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The mechanisms governing adipose tissue macrophage (ATM) metabolic adaptation during diet-induced obesity (DIO) are poorly understood. In obese adipose tissue, ATMs are exposed to lipid fluxes, which can influence the activation of specific inflammatory and metabolic programs and contribute to the development of obesity-associated insulin resistance and other metabolic disorders. In the present study, we demonstrate that the membrane ATP-binding cassette g1 (Abcg1) transporter controls the ATM functional response to fatty acids (FAs) carried by triglyceride-rich lipoproteins, which are abundant in high-energy diets. Mice genetically lacking Abcg1 in the myeloid lineage presented an ameliorated inflammatory status in adipose tissue and reduced insulin resistance. Abcg1-deficient ATMs exhibited a less inflammatory phenotype accompanied by a low bioenergetic profile and modified FA metabolism. A closer look at the ATM lipidome revealed a shift in the handling of FA pools, including a redirection of saturated FAs from membrane phospholipids to lipid droplets, leading to a reduction in membrane rigidity and neutralization of proinflammatory FAs. ATMs from human individuals with obesity presented the same reciprocal relationship between ABCG1 expression and this inflammatory and metabolic status. Abolition of this protective, anti-inflammatory phenotype in Abcg1-deficient ATMs was achieved through restoration of lipoprotein lipase (Lpl) activity, thus delineating the importance of the Abcg1/Lpl axis in controlling ATM metabolic inflammation. Overall, our study identifies the rewiring of FA pools by Abcg1 as a major pathway orchestrating ATM plasticity and insulin resistance in DIO. Editor's summary: Lipid fluxes in adipose tissue can promote inflammation in obesity, but how this occurs is not clear. Dahik et al. show that the ATP-binding cassette G1 (ABCG1) on adipose tissue macrophages controls their inflammatory response to the abundant circulating saturated fatty acids present in obesity. Obese mice with myeloid-specific Abcg1 knockout showed reduced signs of inflammation, fatty acid metabolism, and lipid-associated macrophages, relationships also mirrored in human samples. The authors suggest that these results are attributable to a rerouting of saturated fatty acids from the membrane to lipid droplets, where they are neutralized. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Aims: To determine the predictability of the MARKO questionnaire and/or its domains, individually or in combination with other markers and characteristics (age, gender, smoking history, lung function, 6-min walk test (6 MWT), exhaled breath temperature (EBT), and hsCRP for the incident chronic obstructive pulmonary disease (COPD) in subjects at risk over 2 years follow-up period). Participants and Methods: Patients, smokers/ex-smokers with >20 pack-years, aged 40-65 years of both sexes were recruited and followed for 2 years. After recruitment and signing the informed consent at the GP, a detailed diagnostic workout was done by the pulmonologist; they completed three self-assessment questionnaires--MARKO, SGRQ and CAT, detailed history and physical, laboratory (CBC, hsCRP), lung function tests with bronchodilator and EBT. At the 2 year follow-up visit they performed: the same three self-assessment questionnaires, history and physical, lung function tests and EBT. Results: A sample of 320 subjects (41.9% male), mean (SD) age 51.9 (7.4) years with 36.4 (17.4) pack-years of smoking was reassessed after 2.1 years. Exploratory factor analysis of MARKO questionnaire isolated three distinct domains (breathlessness and fatigue, "exacerbations", cough and expectorations). We have determined a rate for incident COPD that was 4.911/100 person-years (95% CI [3.436-6.816]). We found out that questions about breathlessness and "exacerbations", and male sex were predictive of incident COPD after two years follow-up (AUC 0.79, 95% CI [0.74-0.84], p < 0.001). When only active smokers were analyzed a change in EBT after a cigarette (ΔEBT) was added to a previous model (AUC 0.83, 95% CI [0.78-0.88], p < 0.001). Conclusion: Our preliminary data shows that the MARKO questionnaire combined with EBT (change after a cigarette smoke) could potentially serve as early markers of future COPD in smokers. [ABSTRACT FROM AUTHOR]

