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1.
Proc Natl Acad Sci U S A ; 118(31)2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34312225

RESUMO

Localized carbon reduction strategies are especially critical in states and regions that lack top-down climate leadership. This paper illustrates the use of coupled systems in assessments of subnational climate solutions with a case study of Georgia, a state located in the southeastern United States that does not have statewide climate goals or plans. The paper illustrates how robust place-specific plans for climate action could be derived from foundational global and national work and by embedding that research into the context of socio-ecological-technological systems. Our replicable methodology advances the traditional additive sectoral wedge analysis of carbon abatement potential by incorporating solution interdependencies and by spanning both carbon sources and sinks. We estimate that a system of 20 solutions could cut Georgia's carbon footprint by 35% in 2030 relative to a business-as-usual forecast and by 50% relative to Georgia's emissions in 2005. We also produce a carbon abatement cost curve that aligns private and social costs as well as benefits with units of avoided CO2-e. The solutions are affiliated with various social co-costs and co-benefits that highlight societal concerns extending beyond climate impacts, including public health, environmental quality, employment, and equity.

2.
Environ Manage ; 67(2): 205-227, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33449138

RESUMO

Subnational entities are recognizing the need to systematically examine options for reducing their carbon footprints. However, few robust and comprehensive analyses are available that lay out how US states and regions can most effectively contribute. This paper describes an approach developed for Georgia-a state in the southeastern United States called "Drawdown Georgia", our research involves (1) understanding Georgia's baseline carbon footprint and trends, (2) identifying the universe of Georgia-specific carbon-reduction solutions that could be impactful by 2030, (3) estimating the greenhouse gas reduction potential of these high-impact 2030 solutions for Georgia, and (4) estimating associated costs and benefits while also considering how the solutions might impact societal priorities, such as economic development opportunities, public health, environmental benefits, and equity. We began by examining the global solutions identified by Project Drawdown. The resulting 20 high-impact 2030 solutions provide a strategy for reducing Georgia's carbon footprint in the next decade using market-ready technologies and practices and including negative emission solutions. This paper describes our systematic and replicable process and ends with a discussion of its strengths, weaknesses, and planned future research.


Assuntos
Pegada de Carbono , Gases de Efeito Estufa , Carbono , Clima , Georgia
3.
HPB (Oxford) ; 23(10): 1482-1487, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33814299

RESUMO

BACKGROUND: Increasing use is now made of modalities other than surgery (including endoscopy and interventional radiology) in the care of patients with hepatopancreaticobiliary (HPB) diseases. However, the care of and responsibility for patients managed non-operatively continues to reside with surgical services. This investigation was undertaken to quantify the implications of non-operative patient related admissions our HPB unit over a 24 month period. METHODS: Total admissions from Jan 2018-Dec 2019 in a tertiary HPB unit were analyzed to determine HPB-related non-operative admissions. Cost analysis was also undertaken. RESULTS: There were 1528 admissions in 1029 patients for non-operative indications out of a total of 2576 admissions to the HPB unit. Of these, 707 were for diagnoses related to underlying HPB or upper gastrointestinal diagnoses. Patients were primarily treated with an interventional radiology procedure (n = 180), diagnostic or therapeutic endoscopy (n = 287), palliation (n = 57), symptomatic management (n = 152), other (n = 31). Patient age ≥80 (p < 0.05), acute admission (p < 0.01) and the presence of a stage 4 cancer diagnosis (p < 0.01) were associated with non-operative admission. CONCLUSION: Over half of patient admissions are for non-operative management. The contemporary HPB unit is responsible for providing surgical intervention as well as coordinating multidisciplinary care of patients with HPB disease.

