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1.
Circulation ; 147(19): 1436-1443, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37009731

RESUMO

BACKGROUND: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. METHODS: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. RESULTS: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05465278.


Assuntos
Síndrome Coronariana Aguda , Aterosclerose , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Placa Aterosclerótica , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9 , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Placa Aterosclerótica/tratamento farmacológico , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Síndrome Coronariana Aguda/tratamento farmacológico , Resultado do Tratamento
2.
Eur J Clin Invest ; 54(8): e14197, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38519859

RESUMO

BACKGROUND: The prevalence of cancer patients with concomitant cardiovascular (CV) disease is on the rise due to improved cancer prognoses. The aim of this study is to evaluate the long-term outcomes of cancer patients referred to a cardiology department (CD) via primary care using e-consultation. METHODS: We analysed data from cancer patients with prior referrals to a CD between 2010 and 2021 (n = 6889) and compared two care models: traditional in-person consultations and e-consultations. In e-consultation model, cardiologists reviewed electronic health records (e-consultation) to determine whether the demand could be addressed remotely or necessitated an in-person consultation. We used an interrupted time series regression model to assess outcomes during the two periods: (1) time to cardiology consultation, (2) rates of all-cause and CV related hospital admissions and (3) rates of all-cause and CV-related mortality within the first year after the initial consultation or e-consultation at the CD. RESULTS: Introduction of e-consultation for cancer patients referred to cardiology care led to a 51.8% reduction (95%CI: 51.7%-51.9%) in waiting times. Furthermore, we observed decreased 1-year incidence rates, with incidence rate ratios (iRRs) [IC95%] of .75 [.73-.77] for CV-related hospitalizations, .43 [.42-.44] for all-cause hospitalizations, and .87 [.86-.88] for all-cause mortality. CONCLUSIONS: Compared to traditional in-person consultations, an outpatient care program incorporating e-consultation for cancer patients significantly reduced waiting times for cardiology care and demonstrated safety, associated with lower rates of hospital admissions.


Assuntos
Doenças Cardiovasculares , Neoplasias , Atenção Primária à Saúde , Encaminhamento e Consulta , Humanos , Neoplasias/terapia , Neoplasias/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/epidemiologia , Registros Eletrônicos de Saúde , Cardiologia , Análise de Séries Temporais Interrompida , Consulta Remota , Hospitalização/estatística & dados numéricos , Listas de Espera , Telemedicina , Serviço Hospitalar de Cardiologia/organização & administração
3.
J Appl Microbiol ; 135(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38366933

RESUMO

Chronic wound infections are generally of polymicrobial nature with aerobic and anaerobic bacteria, as well as fungi frequently observed in them. Wound treatment involves a series of steps, including debridement of the wound, flushing, and often the use of multiple wound dressings many of which are antimicrobial. Yet, many wound dressings are tested versus single species of planktonic microbes, which fails to mirror the real-life presence of biofilms. AIMS: Simple biofilm models are the first step to testing of any antimicrobial and wound dressing; therefore, the aim of this study was to develop and validate a simple polymicrobial colony biofilm wound model comprised of Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans on RPMI-1640 agar. The model was then used to evaluate the topical disinfectant chlorohexidine and four commercially available wound dressings using the polymicrobial model. The model used was as a starting point to mimic debridement in clinical care of wounds and the effectiveness of wound dressings evaluated afterwards. METHODS AND RESULTS: Planktonic assessment using AATCC100-2004 demonstrated that all antimicrobial wound dressings reduced the planktonic microbial burden below the limit of detection; however, when challenged with polymicrobial colony biofilms, silver wound dressings showed limited effectiveness (1-2 log CFU reductions). In contrast, a single iodine releasing wound dressing showed potent antibiofilm activity reducing all species CFUs below the limit of detection (>6-10 log) depending on the species. A disrupted biofilm model challenge was performed to represent the debridement of a wound and wound silver-based wound dressings were found to be marginally more effective than in whole colony biofilm challenges while the iodine containing wound dressing reduced microbial recovery below the limit of detection. CONCLUSIONS: In this model, silver dressings were ineffective versus the whole colony biofilms but showed some recovery of activity versus the disrupted colony biofilm. The iodine wound dressing reduced the viability of all species below the level of detection. This suggests that mode of action of wound dressing should be considered for the type of biofilm challenge as should the clinical use, e.g. debridement.


