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1.
J Am Chem Soc ; 144(46): 21136-21145, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36351171

RESUMO

Molecular catalysts for ammonia oxidation to dinitrogen represent enabling components to utilize ammonia as a fuel and/or source of hydrogen. Ammonia oxidation requires not only the breaking of multiple strong N-H bonds but also controlled N-N bond formation. We report a novel ß-diketiminato copper complex [iPr2NNF6]CuI-NH3 ([CuI]-NH3 (2)) as a robust electrocatalyst for NH3 oxidation in acetonitrile under homogeneous conditions. Complex 2 operates at a moderate overpotential (η = 700 mV) with a TOFmax = 940 h-1 as determined from CV data in 1.3 M NH3-MeCN solvent. Prolonged (>5 h) controlled potential electrolysis (CPE) reveals the stability and robustness of the catalyst under electrocatalytic conditions. Detailed mechanistic investigations indicate that electrochemical oxidation of [CuI]-NH3 forms {[CuII]-NH3}+ (4), which undergoes deprotonation by excess NH3 to form reactive copper(II)-amide ([CuII]-NH2, 6) unstable toward N-N bond formation to give the dinuclear hydrazine complex [CuI]2(µ-N2H4). Electrochemical studies reveal that the diammine complex [CuI](NH3)2 (7) forms at high ammonia concentration as part of the {[CuII](NH3)2}+/[CuI](NH3)2 redox couple that is electrocatalytically inactive. DFT analysis reveals a much higher thermodynamic barrier for deprotonation of the four-coordinate {[CuII](NH3)2}+ (8) by NH3 to give the copper(II) amide [CuII](NH2)(NH3) (9) (ΔG = 31.7 kcal/mol) as compared to deprotonation of the three-coordinate {[CuII]-NH3}+ by NH3 to provide the reactive three-coordinate parent amide [CuII]-NH2 (ΔG = 18.1 kcal/mol) susceptible to N-N coupling to form [CuI]2(µ-N2H4) (ΔG = -11.8 kcal/mol).


Assuntos
Amônia , Cobre , Cobre/química , Amônia/química , Catálise , Termodinâmica , Amidas
2.
Ann Surg ; 275(2): e392-e400, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32404661

RESUMO

OBJECTIVE: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. BACKGROUND: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. PATIENTS AND METHODS: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. RESULTS: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ±â€Š0.02 and 0.82 ±â€Š0.09 respectively. CONCLUSION: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Idoso , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Avaliação de Sintomas
3.
BMC Infect Dis ; 22(1): 758, 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175863

RESUMO

BACKGROUND: Environmental contamination contributes to hospital associated infections, particularly those caused by multi-drug resistant organisms (MDRO). This study investigated bioburden presence on surfaces in a critical care center's patient rooms following typical environmental services (EVS) practices and following intervention with hybrid hydrogen peroxide™ (HHP™) fogging. METHODS: Upon patient discharge, following standard cleaning or cleaning with ultraviolet (UV) light use, patient rooms were sampled by swabbing for adenosine triphosphate (ATP) and aerobic colony counts (ACC) from five preset locations. Rooms were then fogged via HHP technology using chemical indicators and Geobacillus stearothermophilus biological indicators for sporicidal validation monitoring. Following fogging, rooms were sampled again, and results were compared. RESULTS: A 98% reduction in ACC was observed after fogging as compared to post EVS practices both with and without UV light use. No statistical difference was seen when comparing cleaning to cleaning with UV light use. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were identified following EVS practices and not detected following HHP fogging. ATP samples were reduced 88% by fogging application. Chemical and biological indicators confirmed correct application of HHP fogging, as seen through its achievement of a 6-log reduction of bacterial spores. CONCLUSION: HHP fogging is a thorough and efficacious technology which, when applied to critical care patient rooms, significantly reduces bioburden on surfaces, indicating potential benefits for implementation as part of infection prevention measures.


