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1.
Analyst ; 148(21): 5476-5485, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37767770

RESUMO

Rapid detection of biologicals is important for a range of applications such as medical screening and diagnostics. Antibodies are typically employed for biosensing with high sensitivity and selectivity but can take months to prepare. Here, we investigate electropolymerized molecularly imprinted polymers (E-MIPs), which are produced in minutes as alternative-antibody rapid biosensors for the selective recognition of model proteins bovine haemoglobin (BHb) and bovine serum albumin (BSA). We evaluated two disposable screen-printed electrodes (SPE) designated AT-Au and BT-Au based on their different annealing temperatures. E-MIPs for BHb demonstrated an imprinting factor of 146 : 1 at 1 nM and 12 : 1 at 0.1 nM, showing high effectiveness of E-MIPs compared to their control non-imprinted polymers. The BHb imprinted E-MIP, when tested against BSA as a non-target protein, gave a selectivity factor of 6 : 1 for BHb. Sensor sensitivity directly depended on the nature of the SPE, with AT-Au SPE demonstrating limits of detection in the sub-micromolar range typically achieved for MIPs, while BT-Au SPE exhibited sensitivity in the sub-nanomolar range for target protein. We attribute this to differences in electrode surface area between AT-Au and BT-Au SPEs. The E-MIPs were also tested in calf serum as a model biological medium. The BT-Au SPE MIPs detected the presence of target protein in <10 min with an LOD of 50 pM and LOQ of 100 pM, suggesting their suitability for protein determination in serum with minimal sample preparation. Using electrochemical impedance spectroscopy, we determine equilibrium dissociation constants (KD) for E-MIPs using the Hill-Langmuir adsorption model. KD of BHb E-MIP was determined to be 0.86 ± 0.11 nM.


Assuntos
Impressão Molecular , Polímeros Molecularmente Impressos , Impressão Molecular/métodos , Polímeros/química , Hemoglobinas/química , Soroalbumina Bovina/química , Anticorpos
2.
Sci Rep ; 13(1): 2121, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36746988

RESUMO

Effective capture of fugitive actinides and daughter radionuclides constitutes a major remediation challenge at legacy or nuclear accident sites globally. The ability of double-layered, anionic clay minerals known as hydrotalcites (HTC) to contemporaneously sequester a range of contaminants from solution offers a unique remedy. However, HTC do not provide a robust repository for actinide isolation over the long term. In this study, we formed HTC by in-situ precipitation in a barren lixiviant from a uranium mine and thermally transformed the resulting radionuclide-laden, nanoscale HTC. Atomic-scale forensic examination of the amorphized/recrystallised product reveals segregation of U to nanometre-wide mineral interfaces and the local formation of interface-hosted mineral grains. This U-phase is enriched in rare earth elements, a geochemical analogue of actinides such as Np and Pu, and represents a previously unreported radionuclide interfacial segregation. U-rich phases associated with the mineral interfaces record a U concentration factor of ~ 50,000 relative to the original solute demonstrating high extraction and concentration efficiencies. In addition, the co-existing host mineral suite of periclase, spinel-, and olivine-group minerals that equate to a lower mantle, high P-T mineral assemblage have geochemical and geotechnical properties suitable for disposal in a nuclear waste repository. Our results record the efficient sequestering of radionuclides from contaminated water and this novel, broad-spectrum, nanoscale HTC capture and concentration process constitutes a rapid solute decontamination pathway and solids containment option in perpetuity.

3.
Perspect Public Health ; 143(5): 272-274, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35766318

RESUMO

BACKGROUND: No Recourse to Public Funds (NRPF) status is applied to individuals and families that are subject to immigration control, resulting in them having restricted access to state-funded benefits within England. NRPF is a public health risk as it increases the risk of destitution among vulnerable migrants. AIMS: The aim of this study was to engage with public and voluntary sector staff within Wolverhampton working with people with a NRPF status to develop and create an easily accessible guide ('protocol') to help facilitate identification of appropriate cross-sector interventions and support. METHODS: Data were collected via an online survey as well as face-to-face semi-structured interviews with local NRPF stakeholders. RESULTS: Four themes emerged from the thematic analysis of participant responses: understanding NRPF statuses, varying support requirements, poor communication and awareness of vulnerabilities. Currently, in England, there does not appear to be a standardised localised protocol which can be used to reduce the complexities and confusion encountered by public and voluntary sectors who support people with NRPF status. CONCLUSION: The findings from this study have allowed the Wolverhampton NRPF to create an online information resource that includes training events to raise the awareness of NRPF, as well as the development of a localised multiagency protocol that has better equipped it to support and safeguard people with NRPF.

