Surrogate markers for atherosclerosis in overweight subjects with atherogenic dyslipidemia: the GEMS project

Metabolic syndrome is a constellation of major risk factors for cardiovascular disease. In affected individuals with this syndrome, the independent contribution of low high-density lipoprotein-cholesterol and increased triglyceride levels to the development of atherosclerosis remains to be clarified. We assessed the relationship between these 2 parameters and several surrogate markers for atherosclerosis. One hundred and twenty overweight cases, defined as having high-density lipoprotein-cholesterol (or=75 percentile) were compared with 120 discordant overweight controls defined on lipid values (high-density lipoprotein-cholesterol >or=50 percentile and triglycerides 相似文献   

The effects of Sarconesiopsis magellanica larvae (Diptera: Calliphoridae) excretions and secretions on fibroblasts

Sarconesiopsis magellanica is a necrophagous blowfly which is relevant in both forensic and medical sciences. Previous studies regarding this species have led to understanding life-cycle, population and reproduction parameters, as well as identifying and characterising proteolytic enzymes derived from larval excretions and secretions (ES). As other studies have shown that ES proteolytic activity plays a significant role in wound healing and fibroblasts play a relevant role in granulation tissue formation during such healing, the present study was aimed at analysing the biological effect of S. magellanica larval ES on fibroblasts. ES were obtained from third-instar larvae and added to fibroblast cells at three concentrations (10, 5 and 1 μg/mL) to evaluate their behaviour. MTT assays were used for analysing cell proliferation and viability, whilst cell adhesion was measured by optical density with 10% SDS. Fibroblast migration and morphology was recorded by microscopic observation. ES did not affect fibroblast viability and induced an increase in cell proliferation; cell adhesion became reduced, whilst cell migration through extracellular matrix increased. ES also induced a decreased cell surface and morphological alterations. Changes in all the above-mentioned parameters were reduced when ES were incubated at 60 °C, probably due to protease denaturation. These results suggested that the proteases contained in S. magellanica larval ES contributed towards granulation tissue formation, increased cell migration and promoted cell proliferation. All these data support carrying out further experiments aimed at validating S. magellanica usefulness in larval therapy.     

Marrow versus peripheral blood for geno-identical allogeneic stem cell transplantation in acute myelocytic leukemia: influence of dose and stem cell source shows better outcome with rich marrow

Several studies have compared bone marrow (BM) and peripheral blood (PB) as stem cell sources in patients receiving allografts, but the cell doses infused have not been considered, especially for BM. Using the ALWP/EBMT registry, we retrospectively studied 881 adult patients with acute myelocytic leukemia (AML), who received a non-T-depleted allogeneic BM (n = 515) or mobilized PB (n = 366) standard transplant, in first remission (CR1), from an HLA-identical sibling, over a 5-year period from January 1994. The BM cell dose ranged from 0.17 to 29 x 10(8)/kg with a median of 2.7 x 10(8)/kg. The PB cell dose ranged from 0.02 to 77 x 10(8)/kg with a median of 9.3 x 10(8)/kg. The median dose for patients receiving BM (2.7 x 10(8)/kg) gave the greatest discrimination. In multivariate analyses, high-dose BM compared to PB was associated with lower transplant-related mortality (RR = 0.61; 95% CI, 0.39-0.98; P =.04), better leukemia-free survival (RR = 0.65; 95% CI, 0.46-0.91; P =.013), and better overall survival (RR = 0.64; 95% CI, 0.44-0.92; P =.016). The present study in patients with AML receiving allografts in first remission indicates a better outcome with BM as compared to PB, when the dose of BM infused is rich.     

TLR2 engagement on CD4+ T cells enhances effector functions and protective responses to Mycobacterium tuberculosis

We have previously demonstrated that mycobacterial lipoproteins engage TLR2 on human CD4⁺ T cells and upregulate TCR‐triggered IFN‐γ secretion and cell proliferation in vitro. Here we examined the role of CD4⁺ T‐cell‐expressed TLR2 in Mycobacterium tuberculosis (MTB) Ag‐specific T‐cell priming and in protection against MTB infection in vivo. Like their human counterparts, mouse CD4⁺ T cells express TLR2 and respond to TLR2 costimulation in vitro. This Th1‐like response was observed in the context of both polyclonal and Ag‐specific TCR stimulation. To evaluate the role of T‐cell TLR2 in priming of CD4⁺ T cells in vivo, naive MTB Ag85B‐specific TCR transgenic CD4⁺ T cells (P25 TCR‐Tg) were adoptively transferred into Tlr2^?/? recipient C57BL/6 mice that were then immunized with Ag85B and with or without TLR2 ligand Pam₃Cys‐SKKKK. TLR2 engagement during priming resulted in increased numbers of IFN‐γ‐secreting P25 TCR‐Tg T cells 1 week after immunization. P25 TCR‐Tg T cells stimulated in vitro via TCR and TLR2 conferred more protection than T cells stimulated via TCR alone when adoptively transferred before MTB infection. Our findings indicate that TLR2 engagement on CD4⁺ T cells increases MTB Ag‐specific responses and may contribute to protection against MTB infection.     

