3,205 research outputs found
A classification of 20-trinucleotide circular codes
No full textAbstractTrinucleotide comma-free codes and trinucleotide circular codes are two important classes of codes in code theory and theoretical biology. A trinucleotide circular code containing exactly 20 elements is called here a 20-trinucleotide circular code. In this paper, solving a combinatorial problem of hard computational complexity, we extend and improve our results of C.J. Michel, G. Pirillo, and M.A. Pirillo (2008) [14] concerning the small class of 528 self-complementary 20-trinucleotide circular codes, to the complete class of the 20-trinucleotide circular codes which contains 12,964,440 elements. A surprising relation with the symmetric group Σ4 appears but it remains unexplained so far
The orthodontist burnout
No full textObjective: The aim of this study was to assess whether the Burnout Syndrome is clearly expressed in orthodontic practice and to identify its impact in both general dentistry and orthodontics. Materials and methods: A questionnaire was administered to 366 operators in the dentistry-orthodontic field, hence a multi-factorial statistical analysis based on the multi-factorial method was carried out. Demographic data, the Maslach Burnout Inventory (MBI), divided into three subsets, Emotional Exhaustion (EE), Depersonalization (DP), and Personal Accomplishment (PA), and a specific questionnaire for orthodontists were analysed. Results: The analysis of the MBI showed that EE affects only 1/5 of the sample, DP significantly affects only 1/3 of the sample, while the RPA was reported to be low in 2/3 of the sample. General dentists were more affected from burnout as compared with orthodontists. The specific questionnaire highlighted that members of both categories had work-related stress, mostly due to management and financial issues related to the workplace. Conclusions: The research suggested that Italian orthodontists were less prone to Burnout Syndrome compared to general dentists. As life-style has a major impact on the onset of the syndrome, preventive measures and solutions could be useful in order to prevent the symptoms of the Brunout Syndrome. © 2011 Società Italiana di Ortodonzia SIDO
Applicazione della spettrometria di massa nello studio delle pneumopatie ostruttive del bambino
No full textAbstract
Background and purposes
The obstructive pulmonary diseases in the world – among which asthma and the chronic obstructive pulmonary disease (COPD) – have been growing constantly. In 2006 about 46 million persons suffered from asthma, and 9.5 millions were children; the COPD has also been growing constantly and, despite the fact that the incidence increases with age, it looks like several factors and previous childhood diseases can influence the subjects’ respiratory function and the evolution of the disease. Despite the many studies that have been carried out, it is not clear yet what are the mechanisms on which these respiratory diseases are based, and therefore further investigations must be made. Mass spectrometry, a sensitive and robust analytic technique, has found more and more applications in the clinical-diagnostic field, thanks to its capacity to determine the metabolites in the biological samples with a mass value or to identify their structure through fragmentation with extremely sensitive, specific and selective characteristics. The possibility to analyze complex blends, thanks to combination with gas or liquid chromatographic techniques, reduced analysis time, the qualitative identification but above all the quantitative dosages of several biomarkers in a single analysis, has made this technique preferable for clinical studies. Especially, besides the classical target approach used to quantify already known or presumably proper to certain pathologies specific compounds, over the past years a new type of approach has developed, the so called untargeted approach, known as “metabolomic”, which sees the study of the entire metabolic profile of a biological sample, by means of highly sensitive and precise analytic techniques, such as high resolution mass spectrometry (HMS). This approach allows the characterization of the general metabolic profile of a group of subjects with a specific pathology as compared to a group of control and extracts the discriminating variables, thanks to multivariate statistic analysis techniques. The untargeted analysis, which is not based upon prior hypotheses, can open the doors to new etiopathological hypotheses, besides helping identify the diagnostic and prognostic biomarkers. The purpose of this PhD thesis was to study the infant obstructive respiratory diseases by applying both of these approaches to urine or exhaled breath condensate (EBC) samples. The EBC is a biofluid which, given the extremely non invasive method of collecting it, represents an ideal biological matrix for studies of the kind, but, since the metabolite concentration is extremely low, is at the same time an analytically complex matrix.
Methods and results
In the first study, the HRMS metabolomic analysis of the EBC was employed to investigate upon the biochemical-metabolic profile of the EBCs of teenagers diagnosed with bronchopulmonary dysplasia (BPD)from birth as compared to a group of healthy teenagers. The samples were analyzed with the LTQ-OrbiTrap mass spectrometer and processed by means of the multivariate statistic analysis. The results have demonstrated that it is possible to discriminate the BPD group from the control group by marking out the EBC samples, obtaining a robust OPLS-DA model (R2: 0.95, Q2:0. 82), indicating how the teenagers who were affected by BPD from birth have a different biochemical-metabolic profile. The individuation of the glycerophospholipids, among the several discriminating variables, has suggested a possible involvement of the alveolar surfactant at the basis of the minor respiratory function in the BPD affected patients, even years later after the severe phase of the disease.
The second study employed the HRMS metabolomic in order to obtain a first biochemical-metabolic characterization of children with frequent bronchospasm or with wheezing in preschool age, in view of a perspective study which would help appreciate which of these children will develop asthma when growing up, and, a posteriori, consider whether prognostic biomarkers exist. The preliminary results of this part of the study have been encouraging: thanks to the analysis of the urine samples with the hybrid Q-TOF mass spectrometer associated to the UPLC, we have had a clear distinction of the subjects affected by wheezing as compared to healthy children, through an OPLSA- DA model.
The preliminary analysis has allowed to obtain a clear distinction between children who suffered from wheezing and healthy children, highlighting some discriminating molecules. The study is still ongoing since it presupposes the evaluation of the same subjects 18 and 36 months later.