Assuntos
Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Trifosfato de Adenosina , Cuidados Críticos , Desinfecção , Humanos , Hidrogênio , Peróxido de Hidrogênio/farmacologia , Quartos de Pacientes
4.
Inorg Chem ; 60(21): 15968-15974, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34184870

RESUMO

Nitric oxide (NO) is a key signaling molecule in health and disease. While nitrite acts as a reservoir of NO activity, mechanisms for NO release require further understanding. A series of electronically varied ß-diketiminatocopper(II) nitrite complexes [CuII](κ2-O2N) react with a range of electronically tuned triarylphosphines PArZ3 that release NO with the formation of O═PArZ3. Second-order rate constants are largest for electron-poor copper(II) nitrite and electron-rich phosphine pairs. Computational analysis reveals a transition-state structure energetically matched with experimentally determined activation barriers. The production of NO follows a pathway that involves nitrite isomerization at CuII from κ2-O2N to κ1-NO2 followed by O-atom transfer (OAT) to form O═PArZ3 and [CuI]-NO that releases NO upon PArZ3 binding at CuI to form [CuI]-PArZ3. These findings illustrate important mechanistic considerations involved in NO formation from nitrite via OAT.

5.
J Am Chem Soc ; 142(43): 18483-18490, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-32956589

RESUMO

Copper(II) alkynyl species are proposed as key intermediates in numerous Cu-catalyzed C-C coupling reactions. Supported by a ß-diketiminate ligand, the three-coordinate copper(II) alkynyl [CuII]-C≡CAr (Ar = 2,6-Cl2C6H3) forms upon reaction of the alkyne H-C≡CAr with the copper(II) tert-butoxide complex [CuII]-OtBu. In solution, this [CuII]-C≡CAr species cleanly transforms to the Glaser coupling product ArC≡C-C≡CAr and [CuI](solvent). Addition of nucleophiles R'C≡C-Li (R' = aryl, silyl) and Ph-Li to [CuII]-C≡CAr affords the corresponding Csp-Csp and Csp-Csp2 coupled products RC≡C-C≡CAr and Ph-C≡CAr with concomitant generation of [CuI](solvent) and {[CuI]-C≡CAr}-, respectively. Supported by density functional theory (DFT) calculations, redox disproportionation forms [CuIII](C≡CAr)(R) species that reductively eliminate R-C≡CAr products. [CuII]-C≡CAr also captures the trityl radical Ph3C· to give Ph3C-C≡CAr. Radical capture represents the key Csp-Csp3 bond-forming step in the copper-catalyzed C-H functionalization of benzylic substrates R-H with alkynes H-C≡CR' (R' = (hetero)aryl, silyl) that provide Csp-Csp3 coupled products R-C≡CR via radical relay with tBuOOtBu as oxidant.

6.
J Am Chem Soc ; 139(27): 9112-9115, 2017 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-28590730

RESUMO

Copper(II) aryl species are proposed key intermediates in Cu-catalyzed cross-coupling reactions. Novel three-coordinate copper(II) aryls [CuII]-C6F5 supported by ancillary ß-diketiminate ligands form in reactions between copper(II) alkoxides [CuII]-OtBu and B(C6F5)3. Crystallographic, spectroscopic, and DFT studies reveal geometric and electronic structures of these Cu(II) organometallic complexes. Reaction of [CuII]-C6F5 with the free radical NO(g) results in C-N bond formation to give [Cu](η2-ONC6F5). Remarkably, addition of the phenolate anion PhO- to [CuII]-C6F5 directly affords diaryl ether PhO-C6F5 with concomitant generation of the copper(I) species [CuI](solvent) and {[CuI]-C6F5}-. Experimental and computational analysis supports redox disproportionation between [CuII]-C6F5 and {[CuII](C6F5)(OPh)}- to give {[CuI]-C6F5}- and [CuIII](C6F5)(OPh) unstable toward reductive elimination to [CuI](solvent) and PhO-C6F5.