Immunoglobulin G (IgG) is the most abundant antibody in the blood and plays a critical role in host immune defense against infectious agents. Glycosylation is known to modulate the effector functions of IgG and is involved in disease development and progression. It is no surprise that the N-glycome of IgG from plasma has already been proposed as a biomarker for various physiological and pathological conditions. However, because saliva is easy to collect, it could be useful for exploring the functional role of salivary IgG N-glycosylation and its potential as a diagnostic biomarker. Therefore, in this study, we described a method for N-glycome analysis of IgG from saliva samples. Salivary IgG N-glycans were analyzed by ultra-high-performance liquid chromatography based on hydrophilic interactions with fluorescence detection (HILIC-UHPLC-FLR). In addition, we compared IgG N-glycan profiles from saliva with those from plasma, assessed the stability of salivary IgG N-glycan profiles under different storage conditions, and evaluated the effects of using a saliva preservation medium. This study provides an ultrasensitive UHPLC method for the analysis of total IgG N-glycosylation from saliva, gives insight into storage stability of salivary IgG, and highlights its (dis)advantages for further biomarker-related research. [ABSTRACT FROM AUTHOR]

Atrial fibrillation is a disease with a complex pathophysiology, whose occurrence and persistence are caused not only by aberrant electrical signaling in the heart, but by the development of a susceptible heart substrate. These changes, such as the accumulation of adipose tissue and interstitial fibrosis, are characterized by the presence of inflammation. N-glycans have shown great promise as biomarkers in different diseases, specifically those involving inflammatory changes. To assess the changes in the N-glycosylation of the plasma proteins and IgG in atrial fibrillation, we analyzed the N-glycosylation of 172 patients with atrial fibrillation, before and six months after a pulmonary vein isolation procedure, with 54 cardiovascularly healthy controls. An analysis was performed using ultra-high-performance liquid chromatography. We found one oligomannose N-glycan structure from the plasma N-glycome and six IgG N-glycans, mainly revolving around the presence of bisecting N-acetylglucosamine, that were significantly different between the case and control groups. In addition, four plasma N-glycans, mostly oligomannose structures and a derived trait that was related to them, were found to be different in the patients who experienced an atrial fibrillation recurrence during the six-month follow-up. IgG N-glycosylation was extensively associated with the CHA2DS2-VASc score, confirming its previously reported associations with the conditions that make up the score. This is the first study looking at the N-glycosylation patterns in atrial fibrillation and warrants further investigation into the prospect of glycans as biomarkers for atrial fibrillation. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is the most common cardiovascular disease (CVD), and previous studies have shown a significant association between N-glycosylation, a highly regulated posttranslational modification, and the development of atherosclerotic plaques. Our aim was to determine whether the N-glycome of immunoglobulin G (IgG) is associated with CAD, as N-glycans are known to alter the effector functions of IgG, which may enhance the inflammatory response in CAD. Therefore, in this study, we isolated IgG from subjects with coronary atherosclerosis (CAD+) and from subjects with clean coronaries (CAD−). The purified IgGs were denatured and enzymatically deglycosylated, and the released and fluorescently labelled N-glycans were analysed by ultra-high performance liquid chromatography based on hydrophilic interactions with fluorescence detection (HILIC-UHPLC-FLR). Sex-stratified analysis of 316 CAD− and 156 CAD+ cases revealed differences in IgG N-glycome composition. The most notable differences were observed in women, where the presence of sialylated N-glycan structures was negatively associated with CAD. The obtained chromatograms provide insight into the IgG N-glycome composition in CAD as well as the biomarker potential of IgG N-glycans in CAD. [ABSTRACT FROM AUTHOR]

