Increased levels of plasma neudesin in adult growth hormone deficiency and their relationship with plasma liver-expressed antimicrobial peptide-2 levels: a cross-sectional study.

PURPOSE: Adult growth hormone deficiency (aGHD) is characterized by an altered metabolic profile and increased cardiovascular risk. Neudesin is a newly discovered protein mainly secreted from adipose tissue and brain, under evaluation for its possible activity as a negative regulator of energy expenditure. Liver-expressed antimicrobial peptide (LEAP)-2 is a competitive antagonist of ghrelin on its receptor. An observational cross-sectional study was performed to test the hypothesis that plasma neudesin levels may be modified in aGHD. Given the role played in the energy balance, any possible relationships between neudesin, LEAP-2 and metabolic and anthropometric parameters were evaluated. SUBJECTS AND METHODS: Thirty-eight patients were included: 18 aGHD patients (7 females and 11 males, aged 59.7 ± 2.6 years, BMI 30.2 ± 2.2 kg/m2); 20 healthy controls (12 females and 8 males, aged 47.1 ± 2.5 years, BMI 24.1 ± 0.9 kg/m2). All patients were evaluated for glucose, insulin, HOMA and QUICKI index, total/LDL/HDL cholesterol, triglycerides, uric acid, and IGF-1. Plasma neudesin, LEAP-2, and ghrelin were measured by ELISA. Fat mass was evaluated by DEXA. RESULTS: Neudesin levels were significantly higher in aGHD versus controls. We confirmed the finding of significantly lower ghrelin levels and significantly higher LEAP-2/ghrelin ratio in aGHD patients and found a significant direct correlation between neudesin and LEAP-2 levels. A significant direct correlation between neudesin and fat mass percentage was found in the whole population. CONCLUSION: These results suggest the onset of adaptive responses to an altered metabolic picture in aGHD. The changes in two distinct pathways that modulate food intake and the still limited knowledge about neudesin suggest future developments in this field.

Outcomes of endoscopic full thickness resection in the colon rectum at an Italian tertiary center.

PURPOSE: Endoscopic full-thickness resection (EFTR) is an innovative technique for the treatment of colonic lesions not feasible by conventional endoscopic resection. Here, we aimed to evaluate the efficacy and safety of a Full-Thickness Resection Device (FTRD) for colonic lesions in a high-volume tertiary referral center. METHODS: A review of a prospectively collected database on patients that underwent EFTR with FTRD for colonic lesions from June 2016 to January 2021 at our institution was performed. Data regarding the clinical history, previous endoscopic treatments, pathological examination, technical and histological success, and follow-up were evaluated. RESULTS: Thirty-five patients (26 males, median age 69 years) underwent FTRD for colonic lesion. Eighteen lesions were in the left colon, three in the transverse, and 12 in the right colon. The median size of the lesions was 13 (range 10-40) mm. Resection was technically successful in 94% of patients. The mean hospital stay was 3.2 (SD ± 1.2) days. Adverse events were reported in four cases (11.4%). Histological complete resection (R0) was achieved in 93.9% of cases. Endoscopic follow-up was available in 96.8% of patients, at a median duration of 14.6 months (3-46 months). Recurrence was observed in 19.4% of cases at a median time of 3 months (3-7 months). Five patients had multiple FTRD performed, with R0 resection in three cases. In this subset, adverse events were observed in 40% of cases. CONCLUSIONS: FTRD is safe and feasible for standard indication. The non-negligible rate of recurrence observed suggests the need for close endoscopic follow-up in these patients. Multiple EFTR could help achieve complete resection in selected cases; however, in this setting, a higher risk of adverse events was observed.

Regular football training down-regulates miR-1303 muscle expression in veterans.