Assuntos
Anti-Infecciosos , Iodo , Infecção dos Ferimentos , Humanos , Prata , Anti-Infecciosos/farmacologia , Bandagens , Iodo/farmacologia , Iodo/uso terapêutico , Biofilmes , Infecção dos Ferimentos/prevenção & controle , Infecção dos Ferimentos/tratamento farmacológico , Pseudomonas aeruginosa
4.
Anal Chem ; 95(11): 5079-5086, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36881460

RESUMO

Previously, metabolites diffused or secreted from microbial samples have been analyzed via liquid chromatography-mass spectrometry (LC-MS) approaches following lengthy extraction protocols. Here, we present a model system for growing biofilms on discs before utilizing rapid and direct surface sampling MS, namely, liquid extraction surface analysis, to study the microbial exometabolome. One of the benefits of this approach is its surface-specific nature, enabling mimicking biofilm formation in a way that the study of planktonic liquid cultures cannot imitate. Even though Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Candida albicans (C. albicans) have been studied previously in isolation, very few studies consider the complexity of the interplay between these pathogens, which are commonly combined causative agents of infection. Our model system provides a route to investigate changes in the exometabolome, such as metabolites that become circulatory in the presence of multiple pathogens. Our results agree with previous reports showing that 2-alkyl-4(1H)-quinolone signal molecules produced by P. aeruginosa are important markers of infection and suggest that methods for monitoring levels of 2-heptyl-4-hydroxyquinoline and 2,4-dihydroxyquinoline, as well as pyocyanin, could be beneficial in the determination of causative agents in interkingdom infection including P. aeruginosa. Furthermore, studying changes in exometabolome metabolites between pqs quorum sensing antagonists in treated and nontreated samples suggests suppression of phenazine production by P. aeruginosa. Hence, our model provides a rapid analytical approach to gaining a mechanistic understanding of bacterial signaling.


Assuntos
Percepção de Quorum , Staphylococcus aureus , Espectrometria de Massas , Biofilmes , Cromatografia Líquida , Pseudomonas aeruginosa/metabolismo
5.
J Med Virol ; 95(2): e28496, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36639903

RESUMO

Colchicine is one of the most widely studied and best-known anti-inflammatory treatments. This study aimed to assess the effect of colchicine on risk of hospitalization due to COVID-19; and its effect on susceptibility to and severity of the virus in patients with COVID-19. We carried out a population-based case-control study. The following groups were applied: (1) to assess risk of hospitalization, cases were patients with a positive PCR who were hospitalized due to COVID-19, and controls without a positive PCR; (2) to assess susceptibility to COVID-19, cases were patients with a positive PCR (hospitalized and non-hospitalized), and the same controls; (3) to determine potential severity, cases were subjects with COVID-19 hospitalized, and controls patients with COVID-19 nonhospitalised. Different electronic, linked, administrative health and clinical databases were used to extract data on sociodemographic variables, comorbidities, and medications dispensed. The study covered 3060 subjects with a positive PCR who were hospitalized, 26 757 with a positive PCR who were not hospitalized, and 56 785 healthy controls. After adjustment for sociodemographic variables, comorbidities and other treatments, colchicine did not modify risk of hospitalization due to COVID-19 (adjusted odd ratio [OR] 1.08 [95% confidence interval (CI) 0.76-1.53]), patients' susceptibility to contracting the disease (adjusted OR 1.12 (95% CI 0.91-1.37)) or the severity of the infection (adjusted OR 1.03 [95% CI 0.67-1.59]). Our results would neither support the prophylactic use of colchicine for prevention of the infection or hospitalization in any type of patient, nor justify the withdrawal of colchicine treatment due to a higher risk of contracting COVID-19.


Assuntos
COVID-19 , Humanos , Colchicina/uso terapêutico , SARS-CoV-2 , Estudos de Casos e Controles , Hospitalização
6.
Opt Express ; 31(12): 20398-20409, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381435

RESUMO

Optical trapping has proven to be a valuable experimental technique for precisely controlling small dielectric objects. However, due to their very nature, conventional optical traps are diffraction limited and require high intensities to confine the dielectric objects. In this work, we propose a novel optical trap based on dielectric photonic crystal nanobeam cavities, which overcomes the limitations of conventional optical traps by significant factors. This is achieved by exploiting an optomechanically induced backaction mechanism between a dielectric nanoparticle and the cavities. We perform numerical simulations to show that our trap can fully levitate a submicron-scale dielectric particle with a trap width as narrow as 56 nm. It allows for achieving a high trap stiffness, therefore, a high Q-frequency product for the particle's motion while reducing the optical absorption by a factor of 43 compared to the cases for conventional optical tweezers. Moreover, we show that multiple laser tones can be used further to create a complex, dynamic potential landscape with feature sizes well below the diffraction limit. The presented optical trapping system offers new opportunities for precision sensing and fundamental quantum experiments based on levitated particles.