Aberrant plasma protein glycosylation is associated with a wide range of diseases, including diabetes, cardiovascular, and immunological disorders. To investigate plasma protein glycosylation alterations due to weight loss and successive weight-maintenance diets, 1850 glycomes from participants of the Diogenes study were analyzed using Ultra-High-Performance Liquid Chromatography (UHPLC). The Diogenes study is a large dietary intervention study in which participants were subjected to a low-calorie diet (LCD) followed by one of five different weight-maintenance diets in a period of 6 months. The most notable alterations of the plasma glycome were 8 weeks after the subjects engaged in the LCD; a significant increase in low-branched glycan structures, accompanied by a decrease in high-branched glycan structures. After the LCD period, there was also a significant rise in N-glycan structures with antennary fucose. Interestingly, we did not observe significant changes between different diets, and almost all effects we observed immediately after the LCD period were annulled during the weight-maintenance diets period. [ABSTRACT FROM AUTHOR]

Chronic inflammation is the main feature of many long-term inflammatory diseases such as autoimmune diseases, metabolic disorders, and cancer. There is a growing number of studies in which alterations of N-glycosylation have been observed in many pathophysiological conditions, yet studies of the underlying mechanisms that precede N-glycome changes are still sparse. Proinflammatory cytokines have been shown to alter the substrate synthesis pathways as well as the expression of glycosyltransferases required for the biosynthesis of N-glycans. The resulting N-glycosylation changes can further contribute to disease pathogenesis through modulation of various aspects of immune cell processes, including those relevant to pathogen recognition and fine-tuning the inflammatory response. This review summarizes our current knowledge of inflammation-induced N-glycosylation changes, with a particular focus on specific subsets of immune cells of innate and adaptive immunity and how these changes affect their effector functions, cell interactions, and signal transduction. [ABSTRACT FROM AUTHOR]

Aims: Biologics have been proven efficacious for patients with severe asthma (SA). It is essential to diagnose such individuals correctly. This study was designed to survey pulmonologists to identify barriers to early diagnosis and subsequent appropriate use of biologics for SA in Croatia. Methods: A pulmonologist group with expertise in SA developed the initial list of questions, with the final questionnaire created according to a 2-round Delphi method. The resulting survey consisted of 23 items consequently divided into 4 domains: 1) Pulmonologists' demographics and professional experiences; 2) Concerns about asthma management; 3) Attitudes toward SA diagnosis; and 4) Beliefs and attitudes regarding the use of biologics in managing SA. The given answers represented the respondents' estimates. Results: Eighty-four surveys were analyzed, with pulmonologists observing that general practitioners often inaccurately diagnose asthma and treat acute exacerbations. Although specialist centers are capably and correctly equipped, the time to diagnose patients with SA is approximately 3.5 months, with initial use of biologics delayed an additional 2 months. The primary indications for prescribing biologics are conventional therapy with oral glucocorticoids (91.7%) and frequent acute exacerbations (82.1%). In addition to improper diagnosis (64.3%), many patients with SA do not receive the indicated biologics owing to strict administrative directives for reimbursement (70.2%) or limited hospital resources (57.1%). Limitations: The limitations of this survey include the subjective nature of the collected data, the relatively small sample size, and the lack of the biologic efficacy evaluation. Conclusions: Croatian pulmonologists observed that a significant number of patients with SA who are eligible for biologics are not prescribed them, largely because of an inaccurate and/or delayed diagnosis, a delayed referral to a specialist center, highly restrictive criteria for reimbursement, and/or institutional budgetary limitations. [ABSTRACT FROM AUTHOR]