7.
Endoscopy ; 47(12): 1106-12, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26158241

RESUMO

BACKGROUND AND AIMS: Currently, eradication of Barrett's epithelium is preferably achieved using radiofrequency ablation (RFA) or spray cryoablation (SCA). However, both modalities suffer from drawbacks such as the need for sizing, multiple deployment steps, large controller units (RFA), imprecise dosing and need for gas-venting (SCA). The new Cryoballoon Focal Ablation System (CbFAS) may address these limitations. This study assessed the safety, feasibility, and dose response of the CbFAS in patients with flat Barrett's epithelium with or without dysplasia. PATIENTS AND METHODS: In this multicenter, prospective non-randomized trial, 39 patients were each treated with one or two ablations of 6, 8, or 10 seconds. Symptoms were assessed immediately and 2 days post-cryoablation. Follow-up endoscopy was performed 6-8 weeks post-procedure to assess response. Outcome parameters were incidence of adverse events, pain, esophageal stricture formation, and ablation response by cryogen dose. RESULTS: Of 62 ablations, 56 (10 with 6 seconds, 28 with 8 seconds, 18 with 10 seconds) were successfully performed. Six ablations failed because of device malfunction (n=3) and procedural or anatomic issues (n=3). Median procedure time was 7 minutes (interquartile range [IQR] 4-10). No major adverse events occurred; six patients experienced a minor mucosal laceration requiring no intervention. Mild pain was reported by 27% of patients immediately after cryoablation and by 14% after 2 days. No strictures were evident at follow-up.  Full squamous regeneration was seen in 47 treated areas (6 [60%] of the 6-second areas; 23 [82%] of the 8-second areas; 18 [100%] of 10-second areas). CONCLUSIONS: Focal cryoablation of Barrett's epithelium with the CbFAS is feasible and safe, resulting in squamous regeneration in the majority of patients.


Assuntos
Esôfago de Barrett , Criocirurgia , Esofagoscopia , Esôfago , Dor Pós-Operatória/diagnóstico , Idoso , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/cirurgia , Criocirurgia/efeitos adversos , Criocirurgia/instrumentação , Criocirurgia/métodos , Esofagoscopia/efeitos adversos , Esofagoscopia/instrumentação , Esofagoscopia/métodos , Esôfago/patologia , Esôfago/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Resultado do Tratamento
8.
Brain Pathol ; : e13285, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010270

RESUMO

Pituitary neuroendocrine tumour Ki-67 proliferation index varies according to the number of tumour cells assessed. Consistent Ki-67 scoring approaches and re-evaluation of the recommended Ki-67 3% cut-off are required to clarify controversies in pituitary neuroendocrine tumour Ki-67 proliferation index assessment.

9.
Biomed Phys Eng Express ; 10(5)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38925106

RESUMO

Detecting the Kirsten Rat Sarcoma Virus (KRAS) gene mutation is significant for colorectal cancer (CRC) patients. TheKRASgene encodes a protein involved in the epidermal growth factor receptor (EGFR) signaling pathway, and mutations in this gene can negatively impact the use of monoclonal antibodies in anti-EGFR therapy and affect treatment decisions. Currently, commonly used methods like next-generation sequencing (NGS) identifyKRASmutations but are expensive, time-consuming, and may not be suitable for every cancer patient sample. To address these challenges, we have developedKRASFormer, a novel framework that predictsKRASgene mutations from Haematoxylin and Eosin (H & E) stained WSIs that are widely available for most CRC patients.KRASFormerconsists of two stages: the first stage filters out non-tumor regions and selects only tumour cells using a quality screening mechanism, and the second stage predicts theKRASgene either wildtype' or mutant' using a Vision Transformer-based XCiT method. The XCiT employs cross-covariance attention to capture clinically meaningful long-range representations of textural patterns in tumour tissue andKRASmutant cells. We evaluated the performance of the first stage using an independent CRC-5000 dataset, and the second stage included both The Cancer Genome Atlas colon and rectal cancer (TCGA-CRC-DX) and in-house cohorts. The results of our experiments showed that the XCiT outperformed existing state-of-the-art methods, achieving AUCs for ROC curves of 0.691 and 0.653 on TCGA-CRC-DX and in-house datasets, respectively. Our findings emphasize three key consequences: the potential of using H & E-stained tissue slide images for predictingKRASgene mutations as a cost-effective and time-efficient means for guiding treatment choice with CRC patients; the increase in performance metrics of a Transformer-based model; and the value of the collaboration between pathologists and data scientists in deriving a morphologically meaningful model.


