Athlete biological passport: longitudinal biomarkers and statistics in the fight against doping.

As novel substances, short time windows, and limits of detection increasingly challenge direct methods of doping detection in sports, indirect tools inevitably take a greater role in the fight against it. One such tool is the athlete biological passport (ABP) - a longitudinal profiling of the measured haematological and biochemical biomarkers, combined with calculated scores, against the background of epidemiological data crucial for doping detection. In both of its modules, haematological and steroidal, ABP parameters are analysed with the Bayesian adaptive model, which individualises reference and cut-off values to improve its sensitivity. It takes into account the confounding factors with proven and potential influence on the biomarkers, such as race and altitude exposure. The ABP has already changed the fight against doping, but its importance will further grow with the new modules (e.g., endocrinological), parameters (e.g., plasma volume-independent parameters), and complementing indirect methods (e.g., transcriptomic).

Compensated Advanced Chronic Liver Disease and Steatosis in Patients with Type 2 Diabetes as Assessed through Shear Wave Measurements and Attenuation Measurements.

Patients with type 2 diabetes (T2D) are at risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the prevalence of compensated advanced chronic liver disease (cACLD) and steatosis in patients with T2D using the new non-invasive diagnostic methods of shear wave measurements (SWMs) and attenuation (ATT) measurements in comparison with those of vibration-controlled transient elastography (VCTE) and the controlled attenuation parameter (CAP), which served as the reference methods. Among 214 T2D patients, steatosis at any grade and cACLD were revealed in 134 (62.6%) and 19 (8.9%) patients, respectively. SWMs showed a high correlation with VCTE (Spearman's ρ = 0.641), whereas SWMs produced lower (mean of -0.7 kPa) liver stiffness measurements (LSMs) overall. At a LSM of >11.0 kPa (Youden), SWMs had an AUROC of 0.951 that was used to diagnose cACLD (defined as a LSM of >15 kPa through VCTE) with 84.2% sensitivity and 96.4% specificity. The performance of ATT measurements in diagnosing liver steatosis at any grade (defined as the CAP of ≥274 dB/m) was suboptimal (AUROC of 0.744 at the ATT measurement cut-off of >0.63 dB/cm/MHz (Youden) with 59% sensitivity and 81.2% specificity). In conclusion, the prevalence of liver steatosis and previously unrecognized cACLD in patients with T2D is high and SWMs appear to be a reliable diagnostic method for this purpose, whereas further investigation is needed to optimize the diagnostic performance of ATT measurements.

Inflammatory Gene Expression in Neck Perivascular and Subcutaneous Adipose Tissue in Men With Carotid Stenosis.

The inflammatory phenotype of neck adipose tissue (NAT) might reflect its involvement in the pathogenesis of carotid atherosclerosis. We investigated inflammatory gene expression in the subcutaneous and the perivascular (pericarotid) adipose tissue from patients with carotid stenosis (CS) undergoing endarterectomy and a control group of patients without significant carotid atherosclerosis undergoing thyroid surgery. Only male patients were included (n = 13 in each study group). Clinical and biochemical data along with serum leptin, adiponectin, and monocyte chemoattractant protein 1 (MCP-1) were collected. Adipose tissue samples were obtained from both the subcutaneous and pericarotid compartments. Real-time polymerase chain reaction was used to measure gene expression of macrophage markers and adipokines. The CS group had higher subcutaneous and pericarotid visfatin gene expression and higher pericarotid expression of MCP-1 and CD68 genes. The ratio between pericarotid CD206 and CD68 gene expression was similar between study groups. Adiponectin gene expression in both NAT compartments did not differ between groups, but it was negatively associated with body weight. These observations suggest that NAT, and especially the pericarotid compartment, express enhanced inflammatory properties in patients with CS, but the proportion of anti-inflammatory macrophages in advanced atherosclerosis seems to be maintained.

Neck adipose tissue - tying ties in metabolic disorders.

Upper body adipose tissue accumulation has been associated with clustering of metabolic disorders and increased cardiovascular risk. Neck circumference (NC) indicated that subcutaneous adipose tissue (SAT) in that region is an independent pathogenic depot that might account for the additional risk missed by visceral adipose tissue (VAT). Neck adipose tissue (NAT) is not only one more ectopic depot but has several particular features that might modulate its metabolic role. Besides a controversial impact on obstructive apnea syndrome, neck fat encompasses carotid arteries as an important perivascular adipose tissue (PVAT) depot. With dysfunctional changes in obesity, physiologic vascular regulation is lost and inflammatory signals accelerate atherogenesis. Unexpected was the discovery of brown and beige adipocytes in the neck of human adults. When stimulated, brown adipose tissue (BAT) dissipates energy through thermogenesis and it is associated with other favorable metabolic effects. Moreover, the neck is the region where the browning mechanism was disclosed. With this unique plastic nature, NAT revealed multiple ties, challenging dynamics and potential new therapeutic targets that might have significant implications on metabolic outcomes and vascular risk.

Under the Surface of Subcutaneous Adipose Tissue Biology.

