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1.
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
2.
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
3.
Int J Food Microbiol ; 413: 110605, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308879

RESUMO

Given the increasing incidence of multidrug-resistant (MDR) Klebsiella pneumoniae infections, it is of great interest to investigate the risk of transmission associated with the prevalence of this pathogen. Some studies have described fresh raw poultry meat as a reservoir of MDR K. pneumoniae, including clinically relevant sequence types (ST) and extended-spectrum ß-lactamase (ESBL) strains, indicating possible consumer exposure. This study compared 47 MDR strains of K. pneumoniae from poultry meat and human clinical isolates to assess similarities, including analysis of antimicrobial resistance profiles and virulence factors involved in infection. In addition, several biofilm culture methods were evaluated for reproducible assessment of biofilm formation in K. pneumoniae strains. Globally, no association between strain origin and STs, hypermucoviscosity, biofilm formation or serum resistance could be found between isolates of food and clinical origin, nor an associated AMR pattern, suggesting overlapping populations. We found that LB supplemented with glucose in microaerobiosis was the best discrimination condition for biofilm formation in the active attachment biofilm cultivation model. The biofilm formation capacity was strongly dependent on culture conditions, with a strain-specific response, but only a minor increase in biofilm levels was recorded in clinical K. pneumoniae populations. Our results suggest that a similar risk of zoonosis transmission from potentially virulent foodborne strains previously observed in E. coli is also present in this high-priority pathogen. This study further confirms that foodborne isolates of K. pneumoniae pose a risk to consumers and therefore this pathogen should be included in the surveillance of foodborne pathogens with high risk of MDR infections and therapeutic failure.


Assuntos
Escherichia coli , Infecções por Klebsiella , Animais , Humanos , Klebsiella pneumoniae , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Zoonoses , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamases , Testes de Sensibilidade Microbiana
4.
RSC Appl Polym ; 2(3): 444-455, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38800514

RESUMO

Antimicrobial resistance is a threat to public health for which new treatments are urgently required. The capability of bacteria to form biofilms is of particular concern as it enables high bacterial tolerance to conventional therapies by reducing drug diffusion through the dense, exopolymeric biofilm matrix and the upregulation of antimicrobial resistance machinery. Quorum sensing (QS), a process where bacteria use diffusible chemical signals to coordinate group behaviour, has been shown to be closely interconnected with biofilm formation and bacterial virulence in many top priority pathogens including Pseudomonas aeruginosa. Inhibition of QS pathways therefore pose an attractive target for new therapeutics. We have recently reported a new series of pqs quorum sensing inhibitors (QSIs) that serve as potentiators for antibiotics in P. aeruginosa infections. The impact on biofilms of some reported QSIs was however hindered by their poor penetration through the bacterial biofilm, limiting the potential for clinical translation. In this study we developed a series of poly(ß-amino ester) (PBAE) triblock copolymers and evaluated their ability to form micelles, encapsulate a QSI and enhance subsequent delivery to P. aeruginosa biofilms. We observed that the QSI could be released from polymer micelles, perturbing the pqs pathway in planktonic P. aeruginosa. In addition, one of the prepared polymer variants increased the QSIs efficacy, leading to an enhanced potentiation of ciprofloxacin (CIP) action and therefore improved reduction in biofilm viability, compared to the non-encapsulated QSI. Thus, we demonstrate QSI encapsulation in polymeric particles can enhance its efficacy through improved biofilm penetration.

5.
Microbiol Resour Announc ; 13(4): e0119223, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38426732

RESUMO

The emergence of convergent Klebsiella pneumoniae strains showing multiresistance, characteristic of nosocomial pathotypes and hypervirulent traits typical of community-acquired isolates, makes them important models for studying K. pneumoniae pathogenesis. Here, we describe the convergent, multidrug-resistant KLEB-33 strain harboring several hypervirulence genes and make its genome available to the scientific community.