Assuntos
Neoplasias Colorretais , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Algoritmos , Receptores ErbB/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Processamento de Imagem Assistida por Computador/métodos , Curva ROC
10.
Am J Community Psychol ; 49(3-4): 483-93, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21553095

RESUMO

As US demographic trends shift toward more diversity, it becomes increasingly necessary to address differential needs of diverse groups of youth in mental health service systems. Cultural and linguistic competence (CLC) is essential to providing the most appropriate mental health services to youth and their families. The successful implementation of CLC often begins at the system level. Though various factors may affect change and system-level factors set the tone for broad acceptance of CLC within systems, there is limited empirical evidence linking culturally competent practices to outcomes. The purpose of the present study was to examine system-level CLC changes over time within systems of care and their associations with service experiences among youth and their families. Participants were 4,512 youth and their families enrolled in the national evaluation of the Children's Mental Health Initiative (CMHI). Results suggest that implementation of CLC at the system level improves over time in funded systems of care. Further, variation exists in specific system-level components of CLC. In addition, the changes in CLC at the system level are related to family/caregiver participation in treatment. Implications for supporting positive changes in CLC among systems of care communities, and specific strategies for community psychologists, are discussed.


Assuntos
Competência Cultural , Cultura , Prestação Integrada de Cuidados de Saúde , Linguística , Satisfação do Paciente , Criança , Serviços Comunitários de Saúde Mental , Família , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Entrevistas como Assunto , Masculino , Estados Unidos
11.
Biopreserv Biobank ; 19(4): 324-331, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33780631

RESUMO

Introduction: Best practices dictate that biobanks ensure accurate determination of tumor content before supplying formalin-fixed, paraffin-embedded (FFPE) tissue samples to researchers for nucleic acid extraction and downstream molecular testing. It is advisable that trained and competent individuals, who understand the requirements of the downstream molecular tests, perform the microscopic morphological examination. However, the special skills, time, and costs associated with these assessments can be prohibitive, especially in large case cohorts requiring extensive pathological review. Determination of tumor content reliably by digital image analysis (DIA) could represent a significant advantage if validated, utilized, and deployed by biobanks. Materials and Methods: Whole slide digital scanned images of colorectal, lung, and breast cancer specimens were created. The scanned images were imported into the DIA software QuPath and digital annotations were completed by biobank technicians, under the direction of trained histopathology senior scientists. Automated cell detection was conducted and tumor epithelial cells were classified and quantified. Results: DIA scores were highly concordant with the manual assessment for 376 of 435 samples (86%). A detailed review of discordant cases indicated digital scores had a higher accuracy than the manual estimation. Conclusion: Automated digital quantification has the potential to replace visual estimations with reduced subjectivity and increased reliability compared with manual tumor estimations. We recommend the use of DIA by biobanks involved in provision of FFPE tissue samples, especially in large research studies requiring high volumes of cases to be analyzed.


Assuntos
Neoplasias , Software , Formaldeído , Humanos , Inclusão em Parafina , Reprodutibilidade dos Testes
12.
Am J Infect Control ; 48(7): 761-764, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911070

RESUMO

BACKGROUND: Clostridioides difficile is a major cause of infectious antibiotic resistant diarrhea. C. difficile spores are shed in patient stool, are hearty and difficult to kill. Bedpans are often used by patients with C. difficile infections and require proper handling and cleaning or disposal to prevent the transmission of C. difficile spores and other infectious microorganisms into the environment. Disposable bedpans are often used for convenience, which has consequences from an environmental sustainability perspective. AIM: This study evaluates the ability for a washer-disinfector device (WD) to efficaciously clean and disinfect C. difficile spores and Escherichia coli from bedpans for sanitary reuse. METHODS: A commercially available WD device was evaluated for both efficacy and thermal disinfection against C. difficile spores and Escherichia coli using one disinfection cycle per test. Bedpans were not rinsed or dumped prior to placement in the WD. Bedpans were sampled using swabs. Microorganisms were eluted from the swabs and log-kill was calculated. FINDINGS: The average log-kill for C. difficile spores was 3.99 and >7.69 for E. coli. Thermal disinfection results showed an average log kill of 4.31 for C. difficile and >7.23 for E. coli. CONCLUSIONS: The WD was efficacious against both C. difficile spores and E. coli when used according to manufacturer's instructions for use, suggesting a viable alternative to disposable bedpan waste management.


