A BSTRACT : Various medical conditions that involve activation of the immune system are associated with psychological and neuroendocrine changes that resemble the characteristics of depression. In this review we present our recent studies, designed to investigate the relationship between the behavioral effects of immune activation and depressive symptomatology. In the first set of experiments, we used a double-blind prospective design to investigate the psychological consequences of illness in two models: (1) vaccination of teenage girls with live attenuated rubella virus, and (2) lipopolysaccharide (LPS) administration in healthy male volunteers. In the rubella study, we demonstrated that, compared to control group subjects and to their own baseline, a subgroup of vulnerable individuals (girls from low socioeconomic status) showed a significant virus-induced increase in depressed mood up to 10 weeks after vaccination. In an ongoing study on the effects of LPS, we demonstrated significant LPSinduced elevation in the levels of depression and anxiety as well as memory deficits. These psychological effects were highly correlated with the levels of LPS-induced cytokine secretion. In parallel experiments, we demonstrated in rodents that immune activation with various acute and chronic immune challenges induces a depressive-like syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. Chronic treatment with antidepressants (imipramine or fluoxetine) attenuated many of the behavioral effects of LPS, as well as LPS-induced changes in body temperature, adrenocortical activation, hypothalamic serotonin release, and the expression of splenic TNF-␣ mRNA. Taken together, these findings suggest that cytokines are involved in the etiology and symptomatology of illness-associated depression.

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To assess the pre-competitive stress levels in rhythmic gymnasts by using non-invasive biochemical methods and anxiety questionnaires. METHODS:The study included 10 rhythmic gymnast competitors (age: 14.7±1.57 years), at the Bulgarian Rhythmic Gymnastics Championships. Saliva was collected by using cotton swab salivates without salivary stimulation at three different times: at home nine days pre-competition (baseline), before a training session five days pre-competition, and just before the competition. The sAA activity and the concentration of salivary protein (sP) and salivary potassium (K + ) were measured. Trait and state anxiety were evaluated by using the Spielberger State-Trait Anxiety Inventory. Comparisons were made using one-way ANOVA with repeated measures. RESULTS:The mean state anxiety score was significantly higher before the training session in contrast to the baseline, 36.90±11.03 vs 30.80±10.26, p<0.05 and before the competition, 40.10±9.57 vs 30.80±10.26, p<0.05). The mean sAA activity was 5.89±0.75 ln(U/mL) at baseline, and increased significantly to 6.56±0.58 ln(U/mL) just before the training session (p<0.05), and it was 6.90±0.70 ln(U/mL) before the competition (p<0.05 vs baseline). The mean sP concentration increased progressively but the differences were not significant 1.84±0.70 [g/L] vs 2.28±0.97 [g/L] vs 2.91±1.44 [g/L], respectively. The mean salivary K + concentration was significantly higher before the competition vs the baseline value (35.73±8.3 mmol/L vs 23.94±4.83 mmol/L, p<0.01). CONCLUSIONS:The sAA activity and salivary K + concentration were both in agreement with the anxiety scores, and they can be applied as useful non-invasive biomarkers of stress. A combination of psychological, biochemical and physiological indicators should be used to establish a comprehensive assessment of stress in competitive sport.

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Background: Patellar tendinopathy is a common chronic condition caused by mechanical loading that leads to patellar tendon (PT) degeneration, with an estimated incidence of 13% across all sports in adolescents. Musculoskeletal ultrasound (MSK-US) evaluation is becoming more common in the diagnostic process, but normative data are extremely rare for the adolescent population. These normative data are needed to aid in proper interpretation of the MSK-US image. Purpose: The purpose of this study was to determine standard reference values for thickness, width, and cross-sectional area (CSA) of the PT using MSK-US in asymptomatic adolescent athletes. Methods: IRB approval, parental consent, and athlete assent were obtained prior to data collection. Bilateral PT were scanned using a portable US unit with a 12-4MHz linear array transducer. Long axis images were captured at the apex and 1cm distal to the patella, 1 cm proximal to the insertion and at the PT insertion (Figure 1a & 1b). Short axis images were captured 1 cm proximal and distal to the attachments. PT thickness, width, and CSA were measured using ImageJ by a single evaluator. Additional exploratory analyses were also conducted. Results: Seventy-one adolescent athletes (27 males, 44 females) between 11-18 years old (13.8 ±1.8 years) volunteered. Mean values for PT thickness, width, and CSA are found in Table 1. Significant differences in PT thickness and CSA between sex were identified at each measurement location (P<.05), with males ranging 4.0-9.9 mm thicker than females. PT width was not significantly different proximally or distally. The left proximal PT was significantly wider than right (P<.0001), but no other side differences were found. Lastly, significant weak positive correlations were present in distal tendon CSA with height (left PT: r(52)=.348, P=.014, right PT: r(49)=.369, P=.007) and weight (left PT: r(50 )=.290, P=.041). There was no correlation with age. Conclusion: These data represent one of the largest healthy cohorts of adolescent athletes from which normative data have been collected. This preliminary analysis reveals some interesting trends, such as the thickness of the PT is greatest at the insertion and origin, while thinner at mid-tendon, with the insertion the thicker of the two. Age was not correlated with PT size, but distal PT CSA was larger with taller and heavier individuals. These data will contribute to the paucity of adolescent PT MSK-US data, which should aid clinicians in interpretation, diagnostic accuracy, and management of active adolescent patients with patellar tendinopathy. [Figure: see text][Table: see text]