4.
Anal Chim Acta ; 1206: 339777, 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35473858

RESUMO

We investigate electropolymerized molecularly imprinted polymers (E-MIPs) for the selective recognition of SARS-CoV-2 whole virus. E-MIPs imprinted with SARS-CoV-2 pseudoparticles (pps) were electrochemically deposited onto screen printed electrodes by reductive electropolymerization, using the water-soluble N-hydroxmethylacrylamide (NHMA) as functional monomer and crosslinked with N,N'-methylenebisacrylamide (MBAm). E-MIPs for SARS-CoV-2 showed selectivity for template SARS-CoV-2 pps, with an imprinting factor of 3:1, and specificity (significance = 0.06) when cross-reacted with other respiratory viruses. E-MIPs detected the presence of SARS-CoV-2 pps in <10 min with a limit of detection of 4.9 log10 pfu/mL, suggesting their suitability for detection of SARS-CoV-2 with minimal sample preparation. Using electrochemical impedance spectroscopy (EIS) and principal component analysis (PCA), the capture of SARS-CoV-2 from real patient saliva samples was also evaluated. Fifteen confirmed COVID-19 positive and nine COVID-19 negative saliva samples were compared against the established loop-mediated isothermal nucleic acid amplification (LAMP) technique used by the UK National Health Service. EIS data demonstrated a PCA discrimination between positive and negative LAMP samples. A threshold real impedance signal (ZRe) ≫ 4000 Ω and a corresponding charge transfer resistance (RCT) ≫ 6000 Ω was indicative of absence of virus (COVID-19 negative) in agreement with values obtained for our control non-imprinted polymer control. A ZRe at or below a threshold value of 600 Ω with a corresponding RCT of <1200 Ω was indicative of a COVID-19 positive sample. The presence of virus was confirmed by treatment of E-MIPs with a SARS-CoV-2 specific monoclonal antibody.


Assuntos
COVID-19 , Polímeros Molecularmente Impressos , Anticorpos Antivirais , COVID-19/diagnóstico , Eletrodos , Humanos , SARS-CoV-2 , Saliva , Medicina Estatal
5.
Anal Chim Acta ; 1196: 339547, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35151409

RESUMO

We report the investigation of electropolymerised molecularly imprinted polymers (E-MIPs) for the determination of dioctyl phthalate (DOP). Low-cost and eco-friendly commercially available screen-printed electrodes (SPEs) were used. E-MIPs were produced using the cyclic voltammetry (CV) technique based on a water-soluble 4-aminophenol as functional monomer. E-MIPs for DOP showed affinity for the template, with 80% binding efficiency and an imprinting factor of 3. The E-MIPs were able to detect absolute levels of DOP in a time-dependent adsorption manner with the presence of 250 µg DOP (equivalent to 12.8 µM) detected in 5 min with a LOD (at 15 min) of 177.1 µg and LOQ of 536.6 µg making them suitable for the measurement of DOP in freshwater when the sample is pre-concentrated.


Assuntos
Dietilexilftalato , Impressão Molecular , Técnicas Eletroquímicas , Eletrodos , Polímeros Molecularmente Impressos , Polímeros
6.
Clin Rheumatol ; 40(12): 4933-4942, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34287723