4.
Air Med J ; 40(1): 36-40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33455623

RESUMO

OBJECTIVE: Ketamine for rapid sequence intubation (RSI) is typically dosed at 1 to 2 mg/kg intravenously. The need to ensure dissociation during RSI led some to administer ketamine at doses greater than 2 mg/kg. This study assessed associations between ketamine dose and adverse events. METHODS: This multisite, retrospective study included adult subjects undergoing RSI with intravenous ketamine. Subjects were categorized into 2 groups: a standard ketamine dose (≤ 2 mg/kg intravenously) or a high dose (> 2 mg/kg intravenously). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for adverse events. RESULTS: Eighty subjects received standard-dose ketamine, and 50 received high-dose ketamine. The high-dose group had a significantly (P < .05) higher proportion of trauma patients, were younger, and had higher predose blood pressure compared with the standard-dose group. High-dose ketamine was associated with greater odds of adverse events including hypotension (OR = 7.0; 95% CI, 3.0-16.6), laryngospasm (OR = 10.8; 95% CI, 1.3-93.4), bradycardia (OR = 7.5; 95% CI, 1.5-36.6), repeat medications (OR = 12.9; 95% CI, 1.5-107.9), oxygen desaturation (OR = 6.0; 95% CI, 1.8-19.9), multiple attempts (OR = 3.2; 95% CI, 1.5-6.8%), and failed airway (OR = 3.6; 95% CI, 1.0-12.7). CONCLUSION: Ketamine at higher doses was associated with increased odds of adverse events. Studies assessing adverse events of ketamine at lower than standard doses in shock patients are needed.


Assuntos
Serviços Médicos de Emergência , Ketamina , Adulto , Humanos , Intubação Intratraqueal , Ketamina/efeitos adversos , Indução e Intubação de Sequência Rápida , Estudos Retrospectivos
6.
ED Manag ; 29(3): 25-28, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29782754

RESUMO

Working with an entrepreneurial startup company, Aurora Health Care in Milwaukee has developed an approach for leveraging the services of one provider who sees patients remotely during the triage process at multiple ED sites. The process has enabled the health system to accelerate throughput times while maximizing provider resources and boosting patient satisfaction. At Aurora Sinai Medical Center in Milwaukee, the approach has reduced door-to-provider times from 60 minutes to about 10 minutes, on average. In addition, the average length of stay has declined by 40 minutes, and the leave-without-being-seen rate has plummeted from 8% to 2%. Providers serving in the virtual triage role average 12-15 patient consults per hour, and the average length of these patient-provider interactions is 80 seconds. Developers say the key to the success of the approach is placing a technician in the ED who can execute the remote physician's orders so that each patient's workup is well underway by the time the patient sees the treating physician on site in the ED. Health system administrators are exploring other ways they can use telemedicine, perhaps to accelerate discharges from the ED and eventually putting remote physicians in charge of low-acuity cases.


Assuntos
Serviço Hospitalar de Emergência , Sistemas Multi-Institucionais , Telemedicina , Triagem , Estudos de Casos Organizacionais , Wisconsin
7.
Proteins ; 84(4): 448-60, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26800223

RESUMO

Genetic experiments with full length AraC and biophysical experiments with its dimerization domain plus linker suggest that arabinose binding to the dimerization domain changes the properties of the inter-domain linker which connects the dimerization domain to the DNA binding domain via interactions that do not depend on the DNA binding domain. Normal AraC function was found to tolerate considerable linker sequence alteration excepting proline substitutions. The proline substitutions partially activate transcription even in the absence of arabinose and hint that a structural shift between helix and coil may be involved. To permit fluorescence anisotropy measurements that could detect arabinose-dependent dynamic differences in the linkers, IAEDANS was conjugated to a cysteine residue substituted at the end of the linker of dimerization domain. Arabinose, but not other sugars, decreased the steady-state anisotropy, indicating either an increase in mobility and/or an increase in the fluorescence lifetime of the IAEDANS. Time-resolved fluorescence measurements showed that the arabinose-induced anisotropy decrease did not result from an increase in the excited-state lifetime. Hence arabinose-induced decreases in anisotropy appear to result from increased tumbling of the fluorophore. Arabinose did not decrease the anisotropy in mutants incapable of binding arabinose nor did it alter the anisotropy when IAEDANS was conjugated elsewhere in the dimerization domain. Experiments with heterodimers of the dimerization domain showed that the binding of arabinose to one subunit of the dimer decreases the fluorescence anisotropy of only a fluorophore on the linker of the other subunit.