6.
ACS Appl Mater Interfaces ; 16(5): 5412-5425, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38289032

RESUMO

To tackle the emerging antibiotic resistance crisis, novel antimicrobial approaches are urgently needed. Bacterial biofilms are a particular concern in this context as they are responsible for over 80% of bacterial infections and are inherently more recalcitrant toward antimicrobial treatments. The high tolerance of biofilms to conventional antibiotics has been attributed to several factors, including reduced drug diffusion through the dense exopolymeric matrix and the upregulation of antimicrobial resistance machinery with successful biofilm eradication requiring prolonged high doses of multidrug treatments. A promising approach to tackle bacterial infections involves the use of polymer drug conjugates, shown to improve upon free drug toxicity and bioavailability, enhance drug penetration through the thick biofilm matrix, and evade common resistance mechanisms. In the following study, we conjugated the antibiotic ciprofloxacin (CIP) to a small library of biodegradable and biocompatible poly(ß-amino ester) (PBAE) polymers with varying central amine functionality. The suitability of the polymers as antibiotic conjugates was then verified in a series of assays including testing of efficacy and resistance response in planktonic Gram-positive and Gram-negative bacteria and the reduction of viability in mono- and multispecies biofilm models. The most active polymer within the prepared PBAE-CIP library was shown to achieve an over 2-fold increase in the reduction of biofilm viability in a Pseudomonas aeruginosa monospecies biofilm and superior elimination of all the species present within the multispecies biofilm model. Hence, we demonstrate that CIP conjugation to PBAEs can be employed to achieve improved antibiotic efficacy against clinically relevant biofilm models.


Assuntos
Anti-Infecciosos , Infecções Bacterianas , Humanos , Ciprofloxacina/farmacologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Polímeros/farmacologia , Biofilmes , Pseudomonas aeruginosa/fisiologia
7.
ACS Omega ; 9(26): 28008-28017, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38973904

RESUMO

Scientific interest in luminescent solar concentrators (LSCs) has reemerged mainly due to the application of semiconductor quantum dots (QDs) as highly efficient luminophores. Recently, LSCs have become attractive proposals for Building-Integrated photovoltaics (BIPV) since they could help conventional photovoltaics to improve sunlight harvesting and reduce production costs. However, most of the modern LSCs rely on heavy-metal QDs which are highly toxic and may cause environmental concerns. Additionally, their absorption spectra give them a characteristic color limiting their potential application in BIPV. Herein, we fabricated transparent and colorless LSCs by embedding nontoxic and cost-effective zinc oxide quantum dots (ZnO QDs) in a PMMA polymer matrix (ZnO-LSC), preserving the QD optical properties and PMMA transparency. The synthesized colloidal ZnO QDs have an average size of 5.5 nm, a hexagonal wurtzite crystalline structure, a broad yellow photoluminescent signal under ultraviolet excitation, and are highly visibly transparent at the employed concentrations (>95% in wavelengths above 400 nm). The optical characterization of the fabricated ZnO-LSCs showed a good visible transparency of 80.3% average visible transmission (AVT), with an LSC concentration factor (C) of 1.02. An optimal device (ZnO-LSC-O) could reach a C value of 2.66 with the combination of optical properties of colloidal ZnO QDs and PMMA. Finally, simulations of the performance of silicon solar cells coupled to the fabricated and optimal LSCs under standard AM 1.5G illumination were performed employing the software COMSOL Multiphysics. The fabricated ZnO-LSC achieved a simulated maximum power conversion efficiency (PCE) of 3.80%, while the optimal ZnO-LSC-O reached 5.45%. Also, the ZnO-LSC generated a maximum power of 15.02 mW and the ZnO-LSC-O generated 40.33 mW, employing the same active area as the simulated solar cell directly illuminated, which generated 14.39 mW. These results indicate that the ZnO QD-based LSCs may be useful as transparent photovoltaic windows for BIPV applications.

8.
Ambio ; 53(9): 1251-1261, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38652237

RESUMO

Expanding in both scope and scale, ecosystem restoration needs to embrace complex social-ecological dynamics. To help scientists and practitioners navigate ever new demands on restoration, we propose the "social-ecological ladder of restoration ambition" as a conceptual model to approach dynamically shifting social and ecological restoration goals. The model focuses on three dynamic aspects of restoration, namely degrading processes, restoration goals and remedial actions. As these three change through time, new reinforcing and balancing feedback mechanisms characterize the restoration process. We illustrate our model through case studies in which restoration has become increasingly ambitious through time, namely forest landscape restoration in Rwanda and grassland restoration in Germany. The ladder of restoration ambition offers a new way of applying social-ecological systems thinking to ecosystem restoration. Additionally, it raises awareness of social-ecological trade-offs, power imbalances and conflicting goals in restoration projects, thereby laying an important foundation for finding more practicable and fairer solutions.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Conservação dos Recursos Naturais/métodos , Alemanha , Ruanda , Florestas , Pradaria , Recuperação e Remediação Ambiental/métodos , Modelos Teóricos
9.
Rev Esp Cardiol (Engl Ed) ; 77(7): 539-546, 2024 Jul.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38191054