7.
Eur J Clin Invest ; 53(3): e13904, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36346678

RESUMO

BACKGROUND: An early diagnosis and early initiation of oral anticoagulants (OAC) are main determinants for outcomes in patients with atrial fibrillation (AF). Inter-clinician electronic consultations (e-consultations) program for the general practitioner referrals to cardiologist may improve health care access by reducing the elapsed time for cardiology care. OBJECTIVE: To evaluate the effect of a reduced elapsed time to care after a inter-clinician e-consultations program implementation (2013-2019) in comparison with previous in-person consultation (2010-2012) in the outpatient health care management in a Cardiology Department. METHODOLOGY: We included 10,488 patients with AF from 1 January 2010, to 31 December 2019. Until 2012, all patients attended an in-person consultation (2010-2012). In 2013, we instituted an e-consult program (2013-2019) for all primary care referrals to cardiologists that preceded patient's in-person consultation when considered. The shared electronic patient dossier (EPD) was available between GP and cardiologist, and any change in therapy advice from cardiologist was directly implemented in this EPD. RESULTS: During the e-consultation period (2013-2019) were referred 6627 patients by GPs to cardiology versus 3861 during the in-person consultation (2010-2012). The e-consultation implementation was associated with a reduction in the elapsed time to anticoagulation prescription (177.6 ± 8.9 vs. 22.5 ± 8.1 days, p < .001), and an increase of OAC use (61% [95% IC: 19.6%-102.4%], p < .001). The e-consult program implementation was associated with a reduction in the 1-year CV mortality (.48 [95% CI: .30-.75]) and all-cause mortality (.42 [95% CI: .29-.62]). The OAC reduces the stroke mortality (.15 [95% CI: .06-.39]) and CV mortality (.43 [95% CI: .29-.62]) and all-cause mortality (.23 [95% CI: .17-.31]). CONCLUSION: A shared EPD-based inter-clinician e-consultation program significantly reduced the elapsed time for cardiology consultation and initiation of OAC. The implementation of this program was associated with a lower risk of stroke and cardiovascular/all-cause mortality.


Assuntos
Fibrilação Atrial , Consulta Remota , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Fibrilação Atrial/complicações , Anticoagulantes/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações , Atenção Primária à Saúde , Administração Oral , Fatores de Risco
8.
Eur J Clin Invest ; 53(9): e14012, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37114978

RESUMO

AIMS: To assess the longer-term results (hospital admissions and mortality) in women versus men referred to a cardiology department from primary care using an e-consultation in our outpatient care programme. METHODS: We selected 61,306 patients (30,312 women and 30,994 men) who visited the cardiology service at least once between 2010 and 2021: 69.1% (19,997 women and 20,462 men) were attended in e-consultation (from 2013 to 2021) and 30.9% (8920 women and 9136 men) in in-person consultations (from 2010 to 2012) without gender differences in the proportion of patients attended in each period. Using an interrupted time series regression model, we analysed the impact of incorporating e-consultation into the healthcare model and evaluated the elapsed time to cardiology care, heart failure (HF), cardiovascular (CV), and all-cause hospital admissions and mortality during the one-year after cardiology consultation. RESULTS: The introduction of e-consultation substantially decreased waiting times to cardiology care; during the in-person consultation period, the mean delay for cardiology care was 57.9 (24.8) days in men and 55.8 (22.8) days in women. During the e-consultation period, the waiting time to cardiology care was markedly reduced to 9.41 (4.02) days in men and 9.46 (4.18) in women. After e-consultation implantation, there was a significant reduction in the 1-year rate of hospital admissions and mortality, both in women and men iRR [IC 95%]: 0.95 [0.93-0.96] for HF, 0.90 [0.89-0.91] for CV and 0.70 [0.69-0.71] for all-cause hospitalization; and 0.93 [0.92-0.95] for HF, 0.86 [0.86-0.87] for CV and 0.88 [0.87-0.89] for all-cause mortality in women; and 0.91 [0.89-0.92] for HF, 0.90 [0.89-0.91] for CV and 0.72 [0.71-0.73] for all-cause hospitalization; and 0.96 [0.93-0.97] for HF, 0.87 [95% CI: 0.86-0.87] for CV and 0.87 [0.86-0.87] for all-cause mortality, in men. CONCLUSION: Compared with the in-person consultation period, an outpatient care programme that includes an e-consultation significantly reduced waiting time to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year, without significative gender differences.