Assuntos
Fator de Transcrição AraC/química , Arabinose/química , Cisteína/química , Proteínas de Escherichia coli/química , Escherichia coli/química , Prolina/química , Subunidades Proteicas/química , Sequência de Aminoácidos , Substituição de Aminoácidos , Fator de Transcrição AraC/genética , Fator de Transcrição AraC/metabolismo , Arabinose/metabolismo , Cisteína/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Polarização de Fluorescência , Expressão Gênica , Mutação , Naftalenossulfonatos/química , Prolina/metabolismo , Ligação Proteica , Domínios Proteicos , Dobramento de Proteína , Multimerização Proteica , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Espectrometria de Fluorescência , Termodinâmica
8.
Ther Drug Monit ; 38(3): 313-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26845112

RESUMO

BACKGROUND: Routine therapeutic drug monitoring of voriconazole seems to be beneficial. This study investigated the therapeutic drug monitoring practices in intensive care to derive possible recommendations for improvement. METHODS: A retrospective chart review was performed for patients aged ≥18 years who started treatment with voriconazole, which lasted for at least 3 days while being admitted to an intensive care unit to assess possible differences between the patients with and without voriconazole trough concentrations measured. RESULTS: In 64 (76%) of the 84 patients, voriconazole trough concentrations were measured. The groups differed significantly with respect to the duration of voriconazole treatment and intensive care unit admission. Time of sampling was very early and therefore inappropriate for 49% of the first measured voriconazole trough concentrations and in 48% of the subsequent measured concentrations. Of the 349 trough concentrations measured, 129 (37%) were outside the therapeutic window. In 11% of these cases, no recommendation was provided without identifiable reason. In addition, 27% of recommended dose adjustments were not implemented, probably because the advice was not suited for the specific clinical situation. CONCLUSIONS: The performance of voriconazole therapeutic drug monitoring can still be improved although voriconazole concentrations were monitored in most patients. A multidisciplinary approach-for instance by means of antifungal stewardship-will probably be able to overcome problems encountered such as timing of sampling, incompleteness of data in clinical context, and lack of implementation of recommendations.


Assuntos
Antifúngicos/farmacocinética , Cuidados Críticos , Monitoramento de Medicamentos/métodos , Voriconazol/farmacocinética , Adulto , Antifúngicos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Voriconazol/administração & dosagem
9.
Antimicrob Agents Chemother ; 59(2): 1177-81, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25487797

RESUMO

Efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Determination of the anidulafungin AUC along with MIC values can therefore be useful. Since obtaining a full concentration-time curve to determine an AUC is not always feasible or appropriate, limited-sampling strategies may be useful in adequately estimating exposure. The objective of this study was to develop a model to predict the individual anidulafungin exposure in critically ill patients using limited-sampling strategies. Pharmacokinetic data were derived from 20 critically ill patients with invasive candidiasis treated with anidulafungin. These data were used to develop a two-compartment model in MW\Pharm using an iterative 2-stage Bayesian procedure. Limited-sampling strategies were subsequently investigated using two methods, a Bayesian analysis and a linear regression analysis. The best possible strategies for these two methods were evaluated by a Bland-Altman analysis for correlation of the predicted and observed AUC from 0 to 24 h (AUC0-24) values. Anidulafungin exposure can be adequately estimated with the concentration from a single sample drawn 12 h after the start of the infusion either by linear regression (R2=0.99; bias, 0.05%; root mean square error [RMSE], 3%) or using a population pharmacokinetic model (R2=0.89; bias, -0.1%; RMSE, 9%) in critically ill patients and also in less severely ill patients, as reflected by healthy volunteers. Limited sampling can be advantageous for future studies evaluating the pharmacokinetics and pharmacodynamics of anidulafungin and for therapeutic drug monitoring in selected patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01047267.).