During the research on the influence of plasma protein glycosylation on achieving LDL cholesterol target values1,2, we analyzed statin-naive patients with the first presentation of acute coronary syndrome. Between September 2022 and September 2023, a total of 61 statin-naive patients with acute coronary syndrome were hospitalized. Patients transferred from local hospitals and patients older than 75 years were excluded from the study. Out of 61 patients, 36 had STEMI (ST-segment elevation myocardial infarction) and 25 NSTEMI (Non-ST elevation myocardial infarction). More than 50% of patients were men (35), and the average age of all patients was 58.34 years. 40 % of patients are smokers. 55% of patients had a BMI greater than 25 kg/m². The average value of the initial high-sensitivity troponin was 2337 pg/ml. All patients underwent percutaneous coronary intervention (PCI), and the average number of implanted stents was 1.02. In the largest percentage (38%), the infarct related artery or culprit lesion was on right coronary artery. In patients with STEMI, 57% received a loading dose of prasugrel and the rest ticagrelor. In patients with NSTEMI, after coronary angiography, 83% of patients received prasugrel, the rest ticagrelor and clopidogrel. All patients were discharged with a recommendation to take atorvastatin at a dose of 80 mg per day. The average value of LDL (low-density lipoprotein) cholesterol during hospitalization was 3.97 mmol/L. At the first control, 2 months after PCI, the average value of LDL cholesterol was 2.26 mmol/L, and 4 patients (6%) achieved target values of 1.4 mmol/L. Ezetimibe was recommended to all patients who did not reach the target values. At the second control, 3 months after PCI, the average value of LDL cholesterol was 1.95 mmol/L, and the target values were achieved by 6 patients (9.8%). The plan is to recruit statin-naive patients with acute coronary syndrome until September 2024, and clinical and laboratory follow-up for 1 year after PCI. [ABSTRACT FROM AUTHOR]

Immunoglobulin G (IgG) glycans are emerging as a new putative biomarker for biological age and different diseases, requiring a robust workflow for IgG glycome analysis, ideally beginning with a simple and undemanding sampling procedure. Here, we report the first comprehensive study on total N-glycans of IgG isolated from dried blood spots (DBSs), which was performed in a high-throughput mode. We compared the IgG N-glycan profiles originating from DBS with those originating from plasma, compared different media for DBS collection, evaluated analytical variation and assessed IgG N-glycan profile stability for different storage conditions. In conclusion, we show that DBSs are a good and stable source material for a robust IgG N-glycan analysis by ultra-performance liquid chromatography, suitable for blood sampling in conditions where no trained personnel and necessary laboratory equipment are available. [ABSTRACT FROM AUTHOR]

Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 ± 4.0 years, body mass index 23.4 ± 1.7 kg/m2) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 ± 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 ± 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters—white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of the measured immune system parameters returned back to the baseline. In summary, this study elucidated a number of molecular pathways presumably explaining immunosuppression in individuals going through prolonged periods of intense training with low-energy availability. Our findings also reinforce the perception that the way in which weight loss is achieved (i.e., dietary restriction, exercise, or both) has a distinct effect on how the immune system is modulated. [ABSTRACT FROM AUTHOR]