Assuntos
Cardiologia , Insuficiência Cardíaca , Masculino , Humanos , Feminino , Fatores Sexuais , Encaminhamento e Consulta , Hospitalização , Acessibilidade aos Serviços de Saúde
9.
J Clin Psychopharmacol ; 43(3): 239-245, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37068034

RESUMO

PURPOSE/BACKGROUND: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. METHODS: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. FINDINGS/RESULTS: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. IMPLICATIONS/CONCLUSIONS: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.


Assuntos
Agranulocitose , Antipsicóticos , Clozapina , Humanos , Clozapina/efeitos adversos , Antipsicóticos/efeitos adversos , Farmacovigilância , Agranulocitose/induzido quimicamente , Reino Unido
10.
Environ Microbiol ; 24(3): 1560-1572, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35049126

RESUMO

Decades after incorporating plastics into consumer markets, research shows that these polymers have spread worldwide. Fragmentation of large debris leads to smaller particles, collectively called microplastics (MPs), which have become ubiquitous in aquatic environments. A fundamental aspect of understanding the implications of MP contamination on ecosystems is resolving the complex interactions of these artificial substrates with microbial cells. Using polystyrene microparticles as model polymers, we conducted an exploratory study where these interactions are quantitatively analyzed using an in vitro system consisting of single-bacterial species capturing and aggregating MPs in water. Here we show that the production of Psl exopolysaccharide by Pseudomonas aeruginosa (PA) does not alter MPs colloidal stability but plays a key role in microspheres adhesion to the cell surface. Further aggregation of MPs by PA cells depends on bacterial mobility and the presence of sufficient flow to prevent rapid sedimentation of early MP-PA assembles. Surprisingly, cells in MP-PA aggregates are not in a sessile state despite the production of Psl, enhancing the motility of the aggregates by an order of magnitude relative to passive diffusion. The generated data could inform the creation of predictive models that accurately describe the dynamics and influence of bacterial growth on plastics debris.


Assuntos
Microplásticos , Poluentes Químicos da Água , Ecossistema , Monitoramento Ambiental , Hidrodinâmica , Plásticos/metabolismo , Polissacarídeos/metabolismo , Pseudomonas aeruginosa/metabolismo , Água/metabolismo , Poluentes Químicos da Água/metabolismo
11.
Environ Microbiol ; 24(9): 4329-4339, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35352448

RESUMO

There is currently a need to develop simple biofilm models that facilitate investigation of the architecture/biology of mature bacterial biofilms in a consistent/standardized manner given their environmental and clinical importance and the need for new anti-biofilm interventions. This study introduces a novel biofilm culture system termed the rolling biofilm bioreactor (RBB). This easily operated system allows adherent microbial cells to be repeatedly exposed to air/solid/liquid interfaces optimizing biofilm growth. The RBB was exploited to investigate biofilm formation in Acinetobacter baumannii. High levels of A. baumannii biofilm biomass reproducibly accumulate in the RBB and, importantly, undergo a maturation step to form large mushroom-shaped structures that had not been observed in other models. Based on image analysis of biofilm development and genetic manipulation, we show how N-acylhomoserine lactone-dependent quorum sensing (QS) impacts on biofilm differentiation, composition and antibiotic tolerance. Our results indicate that extracellular DNA (eDNA) is a key matrix component in mature Acinetobacter biofilms as the mushroom-like structures consist of dense cellular masses encased in an eDNA mesh. Moreover, this study reveals the contribution of QS to A. baumannii biofilm differentiation through Csu pilus assembly regulation. Understanding the mechanisms of structural development of mature biofilms helps to identify new biofilm eradication and removal strategies.