RESUMO

OBJECTIVES: To compare work absenteeism and short-term disability among adults with psoriasis or psoriatic arthritis (PsA), versus controls in the USA. METHODS: Adults eligible for work absenteeism and/or short-term disability benefits between 1/1/2009 and 4/30/2020 were screened in the IBM® MarketScan® Commercial and Health and Productivity Management Databases. The following groups were defined: (1) psoriasis: ≥ 2 psoriasis diagnoses ≥ 30 days apart and no PsA diagnoses; (2) PsA: ≥ 2 PsA diagnoses ≥ 30 days apart; (3) control: absence of psoriasis and PsA diagnoses. Controls were matched to psoriasis and PsA patients based on age, gender, index year, and comorbidities. Non-recreational work absences and sick leaves were evaluated in absentee-eligible patients, and short-term disability was evaluated in short-term disability-eligible patients. Costs (in 2019 USD) associated with each type of work absence were evaluated. RESULTS: 4261 psoriasis and 616 PsA absentee-eligible and 25,213 psoriasis and 3480 PsA short-term disability-eligible patients were matched to controls. Average non-recreational work absence costs were $1681, $1657, and $1217 for the PsA, psoriasis, and control group, respectively. Compared with psoriasis patients and controls, more PsA patients had sick leaves after 1 year (56.2% versus 55.6% and 41.5%, p < 0.0001). Similarly, short-term disability was more frequent in PsA patients than psoriasis patients and controls at year one (8.8% versus 5.6% and 4.7%, p < 0.0001) and corresponding costs were higher ($605, $406, and $335 on average, p < 0.0001). CONCLUSION: Annual work absenteeism and short-term disability were consistently greater among patients with PsA and psoriasis than controls, highlighting the substantial economic burden of psoriatic disease. Key points • Patients with PsA had greater short-term disability compared with patients with psoriasis and patients with neither psoriasis nor PsA. • Patients with PsA and patients with psoriasis incurred greater non-recreational work absences and sick leaves than patients with neither psoriasis nor PsA.


Assuntos
Artrite Psoriásica , Psoríase , Absenteísmo , Adulto , Artrite Psoriásica/epidemiologia , Eficiência , Humanos , Psoríase/epidemiologia , Estudos Retrospectivos , Estados Unidos
7.
Avian Pathol ; 48(6): 564-572, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31294636

RESUMO

In previous studies, we have demonstrated that very virulent plus Marek's disease viruses (vv+MDV) are highly immunosuppressive in commercial meat-type chickens. The specific objectives of this work were to evaluate if vv+MDV immunosuppression (MDV-IS) is induced by reduction of lymphocyte responsiveness and/or viability. Three experiments were conducted to (i) compare vv+MDV 686 with a partially attenuated 686-BAC; (ii) compare vv+MDV strains (648A and 686) with vMDV (GA) and vvMDV (Md5); and (iii) compare chickens vaccinated with Md5-BACΔMEQ and with CVI988 + HVT. In each experiment, spleens were collected at 28-30 days post infection and lymphocytes were isolated and investigated in three ways: their proliferative response to Concanavalin A (ConA) was analysed by MTT proliferation assay; cell death, and expression of CD45 and MHC-I was studied by flow cytometry; and MHC-IA and ß-2 microglobulin (B2M) expression was evaluated by real time RT-PCR. Splenocytes of chickens inoculated with vv+MDV were severely impaired to proliferate when exposed to ConA. Furthermore, vv+MDV induced severe splenocyte death that did not occur after infection with v or vvMDV strains. Vaccination with CVI988 + HVT, and at less level with Md5-BACΔMEQ reduced these negative effects. This is in contrast to our previous results in which Md5-BACΔMEQ but not CVI988 + HVT protected against MDV-IS suggesting that although cell death and decrease lymphocyte function seem to be related to MDV virulence and certainly will be associated with immunosuppression, they might not fully explain the previously reported MDV-IS. RESEARCH HIGHLIGHTS vv+MDV induces extensive death in splenocytes in meat-type chickens 28-30 dpi. vv+MDV impairs lymphocyte function in meat-type chickens 28-30 dpi. Vaccination protects against splenocyte death and reduced lymphocyte function. Cell lysis and reduced lymphocyte function do not fully explain MDV-IS.


Assuntos
Galinhas/virologia , Herpesvirus Galináceo 2/patogenicidade , Doença de Marek/virologia , Doenças das Aves Domésticas/virologia , Animais , Proliferação de Células , Galinhas/imunologia , Feminino , Terapia de Imunossupressão/veterinária , Baço/virologia , Linfócitos T/virologia , Virulência
8.
Br J Cancer ; 118(1): 17-23, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29235566