Introduction: Coronary artery disease (CAD) is the most common cardiovascular disease (CVD), resulting from chronic inflammation of the coronary arteries due to the formation of atherosclerotic plaques, and its presence is a significant marker of adverse cardiovascular events. A growing body of research suggests that alterations in protein N-glycosylation are involved in the development of CVD through various mechanisms and have significant biomarker potential because of their sensitivity to changes that occur in the organism during inflammation-related conditions such as CVD1-3. Our aim was to determine whether the N-glycome of total plasma proteins is associated with CAD, because Nglycans are known to alter the effector functions of proteins, which may enhance their inflammatory response in CAD. Patients and Methods: In this study, we analysed the N-glycome of plasma proteins isolated from patients who underwent coronary angiography and classified into patients with confirmed coronary atherosclerosis and patients with clean coronaries. Proteins were denatured and enzymatically deglycosylated, and the released and fluorescently labelled N-glycans were analysed by ultra-high performance liquid chromatography based on hydrophilic interactions with fluorescence detection (HILIC-UHPLC-FLR) (Figure 1). Because previous studies have shown evidence of sexual dimorphism in CVD and significant sex differences in the association of N-glycans with CVD risk, we performed sex-stratified analysis of plasma N-glycans. Results: The results showed significant differences in plasma N-glycome composition in CAD. Lower abundance of complex biantennary galactosylated N-glycans with core fucose and, conversely, a higher abundance of highly branched (tri- and tetra-antennary) sialylated N-glycan structures with terminal fucose was shown to be associated with CAD. Conclusion: The obtained chromatograms shed light on the composition of plasma protein N-glycans in CAD and provided new insights into N-glycosylation changes in CAD. Overall, because of their sensitivity to changes that occur in an organism, protein Nglycosylation emerges as a significant factor in CAD and holds potential as a diagnostic tool, with glycan-based biomarkers showing promise for predicting cardiovascular health. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Better understanding of type 2 diabetes and its prevention is a pressing need. Changes in human plasma N-glycome are associated with many diseases and represent promising diagnostic and prognostic biomarkers. Variations in glucose metabolism directly affect glycosylation through the hexosamine pathway but studies of plasma glycome in type 2 diabetes are scarce. The aim of this study was to determine whether plasma protein N-glycome is changed in individuals who are at greater risk of developing type 2 diabetes. Methods: Using a chromatographic approach, we analysed N-linked glycans from plasma proteins in two populations comprising individuals with registered hyperglycaemia during critical illness (increased risk for development of type 2 diabetes) and individuals who stayed normoglycaemic during the same condition: AcuteInflammation (59 cases vs 49 controls) and AcuteInflammation Replication (52 cases vs 14 controls) populations. N-glycome was also studied in individuals from FinRisk (37 incident cases of type 2 diabetes collected at baseline vs 37 controls), Orkney Complex Disease Study (ORCADES; 94 individuals with HbA > 6.5% [47.5 mmol/mol] vs 658 controls) and Southall and Brent Revisited (SABRE) cohort studies (307 individuals with HbA > 6.5% [47.5 mmol/mol] vs 307 controls). Results: Individuals with increased risk for diabetes type 2 development (AcuteInflammation and AcuteInflammation Replication populations), incident cases of type 2 diabetes collected at baseline (FinRisk population) and individuals with elevated HbA (ORCADES and SABRE populations) all presented with increased branching, galactosylation and sialylation of plasma protein N-glycans and these changes were of similar magnitude. Conclusions/interpretation: Increased complexity of plasma N-glycan structures is associated with higher risk of developing type 2 diabetes and poorer regulation of blood glucose levels. Although further research is needed, this finding could offer a potential new approach for improvement in prevention of diabetes and its complications. [ABSTRACT FROM AUTHOR]

Chronic low back pain (CLBP) is one of the most common medical conditions, ranking as the greatest contributor to global disability and accounting for huge societal costs based on the Global Burden of Disease 2010 study. Large genetic and -omics studies provide a promising avenue for the screening, development and validation of biomarkers useful for personalized diagnosis and treatment (precision medicine). Multicentre studies are needed for such an effort, and a standardized and homogeneous approach is vital for recruitment of large numbers of participants among different centres (clinical and laboratories) to obtain robust and reproducible results. To date, no validated standard operating procedures (SOPs) for genetic/-omics studies in chronic pain have been developed. In this study, we validated an SOP model that will be used in the multicentre (5 centres) retrospective “PainOmics” study, funded by the European Community in the 7th Framework Programme, which aims to develop new biomarkers for CLBP through three different -omics approaches: genomics, glycomics and activomics. The SOPs describe the specific procedures for (1) blood collection, (2) sample processing and storage, (3) shipping details and (4) cross-check testing and validation before assays that all the centres involved in the study have to follow. Multivariate analysis revealed the absolute specificity and homogeneity of the samples collected by the five centres for all genetics, glycomics and activomics analyses. The SOPs used in our multicenter study have been validated. Hence, they could represent an innovative tool for the correct management and collection of reliable samples in other large-omics-based multicenter studies. [ABSTRACT FROM AUTHOR]