PURPOSE: Regular exercise affects the expression of several genes, proteins and microRNAs (miRNAs) in time- and intensity-dependent manner promoting longevity. We previously identified from GeneChip Array analysis several differentially expressed genes and miRNAs in muscle from veteran football players (VPG) compared to active untrained elderly subjects (CG); here we focussed on miRNA-1303 (miR-1303). The aims of the present research were: to analyse the effects of football training on the expression of miR-1303 and to identify its putative target involved in the longevity pathways in skeletal muscle from VPG compared to CG. METHODS: RNA samples from 12 VPG and 12 CG muscle biopsies were used to validate miR-1303 expression. Crossing four different bioinformatic algorithms, we identified 16 putative targets of miR-1303; from these, BAG-2, KLHL7 and KBTBD6 were chosen for further validation by Western blot analysis in LHCN-M2 human myoblasts transiently transfected with miR-1303. RESULTS: Football training down-regulates miR-1303 expression in muscle from VPG compared to CG and the expression of BAG-2, a chaperon protein involved in the autophagy pathway, inversely correlated to overexpression of miR-1303 in a time-dependent manner, indicating that it is a miR-1303 potential target. CONCLUSIONS: This is the first report, to our knowledge, describing miR-1303 regulation in skeletal muscle by football training and the identification of a target protein, BAG-2, involved in the autophagy pathway. This result contributes to the enlargement of knowledge on the molecular mechanisms linking football training, autophagy and longevity.

Evaluation of responsiveness and estimation of smallest detectable change and minimal important change scores for the Childhood Atopic Dermatitis Impact Scale.

BACKGROUND: The Childhood Atopic Dermatitis Impact Scale (CADIS) is an instrument to measure quality of life in young children affected by atopic dermatitis, and their parents. OBJECTIVES: To evaluate the responsiveness (sensitivity to change), smallest detectable change (SDC) and minimal important change (MIC) of the CADIS. METHODS: Parents and primary caregivers of 300 young children completed the CADIS and a global rating of their child's skin condition at baseline and a 4-week follow-up. Kruskal-Wallis tests, Wilcoxon tests and effect sizes were used to assess responsiveness. The SDC can be seen as a change beyond measurement error. Anchor-based and distribution-based methods, and an integration of both methods were used to estimate the MIC. RESULTS: In total, 270 families provided data at baseline and 228 at follow-up. The CADIS total change score and most of the domain scores had moderate-to-strong correlations with the skin change score. Patients were grouped according to the skin change score, which served as an anchor. Children whose parents noted an improvement of the skin showed lower CADIS scores at follow-up (P < 0·001). For the SDC we obtained score changes of 1·34 points on the total score and < 1·0 points on each domain score. All detected MIC values passed the SDC cut-off. CONCLUSIONS: The CADIS is sensitive to change towards improvement of quality of life. A change > 12% on the total score or each domain score very likely represents a clinically important change. What's already known about this topic? Atopic dermatitis reduces the quality of life of affected children and their parents. The Childhood Atopic Dermatitis Impact Scale (CADIS) has been evaluated and translated into two further languages. What does this study add? Further validation of the responsiveness of the CADIS, and whether it is sensitive to change in patients whose condition had changed. Calculation of the smallest detectable change. What are the clinical implications of this work? Estimation of the minimal important change in CADIS provides benchmarks for clinical practice.

Development of a validated short-form of the Childhood Atopic Dermatitis Impact Scale, the CADIS-SF15.

BACKGROUND: The Childhood Atopic Dermatitis Impact Scale (CADIS) with 45 items may be burdensome to complete. We therefore aimed to develop a CADIS short-form. METHODS: Parents of 300 children completed the prototype CADIS. Exploratory factor analysis was conducted on the 45-item CADIS version. The most representative items were chosen. Confirmatory factor analysis was used to confirm the a priori factor structure. Content validity was assessed in a focus group of patients, parents, clinicians, methodologists and industry delegates. Internal consistency, 48-h test-retest reliability, construct validity and responsiveness of the newly developed short-form were assessed. RESULTS: A total of 270 families provided data at baseline, 34 after 48 h and 228 after 4 weeks. Fourteen items of three different factors fulfilled the proposed eligibility criteria and were included in the draft short-form. After the content validity rating, one item relating to the child's sleep was added to further improve content validity. The confirmatory factor analyses showed good model fit, and a 15-item short-form was initiated, the CADIS-SF15. The total scale and the three domains showed good internal consistency and test-retest reliability. The correlation between SCORAD and other subjective measures was consistent with our hypotheses. Differences in scores between mild, moderate and severe AD patients were significant, and the CADIS-SF15 was able to detect changes in 'improving' patients over time. CONCLUSION: The CADIS-SF15 with 15 items in three domains is an internally consistent, reliable, valid, responsive and brief measure of QoL in children affected with AD and their parents. Further evaluation of clinical applicability is required.