RESUMO

BACKGROUND: We counsel our triple-negative breast cancer (TNBC) patients that the risk of recurrence is highest in the first 5 years after diagnosis. However, there are limited data with extended follow-up on the frequency, characteristics, and predictors of late events. METHODS: We queried the MD Anderson Breast Cancer Management System database to identify patients with stage I-III TNBC who were disease free at 5 years from diagnosis. The Kaplan-Meier method was used to estimate yearly recurrence-free interval (RFI), recurrence-free survival (RFS), and distant relapse-free survival (DRFS), as defined by the STEEP criteria. Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 873 patients who were disease free at least 5 years from diagnosis with median follow-up of 8.3 years. The 10-year RFI was 97%, RFS 91%, and DRFS 92%; the 15-year RFI was 95%, RFS 83%, and DRFS 84%. On a subset of patients with oestrogen receptor and progesterone receptor percentage recorded, low hormone receptor positivity conferred higher risk of late events on multivariable analysis for RFS only (RFI: HR=1.98, 95% CI=0.70-5.62, P-value=0.200; RFS: HR=1.94, 95% CI=1.05-3.56, P-value=0.034; DRFS: HR=1.72, 95% CI=0.92-3.24, P-value=0.091). CONCLUSIONS: The TNBC survivors who have been disease free for 5 years have a low probability of experiencing recurrence over the subsequent 10 years. Patients with low hormone receptor-positive cancers may have a higher risk of late events as measured by RFS but not by RFI or DRFS.


Assuntos
Recidiva Local de Neoplasia/epidemiologia , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Intervalo Livre de Doença , Regulação para Baixo , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Neoplasias de Mama Triplo Negativas/metabolismo
9.
Science ; 359(6371): 97-103, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29097493

RESUMO

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.


Assuntos
Microbioma Gastrointestinal/imunologia , Imunoterapia , Melanoma/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/terapia , Animais , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/genética , Humanos , Melanoma/imunologia , Metagenoma , Camundongos , Neoplasias Cutâneas/imunologia
10.
Acta Biomater ; 28: 121-127, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26363378

RESUMO

We report the fabrication of metal-coded molecularly imprinted polymers (MIPs) using hydrogel-based protein imprinting techniques. A Co(II) complex was prepared using (E)-2-((2 hydrazide-(4-vinylbenzyl)hydrazono)methyl)phenol; along with iron(III) chloroprotoporphyrin (Hemin), vinylferrocene (VFc), zinc(II) protoporphyrin (ZnPP) and protoporphyrin (PP), these complexes were introduced into the MIPs as co-monomers for metal-coding of non-metalloprotein imprints. Results indicate a 66% enhancement for bovine serum albumin (BSA) protein binding capacities (Q, mg/g) via metal-ion/ligand exchange properties within the metal-coded MIPs. Specifically, Co(II)-complex-based MIPs exhibited 92 ± 1% specific binding with Q values of 5.7 ± 0.45 mg BSA/g polymer and imprinting factors (IF) of 14.8 ± 1.9 (MIP/non-imprinted (NIP) control). The selectivity of our Co(II)-coded BSA MIPs were also tested using bovine haemoglobin (BHb), lysozyme (Lyz), and trypsin (Tryp). By evaluating imprinting factors (K), each of the latter proteins was found to have lower affinities in comparison to cognate BSA template. The hydrogels were further characterised by thermal analysis and differential scanning calorimetry (DSC) to assess optimum polymer composition. STATEMENT OF SIGNIFICANCE: The development of hydrogel-based molecularly imprinted polymer (HydroMIPs) technology for the memory imprinting of proteins and for protein biosensor development presents many possibilities, including uses in bio-sample clean-up or selective extraction, replacement of biological antibodies in immunoassays and biosensors for medicine and the environment. Biosensors for proteins and viruses are currently expensive to develop because they require the use of expensive antibodies. Because of their biomimicry capabilities (and their potential to act as synthetic antibodies), HydroMIPs potentially offer a route to the development of new low-cost biosensors. Herein, a metal ion-mediated imprinting approach was employed to metal-code our hydrogel-based MIPs for the selective recognition of bovine serum albumin (BSA). Specifically, Co(II)-complex based MIPs exhibited a 66% enhancement (in comparison to our normal MIPs) exhibiting 92 ± 1% specific binding with Q values of 5.7 ± 0.45 mg BSA/g polymer and imprinting factors (IF) of 14.8 ± 1.9 (MIP/ non-imprinted (NIP) control). The proposed metal-coded MIPs for protein recognition are intended to lead to unprecedented improvement in MIP selectivity and for future biosensor development that rely on an electrochemical redox processes.