RESUMO

INTRODUCTION AND OBJECTIVES: Hypercoagulability and thromboembolism are processes that arise from severe acute respiratory syndrome coronavirus 2 infection and are responsible for a high degree of coronavirus disease 2019 (COVID-19)-related morbidity and mortality. This study sought to assess the effect of antiplatelet drugs on COVID-19 severity (risk of hospitalization and mortality), susceptibility to severe acute respiratory syndrome coronavirus 2 infection, and progression to severe COVID-19. METHODS: We conducted a population-based case-control study in a northwestern region of Spain in 2020. The study involved 3060 participants with a positive polymerase chain reaction test who were hospitalized, 26 757 participants with a positive polymerase chain reaction test who were not hospitalized, and 56 785 healthy controls. RESULTS: Triflusal seemed to be associated with a significant increase in risk of hospitalization (aOR, 1.97; 95%CI, 1.27-3.04) and susceptibility to infection (OR, 1.45; 95%CI, 1.07-1.96). It also appeared to lead to a nonsignificant increase in the risk of mortality (OR, 2.23; 95%CI, 0.89-5.55) and/or progression to more severe disease stages (OR, 1.42; 95%CI, 0.8-2.51). Aspirin seemed to be associated with a statistically significant decrease in susceptibility to severe acute respiratory syndrome coronavirus 2 infection (OR, 0.92; 95%CI, 0.86-0.98). CONCLUSIONS: Triflusal use appears to increase the risk of susceptibility to COVID-19 infection and an even higher risk of hospitalization, whereas the other antiplatelets could be associated with a reduction in the risk of the various outcomes or have no effect on risk. These findings could support reconsideration of triflusal prescription in COVID-19 pandemic situations.


Assuntos
COVID-19 , Progressão da Doença , Hospitalização , Inibidores da Agregação Plaquetária , Índice de Gravidade de Doença , Humanos , COVID-19/epidemiologia , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Feminino , Espanha/epidemiologia , Estudos de Casos e Controles , Pessoa de Meia-Idade , Idoso , Hospitalização/estatística & dados numéricos , SARS-CoV-2 , Suscetibilidade a Doenças , Tratamento Farmacológico da COVID-19 , Salicilatos/uso terapêutico , Adulto , Aspirina/uso terapêutico
10.
Eur Heart J Digit Health ; 5(1): 9-20, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38264693

RESUMO

Aims: To evaluate the impact of an outpatient care management programme that includes a clinician-to-clinician e-consultation on delay time in care, hospital admissions, and mortality in a high-risk group of patients with heart failure (HF) and previous episodes of HF hospitalization (HFH). Methods and results: We selected 6444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4851 were attended in e-consult, and 2230 had previous HFH. Using an interrupted time series regression model, we analysed the impact of incorporating e-consult into the healthcare model in the group of patients with HFH and evaluated the elapsed time to cardiology care, HF, cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). In the group of patients with HFH, the introduction of e-consult substantially decreased waiting times to cardiology care (8.6 [8.7] vs. 55.4 [79.9] days, P < 0.001). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [95%CI]: 0.837 [0.840-0.833]), 0.900 [0.862-0.949] for CV and 0.699 [0.678-0.726] for all-cause hospitalizations. There was also lower mortality (iRR [95%CI]: 0.715 [0.657-0.798] due to HF, 0.737 [0.764-0.706] for CV and 0.687 [0.652-0.718] for all-cause). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH. Conclusion: In patients with HFH, an outpatient care programme that includes an e-consult significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year.

11.
Ambio ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093372

RESUMO

Human-driven land use change can result in unequitable outcomes in the provision and appropriation of ecosystem services (ES). To better address equity-related effects of land use change in decision-making, analyses of land use and ES changes under different land use management alternatives should incorporate ecological and social information and take a disaggregated approach to ES analysis. Because such approaches are still scarce in the literature, we present a generalized social-ecological approach to support equitable land use decision-making (in terms of process and outcomes) and an example of its application to a case study in southwestern Ethiopia. We propose a six-step approach that combines scenario planning with equity-focused, disaggregated analyses of ES. Its application in our study area made equity-related effects of land use change explicit through the recognition of different beneficiary groups, value types, and spatial locations. We recommend the application of our approach in other contexts, especially in the Global South.