Assuntos
Acinetobacter baumannii , Acil-Butirolactonas , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes , Reatores Biológicos , Percepção de Quorum
12.
Environ Microbiol ; 24(12): 5707-5720, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36063363

RESUMO

Biofilms are essential for plant-associated bacteria to colonize their host. In this work, we analysed the interaction of Azospirillum baldaniorum Sp245 and Pseudomonas fluorescens A506 in mixed macrocolony biofilms. We identified certain culture conditions where A. baldaniorum Sp245 exploits P. fluorescens A506 to boost its growth. Azospirillum growth increased proportionally to the initial number of pseudomonads building the biofilm, which in turn were negatively affected in their growth. Physical contact with P. fluorescens A506 was essential for A. baldaniorum Sp245 growth increase. Biofilm ultrastructure analysis revealed that Pseudomonas produces a thick structure that hosts Azospirillum cells in its interior. Additional experimentation demonstrated that Azospirillum growth boost is compromised when interacting with biofilm-deficient Pseudomonas mutants, and that a low oxygen concentration strongly induce A. baldaniorum Sp245 growth, overriding Pseudomonas stimulation. In this line, we used a microaerophilia reporter strain of A. baldaniorum Sp245 to confirm that dual-species macrocolonies contain a higher number of cells under microaerophilic conditions. Taking all the results into consideration, we propose that A. baldaniorum Sp245 can benefit from P. fluorescens A506 partnership in mixed biofilms by taking advantage of the low oxygen concentration and scaffold made up of Pseudomonas-derived matrix, to expand its growth.


Assuntos
Azospirillum brasilense , Pseudomonas fluorescens , Pseudomonas fluorescens/genética , Biofilmes , Pseudomonas/genética , Oxigênio
13.
Pharmacopsychiatry ; 55(2): 73-86, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34911124

RESUMO

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.


Assuntos
Antipsicóticos , Clozapina , Adulto , Antipsicóticos/efeitos adversos , Povo Asiático , Proteína C-Reativa , Clozapina/efeitos adversos , Feminino , Humanos , Masculino , Ácido Valproico/efeitos adversos
14.
Crit Rev Biotechnol ; 41(4): 609-627, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33593221

RESUMO

Bacillus licheniformis is a Gram positive spore-forming bacterial species of high biotechnological interest with numerous present and potential uses, including the production of bioactive compounds that are applied in a wide range of fields, such as aquaculture, agriculture, food, biomedicine, and pharmaceutical industries. Its use as an expression vector for the production of enzymes and other bioproducts is also gaining interest due to the availability of novel genetic manipulation tools. Furthermore, besides its widespread use as a probiotic, other biotechnological applications of B. licheniformis strains include: bioflocculation, biomineralization, biofuel production, bioremediation, and anti-biofilm activity. Although authorities have approved the use of B. licheniformis as a feed additive worldwide due to the absence of toxigenic potential, some probiotics containing this bacterium are considered unsafe due to the possible transference of antibiotic resistance genes. The wide variability in biological activities and genetic characteristics of this species makes it necessary to establish an exact protocol for describing the novel strains, in order to evaluate its biotechnological potential.


Assuntos
Bacillus licheniformis , Bacillus , Probióticos , Aquicultura , Bacillus/genética , Bacillus licheniformis/genética , Bactérias
15.
Chem Rev ; 119(7): 4777-4816, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30869873

RESUMO

Among renewable energies, wind and solar are inherently intermittent and therefore both require efficient energy storage systems to facilitate a round-the-clock electricity production at a global scale. In this context, concentrated solar power (CSP) stands out among other sustainable technologies because it offers the interesting possibility of storing energy collected from the sun as heat by sensible, latent, or thermochemical means. Accordingly, continuous electricity generation in the power block is possible even during off-sun periods, providing CSP plants with a remarkable dispatchability. Sensible heat storage has been already incorporated to commercial CSP plants. However, because of its potentially higher energy storage density, thermochemical heat storage (TCS) systems emerge as an attractive alternative for the design of next-generation power plants, which are expected to operate at higher temperatures. Through these systems, thermal energy is used to drive endothermic chemical reactions, which can subsequently release the stored energy when needed through a reversible exothermic step. This review analyzes the status of this prominent energy storage technology, its major challenges, and future perspectives, covering in detail the numerous strategies proposed for the improvement of materials and thermochemical reactors. Thermodynamic calculations allow selecting high energy density systems, but experimental findings indicate that sufficiently rapid kinetics and long-term stability trough continuous cycles of chemical transformation are also necessary for practical implementation. In addition, selecting easy-to-handle materials with reduced cost and limited toxicity is crucial for large-scale deployment of this technology. In this work, the possible utilization of materials as diverse as metal hydrides, hydroxides, or carbonates for thermochemical storage is discussed. Furthermore, special attention is paid to the development of redox metal oxides, such as Co3O4/CoO, Mn2O3/Mn3O4, and perovskites of different compositions, as an auspicious new class of TCS materials due to the advantage of working with atmospheric air as reactant, avoiding the need of gas storage tanks. Current knowledge about the structural, morphological, and chemical modifications of these solids, either caused during redox transformations or induced wittingly as a way to improve their properties, is revised in detail. In addition, the design of new reactor concepts proposed for the most efficient use of TCS in concentrated solar facilities is also critically considered. Finally, strategies for the harmonic integration of these units in functioning solar power plants as well as the economic aspects are also briefly assessed.