Assuntos
Resinas Acrílicas/química , Hidrogéis/química , Metais/química , Impressão Molecular/métodos , Soroalbumina Bovina/química , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
11.
Invest New Drugs ; 33(4): 977-84, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26062928

RESUMO

BACKGROUND: Src has a critical role in tumor cell migration and invasion. Increased Src activity has been shown to correlate with disease progression and poor prognosis, suggesting Src could serve as a therapeutic target for kinase inhibition. Saracatinib (AZD0530) is a novel selective oral Src kinase inhibitor. METHODS: Metastatic colorectal cancer patients who had received one prior treatment and had measurable disease were enrolled in this phase 2 study. Saracatinib was administered at 175 mg by mouth daily for 28 day cycles until dose-limiting toxicity or progression as determined by staging every 2 cycles. The primary endpoint was improvement in 4 month progression-free survival. Design of Thall, Simon, and Estey was used to monitor proportion of patients that were progression free at 4 months. The trial was opened with plan to enroll maximum of 35 patients, with futility assessment every 10 patients. RESULTS: A total of 10 patients were enrolled between January and November 2007. Further enrollment was stopped due to futility. Median progression-free survival was 7.9 weeks, with all 10 patients showing disease progression following radiographic imaging. Median overall survival was 13.5 months. All patients were deceased by time of analysis. Observed adverse events were notable for a higher than expected number of patients with grade 3 hypophosphatemia (n = 5). CONCLUSION: Saracatinib is a novel oral Src kinase inhibitor that was well tolerated but failed to meet its primary endpoint of improvement in 4 month progression-free survival as a single agent in previously treated metastatic colorectal cancer patients.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Benzodioxóis/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Idoso , Antineoplásicos/efeitos adversos , Benzodioxóis/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/sangue , Quinases da Família src/antagonistas & inibidores
12.
Drug Metab Lett ; 8(2): 88-95, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24910236

RESUMO

Different fungi viz. Aspergillus niger NCIM 589, A.ochraceous NCIM 1140, Cunninghamella blakesleeana NCIM 687, C. echinulata NCIM 691, Rhizopus stolonifer NCIM 880, Mucor rouxi MTCC 386, Trichothecium roseum NCIM 1147 were screened for their potential to biotransform anti-hyperlipidemia and anti-hypertriglyceridemia drug, fenofibrate to fenofibric acid, the active metabolite and other mammalian metabolites. Among the fungi screened C. blakesleeana transformed fenofibrate to fenofibric acid and other three metabolites. HPLC, LC-MS/MS analysis and previous reports confirmed the transformation of fenofibrate and metabolites as fenofibric acid (M1), reduced fenofibric acid (M2), reduced fenofibric acid taurine conjugate (M3), reduced fenofibric acid ester glucuronide (M4), the mammalian metabolites reported previously. The results proved the potential of C.blakesleeana NCIM 687 in the production of mammalian phase I (M1 and M2) and phase II (M3 and M4) metabolites in large quantities and also as an in vitro model for drug metabolism studies.


Assuntos
Fenofibrato/análogos & derivados , Fungos/metabolismo , Hipolipemiantes/metabolismo , Animais , Glicemia/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Fenofibrato/metabolismo , Fenofibrato/farmacologia , Hipolipemiantes/farmacologia , Masculino , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem
13.
Poult Sci ; 93(2): 485-93, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24570473

RESUMO

Avian influenza virus (AIV) is a type A virus of the family Orthomyxoviridae. Avian influenza virus infection can cause significant economic losses to the poultry industry, and raises a great public health threat due to potential host jump from animals to humans. To develop more effective intervention strategies to prevent and control AIV infection in poultry, it is essential to elucidate molecular mechanisms of host response to AIV infection in chickens. The objective of this study was to identify genes and signal pathways associated with resistance to AIV infection in 2 genetically distinct highly inbred chicken lines (Fayoumi, relatively resistant to AIV infection, and Leghorn, susceptible to AIV infection). Three-week-old chickens were inoculated with 10(7) EID50 of low pathogenic H5N3 AIV, and lungs and trachea were harvested 4 d postinoculation. Four cDNA libraries (1 library each for infected and noninfected Leghorn, and infected and noninfected Fayoumi) were prepared from the lung samples and sequenced by Illumina Genome Analyzer II, which yielded a total of 116 million, 75-bp single-end reads. Gene expression levels of all annotated chicken genes were analyzed using CLC Genomics Workbench. DESeq was used to identify differentially expressed transcripts between infected and noninfected birds and between genetic lines (false discovery rate < 0.05 and fold-change > 2). Of the expressed transcripts in a total of 17,108 annotated chicken genes in Ensembl database, 82.44 and 81.40% were identified in Leghorn and Fayoumi birds, respectively. The bioinformatics analysis suggests that the hemoglobin family genes, the functional involvements for oxygen transportation and circulation, and cell adhesion molecule signaling pathway play significant roles in disease resistance to AIV infection in chickens. Further investigation of the roles of these candidate genes and signaling pathways in the regulation of host-AIV interaction can lead new directions for the development of antiviral drugs or vaccines in poultry.


