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1.
Environ Pollut ; 359: 124695, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39122170

RESUMO

Globally, pharmaceuticals and personal care products (PPCPs) are detected in surface waters receiving wastewater, yet their presence in biota, remain largely understudied. To address this, we conducted a study that measured 46 PPCPs in spot water samples and fish caught up- and downstream from wastewater treatment plants (WWTPs) in Victoria, Australia. We sampled 15 sites located along four waterways following a 3-site design: WWTP-discharge('hotspot'), 'upstream'(∼2 km) and 'downstream'(∼2 km). Spot water and fish were also sampled at reference sites >100 km from WWTP discharge (n = 3). Additionally, spot water samples were taken from WWTP effluent outflows (n = 3). From each locality, we analysed 3-12 fish (n = 131 total). In waterways, passive samplers (POCIS; ∼28d, n = 19 PPCPs) were also deployed. Individual fish (axial muscle) and water were analysed with LC-MS-MS. We found that PPCP concentrations in environmental surface water ranged from<0.02-0.97 µg/L. In WWTP effluent, the range was <0.02-1.4 µg/L. Of the 46 PPCPs analysed, 12 were detected in spot water samples and five in fish. In water, the highest concentration detected was for antidepressant venlafaxine (3 µg/L). The most frequently detected PPCPs: venlafaxine (54.9%), metoprolol (41.2%), propranolol (29.4%), carbamazepine (29.4%), caffeine (17.6%) and sulfamethoxazole (17.6%). Out of 131 fish analysed, 35 fish had detectable levels of PPCPs in the muscle tissue. The highest muscle concentrations were: venlafaxine (150 µg/kg, redfin perch), and sertraline (100 µg/kg, eel). Bioaccumulation factors ranged from 104 to 341L/kg for venlafaxine in redfins, 21-1,260L/kg for carbamazepine in redfins and eels, and 367-3,333L/kg for sertraline in eels. Based on our human health risk calculations for venlafaxine, carbamazepine, sertraline, triclosan, and caffeine, consumption of fish does not pose a significant risk to human health. Despite this, most of the detected PPCPs in surface waters exceeded 10 ng/L trigger value, which has led to further investigations by EPA. Our study highlights the need for using multiple lines of evidence for estimating risks of PPCPs.

2.
Dermatol Ther (Heidelb) ; 14(5): 1327-1335, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38649673

RESUMO

INTRODUCTION: Nail psoriasis is highly prevalent among patients with psoriasis yet remains one of the most challenging areas to treat. To better understand the treatment landscape for psoriatic nail disease, more studies are needed that compare the effectiveness of different biologics for patients with nail psoriasis. This study contributes to this objective by directly comparing the effectiveness of approved biologics in improving nail psoriasis for patients up to month 12 in a real-world setting. METHODS: Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. This study assessed the change in modified Nail Psoriasis Severity Index (mNAPSI) score from baseline to months 3, 6 and 12 for 763 patients and compared the effectiveness of anti-interleukin (IL)-17A biologics versus other approved biologics, as well as ixekizumab versus secukinumab, guselkumab, risankizumab and adalimumab. Comparative adjusted analyses used frequentist model averaging (FMA). Least square mean difference (LSMD) in mNAPSI scores are presented as observed. RESULTS: Irrespective of the severity of nail psoriasis at baseline, the anti-IL-17A cohort had greater mean mNAPSI reductions from baseline compared to the other biologics cohort through month 12, reaching significance at months 3 and 6 in the adjusted analysis. For patients with moderate-to-severe nail psoriasis, ixekizumab showed numerically higher mean reductions in mNAPSI scores compared to all other studied biologics, reaching significance versus guselkumab at all timepoints and risankizumab at month 6. CONCLUSION: This real-world study showed that patients with moderate-to-severe psoriasis and any severity of concomitant nail involvement had significantly faster and more substantial improvements in nail psoriasis up to month 6 in the anti-IL-17A cohort compared to the other biologics cohort. Of the individual biologics studied, ixekizumab showed the highest numerical improvements in nail psoriasis at month 12. TRIAL REGISTRATION: EUPAS24207.

