RESUMO
Brevinin-2-related peptide (BR-II), a novel antimicrobial peptide isolated from the skin of frog, Rana septentrionalis, shows a broad spectrum of antimicrobial activity with low haemolytic activity. It has also been shown to have antiviral activity, specifically to protect cells from infection by HIV-1. To understand the active conformation of the BR-II peptide in membranes, we have investigated the interaction of BR-II with the prokaryotic and eukaryotic membrane-mimetic micelles such as sodium dodecylsulfate (SDS) and dodecylphosphocholine (DPC), respectively. The interactions were studied using fluorescence and circular dichroism (CD) spectroscopy. Fluorescence experiments revealed that the N-terminus tryptophan residue of BR-II interacts with the hydrophobic core of the membrane mimicking micelles. The CD results suggest that interactions with membrane-mimetic micelles induce an α-helix conformation in BR-II. We have also determined the solution structures of BR-II in DPC and SDS micelles using NMR spectroscopy. The structural comparison of BR-II in the presence of SDS and DPC micelles showed significant conformational changes in the residues connecting the N-terminus and C-terminus helices. The ability of BR-II to bind DNA was elucidated by agarose gel retardation and fluorescence experiments. The structural differences of BR-II in zwitterionic versus anionic membrane mimics and the DNA binding ability of BR-II collectively contribute to the general understanding of the pharmacological specificity of this peptide towards prokaryotic and eukaryotic membranes and provide insights into its overall antimicrobial mechanism.
Assuntos
Proteínas de Anfíbios/química , Fármacos Anti-HIV/química , Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/química , Proteínas de Ligação a DNA/química , DNA/metabolismo , Bicamadas Lipídicas/química , Modelos Moleculares , Proteínas de Anfíbios/metabolismo , Animais , Fármacos Anti-HIV/metabolismo , Anti-Infecciosos/metabolismo , Peptídeos Catiônicos Antimicrobianos/metabolismo , Dicroísmo Circular , DNA/química , Proteínas de Ligação a DNA/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas/metabolismo , Micelas , Conformação Molecular , Ressonância Magnética Nuclear Biomolecular , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Fosforilcolina/metabolismo , Ranidae/metabolismo , Pele/química , Dodecilsulfato de Sódio/química , Dodecilsulfato de Sódio/metabolismo , Solubilidade , Espectrometria de Fluorescência , Tensoativos/química , Tensoativos/metabolismoRESUMO
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterized by relapsing-remitting or progressive neurologic symptoms and focal white matter lesions. The hallmark of the disease is the dissemination of CNS lesions in space and time, which is defined by the McDonald criteria. MRI is an essential diagnostic and prognostic biomarker for MS which can evaluate the entire CNS. MS mimics must be excluded before a diagnosis of MS is made.
Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Imageamento por Ressonância Magnética/métodos , EncéfaloRESUMO
Background and Objectives: To compare long-term seizure control in patients with long-term VNS (vagal nerve stimulator) stimulation (VNS-on) with those who discontinued VNS after >3 years (VNS-off). Methods: Patients with refractory epilepsy with VNS therapy for >3 years (and follow-up for >2 years after VNS discontinuation for VNS-off patients) were included. Patients with brain surgery <3 years after VNS were excluded. We compared the percentage of patients with ≥50% seizure reduction (50% responder rate) and change in seizure frequency within and between groups in follow-up. Results: Thirty-three VNS-on and 16 VNS-off patients were evaluated. VNS-on patients underwent stimulation for 9.7 years (mean). VNS-off patients had VNS treatment for 6.5 years (mean), discontinued treatment, then had additional 8.0 years (mean) follow-up. 50% responder rates were similar between groups (VNS-on: 54.5% vs VNS-off at last-on: 37.5%, p = 0.26; vs VNS-off at the last follow-up: 62.5%, p = 0.60). VNS-on patients had a significant reduction in seizure frequency at the last follow-up compared with baseline (median [Mdn] = -4.5 seizures/month, interquartile range [IQR] = 14.0, 56% reduction, p = 0.013). VNS-off patients also showed significant seizure reduction while still continuing VNS therapy (Mdn = -1.0 seizures/month, IQR = 13.0, 35% reduction, p = 0.020) and, after discontinuing therapy, at the last follow-up compared with baseline (Mdn = -3.2, IQR = 11.0, 52% reduction, p = 0.020). The 2 groups were comparable in seizure frequency change both at the last-on visit (absolute change, p = 0.62; relative change, p = 0.50) at the last follow-up (absolute change, p = 0.67; relative change, p = 0.76). Discussion: Patients who discontinued VNS therapy and those who continued therapy had similar response during active treatment and similar long-term outcomes, suggesting that factors such as the natural disease course and/or medication treatment strongly affect long-term outcomes.