12.
Obes Surg ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093385

RESUMO

BACKGROUND: The partial diversion of intestinal contents facilitates achieving and maintaining weight loss and improving glycemic control in patients with obesity and with or without T2DM. The purpose of this study is to report our experience and 1-year follow-up with novel modification of SADI-S. METHODS: This study is a part of a multicentric trial of patients that underwent primary side-to-side duodeno-ileostomy and sleeve gastrectomy (SG) with GT metabolic solutions magnetic anastomosis system. Feasibility, safety, and initial efficacy were evaluated. RESULTS: The mean age of the patients included was 48 ± 8.75 years and the preoperative BMI was 43.32 ± 2.82 kg/m2. The complications were present in 30% of patients. The anastomosis patency was confirmed by the passage of radiological contrast under fluoroscopy at a mean of 17 days (17-29 days), and the mean expulsion time was 42 days (32-62). The mean diameter of the anastomosis after the magnet expulsion was 13.8 × 11.4 mm. The percentage of total weight lost at 1 year was 38.68 ± 8.48% (p < 0.001). The percentage of excess weight loss 82.5 ± 18.44% (p < 0.001) and improvements in glucose profiles were observed. Mean baseline HbA1c 5.77 ± 0.31% was reduced to 5.31 ± 0.26% (p < 0.024). CONCLUSIONS: Latero-lateral duodeno-ileostomy + SG with magnetic duodenal bipartition is afeasible and reasonably safe technique and induces weight loss in patients with obesity and improvement of glycemic control. This modification could be considered as an option to standard SADI-S or as a first step in two stages procedure. However, larger studies are needed. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: #NCT05322122.

13.
Circ Cardiovasc Imaging ; 17(1): e016206, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38205656

RESUMO

BACKGROUND: Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia. METHODS: The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy. RESULTS: One hundred and four patients were enrolled. Median age was 53.3 (46.2-59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up, which is -4.6% (-7.7% to -1.9%; P<0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9-22.3] to 8.0 [6.4-10.6]; -6.6%; P<0.001) was found. A greater PB (ß, 0.36 [0.13-0.59]; P=0.002) and a higher proportion of unstable core (ß, 0.15 [0.08-0.22]; P<0.001) were significantly related to PB regression. CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.


Assuntos
Anticorpos Monoclonais Humanizados , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Placa Aterosclerótica , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/complicações , Hipercolesterolemia/induzido quimicamente , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , LDL-Colesterol/uso terapêutico , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Resultado do Tratamento
14.
J Med Chem ; 67(2): 1008-1023, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38170170

RESUMO

Pseudomonas aeruginosa is one of the top priority pathogens that requires immediate attention according to the World Health Organisation (WHO). Due to the alarming shortage of novel antimicrobials, targeting quorum sensing (QS), a bacterial cell to cell signaling system controlling virulence, has emerged as a promising approach as an antibiotic adjuvant therapy. Interference with the pqs system, one of three QS systems in P. aeruginosa, results in reduction of bacterial virulence gene expression and biofilm maturation. Herein, we report a hit to lead process to fine-tune the potency of our previously reported inhibitor 1 (IC50 3.2 µM in P. aeruginosa PAO1-L), which led to the discovery of 2-(4-(3-((6-chloro-1-isopropyl-1H-benzo[d]imidazol-2-yl)amino)-2-hydroxypropoxy)phenyl)acetonitrile (6f) as a potent PqsR antagonist. Compound 6f inhibited the PqsR-controlled PpqsA-lux transcriptional reporter fusion in P. aeruginosa at low submicromolar concentrations. Moreover, 6f showed improved efficacy against P. aeruginosa CF isolates with significant inhibition of pyocyanin, 2-alkyl-4(1H)-quinolones production.