3.
Skin Health Dis ; 3(4): e232, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37538337

RESUMO

The prevalence of active atopic dermatitis (AD) in adults in the UK according to disease severity shows variability. This study evaluated disease prevalence and treatment patterns among the adult UK population with AD. Data were obtained from the Clinical Practice Research Datalink (CPRD) database. Adults with active AD were identified by an AD-related prescription or general practitioner visit within the same calendar year. Prevalence was defined as the number of patients with active AD on 1 January of each year as a percentage of the number of adults in the CPRD population on that date. Moderate-to-severe disease was classified as either referral to a specialist or prescription(s) for topical calcineurin inhibitors, phototherapy, or systemic treatment. Patient characteristics and treatment and referral patterns were analysed for patients with active AD in 2019. The overall prevalence of AD was stable at 2.4% per year during the period 2015-2019. In 2019, mean patient age (± standard deviation) was 52.6 ± 21.0 years, 58.2% of patients were female and mean disease duration was 9.4 ± 5.9 years. The most prescribed treatment was topical corticosteroids, in 78.5% of patients. 36.7% of patients with moderate-to-severe AD were prescribed systemic agents and 59.8% (vs. 32.3% of patients with mild AD) were referred to any secondary care or specialist treatment. The prevalence of active AD in the adult UK population was stable over the 5-year period (2015-2019) and was comparable to estimates from similar studies based on UK primary healthcare records.

4.
PNAS Nexus ; 2(5): pgad156, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37234204

RESUMO

Cardiovascular disease is thought to account for nearly a third of deaths worldwide, with ischemic heart disease, including acute coronary syndromes such as myocardial infarction, accounting for 1.7 million deaths per year. There is a clear need for interventions to impart cardioprotection against ischemia. Here, we show that the slowly activating voltage-gated potassium current (IKs) potentiator ML277 imparts cardioprotection against ischemia in cellular and whole-heart models by modulating the action potential duration. In three different metabolic inhibition and reperfusion models, an increased contractile recovery and cell survival was observed with ML277, indicative of protection. Finally, ML277 reduced infarct size in an ex vivo Langendorff coronary ligation model, including if only applied on reperfusion. In conclusion, potentiation of the IKs with ML277 imparted a cardioprotection that was equivalent to the protection reported previously by ischemic preconditioning. These data suggest that IKs potentiation may be therapeutically useful in acute coronary syndromes.

5.
Afr J Emerg Med ; 12(3): 191-198, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35702138

RESUMO

Introduction: Medical records are an integral part of patient care. Information loss during the handover from Emergency Care Providers to hospital staff is common and has a significant impact on patient care. Information loss can be prevented with medical documentation that is accurate, complete and contains the relevant information regarding patient management. Patient report Forms (PRF's) are used by Emergency Care Providers to record the details of their patient care and they form part of the patients' medical records. Quality assuring of PRF's is required to determine if the required information has been recorded on the PRF. Checklists are one the means of quality assuring PRF, by comparing the points on the checklist to the content of the PRF. Methods: An three-round Delphi survey was conducted with experts to determine the relevant information (data elements) required for the completion of a PRF including any additional South African - specific elements. Results: Thirty-two experts participated in the Delphi survey, which identified 166 data elements for the check list and this was refined to a final 133 elements after collation by the researchers. A proposed checklist was developed. Discussion: The Delphi process is a useful technique to develop a checklist. A checklist consisting of 133 total possible data elements to quality assure PRFs was designed. Further research regarding the use and reliability of the checklist is required.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35682096

RESUMO

Identifying institutional capacity to reduce and reallocate food waste is important to reduce both greenhouse gas emissions and food insecurity. The goal of this study was to examine food waste concern, reduction and repurposing strategies, and perceived barriers to these strategies among U.S. university foodservice representatives. We surveyed 57 U.S. university foodservice representatives about foodservice operations, campus food insecurity, food waste reduction and repurposing activities, and obstacles to composting and donating food waste. Data were collected September 2019-February 2020. Roughly three-quarters of respondents tracked campus food waste, reported that food waste reduction was a high/very high priority, and reported concern about campus food insecurity. The most common food-waste-reduction strategies included forecasting demand to prevent overproduction and preparing smaller batches. The most common repurposing strategies included donation and composting. Top barriers to food donation included liability concerns and lack of labor. Barriers to composting food included lack of infrastructure and knowledge/experience. Addressing perceived barriers to university foodservices' food waste reduction and repurposing efforts could lead to reduced greenhouse gas emissions and improved food security for millions of Americans.