16.
Oecologia ; 196(4): 1179-1193, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34331567

RESUMO

Water is the main limiting factor for groundwater-dependent ecosystems (GDEs) in drylands. Predicted climate change (precipitation reductions and temperature increases) and anthropogenic activities such as groundwater drawdown jeopardise the functioning of these ecosystems, presenting new challenges for their management. We developed a trait-based analysis to examine the spatiotemporal variability in the ecophysiology of Ziziphus lotus, a long-lived phreatophyte that dominates one of the few terrestrial GDEs of semiarid regions in Europe. We assessed morpho-functional traits and stem water potential along a naturally occurring gradient of depth-to-groundwater (DTGW, 2-25 m) in a coastal aquifer, and throughout the species-growing season. Increasing DTGW and salinity negatively affected photosynthetic and transpiration rates, increasing plant water stress (lower predawn and midday water potential), and positively affected Huber value (sapwood cross-sectional area per leaf area), reducing leaf area and likely, plant hydraulic demand. However, the species showed greater salt-tolerance at shallow depths. Despite groundwater characteristics, higher atmospheric evaporative demand in the study area, which occurred in summer, fostered higher transpiration rates and water stress, and promoted carbon assimilation and water loss more intensively at shallow water tables. This multiple-trait analysis allowed us to identify plant ecophysiological thresholds related to the increase in salinity, but mostly in DTGW (13 m), and in the evaporative demand during the growing season. These findings highlight the existence of tipping points in the functioning of a long-lived phreatophyte in drylands and can contribute to the sustainable management of GDEs in southern Europe, paving the way for further studies on phreatophytic species.


Assuntos
Ecossistema , Água Subterrânea , Mudança Climática , Salinidade , Água
17.
Mar Drugs ; 19(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33401388

RESUMO

Although Psychrobacter strain M9-54-1 had been previously isolated from the microbiota of holothurians and shown to degrade quorum sensing (QS) signal molecules C6 and C10-homoserine lactone (HSL), little was known about the gene responsible for this activity. In this study, we determined the whole genome sequence of this strain and found that the full 16S rRNA sequence shares 99.78-99.66% identity with Psychrobacter pulmonis CECT 5989T and P. faecalis ISO-46T. M9-54-1, evaluated using the agar well diffusion assay method, showed high quorum quenching (QQ) activity against a wide range of synthetic N-acylhomoserine lactone (AHLs) at 4, 15, and 28 °C. High-performance liquid chromatography-mass-spectrometry (HPLC-MS) confirmed that QQ activity was due to an AHL-acylase. The gene encoding for QQ activity in strain M9-54-1 was identified from its genome sequence whose gene product was named AhaP. Purified AhaP degraded substituted and unsubstituted AHLs from C4- to C14-HSL. Furthermore, heterologous expression of ahaP in the opportunistic pathogen Pseudomonas aeruginosa PAO1 reduced the expression of the QS-controlled gene lecA, encoding for a cytotoxic galactophilic lectin and swarming motility protein. Strain M9-54-1 also reduced brine shrimp mortality caused by Vibrio coralliilyticus VibC-Oc-193, showing potential as a biocontrol agent in aquaculture.