The third part of the study was related to the use of the target MS and was meant to evaluate and quantify some oxidative stress indicators in EBC samples belonging to subjects affected by asthma. A UPLC-MS/MS method was developed and validated for the quantitative analysis of the dimethyl arginine, ADMA and SDMA, in samples of EBC. The analysis was conducted by means of MRM technique in quadrupole mass spectrometry associated to UPLC, with a on line sample enrichment system. The analytic system has come out robust (r2>0.992, %Bias <3% intra- CV% inter-intra assay =20%, recovery between 97 and 102%), rapid (5 minutes chromatographic run) and sensitive, also suitable for the analysis of diluted biological samples, such as the EBCs.
The quantification of these metabolites, conducted on samples of asthmatic and healthy children, has pointed out a rise of the ADMA in the EBCs of the asthmatic subjects, indicating a role of the ADMA in the tissue damage of the respiratory tract which typically characterizes the bronchial asthma.
Conclusions
This research has demonstrated that instrumentally highly sensitive mass spectrometry, which has allowed us to obtain significant information even from small quantities of samples and from extremely diluted matrixes, can be successfully applied to the study of obstructive respiratory diseases, making the follow up studies easier, and also helping medical doctors identify possible markers useful to the diagnosis and/or new therapeutic targets
The burden of hypercholesterolemia and ischemic heart disease in an ageing world
No full textDespite a general improvement in global health conditions in the last decades, cardiovascular diseases (CVDs) are still the first global cause of death and disability worldwide, with ischemic heart disease (IHD) being responsible for half of CVD deaths. Hypercholesterolemia is a major causal risk factor for IHD. Although the availability of effective cholesterol-lowering drugs largely increased in the last few years, we are still facing disparities in the awareness of dyslipidaemia as a CVD-associated risk factor and therefore in health expenditure among different world areas. Although no significant changes have been reported globally in the levels of plasma cholesterol in the last three decades, relevant differences among world areas according to their economic status can be observed. Only high-income countries have experienced an improvement in plasma lipid profile which translated into a substantial decrease in the deaths and disabilities due to IHD, whereas countries in other income groups showed no reduction or even an increase. As expected, most of the deaths for IHD attributable to high LDL-C occur in people aged 60 years and above, although significant differences can be observed according to income. Altogether these observations suggest the need for measures to reduce the gap in treating hypercholesterolemia among income groups, with special attention to women and older people
Therapy and clinical trials: aggressive statin therapy versus combined and emerging approaches
No full textHDLs, immunity, and atherosclerosis
No full textPURPOSE OF REVIEW: HDLs possess several physiological activities that may explain their antiatherosclerotic properties. Among them, the most relevant is the ability of HDL to promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion.
RECENT FINDINGS: The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis, including monocyte-macrophages, B and T lymphocytes. HDL also acts as a reservoir for a number of biologically active substances that may impact the immune system, and as the HDL composition varies to a large extent during inflammation.
SUMMARY: The understanding of how these interactions take place and how biologically active substances can be delivered to relevant targets during atherogenesis is of great interest and may provide a better understanding for the role of HDL in atherogenesis
LOX-1, OxLDL, and Atherosclerosis
No full textOxidized low-density lipoprotein (OxLDL) contributes to the atherosclerotic plaque formation and progression by several mechanisms, including the induction of endothelial cell activation and dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation. Vascular wall cells express on their surface several scavenger receptors that mediate the cellular effects of OxLDL. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the main OxLDL receptor of endothelial cells, and it is expressed also in macrophages and smooth muscle cells. LOX-1 is almost undetectable under physiological conditions, but it is upregulated following the exposure to several proinflammatory and proatherogenic stimuli and can be detected in animal and human atherosclerotic lesions. The key contribution of LOX-1 to the atherogenic process has been confirmed in animal models; LOX-1 knockout mice exhibit reduced intima thickness and inflammation and increased expression of protective factors; on the contrary, LOX-1 overexpressing mice present an accelerated atherosclerotic lesion formation which is associated with increased inflammation. In humans, LOX-1 gene polymorphisms were associated with increased susceptibility to myocardial infarction. Inhibition of the LOX-1 receptor with chemicals or antisense nucleotides is currently being investigated and represents an emerging approach for controlling OxLDL-LOX-1 mediated proatherogenic effects
Strategies for the use of nonstatin therapies
No full textPurpose of review Dyslipidaemias are a major risk factor for cardiovascular disease (CVD); in particular, high levels of low-density lipoprotein cholesterol (LDL-C) have been associated to a higher cardiovascular risk. Reducing LDL-C levels decreases the risk of coronary heart disease (CHD), and the greater the LDL-C reduction, the greater the decrease in cardiovascular risk. Although statins represent the first line lipid-lowering therapy, many patients do not reach the recommended goals or exhibit adverse side effects leading to therapy discontinuation; in addition, a significant percentage of statin-treated patients continue to experience cardiovascular events even in the presence of well controlled LDL-C levels, because of alterations in other lipid/lipoprotein classes, including triglycerides and high-density lipoprotein cholesterol.
Recent findings These conditions require further therapeutic interventions to achieve the recommended lipid goals. Several drugs have been developed to address these needs. Recent studies have shown that the association of ezetimibe with rosuvastatin or atorvastatin results in a better hypolipidaemic effect; in addition to this, PCSK9 inhibitors significantly reduce LDL-C levels and cardiovascular events.
Summary For patients who are intolerant to statins or not able to reach the recommended LDL-C levels, despite maximal tolerated dose of statin, or exhibiting additional lipid alterations, several drugs are available that can be used either in monotherapy or on top of the maximally tolerated dose of statins
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