Assuntos
Gases de Efeito Estufa , Eliminação de Resíduos , Gerenciamento de Resíduos , Alimentos , Humanos , Universidades
7.
Dermatol Pract Concept ; 12(2): e2022104, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35646453

RESUMO

Introduction: The randomized, open-label, assessor-blinded, parallel-group SPIRIT-H2H trial (NCT03151551) demonstrated superiority of ixekizumab over adalimumab in simultaneously achieving improvement in joint symptoms (American College of Rheumatology [ACR]50) and skin clearance (Psoriasis Area and Severity Index [PASI]100) in biologic-naïve patients with active psoriatic arthritis (PsA) and plaque psoriasis (PsO) at Week (W) 24. Higher efficacy of ixekizumab versus adalimumab was maintained through W52. Objectives: This analysis investigated efficacy and safety of ixekizumab and adalimumab in the subgroup of patients with PsA and moderate-to-severe PsO through W52. Methods: Efficacy and safety outcomes were analyzed in patients with PsA and moderate-to-severe PsO (PASI ≥ 12, Body Surface Area ≥ 10%, static Physician Global Assessment ≥ 3) through W52. Categorical and continuous outcomes were analyzed using logistic regression models and mixed model for repeated measures, respectively. Results: More ixekizumab-versus adalimumab-treated patients simultaneously achieved PASI100 and ACR50 at W24 (40.8% versus 17.6%, P = 0.015) and W52 (38.8% versus 17.6%, P = 0.026). Likewise, more ixekizumab-versus adalimumab-treated patients achieved PASI100 (59.2% versus 25.5%, P = 0.001) and PASI90 (81.6% versus 60.8%, P = 0.028) through W52, and nail PsO clearance at W24. Joint symptom improvements were comparable between groups. No new safety findings were reported. Conclusions: Ixekizumab had higher efficacy than adalimumab in simultaneous achievement of ACR50 and PASI100 at W24 and W52 in patients with PsA and moderate-to-severe PsO. Ixekizumab-treated patients showed higher response rates for nail PsO clearance and for reporting minimal or no impact on quality of life at W24.

8.
Head Neck ; 43(4): 1194-1201, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33355962

RESUMO

BACKGROUNDS: Pathologic features of oropharyngeal squamous cell carcinoma (OPSCC) treated with trans-oral robotic surgery predict prognosis and adjuvant therapy. We hypothesized that pathologic muscle invasion (pMI) is associated with poor pathological markers. METHODS: Retrospective review of surgically treated OPSCC to identify pMI and its association with poor pathologic markers. RESULTS: pMI was present in 12/37 patients, and compared to non-pMI, was associated with higher rates of lymphovascular invasion (75% vs. 36%, p = 0.03), perineural invasion (16.7% vs. 0%, p = 0.04), extranodal extension (66.7% vs. 20%, p < 0.01), and tumor stage (8.3% vs. 48% pT1, 75% vs. 52% pT2 and 16.7% vs. 0% pT3). pMI was associated with having a positive margin on main specimen (41.7% vs. 12%, p = 0.04) but not after considering additional margins. CONCLUSIONS: Muscle invasion was associated with higher pathologic tumor staging, poor pathologic factors, and higher rates of positive margin on main specimen.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Músculos/patologia , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/cirurgia , Estudos Retrospectivos
9.
BMJ Open Qual ; 10(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33495196