Assuntos
Infecções por Pseudomonas , Quinolonas , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Percepção de Quorum , Biofilmes , Quinolonas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/metabolismo , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Imidazóis/metabolismo , Pseudomonas aeruginosa/metabolismo , Proteínas de Bactérias , Fatores de Virulência
15.
J Gastrointest Surg ; 28(6): 923-932, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38574966

RESUMO

BACKGROUND: Sleeve gastrectomy (SG) is one of the most commonly performed bariatric surgeries. SG treats type 2 diabetes mellitus better than several drugs. The mechanisms that underlie this phenomenon are not clear. This study proposed that somatostatin (SST) isoforms SST-14 and SST-28 are key in the carbohydrate after SG. METHODS: Surgeries were performed on 3 groups of Wistar rats: the fasting, surgery control, and SG groups. Plasma levels of glucose, insulin, SST-14, and SST-28 were measured at 2 survival periods after surgery. Islet SST receptor (SSTR) and cell populations were studied. We performed a pasireotide (SST-28 analogue) infusion assay in another group of rats to confirm the influence of SST-28 plasma levels on the delta-cell population. RESULTS: This study found an elevation in the insulin response after SG in animals but a decrease in the insulin response over the long term with a loss of beta-cell mass. An increase in duodenal SST-28-producing cells in the duodenum and a loss of pancreatic SST-14-producing cells were observed after SG in animals but not in controls. The expression of SSTR type 5 in delta-cell populations from each group and the ability of the pasireotide infusion assay to decrease the delta-cell population indicated the effect of SST-28 plasma levels on delta-cell maintenance. CONCLUSION: After SG initiates a compensatory response in the duodenum, beta-cell mass is depleted after loss of the brake that regulates SST-14 at the paracrine level in a nonobese, normoglycemic rat model. This was an experimental model, with no clinical translation to the human clinic, with a preliminary importance regarding new pathophysiologic perspectives or pathways.


Assuntos
Glicemia , Gastrectomia , Insulina , Ratos Wistar , Receptores de Somatostatina , Somatostatina , Animais , Somatostatina/análogos & derivados , Gastrectomia/métodos , Ratos , Masculino , Receptores de Somatostatina/metabolismo , Glicemia/metabolismo , Insulina/sangue , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Duodeno/metabolismo , Duodeno/cirurgia
16.
Lancet Diabetes Endocrinol ; 12(9): 643-652, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39098315

RESUMO

BACKGROUND: Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. METHODS: SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. FINDINGS: Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. INTERPRETATION: Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. FUNDING: Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.


Assuntos
Aterosclerose , Hiperlipoproteinemia Tipo II , Humanos , Masculino , Feminino , Hiperlipoproteinemia Tipo II/epidemiologia , Espanha/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Aterosclerose/epidemiologia , Idoso , Fatores Sexuais , Heterozigoto , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Seguimentos
17.
Schizophr Bull Open ; 4(1): sgad008, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39145333

RESUMO

Background and Hypothesis: It is argued that availability of diagnostic models will facilitate a more rapid identification of individuals who are at a higher risk of first episode psychosis (FEP). Therefore, we developed, evaluated, and validated a diagnostic risk estimation model to classify individual with FEP and controls across six countries. Study Design: We used data from a large multi-center study encompassing 2627 phenotypically well-defined participants (aged 18-64 years) recruited from six countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions study. To build the diagnostic model and identify which of important factors for estimating an individual risk of FEP, we applied a binary logistic model with regularization by the least absolute shrinkage and selection operator. The model was validated employing the internal-external cross-validation approach. The model performance was assessed with the area under the receiver operating characteristic curve (AUROC), calibration, sensitivity, and specificity. Study Results: Having included preselected 22 predictor variables, the model was able to discriminate adults with FEP and controls with high accuracy across all six countries (rangesAUROC = 0.84-0.86). Specificity (range = 73.9-78.0%) and sensitivity (range = 75.6-79.3%) were equally good, cumulatively indicating an excellent model accuracy; though, calibration slope for the diagnostic model showed a presence of some overfitting when applied specifically to participants from France, the UK, and The Netherlands. Conclusions: The new FEP model achieved a good discrimination and good calibration across six countries with different ethnic contributions supporting its robustness and good generalizability.