Background: Main risk factor for the development of chronic obstructive pulmonary disease (COPD) is smoking, although only less than 1/3 of smokers develop clinically manifest COPD. COPD's progressive nature with high disability and mortality makes it plausible to detect it as early as possible thus allowing for an early intervention. The only tool for an early diagnosis that could be used on the global scale is spirometry, even though symptoms and deprivation of health related quality of life (HRQoL) precede relevant spirometric changes. Existing HRQoL questionnaires are too complicated or not developed for an early detection of COPD. The aim of our study was to develop a new simple HRQoL tool that will allow (alone or in combination with other markers) early detection of patients with COPD.Methods: A multicenter prospective cohort study recruiting 500 subjects at risk for COPD (smokers/ex-smokers ≥20 pack-years, 40-65 years, both sexes, with no prior diagnosis of COPD) will be carried out in two phases: (1) cross-sectional - development and validation of a new questionnaire; and (2) prospective - follow-up of a cohort of patients at risk for COPD. Subjects were recruited by 25 GPs and assessed for COPD by dedicated pulmonologists in 7 hospital centers using a predefined protocol: HRQoL, history, physical, blood sampling, exhaled breath temperature (EBT), lung function, 6-min walk test (6MWT). Patients without COPD and those in GOLD stage 1 at initial assessment will be reassessed for disease progression by the same pulmonologist after 2 and 5 years.Discussion: This is one of the first cohort studies attempting to establish the incidence of COPD in the pre-symptomatic stage before significant end organ damage. We intend to assess the validity, predictability and discriminative power ('healthy' smokers vs. pre-symptomatic phase in newly developed COPD) of newly developed HRQoL tool alone or in combination with other markers; EBT, lung function, 6MWT, genomics, transcriptomics, proteomics). We expect that the results of this study can improve our understanding of the development of COPD, identify some new underlying pathophysiological pathways, and offer to sensitive smokers/ex-smokers new preventive and early intervention measures thus improving the management of COPD.Trial Registration: Clinicaltrial.gov NCT01550679 retrospectively registered February 28, 2012. [ABSTRACT FROM AUTHOR]

Although only less than one-third of smokers develop COPD, early marker(s) of COPD development are lacking. The aim of this research was to assess the ability of an average equilibrium exhaled breath temperature (EBT) in identifying susceptibility to cigarette smoke so as to predict COPD development in smokers at risk. The study was a part of a multicenter prospective cohort study in current smokers (N = 140, both sexes, 40–65 years, ≥20 pack-years) with no prior diagnosis of COPD. Diagnostic workup includes history, physical, quality of life, hematology and highly sensitive CRP, EBT before and after smoking a cigarette, lung function with bronchodilator test, and 6-minute walk test. Patients without a diagnosis of COPD and in GOLD 1 stage at initial assessment were reassessed after 2 years. COPD was additionally diagnosed based on lower level of normal (LLN) lung function criteria. Utility of EBT for disease progression was analyzed using receiver operator curve (ROC) and logistic regression analyses. Change in EBT after smoking a cigarette at initial visit (ΔEBT) was significantly predictive for disease progression (newly diagnosed COPD; newly diagnosed COPD + severity progression) after 2 years (p< 0.05 for both). ΔEBT had an AUC of 0.859 (p= 0.011) with sensitivity of 66.7% and specificity of 98.1% for newly diagnosed COPD using LLN criteria. We conclude that EBT shows potential for predicting the future development of COPD in current smokers. This was best seen using LLN to diagnose COPD, adding further evidence to question the use of GOLD criteria for diagnosing COPD. [ABSTRACT FROM PUBLISHER]