Assuntos
Equinocandinas/farmacocinética , Adulto , Idoso , Anidulafungina , Teorema de Bayes , Candidíase Invasiva/tratamento farmacológico , Estado Terminal , Equinocandinas/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
10.
Antimicrob Agents Chemother ; 58(12): 7098-101, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25223994

RESUMO

Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. Inflammation may be a contributing factor, as inflammatory stimuli can change the activities and expression levels of cytochrome P450 isoenzymes. We explored the correlation between inflammation, reflected by C-reactive protein (CRP) concentrations, and voriconazole trough concentrations. A retrospective chart review of patients with at least one steady-state voriconazole trough concentration and a CRP concentration measured on the same day was performed. A total of 128 patients were included. A significantly (P < 0.001) higher voriconazole trough concentration was observed in patients with severe inflammation (6.2 mg/liter; interquartile range [IQR], 3.4 to 8.7 mg/liter; n = 20) than in patients with moderate inflammation (3.4 mg/liter; IQR, 1.6 to 5.4 mg/liter; n = 60) and in patients with no to mild inflammation (1.6 mg/liter; IQR, 0.8 to 3.0 mg/liter; n = 48). The patients in all three groups received similar voriconazole doses based on mg/kg body weight (P = 0.368). Linear regression analyses, both unadjusted and adjusted for covariates of gender, age, dose, route of administration, liver enzymes, and interacting coadministered medications, showed a significant association between voriconazole and CRP concentration (P < 0.001). For every 1-mg/liter increase in the CRP concentration, the voriconazole trough concentration increased by 0.015 mg/liter (unadjusted 95% confidence interval [CI], 0.011 to 0.020 mg/liter; adjusted 95% CI, 0.011 to 0.019 mg/liter). Inflammation, reflected by the C-reactive protein concentration, is associated with voriconazole trough concentrations. Further research is necessary to assess if taking the inflammatory status of a patient into account is helpful in therapeutic drug monitoring of voriconazole to maintain concentrations in the therapeutic window, thereby possibly preventing suboptimal treatment or adverse events.


Assuntos
Antifúngicos/farmacocinética , Aspergilose/tratamento farmacológico , Proteína C-Reativa/metabolismo , Voriconazol/farmacocinética , Adulto , Fatores Etários , Antifúngicos/sangue , Antifúngicos/farmacologia , Aspergilose/sangue , Aspergilose/microbiologia , Aspergilose/patologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/crescimento & desenvolvimento , Monitoramento de Medicamentos , Feminino , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Inflamação/patologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Voriconazol/sangue , Voriconazol/farmacologia
11.
Antimicrob Agents Chemother ; 58(1): 304-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24165173

RESUMO

The efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Patients in intensive care may be at risk for underexposure. In critically ill patients with an invasive Candida infection, the anidulafungin exposure and a possible correlation with disease severity or plasma protein levels were explored. Concentration-time curves were therefore obtained at steady state. Anidulafungin concentrations were measured with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The MIC values of the Candida species were determined with the Etest. The target AUC/MIC ratio was based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) data. Twenty patients were included. The patients received a maintenance dose of 100 mg once daily after a loading dose of 200 mg on the first day. The mean (±standard deviation) AUC, maximum concentration of drug in plasma (Cmax), and minimum concentration of drug in plasma (Cmin) were 69.8 ± 24.1 mg · h/liter, 4.7 ± 1.4 mg/liter, and 2.2 ± 0.8 mg/liter, respectively. The MIC values of all cultured Candida species were below the EUCAST MIC breakpoints. The exposure to anidulafungin in relation to the MIC that was determined appeared sufficient in all patients. The anidulafungin exposure was low in our critically ill patients. However, combined with the low MICs of the isolated Candida strains, the lower exposure observed in comparison to the exposure in the general patient population resulted in favorable AUC/MIC ratios, based on EUCAST data. No correlation was observed between anidulafungin exposure and disease severity or plasma protein concentrations. In patients with less-susceptible Candida albicans or glabrata strains, we recommend considering determining the anidulafungin exposure to ensure adequate exposure. (This trial has been registered at ClinicalTrials.gov under registration no. NCT01047267.).


Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Estado Terminal , Equinocandinas/uso terapêutico , Idoso , Anidulafungina , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Equinocandinas/farmacologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade
12.
World J Surg ; 37(10): 2428-35, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23720122

RESUMO

BACKGROUND: Fluid therapy (FT) is a critical intervention in managing acute pancreatitis (AP). There is a paucity of evidence to guide FT and virtually no data on current prescribing practice. This survey aims to characterize current practice and opinion with regard to FT in AP throughout New Zealand. METHODS: Information was collected on fluid selection, administration, and goal-directed FT. The survey was distributed online and in print to all doctors employed in General Surgery Departments in New Zealand on 1 May 2012. Monthly email reminders were sent for 6 months. RESULTS: The overall response rate was 47 % (n = 190/408). Crystalloids were the preferred initial fluid for all categories of severity; however, colloid use increased with severity (p < 0.001). Fluid volume also increased with severity (p = 0.001), with 74 % of respondents prescribing >4 L for AP with organ failure (OF). Clinicians treating 26-50 patients per year with AP were less likely to prescribe colloid for AP with OF (8 vs 43 %) (p = 0.001). Rate of fluid administration in AP with OF varied according to physicians' seniority (p = 0.004); consultants prescribed >4 L more than other groups (83 vs 68 %). Only 17 % of respondents reported the use of guidelines. CONCLUSIONS: This survey reveals significant variation in prescription of FT for AP, and aggressive FT is commonly prescribed for AP with OF. There is little adherence to published guidelines or best available evidence.


Assuntos
Hidratação/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Pancreatite/terapia , Padrões de Prática Médica/estatística & dados numéricos , Doença Aguda , Atitude do Pessoal de Saúde , Medicina Baseada em Evidências , Hidratação/métodos , Hidratação/normas , Cirurgia Geral/métodos , Cirurgia Geral/normas , Cirurgia Geral/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Humanos , Nova Zelândia , Guias de Prática Clínica como Assunto
13.
Polyhedron ; 57: 64-69, 2013 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-23745014

RESUMO

The synthesis and photophysical properties of new metallo-octabutoxynaphthalocyanines with Rh(III), Ir(III), and Pt(II) are reported. Various metals were inserted into the metal-free octabutoxynaphthalocyanine and the resultant metal complexes were fully characterized by NMR, UV-vis spectroscopy, and mass spectrometry. The absorption and emission properties of these new complexes were also examined and compared to those of Co(II), Ni(II), and Pd(II) octabutoxynaphthalocyanines. The results provide useful information to understand the effect of these transition metals on the properties of this macrocyclic ring.

14.
Infect Prev Pract ; 5(4): 100322, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38028361

RESUMO

Background: Due to the disadvantages of manual disinfection of patient rooms, mobile disinfection robots using ultraviolet C (UV-C) radiation are increasingly being used. Assessing their in situ effectiveness remains challenging. Aim: This study describes a new method to prove adequate in situ disinfection (≥5-log reduction in bacterial load), and uses this method to assess the efficacy of a mobile disinfection robot using UV-C radiation. Methods: Agar plates serving as proxies for smooth surfaces in patient rooms were inoculated with bacterial suspension and placed on various surfaces in a patient room. After irradiation by an automated mobile UV-C robot, reduction in colony growth was determined by comparing the irradiated plates to a reference series of non-irradiated plates, enabling the evaluation of whether an adequate reduction in colony-forming units (CFU's) of ≥5-log was reached on these irradiated surfaces. Findings: The new technique described here proved a successful method for demonstrating an in situ ≥5-log reduction in CFU's for five different bacterial pathogens. Of the 32 plates placed on UV-accessible surfaces, 31 showed an adequate reduction in CFU's of ≥5-log. One plate could not be assessed. Conclusion: Inoculated agar plates placed in patient rooms before irradiation and subsequently compared to a reference series can be used to assess in situ efficacy of mobile disinfection robots using UV-C radiation. Our findings support the idea that UV-C robots, used adjunctively to conventional manual washing and disinfection, may achieve adequate bacterial load reduction on UV-accessible smooth surfaces in patient rooms for a selected subset of pathogens.