Assuntos
Aparelho Sanitário , Clostridioides difficile , Detergentes , Desinfecção , Escherichia coli , Humanos , Plásticos , Esporos Bacterianos
13.
J Thorac Oncol ; 14(1): 45-53, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30296485

RESUMO

INTRODUCTION: Patient suitability to anti-programmed death ligand 1 (PD-L1) immune checkpoint inhibition is key to the treatment of NSCLC. We present, applied to PD-L1 testing: a comprehensive cross-validation of two immunohistochemistry (IHC) clones; our descriptive experience in diagnostic reflex testing; the concordance of IHC to in situ RNA (RNA-ISH); and application of digital pathology. METHODS: Eight hundred thirteen NSCLC tumor samples collected from 564 diagnostic samples were analyzed prospectively, and 249 diagnostic samples analyzed retrospectively in tissue microarray format. Validated methods for IHC and RNA-ISH were tested in tissue microarrays and full sections and the QuPath system were used for digital pathology analysis. RESULTS: Antibody concordance of clones SP263 and 22C3 validation was 97% to 98% in squamous cell carcinoma and adenocarcinomas, respectively. Clinical NSCLC cases were reported as PD-L1-negative (48%), 1% to 49% (23%), and more than 50% (29%), with differences associated to tissue-type and EGFR status. Comparison of IHC and RNA-ISH was highly concordant in both subgroups. Comparison of digital assessment versus manual assessment was highly concordant. Discrepancies were mostly around the 1% clinical threshold. Challenging IHC interpretation included 1) calculating the total tumor cell denominator and the nature of PD-L1 expressing cell aggregates in cytology samples; 2) peritumoral expression of positive immune cells; 3) calculation of positive tumor percentages around clinical thresholds; and 4) relevance of the 100 malignant cell rule. CONCLUSIONS: Sample type and EGFR status dictate differences in the expected percentage of PD-L1 expression. Analysis of PD-L1 is challenging, and interpretative guidelines are discussed. PD-L1 evaluations by RNA-ISH and digital pathology appear reliable, particularly in adenocarcinomas.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Receptor de Morte Celular Programada 1/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia
14.
Am J Infect Control ; 46(6): 620-626, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29397229

RESUMO

BACKGROUND: Healthcare-associated infections (HAIs) affect millions of patients every year. Pathogen transmission via fomites and healthcare workers (HCWs) contribute to the persistence of HAIs in hospitals. A critical parameter needed to assess risk of environmental transmission is the pathogen transfer efficiency between fomites and fingers. Recent studies have shown that pathogen transfer is not symmetric. In this study,we evaluated how the commonly used assumption of symmetry in transfer efficiency changes the dynamics of pathogen movement between patients and rooms and the exposures to uncolonized patients. METHODS: We developed and analyzed a deterministic compartmental model of Acinetobacter baumannii describing the contact-mediated process among HCWs, patients, and the environment. We compared a system using measured asymmetrical transfer efficiency to 2 symmetrical transfer efficiency systems. RESULTS: Symmetric models consistently overestimated contamination levels on fomites and underestimated contamination on patients and HCWs compared to the asymmetrical model. The magnitudes of these miscalculations can exceed 100%. Regardless of the model, relative percent reductions in contamination declined after hand hygiene compliance reached approximately 60% in the large fomite scenario and 70% in the small fomite scenario. CONCLUSIONS: This study demonstrates how healthcare facility-specific data can be used for decision-making processes. We show that the incorrect use of transfer efficiency data leads to biased effectiveness estimates for intervention strategies. More accurate exposure models are needed for more informed infection prevention strategies.