Introduction: Chronic low back pain (CLBP) produces considerable direct costs as well as indirect burdens for society, industry and health systems. CLBP is characterised by heterogeneity, inclusion of several pain syndromes, different underlying molecular pathologies and interaction with psychosocial factors that leads to a range of clinical manifestations. There is still much to understand in the underlying pathological processes and the non-psychosocial factors which account for differences in outcomes. Biomarkers that may be objectively used for diagnosis and personalised, targeted and cost-effective treatment are still lacking. Therefore, any data that may be obtained at the '-omics' level (glycomics, Activomics and genome-wide association studies--GWAS) may be helpful to use as dynamic biomarkers for elucidating CLBP pathogenesis and may ultimately provide prognostic information too. By means of a retrospective, observational, case-cohort, multicentre study, we aim to investigate new promising biomarkers potentially able to solve some of the issues related to CLBP. Methods and analysis: The study follows a two-phase, 1:2 case-control model. A total of 12 000 individuals (4000 cases and 8000 controls) will be enrolled; clinical data will be registered, with particular attention to pain characteristics and outcomes of pain treatments. Blood samples will be collected to performomics studies. The primary objective is to recognise genetic variants associated with CLBP; secondary objectives are to study glycomics and Activomics profiles associated with CLBP. Ethics and dissemination: The study is part of the PainOMICS project funded by European Community in the Seventh Framework Programme. The study has been approved from competent ethical bodies and copies of approvals were provided to the European Commission before starting the study. Results of the study will be reviewed by the Scientific Board and Ethical Committee of the PainOMICS Consortium. The scientific results will be disseminated through peer-reviewed journals. [ABSTRACT FROM AUTHOR]

Background: COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk. The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/exsmokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard. Methods: Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD. Results: COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP’s office with a specificity of 100 % (95 % CI, 97.95–100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49–47.48 %). Significant agreement for forced expiratory volume in 1 s measured at GP’s office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all). Conclusions: Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD). Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral. [ABSTRACT FROM AUTHOR]

Objective Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA-DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case-control study to determine whether SLE is associated with altered IgG glycosylation. Methods Using ultra-performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China). Results Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N-acetylglucosamine (which affect antibody-dependent cell-mediated cytotoxicity). Conclusion The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE. [ABSTRACT FROM AUTHOR]

Protein glycosylation is the most common epiproteomic modification involved in numerous physiological and pathological processes. Previous studies reported strong associations between human plasma N-glycans and age, prompting us to evaluate the potential application of this biological phenomenon in the field of forensics. Blood from 526 blood donors from different parts of Croatia was collected on bloodstain cards during the period 2004-2007 and stored at 4°C for 6-9 years. Glycosylation profiles of the bloodstains were analysed using hydrophilic interaction ultra performance liquid chromatography (HILIC-UPLC) and divided into 38 glycan groups (GP1-GP38). A statistically significant correlation between N-glycan profiles of bloodstains and chronological age was found and a statistical model that can be used for the age prediction was designed (Age = 75.59 - 5.15 × (GP4)+ 17.07 × GP6 - 5.30 × (GP10) - 16.56 × GP16 + 20.07 × GP20 - 7.54 × (GP20) + 16.47 × GP22). This model explains 47.78 % of the variation in age, with a prediction error of 9.07 years. Our findings demonstrate that analysing the N-glycan profile could be a new tool in forensics, offering an approximate human age estimation from dried bloodstains found at a crime scene. [ABSTRACT FROM AUTHOR]