The global obesity epidemic enhanced contemporary interest in adipose tissue biology. Two structurally and functionally distinct depots, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), are spread throughout the body. Their distribution was recognized to be a major determinant of metabolic risk. Unlike VAT, SAT showed some protective endocrine and inflammatory features that might explain the occurrence of obese but metabolically healthy persons. The unique developmental gene expression signature, angiogenesis, and adipogenic potential of SAT determines its growth ability under the positive energy balance. The overflow hypothesis suggested that when SAT is unable to expand sufficiently, fat overflows towards metabolically adverse ectopic depots. Besides white adipose tissue, recent studies found important brown adipose tissue activity responsible for thermogenesis and energy dissipation in adults as well. SAT is prone to "browning" - the appearance of particular beige adipocytes that contribute to its favorable metabolic effects. Morbid obesity, aging, hormonal status, nutrition, low physical activity, and other environmental factors impair SAT relative resistance to dysfunctional changes and promote development of metabolic disorders. The popular approach considering SAT mainly as the subject of cosmetic procedures for improving the appearance of body contours should be avoided. Complex heterogeneity of obesity revealed that a tissue of an extreme plasticity and rich interactions with vital functions of the body lies under the surface. Therapeutic manipulations to preserve and enhance healthier fat in order to correct obesity-related metabolic disorders seem to be a relevant but still unexplored opportunity.

Association of monocyte CCR2 expression with obesity and insulin resistance in postmenopausal women.

PURPOSE: Monocytes actively participate in inflammatory mechanisms that contribute to the development of adipose tissue dysfunction and atherogenesis. The aim of this study was to evaluate the association of monocyte CCR2 chemokine receptor expression and intracellular oxidative burst with the metabolic and inflammatory factors related to body weight. METHODS: The study was performed in 67 postmenopausal women with normal, overweight and obese body mass index. Monocyte CCR2 surface expression and intracellular oxidative burst activity (determined using 2', 7'-dichlorofluorescin diacetate) were analyzed by flow cytometry. Serum levels of HMW adoponectin, monocyte chemoattractant protein-1 (MCP-1), insulin, glucose, lipids and C-reactive protein were determined. RESULTS: Subjects with homeostasis model assessment-estimated insulin resistance (HOMA-IR) above the median had significantly higher proportion of CCR2+ monocytes and higher mean fluorescence intensity (MFI) of CCR2 and oxidative burst. The proportion of CCR2+ monocytes and CCR2 MFI were correlated with body weight, body mass index, fat mass, insulin and HOMA-IR. Oxidative burst also correlated with anthropometric measures, fat mass and expression of CCR2. No correlations were found between these markers of monocyte activation and HMW adiponectin or monocyte chemoattractant protein-1. The absolute number of monocytes was associated with insulin and this association remained significant after adjusting for C-reactive protein. In the multiple regression model the monocyte number was determined to be an independent predictor of insulin level. CONCLUSION: These results provide support for significant associations of monocyte number and markers involved in monocyte activation with obesity and insulin resistance.

["Returning to the Sun" of Antun Branko Simic]. / "Vracanje suncu" Antuna Branka Simica.

Antun Branko Simic, one of the greatest Croatian poets, died very young, at the age of 27, from tuberculosis. The history of his disease has not been reconstructed for eight decades although that could also open a more accurate view on his literary work. By uncovering the original documents, his disease and death could be positioned in historical, social and cultural context. It was shown that those who emphasized the crucial impact of disease on his entire literary work were wrong. No doubt that A. B. Simic has written under the influence of his disease but that can refer only to the small number of poems and essays. First of all he wrote in line with world poetry of his time--expressionism, which was significantly inspired by patients' and social sufferings.

Monocytes in metabolic disorders--opportunities for flow cytometry contributions.

Chronic inflammation has arised as a major underlying cause of atherosclerosis, obesity and diabetes. It is mediated by cells of innate immune system like macrophages but also by their antecedents, circulating monocytes. Roles of monocyte subsets and different markers of monocyte activation in the context of metabolic disorders have been reviewed. Applying cell based approach through flow cytometry in this field has resulted with new understanding of pathophysiologic mechanisms. Possible implications of these insights in diagnosis, prognosis and revealing of therapeutic targets in metabolic disorders remain a challenge for future.

[Adipocytokines as mediators of metabolic role of adipose tissue]. / Adipocitokini kao posrednici metabolicke uloge masnog tkiva.

The discovery of adipocytokines, products of adipose tissue, has been a turning point in the understanding of metabolic disorders. Historically considered as a passive depot of energy, adipose tissue has become an important active participant and adipocytokines crucial mediators of its metabolic role. Among a number of adipose tissue products, leptin and adiponectin are exclusively secreted by adipocytes. Leptin regulates energy homeostasis and interferes with several neuroendocrine and immune functions. Adiponectin is an intriguing adipocytokine with its serum level inversely correlated with fatness. It has been related to enhanced insulin sensitivity, anti-inflammatory and anti-atherogenic actions. Recent investigations have also emphasized the important role of resistin, visfatin, retinol binding protein 4, and of a whole list of cytokines like interleukin-6, tumor necrosis factor a, plasminogen activator inhibitor-1, or a chemokine, monocyte chemoattractant protein-1. The fact that secretory balance of adipose tissue in obesity is shifted towards the proinflammatory spectrum has supported the hypothesis on the development of dysfunctional adipose tissue in these circumstances. It contributes to the state of chronic inflammation and insulin resistance, and it seems to be a fundamental link between obesity and atherosclerosis.

From ancient enigmas to novel paradigms: a depiction of multiple symmetric lipomatosis.

A rare case of multiple symmetric lipomatosis type 2 in a female patient was presented. New possible iconographic representations of multiple symmetric lipomatosis were considered and some metabolic aspects of this disease were reviewed.

Multiple symmetric lipomatosis type 2 in females--report of two cases.

Two patients with features of multiple symmetric lipomatosis type 2 are presented. This particular disorder with a characteristic distribution of fat should be considered on differential diagnosis of obesity. Besides being rare, it may occasionally be unrecognized, especially in females. The etiology remains unknown; however, the association with high alcohol consumption is very strong. Several issues about the possible metabolic role of lipomatous adipose tissue have been discussed. Patients with multiple symmetric lipomatosis should be treated by liposuction or surgery instead of being submitted to diets.