RESUMO

OBJECTIVES: To identify root causes of preventable adverse drug events (pADEs) contributing to hospital admission; to develop key messages which identify actions patients/families and healthcare providers can take to prevent common pADEs found; to develop a surveillance learning system for the community. METHODS: Cross-sectional observational study; 120 patients and families, 61 associated healthcare providers were interviewed then root cause analysis was performed to develop key learning messages and an electronic reporting tool was designed. Most common pADE-related medical conditions and their root causes and most common pADE root causes of entire cohort are reported. RESULTS: Most common pADE-related medical conditions: chronic obstructive pulmonary disease/asthma (13.3%), bleeding (12.5%), hypotension (12%), heart failure (10%), acute kidney injury (5%) and pneumonia (5%). Most common root causes were: providers not confirming that the patient/family understands information given (29.2%), can identify how a medication helps them/have their concerns addressed (16.7%), can identify if a medication is working (14.1%) or causing a side effect (23.3%); can enact medication changes (7.5%); absence of a sick day management plan (12.5%), and other action plans to help patients respond to changes in their clinical status (10.8%); providers not assessing medication use and monitoring competency (19.2%). Ten key learning messages were developed and a pADE surveillance learning system was implemented. CONCLUSIONS: To prevent pADEs, providers need to confirm that patients/families understand information given, how a medication helps them, how to recognise and respond to side effects, how to enact medication changes and follow action plans; providers should assess patient's/families' medication use and monitoring competency.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hospitais Comunitários , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Hospitalização , Humanos , Erros de Medicação
10.
J Appl Psychol ; 94(3): 806-13, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19450016

RESUMO

At Time 1 (T1), the authors surveyed 277 unemployed adults using measures of human capital, goal orientation, self-regulation (emotion control, motivation control, work commitment), and job-seeking intensity. At Time 2 (T2), 4 months later, 155 participants indicated their reemployment outcomes in number of job interviews and number of job offers. Using T1 data, the authors tested the predictors of job-seeking intensity and whether self-regulation mediated between goal orientation and job-seeking intensity. Using T1 and T2 data, they tested for predictors of reemployment outcomes and whether job-seeking intensity mediated the relationship between T1 antecedent variables and the reemployment outcomes. Learning goal orientation and self-regulation predicted job-seeking intensity, and self-regulation mediated between learning goal orientation and job-seeking intensity. Job-seeking intensity did not mediate the relationship among human capital, goal orientation, and self-regulation variables and reemployment outcomes.


Assuntos
Objetivos , Controle Interno-Externo , Candidatura a Emprego , Desemprego/psicologia , Adulto , Feminino , Humanos , Masculino , Seleção de Pessoal , Adulto Jovem
11.
J Invest Dermatol ; 139(9): 1975-1984.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30910759

RESUMO

FK228 (romidepsin) and suberoylanilide hydroxamic acid (vorinostat) are histone deacetylase inhibitors (HDACi) approved by the US Food and Drug Administration for cutaneous T-cell lymphoma (CTCL), including the leukemic subtype Sézary syndrome. This study investigates RAD23B and STAT3 gene perturbations in a large cohort of primary Sézary cells and the effect of FK228 treatment on tyrosine phosphorylation of STAT3 (pYSTAT3) and RAD23B expression. We report RAD23B copy number variation in 10% (12/119, P ≤ 0.01) of SS patients, associated with reduced mRNA expression (P = 0.04). RAD23B knockdown in a CTCL cell line led to a reduction in FK228-induced apoptosis. Histone deacetylase inhibitor treatment significantly reduced pYSTAT3 in primary Sézary cells and was partially mediated by RAD23B. A distinct pattern of RAD23B-pYSTAT3 co-expression in primary Sézary cells was detected. Critically, Sézary cells harboring the common STAT3 Y640F variant were less sensitive to FK228-induced apoptosis and exogenous expression of STAT3 Y640F, and D661Y conferred partial resistance to STAT3 transcriptional inhibition by FK228 (P ≤ 0.0024). These findings suggest that RAD23B and STAT3 gene perturbations could reduce sensitivity to histone deacetylase inhibitors in SS patients.


