Influence of lifestyle on the course of type 1 diabetes mellitus

Type 1 diabetes (T1DM) is an autoimmune disease that requires insulin treatment from the time of diagnosis. Its clinical course depends on both genetic and environmental factors, and the lifestyle of a patient modulates their interaction. The evidence about the influence of lifestyle on the course of T1DM is increasing. In this paper, we present evidence on the relationship between lifestyle parameters and diabetes-related outcomes. We discuss the most commonly addressed factors associated with lifestyle, such as physical activity, nutrition and smoking, and those with sparse evidence in T1DM, such as socioeconomic status, sleep duration, psychological stress and illicit drugs intake.     

Preparation of Nanoparticles by Solvent Displacement Using a Novel Recirculation System

Submicron colloidal suspensions of poly(ε-caprolactone) (PCL) were prepared by the solvent displacement method, using either the conventional form or a new recirculation device. In the latter case, a process that allows the recirculation of the aqueous phase into a device, providing a continuous flow, is proposed. The influence of the organic solution injection rate and polymer concentration on mean particle size and process yield were studied for both methods. The recirculation rate was also analyzed for the recirculation system. Nanoparticles (NPs) showed mean sizes that ranged from 156 to 381. The smallest particles were obtained when recirculation rate, injection rate and polymer concentration were maximized but at the expense of the yield. The only acceptable yields (83–96%) were obtained at the lowest PCL concentration (2.5% w/v). ANOVA tests (α = 0.05) showed that the variables implicated in the recirculation system significantly affected the mean particle size and the process yield. The entrapment efficiencies of NPs prepared by the conventional method were not significantly different (α = 0.05) from those obtained by the recirculation system.     

Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

Acanthamoeba is an opportunistic pathogen in humans, whose infections most commonly manifest as Acanthamoeba keratitis or, more rarely, granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba, they are generally lengthy and/or have limited efficacy. Therefore, there is a requirement for the identification, validation, and development of novel therapeutic targets against these pathogens. Recently, RNA interference (RNAi) has been widely used for these validation purposes and has proven to be a powerful tool for Acanthamoeba therapeutics. Ergosterol is one of the major sterols in the membrane of Acanthamoeba. 3-Hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, one of the precursors for the production of cholesterol in humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which inhibit this enzyme and so are promising as chemotherapeutics. In order to validate whether this enzyme could be an interesting therapeutic target in Acanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and used to evaluate the effects induced by the inhibition of Acanthamoeba HMG-CoA. It was found that HMG-CoA is a potential drug target in these pathogenic free-living amoebae, and various statins were evaluated in vitro against three clinical strains of Acanthamoeba by using a colorimetric assay, showing important activities against the tested strains. We conclude that the targeting of HMG-CoA and Acanthamoeba treatment using statins is a novel powerful treatment option against Acanthamoeba species in human disease.     

基于晶闸管导通角控制的脉宽调制旋转阳极控制技术的设计与实验

针对X线检查大型医疗设备整机价格昂贵、维保费用高、生命周期短、场地要求严苛等问题,研究一种能够应用于教学示教及技能培训、故障演练测试的教学器具,结合旋转阳极电路的基本功能要素,涵盖高压启动、低压维持、延时保护、运转检测等基本流程,结果表明,该装置能够准确地演练实际工作环境,起到培育医疗设备维修人员检修旋转阳极时所需要的实际技能的作用,降低了实际教学成本,满足了工位数需求,增加了实践动手训练机会,提升了技能培训效果。     

A clinical trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) for treating intermediate and high-risk non-muscle invasive bladder cancer

Purpose: Ths paper reports a pilot/feasibility trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) prior to transurethral resection of bladder tumour (TURBT) for non-muscle invasive bladder cancer (NMIBC). Materials and methods: A pilot/feasibility clinical trial was performed and 15 patients with intermediate to high-risk NMIBC received HIVEC prior to TURBT. HIVEC consisting of eight weekly instillations of intravesical MMC (80?mg in 50?mL) delivered with the novel Combat BRS® system at a temperature of 43?°C for 60?min. Treatment-related adverse effects were measured and patients were followed for 2 years for disease recurrence. Results: A total of 119 HIVEC treatments occurred. Grade 1 adverse events consisted of irritative bladder symptoms (33%), bladder spasms (27%), pain (27%), haematuria (20%) and urinary tract infection (UTI; 14%). Grade 2 adverse events were bladder calcification (7%) and reduced bladder capacity (7%). No grade 3 or higher toxicity was observed. At TURBT, eight patients (53%) were complete responders (pT0) while seven (47%) were partial responders. With a median follow-up of 29 months, the 3-year cumulative incidence of recurrence was 15%. Conclusions: The Combat BRS® system achieved target bladder temperatures and delivered HIVEC with a favourable side-effect profile. Our pilot trial also provides preliminary evidence of treatment efficacy.     