Assuntos
Infecções por Acinetobacter/transmissão , Infecção Hospitalar/transmissão , Transmissão de Doença Infecciosa , Exposição Ambiental , Dedos/microbiologia , Fômites/microbiologia , Modelos Estatísticos , Meio Ambiente , Instalações de Saúde , Pessoal de Saúde , Humanos , Pacientes
15.
Metabolism ; 56(1): 58-67, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17161227

RESUMO

Carbohydrate-restricted diets (CRDs) promote weight loss, reductions in plasma triacylglycerol (TAG) levels, and increases in high-density lipoprotein cholesterol (HDL-C) levels but may cause undesirable low-density lipoprotein cholesterol (LDL-C) responses in some people. The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease. Using a parallel-arm, double-blind, placebo-controlled design, 30 overweight and obese men (body mass index, 25-35 kg/m(2)) were randomly assigned to supplement a CRD with soluble fiber (Konjac-mannan, 3g/d) (n = 15) or placebo (n = 15). Plasma lipids, anthropometrics, body composition, blood pressure, and nutrient intake were evaluated at baseline and at 6 and 12 weeks. Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria. Both groups experienced decreases in (P < .01) body weight, percent body fat, systolic blood pressure, waist circumference, and plasma glucose levels. After 12 weeks, HDL-C and TAG improved significantly in the fiber (10% and -34%) and placebo (14%, -43%) groups. LDL-C decreased by 17.6% (P < .01) at week 6 and 14.1% (P < .01) at week 12 in the fiber group. Conversely, LDL-C reductions were significant in the placebo group only after 12 weeks (-6.0%, P < .05). We conclude that although clearly effective at lowering LDL-C, adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone. Furthermore, a CRD led to clinically important positive alterations in cardiovascular disease risk factors.


Assuntos
Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Dieta com Restrição de Carboidratos/métodos , Mananas/farmacologia , Adulto , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Composição Corporal/fisiologia , Peso Corporal/fisiologia , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Fibras na Dieta/administração & dosagem , Método Duplo-Cego , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
16.
Oncotarget ; 8(55): 93392-93403, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29212158

RESUMO

Immunohistochemistry remains the overwhelming technique of choice for test biomarker evaluation in both clinical or research settings when using formalin-fixed, paraffin embedded tissue sections. However, validations can be complex with significant issues about specificity, sensitivity and reproducibility. The vast array of commercially available antibodies from many vendors may also lead to non-standard approaches which are difficult to cross-reference. In contrast mRNA detection, by in situ hybridization (ISH) with sequence specific probes, offers a realistic alternative, with less validation steps and more stringent and reproducible assessment criteria. In the present study mRNA ISH was evaluated in prospectively and retrospectively collected FFPE samples within a cancer biobank setting. Three positive control probes, POLR2A, PPIB and UBC were applied to FFPE sections from a range of tumour types in FFPE whole-face (prospective collection) or TMA (retrospective collection) formats and evaluated semi-quantitatively and by image analysis. Results indicate that mRNA can be robustly evaluated by ISH in prospectively and retrospectively collected tissue samples. Furthermore, for 2 important test biomarkers, PD-L1 and c-MET, we show that mRNA ISH is a technology that can be applied with confidence in the majority of tissue samples because there are quantifiable levels of control probes indicating overall mRNA integrity.

17.
Am J Infect Control ; 44(5): e65-71, 2016 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-26851196

RESUMO

BACKGROUND: Acinetobacter baumannii is a gram-negative, opportunistic pathogen. Its ability to form biofilm and increasing resistance to antibiotic agents present challenges for infection control. A better understanding of the influence of biofilm formation and antibiotic resistance on environmental persistence of A baumannii in hospital settings is needed for more effective infection control. METHODS: A baumannii strains isolated from patients and the hospital environment were identified via Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) mass spectrometry (Bruker Daltonics, Bellerica, MA), repetitive extragenic palindromic polymerase chain reaction genotyped, and antibiotic resistance was determined using Vitek 2 (bioMérieux, Inc, Durham NC). Biofilm mass was quantified via microtiter plate method and desiccation tolerance determined up to 56 days. RESULTS: High biofilm forming, clinical, multidrug-resistant- (MDR) positive strains were 50% less likely to die of desiccation than low biofilm, non-MDR strains. In contrast, environmental, MDR-positive, low biofilm forming strains had a 2.7 times increase in risk of cell death due to desiccation compared with their MDR-negative counterparts. MDR-negative, high biofilm forming environmental strains had a 60% decrease in risk compared with their low biofilm forming counterparts. CONCLUSION: The MDR-positive phenotype was deleterious for environmental strains and the high biofilm phenotype was critical for survival. This study provides evidence of the trade-off between antibiotic resistance and desiccation tolerance, driven by condition-dependent adaptation, and establishes rationale for research into the genetic basis of the variation in fitness cost between clinical and environmental isolates.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/fisiologia , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla , Microbiologia Ambiental , Viabilidade Microbiana , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Adulto , Técnicas Bacteriológicas , Biofilmes/efeitos dos fármacos , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
18.
Am J Infect Control ; 43(9): 928-34, 2015 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-26141689