Assuntos
Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Depsipeptídeos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Histona Desacetilases/farmacologia , Fator de Transcrição STAT3/genética , Síndrome de Sézary/genética , Neoplasias Cutâneas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Apoptose/genética , Linfócitos T CD4-Positivos , Variações do Número de Cópias de DNA , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Depsipeptídeos/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Células Neoplásicas Circulantes , Fosforilação/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Cultura Primária de Células , Fator de Transcrição STAT3/metabolismo , Síndrome de Sézary/sangue , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/patologia , Pele/citologia , Pele/patologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas , Tirosina/metabolismo
12.
Mol Phylogenet Evol ; 49(1): 1-16, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18675920

RESUMO

The majority of the approximately 80-90 species in subtribe Arctotidinae occur in southern Africa with the centre of diversity in the winter-rainfall region. Three species are restricted to afromontane eastern Africa and three species are endemic to Australia. To investigate biogeographic and phylogenetic relationships within Arctotidinae, sequence data from four cpDNA regions (psbA-trnH, trnT-trnL and trnL-trnF spacers and trnL intron) and the ITS nrDNA region for 59 Arctotidinae species were analyzed with parsimony and Bayesian-inference approaches. Eight well-supported major lineages were resolved. The earliest-diverging extant lineages are afromontane or inhabit mesic habitats, whereas almost all sampled taxa from the winter-rainfall and semi-arid areas have diverged more recently. Molecular dating estimated that the major clades diverged during the Miocene and Pliocene, which is coincident with the trend of increasing rainfall seasonality, aridification and vegetation changes in southwestern Africa. Trans-oceanic dispersal to Australia was estimated to have occurred during the Pliocene.


Assuntos
Asteraceae/genética , Evolução Molecular , Filogenia , África , Asteraceae/classificação , Teorema de Bayes , DNA Intergênico/genética , DNA de Plantas/genética , Ecossistema , Genes de Plantas , Cadeias de Markov , Alinhamento de Sequência , Análise de Sequência de DNA , Especificidade da Espécie
13.
J Otolaryngol Head Neck Surg ; 47(1): 57, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30223884

RESUMO

BACKGROUND: To describe and evaluate a four step systematic approach to dissecting the recurrent laryngeal nerve (RLN) starting at the cricothyroid junction during thyroid surgery (subsequently referred to as the retrograde medial approach). METHODS: All thyroidectomies completed by the senior author between August 2014 and January 2016 were retrospectively reviewed. Patients were excluded if concurrent lateral or central neck dissection was performed. A follow up period of 1 year was included. RESULTS: Surgical photographs and illustrations demonstrate the four steps in the retrograde medial approach to dissection of the RLN in thyroid surgery. Three hundred forty-two consecutive thyroid surgeries were performed in 17 months, including 213 hemithyroidectomies, 91 total thyroidectomies, and 38 completion thyroidectomies. The rate of temporary and permanent hypocalcemia was 13% (95% confidence interval [CI]: 8-20%) and 3% (95% CI: 1-8%) respectively. The rate of temporary and permanent vocal cord palsy was 9% (95% CI: 6-12%) and 0.3% (95%CI: 0.01-2%) respectively. The median surgical times for hemithyroidectomy, total thyroidectomy, and completion thyroidectomy were 39 min (Interquartile range [IQR]: 33-47 min), 48 min (IQR: 40-60 min), and 40 min (IQR: 35-51 min) respectively. 1% of cases required conversion to an alternative surgical approach. CONCLUSION: In a tertiary endocrine head and neck practice, the routine use of the retrograde medial approach to RLN dissection is safe and results in a short operative time, and a low conversion rate to other RLN dissection approaches.


Assuntos
Complicações Pós-Operatórias/prevenção & controle , Traumatismos do Nervo Laríngeo Recorrente/prevenção & controle , Nervo Laríngeo Recorrente/cirurgia , Tireoidectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Nervo Laríngeo Recorrente/anatomia & histologia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Adulto Jovem
14.
J Invest Dermatol ; 136(6): 1238-1246, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26872600