Background: Delayed diagnosis and treatment of tuberculosis increase both the severity of the disease and the duration of infectivity. A number of studies have addressed the issue of health system delays in the treatment of tuberculosis, but mostly in countries with a high or low incidence of the disease. Our understanding of delay is quite limited in settings with an intermediate burden of tuberculosis. We explore the duration and factors associated with delays in the Croatian health system which has free health care and a sufficient network of health services providing tuberculosis diagnosis and care. Methods: A total of 241 consecutive adults with culture-confirmed pulmonary tuberculosis were interviewed in seven randomly selected Croatian counties and their medical records were evaluated. A health system delay was defined as the number of days from the first consultation with a physician to the initiation of anti-tuberculosis treatment. A long delay was defined as a period exceeding the median delay, while an extreme delay was considered to be above the 75th percentile delay. Results: The median health system delay was 15 days while the 75th percentile was 42 days (the 5th and 95th percentile being 1 and 105 days respectively). Almost 30% of tuberculosis patients remained undiagnosed for more than 30 days after the initial health care visit. Female patients (p = 0.005), patients with a negative sputum smear (p = 0.002) and patients having symptoms other than the usual ones (0.027) were found to be in significant correlation with a long delay. In a multivariate model, a long delay remained associated with the same variables (p = 0.008, p = 0.003, and p = 0.037, respectively). Conclusions: Our findings suggest that some groups of tuberculosis patients experienced a health system delay. In such a setting where tuberculosis incidence is decreasing, which leads to a lack of physician experience and expertise, training in tuberculosis is required. Such measure may be useful in reducing the number of missed opportunities for tuberculosis diagnosis. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Industrial Hygiene & Toxicology / Arhiv za Higijenu Rada I Toksikologiju is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Cardiologia Croatica is the property of Croatian Cardiac Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose of Review: Protein glycosylation has been observed to associate with different diseases, including cardiovascular diseases (CVDs). Most of these observations are related to O-glycosylation, yet N-glycosylation changes have recently gained more attention.Recent Findings: N-Glycosylation alterations are associated with CVDs and play an important role in disease development: directly and indirectly through risk factors associated with the disease.Summary: The changes of N-glycosylation are a new risk factor for CVDs and have significant biomarker potential for disease development, progression, and therapy monitoring. [ABSTRACT FROM AUTHOR]

The authors regret that Nish Chaturvedi's name was spelt incorrectly in the author list. The details given in this correction are correct. [ABSTRACT FROM AUTHOR]

Background: Delayed diagnosis and treatment of tuberculosis increase both the severity of the disease and the duration of infectivity. A number of studies have addressed the issue of health system delays in the treatment of tuberculosis, but mostly in countries with a high or low incidence of the disease. Our understanding of delay is quite limited in settings with an intermediate burden of tuberculosis. We explore the duration and factors associated with delays in the Croatian health system which has free health care and a sufficient network of health services providing tuberculosis diagnosis and care.Methods: A total of 241 consecutive adults with culture-confirmed pulmonary tuberculosis were interviewed in seven randomly selected Croatian counties and their medical records were evaluated. A health system delay was defined as the number of days from the first consultation with a physician to the initiation of anti-tuberculosis treatment. A long delay was defined as a period exceeding the median delay, while an extreme delay was considered to be above the 75th percentile delay.Results: The median health system delay was 15 days while the 75th percentile was 42 days (the 5th and 95th percentile being 1 and 105 days respectively). Almost 30% of tuberculosis patients remained undiagnosed for more than 30 days after the initial health care visit. Female patients (p = 0.005), patients with a negative sputum smear (p = 0.002) and patients having symptoms other than the usual ones (0.027) were found to be in significant correlation with a long delay. In a multivariate model, a long delay remained associated with the same variables (p = 0.008, p = 0.003, and p = 0.037, respectively).A significant association was demonstrated between both the female gender (p = 0.042) and a negative sputum smear (p < 0.001) and extreme delay, while only a negative sputum smear (p < 0.001) remained significant in the multivariate analysis.Conclusions: Our findings suggest that some groups of tuberculosis patients experienced a health system delay. In such a setting where tuberculosis incidence is decreasing, which leads to a lack of physician experience and expertise, training in tuberculosis is required. Such measure may be useful in reducing the number of missed opportunities for tuberculosis diagnosis. [ABSTRACT FROM AUTHOR]