RESUMO
BACKGROUND: Previous work assessing the frequency of adverse events in emergency medicine has been limited. The emergency department (ED) provides an initial point of care for millions of patients. Given the volume of patient encounters and the complexity of medical conditions treated in the ED, it is necessary to determine the system-based issues and associated contributing factors impacting patient safety. OBJECTIVES: The aim of this retrospective study were to use root cause analysis reports of adverse events occurring in Veterans Health Administration EDs to understand the range of events that were happening and to determine the primary causes of these events as well as actions to prevent them. METHODS: Retrospective safety reports from EDs from Veterans Health Administration medical centers across the nation for a 2-year period (2015-2016) were coded by event type, root cause, and recommended actions. RESULTS: One hundred forty-four cases were included for analysis. The most common adverse events were as follows: delays in care (n = 38, 26.4%), elopements (n = 21, 14.6%), suicide attempts and deaths by suicide (n = 15, 10.4%), inappropriate discharges (n = 15, 10.4%), and errors in following procedures (n = 14, 9.7%). Overall, the most common root cause categories leading to adverse events were knowledge/educational deficits (11.4%), policies/procedures needing improvement (11.1%), and lack of standardized policies/procedures (9.4%). DISCUSSION: Root cause analysis reports are a useful tool to determine the primary systems-based factors of common adverse events in the ED. Recommendations made in this article for addressing these root causes and potentially ameliorating these events will be useful to EDs and related health systems.
Assuntos
United States Department of Veterans Affairs , Saúde dos Veteranos , Serviço Hospitalar de Emergência , Humanos , Estudos Retrospectivos , Análise de Causa Fundamental , Estados UnidosRESUMO
OBJECTIVE: Dietary supplements and alternative therapies are commercialized as a panacea for obesity/weight gain as a result of the minimal regulatory requirements in demonstrating efficacy. These products may indirectly undermine the value of guideline-driven obesity treatments. Included in this study is a systematic review of the literature of purported dietary supplements and alternative therapies for weight loss. METHODS: A systematic review was conducted to evaluate the efficacy of dietary supplements and alternative therapies for weight loss in participants aged ≥18 years. Searches of Medline (PubMed), Cochrane Library, Web of Science, CINAHL, and Embase (Ovid) were conducted. Risk of bias and results were summarized qualitatively. RESULTS: Of the 20,504 citations retrieved in the database search, 1,743 full-text articles were reviewed, 315 of which were randomized controlled trials evaluating the efficacy of 14 purported dietary supplements, therapies, or a combination thereof. Risk of bias and sufficiency of data varied widely. Few studies (n = 52 [16.5%]) were classified as low risk and sufficient to support efficacy. Of these, only 16 (31%) noted significant pre/post intergroup differences in weight (range: 0.3-4.93 kg). CONCLUSIONS: Dietary supplements and alternative therapies for weight loss have a limited high-quality evidence base of efficacy. Practitioners and patients should be aware of the scientific evidence of claims before recommending use.
Assuntos
Terapias Complementares , Redução de Peso , Adolescente , Adulto , Suplementos Nutricionais , Humanos , Obesidade/terapiaRESUMO
OBJECTIVE: Bisphosphonate-related osteonecrosis of the jaws is a rare, but morbid, condition. We present the clinical and imaging features of 19 patients. METHODS: A review of 19 bisphosphonate-related osteonecrosis patients was performed. Patient demographics, diagnosis, dental procedures, symptoms and clinical findings, location and pattern of involvement, and presence of fractures, sequestra, and fistulae were documented. RESULTS: Patients included 14 women and 5 men aged 48 to 80 years. Diagnoses included breast carcinoma (n = 11), multiple myeloma (n = 4), osteoporosis (n = 4), prostate carcinoma (n = 2), and lymphoma (n = 1). Seventeen patients received intravenous and 2 received oral bisphosphonates for 2 to 5 years. Bone involvement was noted in the mandible (74%), maxilla (16%), and both (10%). A lytic and sclerotic pattern was most common (58%). Additional findings included fractures (n = 5), sequestra (n = 4), and oroantral fistulae (n = 2). CONCLUSIONS: Bisphosphonate-related osteonecrosis is a rare, but morbid, condition, and imaging features can mimic other conditions. It is important for the radiologist to consider this entity in the appropriate clinical setting.