RESUMO

Methylthioadenosine phosphorylase (MTAP) and the tumor suppressor genes CDKN2A-CDKN2B are frequently deleted in malignancies. The specific role of MTAP in cutaneous T-cell lymphoma subgroups, mycosis fungoides (MF) and Sézary syndrome (SS), is unknown. In 213 skin samples from patients with MF/SS, MTAP copy number loss (34%) was more frequent than CDKN2A (12%) in all cutaneous T-cell lymphoma stages using quantitative reverse transcription PCR. Importantly, in early stage MF, MTAP loss occurred independently of CDKN2A loss in 37% of samples. In peripheral blood mononuclear cells from patients with SS, codeletion with CDKN2A occurred in 18% of samples but loss of MTAP alone was uncommon. In CD4(+) cells from SS, reduced MTAP mRNA expression correlated with MTAP copy number loss (P < 0.01) but reduced MTAP expression was also detected in the absence of copy number loss. Deep sequencing of MTAP/CDKN2A-CDKN2B loci in 77 peripheral blood mononuclear cell DNA samples from patients with SS did not show any nonsynonymous mutations, but read-depth analysis suggested focal deletions consistent with MTAP and CDKN2A copy number loss detected with quantitative reverse transcription PCR. In a cutaneous T-cell lymphoma cell line, promoter hypermethylation was shown to downregulate MTAP expression and may represent a mechanism of MTAP inactivation. In conclusion, our findings suggest that there may be selection in early stages of MF for MTAP deletion within the cutaneous tumor microenvironment.


Assuntos
Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Linfoma Cutâneo de Células T/genética , Purina-Núcleosídeo Fosforilase/genética , Neoplasias Cutâneas/genética , Adulto , Estudos de Coortes , Metilação de DNA/genética , Feminino , Genes p16 , Humanos , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real/métodos , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas , Microambiente Tumoral/genética
15.
J Chromatogr Sci ; 40(2): 77-82, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11881708

RESUMO

A procedure for the sampling and analysis of energetics and related compounds in the atmosphere is described. The basic procedure consists of the collection of air samples using sampling cartridges containing XAD-2 resin, extraction of the resin with isoamyl acetate, and an analysis of the extract using gas chromatography with electron capture detection. Modifications and additions to this procedure are discussed, such as the use of a prefilter before the resin sampler to collect particulates and the use of a mass selective detector to analyze for some propellant compounds of interest or for quantitative confirmation purposes. Two differing sizes of samplers are evaluated according to the air volumes required for collection. The procedure is tested through the analysis of spiked resin samples, which had air pulled through them for periods of time corresponding with the required sampling volumes. This procedure has application toward the measurement of energetic residues in atmospheres resulting from weapons testing and operations during training exercises involving munitions.

16.
J Invest Dermatol ; 132(8): 2042-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22495182

RESUMO

T-plastin (PLS3) is an actin-bundling protein normally expressed in epithelial cells but absent in cells of hematopoietic origin. Aberrant PLS3 expression has been demonstrated in lymphocytes from Sézary syndrome (SS) patients and has been proposed as a biomarker for SS; however, the mechanism underlying dysregulation of PLS3 has not been determined. In this study, PLS3 mRNA expression was demonstrated in 21/35 (60%) SS patients and in 3/8 (38%) mycosis fungoides patients, all of whom had clonal blood involvement. No evidence for PLS3 mutations within coding or promoter regions was found, but significant hypomethylation of CpG dinucleotides 95-99 within the PLS3 CpG island was observed and this was restricted to the PLS3+ population. A polyclonal antibody specific to PLS3 was raised to examine coexpression of PLS3 with a panel of T-cell differentiation markers. All PLS3+ cells were CD3+CD4+ and CD26-, suggesting that loss of CD26 is consistently associated with gain of PLS3, whereas all other markers were distributed heterogeneously. However, a patient-specific TCR copy number assay also demonstrated heterogeneity in PLS3 expression in tumor cell populations. Importantly, our findings demonstrate PLS3 expression in the majority of SS patients and provide insight into the molecular regulation of PLS3 expression in CTCL.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Linfoma Cutâneo de Células T/genética , Linfoma Cutâneo de Células T/metabolismo , Glicoproteínas de Membrana/biossíntese , Proteínas dos Microfilamentos/biossíntese , Regiões Promotoras Genéticas , Biomarcadores/metabolismo , Complexo CD3/biossíntese , Antígenos CD4/biossíntese , Ilhas de CpG , Dipeptidil Peptidase 4/biossíntese , Humanos , Mutação , Micose Fungoide/genética , Micose Fungoide/metabolismo , Nucleotídeos/genética , RNA Mensageiro/metabolismo , Síndrome de Sézary/metabolismo
17.
Int J Pharm Compd ; 14(4): 284-300, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-23965535