15.
Front Immunol ; 14: 1182544, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37251403

RESUMO

Background: Post-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis. Methods: A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL). Results: 415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p<.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p<.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p<.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)]. Conclusions: PASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Estudos Transversais , Lipoproteínas LDL/metabolismo , Proteína C-Reativa/metabolismo , Progressão da Doença
16.
Stroke Vasc Neurol ; 8(3): 229-237, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36572506

RESUMO

BACKGROUND: The optimal management of ipsilateral extracranial internal carotid artery (ICA) stenosis during endovascular treatment (EVT) is unclear. We compared the outcomes of two different strategies: EVT with vs without carotid artery stenting (CAS). METHODS: In this observational study, we included patients who had an acute ischaemic stroke undergoing EVT and a concomitant ipsilateral extracranial ICA stenosis of ≥50% or occlusion of presumed atherosclerotic origin, from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry (2014-2017). The primary endpoint was a good functional outcome at 90 days, defined as a modified Rankin Scale score ≤2. Secondary endpoints were successful intracranial reperfusion, new clot in a different vascular territory, symptomatic intracranial haemorrhage, recurrent ischaemic stroke and any serious adverse event. RESULTS: Of the 433 included patients, 169 (39%) underwent EVT with CAS. In 123/168 (73%) patients, CAS was performed before intracranial thrombectomy. In 42/224 (19%) patients who underwent EVT without CAS, a deferred carotid endarterectomy or CAS was performed. EVT with and without CAS were associated with similar proportions of good functional outcome (47% vs 42%, respectively; adjusted OR (aOR), 0.90; 95% CI, 0.50 to 1.62). There were no major differences between the groups in any of the secondary endpoints, except for the increased odds of a new clot in a different vascular territory in the EVT with CAS group (aOR, 2.96; 95% CI, 1.07 to 8.21). CONCLUSIONS: Functional outcomes were comparable after EVT with and without CAS. CAS during EVT might be a feasible option to treat the extracranial ICA stenosis but randomised studies are warranted to prove non-inferiority or superiority.


Assuntos
Isquemia Encefálica , Estenose das Carótidas , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/terapia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Isquemia Encefálica/etiologia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/terapia , AVC Isquêmico/etiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Constrição Patológica/etiologia , Procedimentos Endovasculares/efeitos adversos , Stents , Sistema de Registros
17.
Biochemistry ; 51(41): 8085-91, 2012 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-23002904

RESUMO

AraC protein, which regulates expression of the l-arabinose operon in Escherichia coli, is a dimer whose DNA binding affinity for pairs of DNA half-sites is controlled by arabinose. Here we have addressed the question of whether the arabinose response of AraC requires the binding of one or two molecules of arabinose. This was accomplished by measuring the DNA dissociation rates of wild-type AraC and heterodimeric AraC constructs in which one subunit is capable of binding arabinose and the other subunit does not bind arabinose. Solutions consisting entirely of heterodimers were formed by spontaneous subunit exchange between two different homodimers, with heterodimers being trapped by the formation of an intersubunit disulfide bond between cysteine residues strategically positioned within the dimerization interface. We found that the normal arabinose response of AraC requires the binding of two arabinose molecules. These results provide additional constraints on mechanistic models for the action of AraC.


Assuntos
Fator de Transcrição AraC/metabolismo , Arabinose/metabolismo , Proteínas de Escherichia coli/metabolismo , Fator de Transcrição AraC/genética , Arabinose/química , Sequência de Bases , DNA Bacteriano/metabolismo , Dimerização , Proteínas de Escherichia coli/genética , Cinética , Mutagênese
18.
Crit Care Med ; 40(3): 762-5, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21946656

RESUMO

OBJECTIVES: Insulin administration lowers plasma potassium concentration by augmenting intracellular uptake of potassium. The effect of insulin administration on renal potassium excretion is unclear. Some studies suggest that insulin has an antikaliuretic effect although plasma potassium levels were poorly controlled. Since the introduction of glycemic control in the intensive care unit, insulin use has increased. We examined the relation between administered insulin and renal potassium excretion in critically ill patients under computer-assisted glucose and potassium regulation. DESIGN: Prospective observational study. SETTING: Twelve-bed surgical intensive care unit of a university teaching hospital. PATIENTS: Consecutive intensive care unit patients. INTERVENTIONS: Potassium and glucose levels were regulated by a computer-assisted decision support system. Both potassium and insulin were continuously administered by syringe pump. MEASUREMENTS AND MAIN RESULTS: Renal potassium excretion was measured daily in the 24-hr urine collections. The 24-hr urinary samples of patients with kidney failure or on renal replacement therapy were excluded. Multivariate analysis with potassium excretion as the dependent variable was performed. In 178 consecutive patients, 1,456 24-hr urinary samples, were analyzed. Mean ± SD plasma potassium was 4.2 ± 0.3 mmol/L, with 79 ± 46 mmol/d of potassium administered and a mean insulin dose of 53 ± 38 U/day. Renal potassium excretion was 126 ± 51 mmol/day. After multivariate analysis correcting for relevant variables (including diuretics, pH, potassium levels and renal sodium excretion), insulin administration was independently and positively associated with renal potassium excretion. Other significant variables were potassium levels, potassium administration, renal sodium and chloride excretion, creatinine clearance, diuretic therapy, pH, known diabetes and intensive care unit admission day (R = .52; p <. 001). CONCLUSION: Insulin administration is associated with an increase in the renal potassium excretion in critically ill patients.