18.
Rev. Esc. Enferm. USP ; 56: e20220308, 2022. tab
Artigo em Inglês | LILACS, BDENF | ID: biblio-1422739

RESUMO

ABSTRACT Objective: To analyze the transition of care from the perspective of cancer patients, in a Southern Brazil hospital, correlating perspectives with sociodemographic and clinical characteristics. Method: Cross-sectional study using the Care Transitions Measure (CTM) with cancer patients undergoing clinical or surgical treatment following hospital discharge. Data collection was completed by telephone, between June and September 2019. Data analysis was performed using descriptive and inferential statistics. Results: The average CTM score was 74.1, which was considered satisfactory. The CTM factors: understanding about medications (83.3) and preparation for self-management (77.7) were deemed satisfactory; while: secured preferences (69.4) and care plan (66.1) were unsatisfactory for an effective and safe care transition. No statistically significant difference was found between sociodemographic variables and the CTM. Among the clinical variables, primary cancer and the secured preferences factor showed a significant difference (p = 0.044). Conclusion: The transition from hospital care to the community was considered satisfactory in the overall assessment.


RESUMO Objetivo: Analisar a transição do cuidado na perspectiva de pacientes oncológicos, em um hospital do sul do Brasil, correlacionando perspectivas com características sociodemográficas e clínicas. Método: Estudo transversal utilizando o Care Transitions Measure (CTM) com pacientes oncológicos em tratamento clínico ou cirúrgico após a alta hospitalar. A coleta de dados foi realizada por telefone entre junho e setembro de 2019. A análise dos dados foi realizada por meio de estatística descritiva e inferencial. Resultados: A pontuação média do CTM de 74,1, foi considerada satisfatória. Os fatores CTM: compreensão sobre medicamentos (83,3) e preparo para autocuidado (77,7) foram satisfatórios, enquanto: preferências garantidas (69,4) e plano de cuidados (66,1) foram insatisfatórios para uma transição de cuidado efetiva e segura. Não foi encontrada diferença estatisticamente significativa entre as variáveis sociodemográficas e o CTM. Entre as variáveis clínicas, o câncer primário e o fator de preferências garantidas apresentaram diferenças significativas (p = 0,044). Conclusão A transição da assistência hospitalar para a comunidade foi considerada satisfatória na avaliação geral.


RESUMEN Objetivo: Analizar la transición de la atención desde la perspectiva de los pacientes con cáncer en un hospital del sur de Brasil, correlacionando las perspectivas con las características sociodemográficas y clínicas. Método: Estudio transversal utilizando el Care Transitions Measure (CTM) con pacientes oncológicos en tratamiento clínico o quirúrgico tras el alta hospitalaria. La recogida de datos se realizó por teléfono entre junio y septiembre de 2019. Los datos se analizaron mediante estadísticas descriptivas e inferenciales. Resultados: La puntuación media de la CTM, 74,1, se consideró satisfactoria. Los factores de la CTM: comprensión sobre la medicación (83,3) y preparación para el autocuidado (77,7) fueron satisfactorios, mientras que: preferencias garantizadas (69,4) y plan de cuidados (66,1) fueron insatisfactorios para una transición de cuidados eficaz y segura. No se encontraron diferencias estadísticamente significativas entre las variables sociodemográficas y las medidas de CTM. Entre las variables clínicas, el cáncer primario y el factor de preferencias garantizadas mostraron diferencias significativas (p = 0,044). Conclusión: La transición de la atención hospitalaria a la comunitaria se consideró satisfactoria en la evaluación global. (175 palavras)


Assuntos
Segurança do Paciente , Continuidade da Assistência ao Paciente , Cuidado Transicional , Neoplasias
19.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1387564

RESUMO

Resumen: Introducción: Los pacientes con insuficiencia cardiaca (IC) seguidos por los servicios de medicina interna son más ancianos y presentan más comorbilidades asociadas. Por ello presentan un riesgo elevado de ingreso hospitalario y de mortalidad. En este estudio se evaluaron los objetivos alcanzados en términos de ingresos, visitas a urgencias y mortalidad, así como la actividad realizada para conseguirlos, en una unidad dirigida a este perfil de pacientes y caracterizada por una atención integral y continuada (programa UMIPIC). Métodos: Se analizaron retrospectivamente los datos de los 329 pacientes con IC atendidos en la unidad de IC, modelo UMIPIC, del servicio de Medicina Interna del Hospital de Lugo. Se recogieron desde enero del 2020, hasta diciembre 2020 los ingresos por IC y totales, las visitas a urgencias por IC y totales, la mortalidad, las consultas realizadas, y los rescates realizados en régimen de hospital de día (HDD). Resultados: Se recogieron 108 ingresos, 40 por IC y 68 por otras causas, 99 visitas a urgencias, 25 por IC y 74 por otras causas. Se produjeron 57 fallecimientos, 37 fueron en el hospital (15 por IC, 12 por otras causas) y 20 fueron extra-hospitalarios. Se realizaron 1179 consultas médico-enfermería, 1554 consultas de enfermería exclusiva y se realizaron 406 tratamientos en HDD. Conclusiones: Los estándares de actividad y resultados conseguidos pueden ser orientativos de la actividad a desarrollar en una unidad de IC modelo UMIPIC.