Assuntos
Proteínas Aviárias/genética , Galinhas/fisiologia , Resistência à Doença , Influenza Aviária/virologia , Pulmão/virologia , Transdução de Sinais , Animais , Proteínas Aviárias/metabolismo , Galinhas/genética , Vírus da Influenza A/fisiologia , Reação em Cadeia da Polimerase/veterinária , Análise de Sequência de RNA/veterinária , Transcriptoma
14.
Br J Cancer ; 109(4): 872-81, 2013 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-23922112

RESUMO

BACKGROUND: Post-diagnosis weight gain in breast cancer patients has been associated with increased cancer recurrence and mortality. Our study was designed to identify risk factors for this weight gain and create a predictive model to identify a high-risk population for targeted interventions. METHODS: Chart review was conducted on 459 breast cancer patients from Northwestern Robert H. Lurie Cancer Centre to obtain weights and body mass indices (BMIs) over an 18-month period from diagnosis. We also recorded tumour characteristics, demographics, clinical factors, and treatment regimens. Blood samples were genotyped for 14 single-nucleotide polymorphisms (SNPs) in fat mass and obesity-associated protein (FTO) and adiponectin pathway genes (ADIPOQ and ADIPOR1). RESULTS: In all, 56% of patients had >0.5 kg m(-2) increase in BMI from diagnosis to 18 months, with average BMI and weight gain of 1.9 kg m(-2) and 5.1 kg, respectively. Our best predictive model was a primarily SNP-based model incorporating all 14 FTO and adiponectin pathway SNPs studied, their epistatic interactions, and age and BMI at diagnosis, with area under receiver operating characteristic curve of 0.85 for 18-month weight gain. CONCLUSION: We created a powerful risk prediction model that can identify breast cancer patients at high risk for weight gain.


Assuntos
Adiponectina/genética , Neoplasias da Mama , Carcinoma , Proteínas/genética , Receptores de Adiponectina/genética , Aumento de Peso/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Feminino , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Curva ROC , Estudos Retrospectivos , Medição de Risco , Aumento de Peso/fisiologia
15.
Br J Dermatol ; 168(1): 210-2, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23278559

RESUMO

Psoriasis is a chronic inflammatory skin condition, characterized by T-helper (Th) 1 and Th17 cell activation. Ustekinumab is a fully human immunoglobulin G1κ monoclonal antibody that targets the common p40 subunit that is shared by both interleukin (IL)-12 and IL-23, consequently inhibiting T-cell differentiation along both Th1 and Th17 pathways. This is a report of two patients who developed psoriatic arthritis during ustekinumab treatment for psoriasis. Neither patient had a personal or family history of arthritis.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Psoriásica/induzido quimicamente , Fármacos Dermatológicos/efeitos adversos , Psoríase/tratamento farmacológico , Adulto , Humanos , Masculino , Ustekinumab
16.
Eur J Clin Microbiol Infect Dis ; 32(6): 815-20, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23354672