Assuntos
Estado Terminal , Insulina/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Potássio/urina , Feminino , Humanos , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Neurocrit Care ; 17(2): 260-4, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22847396

RESUMO

BACKGROUND: Propofol infusion syndrome (PRIS) is well known, often associated with, lethal complication of sedation with propofol. PRIS seems to be associated with young age, traumatic brain injury (TBI), higher cumulative doses of propofol, and the concomitant use of catecholamines. Known manifestations of PRIS are metabolic acidosis, rhabdomyolysis, and cardiac failure. While fatal PRIS can occur suddenly and rapidly, there is no sensitive test or early warning sign, and the only preventive measure is to limit propofol dosage and its duration. METHODS: DESCRIPTION OF A SINGLE CASE: A case report was used for investigation purposes of this study. RESULTS: We report the case study of a young patient with severe TBI, receiving propofol sedation because of high intracranial pressure. Seven days after the trauma, the patient developed metabolic acidosis and refractory circulatory shock, probably caused by PRIS. Reversal of T-waves was seen on the electrocardiogram (ECG) 29 h before circulation failure occurred. In the absence of other signs of cardiac dysfunction or ischemia, these reversed T-waves probably represent an early warning sign of developing PRIS. CONCLUSION: From the findings of this study, we conclude that meticulous observation and analysis of the ECG during propofol sedation might result in earlier recognition of developing PRIS.


Assuntos
Acidose/induzido quimicamente , Lesões Encefálicas/complicações , Hipnóticos e Sedativos/efeitos adversos , Hipertensão Intracraniana/tratamento farmacológico , Propofol/efeitos adversos , Choque/induzido quimicamente , Eletrocardiografia , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipertensão Intracraniana/complicações , Masculino , Propofol/administração & dosagem , Síndrome , Adulto Jovem
20.
J Environ Manage ; 95(1): 49-55, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22115510

RESUMO

The milking process on dairy farms produces wastewaters, known as dairy soiled waters (DSW), which contain variable concentrations of nutrients. The most common method of disposal is by application to land. However, this practise can result in the pollution of nearby receiving water bodies. A laboratory study, comprising two sets of 0.5 m, 1 m and 1.5 m-deep filters loaded at two loading rates, examined the performance of woodchip filters in treating DSW. The filters comprised de-barked Sitka spruce (Picea sitchensis) woodchips. Dried DSW was reconstituted to 1% and 3% suspended solids (SS) concentrations and was applied at 28 L/m(2).d to the surface of the filters at loading rates of 280 g SS/m(2).d and 840 g SS/m(2).d, respectively. Filters were loaded for a maximum of 277 days. The filters achieved substantial decreases in SS (>99%), chemical oxygen demand (COD) (>97%) and total nitrogen (TN) (>89%). The dominant treatment mechanism appears to be physical filtration, but sorption and biological uptake likely also play a role. As the filters are aerobic, mineralisation and nitrification occur, but gaseous N losses are probably not significant. Woodchip shows potential as a filter medium for treating DSW, significantly decreasing the concentrations of SS, COD and TN.


Assuntos
Indústria de Laticínios , Filtração/métodos , Resíduos Industriais , Eliminação de Resíduos Líquidos/métodos , Madeira , Picea
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