RESUMO

Although the terms humidity and relative humidity are often used interchangeably, they are not synonymous. Humidity is the amount of water in the air, and relative humidity is the ratio of the amount of water vapor in the air at a specific temperature to the maximum possible amount of water vapor in the air at that temperature. Thus humidity and temperature are inextricably bound in their effects on the environment. In a compounding pharmacy, humidity can affect the stability and quality of the compounds prepared, as well as equipment, chemicals, and polymers. Devices that measure relative humidity (hygrometers) or humidity and temperature (thermohygrometers) are essential instruments in a compounding pharmacy. They must be chosen carefully, however, to ensure that the measurements they yield are accurate, that they are reliable over time. Most desirable are devices that alert the pharmacist immediately at any time if levels of humidity or temperature at a designated site differ from a specific norm. In this report, we discuss the effects of humidity on the process of compounding and on the agents used in customized preparations. A Table that lists essential features of a variety of hygrometers and thermohygrometers appropriate for use in a compounding pharmacy is presented for easy reference.

18.
J Invest Dermatol ; 130(4): 1116-25, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19759548

RESUMO

Sézary Syndrome (SS) is an aggressive leukemic variant of primary cutaneous T-cell lymphoma characterized by the presence of tumor or Sézary cells that generally display a mature memory T-cell immunophenotype. Sézary cells proliferate poorly and therefore their accumulation may be due to defective T-cell homeostasis involving resistance to apoptosis. In this study, we analyzed Fas expression in CD4+ lymphocytes at the mRNA and protein levels in a large cohort of SS patients as compared with healthy controls. Fas mRNA expression was dysregulated in 34/47 patients, with significant under- and overexpression of Fas mRNA detected in 21 and 13 patients respectively (P<0.01). Examination of cell-surface Fas expression showed correlation with the observed downregulation of mRNA in CD4+ T cells. Mutational analysis demonstrated that functional FAS gene mutations are rare. Moreover, 16 SS patients who showed significant under-expression of Fas mRNA also showed significant positional hypermethylation within the FAS CpG island, which was not present in healthy controls or SS patients determined to have normal or overexpression of Fas mRNA. These data demonstrate that dysregulation of Fas expression is a common feature of SS, and provide a rationale for targeted therapies to restore the extrinsic Fas-dependent apoptotic pathway in this malignancy.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Síndrome de Sézary/genética , Síndrome de Sézary/fisiopatologia , Receptor fas/genética , Apoptose/fisiologia , Biomarcadores Tumorais , Linfócitos T CD4-Positivos/fisiologia , Ilhas de CpG/fisiologia , Regulação para Baixo/fisiologia , Humanos , Memória Imunológica/fisiologia , Polimorfismo Conformacional de Fita Simples , Regiões Promotoras Genéticas/fisiologia , RNA Mensageiro/metabolismo , Síndrome de Sézary/patologia , Receptor fas/metabolismo
19.
Am J Bot ; 93(8): 1222-35, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21642186

RESUMO

Asteraceae are the largest family in southern Africa. Elucidating its origins and radiation in the region requires well-supported species-level phylogenies of the lineages. This paper presents a phylogenetic framework for subtribe Arctotidinae, which have a southern and eastern African-Australian distribution centered in the winter-rainfall region of South Africa. DNA sequence data from five chloroplast fragments (ndhF, psbA-trnH, rps16, trnS-trnfM, and trnT-trnF) and the nuclear ITS region were analyzed separately and in combination using parsimony and Bayesian methods. The data sets comprised exemplars from 18 ingroup species, representing the five currently accepted genera, and four outgroup species from Gorteriinae. All analyses indicated Arctotis and Haplocarpha are polyphyletic as presently circumscribed. The Australian-endemic Cymbonotus lawsonianus was placed within a strongly supported clade also containing A. arctotoides from South Africa and H. schimperi from eastern Africa. Retention of Dymondia and resurrection of Landtia at generic level are strongly supported. The phylogenetic hypotheses indicate the subtribe might have originated in temperate southern or eastern Africa, or it was ancestrally widespread in southern Africa and has diversified vicariously. The derived placement of C. lawsonianus indicates long-distance dispersal from southern Africa to Australia occurred.

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