Delineation of EFTUD2 Haploinsufficiency‐Related Phenotypes Through a Series of 36 Patients

Mandibulofacial dysostosis, Guion‐Almeida type (MFDGA) is a recently delineated multiple congenital anomalies/mental retardation syndrome characterized by the association of mandibulofacial dysostosis (MFD) with external ear malformations, hearing loss, cleft palate, choanal atresia, microcephaly, intellectual disability, oesophageal atresia (OA), congenital heart defects (CHDs), and radial ray defects. MFDGA emerges as a clinically recognizable entity, long underdiagnosed due to highly variable presentations. The main differential diagnoses are CHARGE and Feingold syndromes, oculoauriculovertebral spectrum, and other MFDs. EFTUD2, located on 17q21.31, encodes a component of the major spliceosome and is disease causing in MFDGA, due to heterozygous loss‐of‐function (LoF) mutations. Here, we describe a series of 36 cases of MFDGA, including 24 previously unreported cases, and we review the literature in order to delineate the clinical spectrum ascribed to EFTUD2 LoF. MFD, external ear anomalies, and intellectual deficiency occur at a higher frequency than microcephaly. We characterize the evolution of the facial gestalt at different ages and describe novel renal and cerebral malformations. The most frequent extracranial malformation in this series is OA, followed by CHDs and skeletal abnormalities. MFDGA is probably more frequent than other syndromic MFDs such as Nager or Miller syndromes. Although the wide spectrum of malformations complicates diagnosis, characteristic facial features provide a useful handle.     

Factors Influencing Report of Common Mental Health Problems Among Psychologically Distressed Adults

This study investigates the sociodemographic factors associated with self-report of common mental problems by the psychologically distressed in order to gain insight into the profile of the population subgroups least likely to receive mental health support whenever needed. Data from the 2006–2008 french National Survey on Health, Health Care and Insurance, were used, measuring psychological distress based on the Mental Health Inventory MHI-5. The patterns associated with education, employment situation and living arrangement were investigated in a sample of 11,543 subjects aged 30–54 years. Men with lower educational level were found to be doubly disadvantaged, as they were more subjected to distress than those with higher educational level and at the same time less likely to report common mental problems whenever distressed. While in both genders subjects not living with a spouse and non-employed subjects were also more subjected to distress, they were more likely than the others to report common mental problems in presence of distress. The findings were discussed in terms of living conditions, stigma, mental health literacy and help-seeking behaviour. Mental health promotion programmes should aim at educating the public, and particularly men and the lower educated public, on the signs of distress and their significance.     

Systematic review of guidelines on peripheral artery disease screening

BackgroundPeripheral artery disease (PAD) screening may be performed to prevent progression of PAD or future cardiovascular disease in general. Recommendations for PAD screening have to be derived indirectly because no randomized trials comparing screening versus no screening have been performed. We performed a systematic review of guidelines to evaluate the value of PAD screening in asymptomatic adults.MethodsGuidelines in English published between January 1, 2003 and January 20, 2011 were retrieved using MEDLINE, CINAHL, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the G-I-N International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on PAD screening, were included. Two reviewers independently assessed rigor of guideline development using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. One reviewer performed full extraction of recommendations, which was validated by a second reviewer.ResultsOf 2779 titles identified, 8 guidelines were included. AGREE scores varied from 33% to 81%. Five guidelines advocated PAD screening, others found insufficient evidence for PAD screening or were against it. Measurement of the ankle-brachial index (ABI) was generally recommended for middle-aged populations with elevated cardiovascular risk levels. Those identified as having PAD are reclassified as high risk, warranting intensive preventive interventions to reduce their risk of a cardiovascular event. The underlying evidence mainly consisted of studies performed in patients with established PAD. A meta-analysis that evaluated ABI testing in the context of traditional cardiovascular risk assessment was interpreted differently.ConclusionsRecommendations on PAD screening vary across current guidelines, making the value of PAD screening uncertain. The variation seems to reflect lack of studies that show added value of detection of early PAD beyond expectant management and traditional risk assessment.