Abstract: Introduction: Patients with heart failure (HF) followed by internal medicine services are older and have more associated comorbidities. For this reason, they present a high risk of hospital admission and mortality. In this study, the objectives achieved in terms of admissions, emergency room visits and mortality, as well as the activity carried out to achieve them, were evaluated in a unit aimed at this patient profile and characterized by comprehensive and continuous care (UMIPIC program). Methods: The data of the 329 patients with HF treated in the HF unit, model UMIPIC, of the Internal Medicine service of the Hospital de Lugo, were retrospectively analyzed. From January 2020, to December 2020, total and HF admissions, total and HF emergency visits, mortality, consultations made, and rescues performed in a day hospital (HDD) were collected. Results: 108 admissions were collected, 40 for HF and 68 for other causes, 99 visits to the emergency room, 25 for HF and 74 for other causes. There were 57 deaths, 37 were in the hospital (15 due to HF, 12 due to other causes) and 20 were extra-hospital. 1179 medical-nursing consultations were carried out, 1554 exclusive nursing consultations and 406 treatments were carried out in HDD. Conclusions: The activity standards and results achieved can be indicative of the activity to be carried out in an IC model UMIPIC unit.


Resumo: Introdução: Pacientes com insuficiência cardíaca (IC) acompanhados por serviços de medicina interna são mais velhos e apresentam mais comorbidades associadas. Portanto, apresentam alto risco de admissão hospitalar e mortalidade. Neste estudo, os objetivos alcançados em termos de internações, atendimentos de emergência e mortalidade, bem como a atividade desenvolvida para os atingir, foram avaliados numa unidade dirigida a este perfil de doente e caracterizada por um atendimento integral e contínuo (programa UMIPIC). Métodos: Foram analisados ​​retrospectivamente os dados dos 329 pacientes com IC atendidos na unidade de IC, modelo UMIPIC, do serviço de Clínica Médica do Hospital de Lugo. No período de janeiro de 2020 a dezembro de 2020, foram coletadas internações totais e por IC, atendimentos totais e de emergência por IC, mortalidade, consultas realizadas e resgates realizados em regime de hospital-dia (HDD). Resultados: foram coletadas 108 internações, sendo 40 por IC e 68 por outras causas, 99 visitas ao pronto-socorro, 25 por IC e 74 por outras causas. Ocorreram 57 óbitos, 37 foram hospitalares (15 por IC, 12 por outras causas) e 20 extra-hospitalares. Foram realizadas 1179 consultas médico-enfermagem, 1554 consultas exclusivas de enfermagem e 406 atendimentos em HDD. Conclusões: Os padrões de atividade e os resultados alcançados podem ser indicativos da atividade a ser desenvolvida numa unidade IC modelo UMIPIC.

20.
Rev. colomb. ortop. traumatol ; 33(S3): 17-24, 2019. ilus.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1381521

RESUMO

El hallux valgus juvenil e infantil es una condición usualmente hereditaria y raramente sintomática en este grupo de edad, puede volverse sintomática por el inadecuado uso del calzado; el tratamiento debe comenzar con modificaciones en el calzado y el estilo de vida; el tratamiento quirúrgico está reservado para aquellos casos en que el tratamiento no quirúrgico ha fallado. No hay un único procedimiento que resuelva todas las condiciones y para tomar la decisión debe tenerse en cuenta la presencia de fisis abiertas. La cirugía esta basada en osteotomías, procedimientos de tejidos blandos o artrodesis.


Juvenile and infantile hallux valgus is usually a hereditary condition and rarely symptomatic in this age group. It can become symptomatic by the use of footwear, and treatment must begin with changes in footwear and lifestyle, Surgical treatment is reserved for those cases in which non-surgical treatment has failed. There is no single procedure that resolves all the conditions, and the presence of the open physis must be taken into account to make the decision. The surgery is based on osteotomies, soft tissue procedures, or arthrodesis.


Assuntos
Humanos , Hallux Valgus , Terapêutica , Criança , Adolescente
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