RESUMO

BACKGROUND: Acinetobacter baumannii is a significant health care-associated pathogen because it is easily transmitted via fomites, extremely difficult to eradicate from the environment, and highly drug resistant. Understanding the environmentally mediated transmission dynamics of A baumannii is critical for more effective infection control. However, transfer efficiency of pathogen pick-up and deposit remains poorly understood. Our study estimates the transfer efficiency of A baumannii with and without latex glove use from the fingerpad to a fomite and from a fomite to the fingerpad. METHODS: Fomite-fingerpad transfer efficiencies were determined for 6 materials (glass, stainless steel, porcelain, polypropylene, polycarbonate, and rubber). RESULTS: For A baumannii, the fomite-to-fingerpad transfer efficiency was 24.1%, and the fingerpad-to-fomite transfer efficiency was 5.6%. When latex gloves were worn, the fomite-to-fingerpad transfer efficiency was reduced by 55.9% (to 10.6%) and the fingerpad-to-fomite transfer efficiency was reduced by 47.1% (to 3.0%). The average transfer efficiency between 2 skin surfaces was 32.5%. CONCLUSIONS: The fomite-to-fingerpad transfer efficiency of A baumannii was statistically significantly higher than the fingerpad-to-fomite transfer efficiency, regardless of glove use. There was no significant difference in transfer efficiency by material type, except for rubber, which resulted in marginally higher transfer efficiencies. Our results underscore the importance of frequently changing gloves during patient care and frequent handwashing-hand hygiene during bare-handed care for the reduction of pathogen transmission.


Assuntos
Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/isolamento & purificação , Infecção Hospitalar/prevenção & controle , Fômites/microbiologia , Higiene das Mãos , Infecções por Acinetobacter/microbiologia , Cerâmica , Meio Ambiente , Equipamentos e Provisões , Vidro , Luvas Protetoras/microbiologia , Hospitais , Humanos , Látex , Polímeros , Polipropilenos , Borracha , Aço Inoxidável
20.
Implement Sci ; 4: 83, 2009 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-20043824

RESUMO

BACKGROUND: The goal of this study is to extend research on evidence-based practice (EBP) implementation by examining the impact of organizational type (public versus private) and organizational support for EBP on provider attitudes toward EBP and EBP use. Both organization theory and theory of innovation uptake and individual adoption of EBP guide the approach and analyses in this study. We anticipated that private sector organizations would provide greater levels of organizational support for EBPs leading to more positive provider attitudes towards EBPs and EBP use. We also expected attitudes toward EBPs to mediate the association of organizational support and EBP use. METHODS: Participants were mental health service providers from 17 communities in 16 states in the United States (n = 170). Path analyses were conducted to compare three theoretical models of the impact of organization type on organizational support for EBP and of organizational support on provider attitudes toward EBP and EBP use. RESULTS: Consistent with our predictions, private agencies provided greater support for EBP implementation, and staff working for private agencies reported more positive attitudes toward adopting EBPs. Organizational support for EBP partially mediated the association of organization type on provider attitudes toward EBP. Organizational support was significantly positively associated with attitudes toward EBP and EBP use in practice. CONCLUSION: This study offers further support for the importance of organizational context as an influence on organizational support for EBP and provider attitudes toward adopting EBP. The study demonstrates the role organizational support in provider use of EBP in practice. This study also suggests that organizational support for innovation is a malleable factor in supporting use of EBP. Greater attention should be paid to organizational influences that can facilitate the dissemination and implementation of EBPs in community settings.

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