Assuntos
Amidoidrolases/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Psychrobacter/química , Percepção de Quorum/efeitos dos fármacos , Vibrio/efeitos dos fármacos , Vibrio/patogenicidade , Virulência/efeitos dos fármacos , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , Acil-Butirolactonas/metabolismo , Animais , Artemia , Genoma Bacteriano/genética , Estrutura Molecular , Psychrobacter/genética , RNA Ribossômico 16S
18.
J Adv Nurs ; 77(1): 255-265, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33136314

RESUMO

AIMS: To determine the effect of a comprehensive nurse-led programme for patients with chronic non-malignant pain, on quality of life, level of pain, anxiety, and depression, as primary outcomes and patients' satisfaction as a secondary end point. DESIGN: An open-label randomized controlled trial was carried out. METHODS: The experimental group received both a nurse-led intervention on healthy lifestyles, education on self-esteem, pain awareness, communication, and relaxation techniques. The control group received usual care. Quality of life, level of pain, anxiety, and depression were the main outcomes. Data were obtained at baseline, immediately after the intervention, and 6 and 9 months. The study was carried out from 2015-2017. RESULTS: The sample was composed of 279 patients. At 9 months, the effect size (non-parametric effect size statistic A) favoured the intervention group for SF-36 mental health score (A = 0.79; 95% CI: 0.73-0.85), anxiety (A = 0.58; 95% CI: 0.51-0.65), pain intensity (A = 0.57; 95% CI: 0.51-0.64), and depression (A = 0.58; 95% CI: 0.51-0.65). Smaller differences were found on physical scores between the intervention and the usual care group. Patients showed a high level of satisfaction with the introduced intervention. CONCLUSION: A comprehensive nurse-led programme for patients with chronic non-malignant pain has a positive impact on their quality of life, level of pain, and mental health. IMPACT: Studies have reported that the problem of chronic pain is not optimally controlled. A structured nurse-led programme has been tested to facilitate healthy behaviours to help patients manage their chronic pain and to provide them with the necessary tools for their self-care. This nurse-led intervention improved their mental health and decreased their level of pain.


Assuntos
Dor Crônica , Qualidade de Vida , Ansiedade/prevenção & controle , Humanos , Papel do Profissional de Enfermagem , Autocuidado
19.
J Food Sci Technol ; 58(7): 2725-2733, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34194108

RESUMO

Crude extracts of collagenases from jumbo squid (Dosidicus gigas) hepatopancreas and sierra fish (Scomberomorus sierra) viscera were used to hydrolyse squid muscle collagen into peptides with inhibitory capacity over angiotensin I-converting enzyme (ACE) and ABTS free radicals [2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid)], as a measure of their antihypertensive potential and antioxidant activity, respectively. Proteins from 20 to 200 kDa were found in both enzyme extracts; however, in comparison to the jumbo squid extract (JSE), the extraction yield and specific activity of the enzymatic sierra fish extract (SFE) were ≈ 40% greater, suggesting the presence of enzymes with different collagenolytic activity. Moreover, the utilised collagen was obtained with a yield of 0.98 ± 0.09 g/100 g muscle from jumbo squid arms, which after an incubation with JSE and SFE generated peptides with different biological activity. However, the collagen hydrolysates from the enzymatic SFE contained a higher proportion of low-molecular-weight peptides than that obtained from JSE (15.2 and 7.9% of < 3 kDa peptides, respectively). Finally, the antioxidant potential and ACE-inhibitory activity were increased after hydrolysis, being the SFE the one that showed a greater increase of both biological activities (82.28% of ACE inhibition and 64% of ABTS inhibition).

20.
Clin Transplant ; 34(8): e13899, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32383200

RESUMO

Normothermic regional perfusion (NRP) in controlled donation after circulatory death is becoming a popular method due to the favorable results of the grafts procured under this technique. This procedure requires experience, and, sometimes, the availability of extracorporeal membrane oxygenation (ECMO) machines to implement NRP is limited to tertiary hospitals. In order to provide support with NRP in controlled donation after circulatory death across the different hospitals of the Autonomous Community of Madrid, a mobile NRP team was created. In the first 18 months since its creation, the mobile NRP team participated in 33 procurements across nine different hospitals, representing 72% of all controlled donations after circulatory death in the Autonomous Community of Madrid. NRP was successfully performed in 29 (88%) cases, with a mean duration of 69 ± 27 minutes. A total of 39 kidneys, 12 livers, and 5 bilateral lungs were recovered and transplanted. None of the livers were discarded due to an elevation in transaminases during NRP. A mobile NRP team is a feasible option and, in our series, aided in the optimization and recovery of organs from donors after controlled circulatory death in centers where ECMO technology was not available.


Assuntos
Oxigenação por Membrana Extracorpórea , Obtenção de Tecidos e Órgãos , Morte , Humanos , Preservação de Órgãos , Perfusão , Projetos Piloto , Doadores de Tecidos
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