RESUMO

In the majority of cases of vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant Enterococcus faecalis (VR E. faecalis) served as the vanA donor to S. aureus. Previous studies that evaluated the risk factors for co-colonization with VRE and MRSA did not differentiate between VR E. faecalis and VR E. faecium. This study aimed to identify variables associated with VR E. faecalis and MRSA co-colonization. A retrospective case-control study from January 2008 to December 2009 was conducted at the Detroit Medical Center. Data were extracted from charts and pharmacy records. Unique patients co-colonized with VR E. faecalis and MRSA (defined as isolation of MRSA within 7 days of VR E. faecalis isolation) were compared with patients with VR E. faecalis who were not co-colonized with MRSA. A total of 546 patients with VR E. faecalis isolation were identified. 85 (15.6 %) VR E. faecalis patients were co-colonized with MRSA and 461 (84.4 %) VR E. faecalis patients were not co-colonized with MRSA. The mean age of the study cohort was 65.9 ± 16.4 years, 424 (77.7 %) were African-American, and 270 (49.5 %) were residing in long-term care institutions. Independent predictors of co-colonization of VR E. faecalis and MRSA were male gender, impaired consciousness, ICU stay prior to VR E. faecalis isolation, indwelling devices, and isolation of VR E. faecalis from wounds. MRSA was frequently isolated from the same culture specimen as VR E. faecalis (n = 39, 45.9 %), most commonly from wounds. This large study of patients with VR E. faecalis identified the severity of illness, indwelling devices, and chronic wounds as independent predictors of co-colonization with VR E. faecalis and MRSA.


Assuntos
Coinfecção , Farmacorresistência Bacteriana , Enterococcus faecalis/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/epidemiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/epidemiologia , Vancomicina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Enterococcus faecalis/isolamento & purificação , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco
17.
Microb Biotechnol ; 5(6): 674-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22513201

RESUMO

Rhodopseudomonas acidophila KU001 was isolated from leather industry effluents and the effect of different cultural conditions on hydrogen production was studied. Anaerobic light induced more hydrogen production than anaerobic dark conditions. Growing cells produced more amounts of hydrogen between 96 and 144 h of incubation. Resting and growing cells preferred a pH of 6.0 ± 0.24 for hydrogen production. Succinate was the most preferred carbon source for the production of hydrogen while citrate was a poor source of carbon. Acetate and malate were also good carbon sources for hydrogen production under anaerobic light. Among the nitrogen sources, R. acidophila preferred ammonium chloride followed by urea for production of hydrogen. L-tyrosine was the least preferred nitrogen source by both growing and resting cells.


Assuntos
Hidrogênio/metabolismo , Rodopseudomonas/metabolismo , Anaerobiose , Carbono/metabolismo , Escuridão , Microbiologia Ambiental , Concentração de Íons de Hidrogênio , Microbiologia Industrial , Luz , Nitrogênio/metabolismo , Rodopseudomonas/crescimento & desenvolvimento , Rodopseudomonas/isolamento & purificação , Rodopseudomonas/efeitos da radiação
18.
Appl Biochem Biotechnol ; 165(5-6): 1120-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21837380

RESUMO

In the present investigation, thermophilic fungus Rhizomucor pusillus was used to study biotransformation of antihelmintic drug albendazole to produce its active metabolite, albendazole sulfoxide and novel metabolites of commercial interest. A two-stage fermentation procedure was followed for biotransformation of albendazole. The transformation was identified and structures were confirmed by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analysis. Four metabolites albendazole sulfoxide, the active metabolite, albendazole sulfone, N-methyl metabolite of albendazole sulfoxide, and a novel metabolite were produced. The study demonstrates the biotransformation ability of thermophilic fungus R. pusillus NRRL28626 in the production of, the active metabolite of albendazole which has industrial and economic importance, other metabolites and a novel metabolite in an ecofriendly way.


Assuntos
Albendazol/metabolismo , Anti-Helmínticos/metabolismo , Rhizomucor/metabolismo , Albendazol/química , Anti-Helmínticos/química , Biotransformação , Temperatura Alta , Estrutura Molecular , Rhizomucor/química
20.
Indian J Microbiol ; 51(1): 82-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22282633

RESUMO

Influence of carbon and nitrogen source, on biotransformation of meloxicam was studied by employing Cunninghamella blakesleeana NCIM 687 with an aim to achieve maximum transformation of meloxicam and in search of new metabolites. The transformation was confirmed by HPLC and based on LC-MS-MS data and previous reports the metabolites were predicted as 5-hydroxymethyl meloxicam, 5-carboxy meloxicam and a novel metabolite. The quantification of metabolites was performed using HPLC peak areas. The results obtained indicate that glucose as carbon source, ammonium nitrate as nitrogen source, were found to be optimum for maximum transformation of meloxicam. The study suggests the significance of these factors in biotransformation of meloxicam using microbial cultures. The fermentation was scaled up to 1 l level.

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