Fondements physico-biologiques de la fluorescence cutanée – Revue

Fluorescence is a peculiar aspect of photoluminescence. Some intrinsic components of the skin are fluorophores. Other synthetic components are metabolized into fluorophores. These characteristics may be used for identifying some specific aspects of skin physiopathology. Recent technological evolution has provided new devices bringing sensitive and specific information from the skin. This review presents a synthesis of the progress made in the field of fluorescence and specular reflexion of incident UV light on the skin.     

Prognostic factors for recurrence of gastrointestinal bleeding due to Dieulafoy's lesion

AIM: To analyze the effectiveness of the endoscopic therapy and to identify prognostic factors for recurrent bleeding.METHODS: Retrospective study of patients with gastrointestinal bleeding secondary to Dieulafoy’s lesion (DL) from 2005 to 2011. We analyzed the demographic characteristics of the patients, risk factors for gastrointestinal bleeding, endoscopic findings, characteristics of the endoscopic treatment, and the recurrence of bleeding. We included cases in which endoscopy described a lesion compatible with Dieulafoy. We excluded patients who had potentially bleeding lesions such as angiodysplasia in other areas or had undergone other gastrointestinal endoscopic procedures.RESULTS: Twenty-nine patients with DL were identified. Most of them were men with an average age of 71.5 years. Fifty-five percent of the patients received antiaggregatory or anticoagulant therapy. The most common location for DL was the stomach (51.7%). The main type of bleeding was oozing in 65.5% of cases. In 27.6% of cases, there was arterial (spurting) bleeding, and 6.9% of the patients presented with an adherent clot. A single endoscopic treatment was applied to nine patients (31%); eight of them with adrenaline and one with argon, while 69% of the patients received combined treatment. Six patients (20.7%) presented with recurrent bleeding at a median of 4 d after endoscopy (interquartile range = 97.75). Within these six patients, the new endoscopic treatment obtained a therapeutic success of 100%. The presence of arterial bleeding at endoscopy was associated with a higher recurrence rate for bleeding (50% vs 33.3% for other type of bleeding) [P = 0.024, odds ratio (OR) = 8.5, 95% CI = 1.13-63.87]. The use of combined endoscopic treatment prevented the recurrence of bleeding (10% vs 44.4% of single treatment) (P = 0.034, OR = 0.14, 95% CI = 0.19-0.99).CONCLUSION: Endoscopic treatment of DL is safe and effective. Adrenaline monotherapy and arterial (spurting) bleeding are associated with a high rate of bleeding recurrence.     

C-Terminal Peptide of γ-Enolase Impairs Amyloid-β-Induced Apoptosis Through p75NTR Signaling

γ-Enolase acts as a neurotrophic-like factor promoting growth, differentiation, survival and regeneration of neurons. It is shown in this study to exert a protective effect against amyloid-β-peptide (Aβ)-induced neurotoxicity in rat pheochromocytoma PC12 cells. Aβ-induced toxicity was abolished in the presence of the active C-terminal peptide of γ-enolase (γ-Eno) as measured by cell viability, lactate dehydrogenase release, sub-G1 cell population, intracellular reactive oxygen species, mitochondrial functions and apoptotic morphology. γ-Eno caused downregulation of the pro-apoptotic protein Bax and upregulation of the anti-apoptotic protein Bcl-2, as well as reduced caspase-3 activation. Exposure to Aβ increased surface expression of p75 neurotrophin receptor (p75^NTR), and the increase was abolished in the presence of γ-Eno peptide. Further, pretreatment with γ-Eno suppressed the activation of mitogen-activated protein kinases p38 and Jun-N-terminal kinase, which are p75^NTR downstream effectors in apoptotic signaling. Moreover, Aβ triggered γ-enolase co-immunoprecipitation with p75^NTR as well as their strong association in the perimembrane region as shown by confocal microscopy, which further supports the interaction between these two proteins in cells insulted by Aβ peptide. Our results indicate the possible use of γ-enolase C-terminal peptide for treating or preventing Alzheimer’s disease.