Pigmented purpuric dermatosis in children: a retrospective cohort with emphasis on treatment and outcomes.

BACKGROUND: Data regarding the course and treatment of pigmented purpuric dermatoses (PPD) in the paediatric population are limited. Although treatments for pigmented purpura are not well established, vitamin C and rutoside have been reported to be an effective treatment option and are widely utilized. OBJECTIVE: To assess the clinical course and utility of vitamin C and rutoside in paediatric patients with PPD treated at Ann & Robert H. Lurie Children's Hospital of Chicago between 2008 and 2018. METHODS: A retrospective review of all children with PPD managed at our hospital between 2008 and 2018 was performed. Additional follow-up was obtained via telephone interviews. RESULTS: A total of 101 patients met inclusion criteria. The female: male ratio was 1.3 : 1, and the median age at diagnosis was 8.8 years (IQR, 5.7-12.9). Median follow-up was 7.13 months (IQR, 3-17.4). The most common PPD subtypes were lichen aureus (43%) and Schamberg (34%). Fifty-three (52%) patients had evaluable follow-up documentation via their medical record or phone questionnaire. Twenty-eight patients were treated with vitamin C or rutoside or combination therapy. Twenty-five patients received no treatment. Clearance of the rash was noted in 24 (45.3%) patients overall, including 10 (42%) patients in the treated group and 14 (58%) patients in the untreated group. Recurrence was noted in seven (13.2%) patients. Treatment with vitamin C and/or rutoside was well tolerated without side effects. None of the patients were subsequently diagnosed with vasculitis, coagulopathy or cutaneous T-cell lymphoma. CONCLUSION: Pigmented purpuric dermatosis in children is a benign disorder with high rates of complete resolution. Treatment with vitamin C and rutoside is well tolerated, but in this cohort, there did not appear to be an advantage over watchful waiting without therapy.

Distinguishing postpartum and antepartum depressive trajectories in a large population-based cohort: the impact of exposure to adversity and offspring gender.

BACKGROUND: Distinguishing temporal patterns of depressive symptoms during pregnancy and after childbirth has important clinical implications for diagnosis, treatment, and maternal and child outcomes. The primary aim of the present study was to distinguish patterns of chronically elevated levels of depressive symptoms v. trajectories that are either elevated during pregnancy but then remit after childbirth, v. patterns that increase after childbirth. METHODS: The report uses latent growth mixture modeling in a large, population-based cohort (N = 12 121) to investigate temporal patterns of depressive symptoms. We examined theoretically relevant sociodemographic factors, exposure to adversity, and offspring gender as predictors. RESULTS: Four distinct trajectories emerged, including resilient (74.3%), improving (9.2%), emergent (4.0%), and chronic (11.5%). Lower maternal and paternal education distinguished chronic from resilient depressive trajectories, whereas higher maternal and partner education, and female offspring gender, distinguished the emergent trajectory from the chronic trajectory. Younger maternal age distinguished the improving group from the resilient group. Exposure to medical, interpersonal, financial, and housing adversity predicted membership in the chronic, emergent, and improving trajectories compared with the resilient trajectory. Finally, exposure to medical, interpersonal, and financial adversity was associated with the chronic v. improving group, and inversely related to the emergent class relative to the improving group. CONCLUSIONS: There are distinct temporal patterns of depressive symptoms during pregnancy, after childbirth, and beyond. Most women show stable low levels of depressive symptoms, while emergent and chronic depression patterns are separable with distinct correlates, most notably maternal age, education levels, adversity exposure, and child gender.

Serum from differently exercised subjects induces myogenic differentiation in LHCN-M2 human myoblasts.

Myogenesis is the formation of muscle tissue from muscle precursor cells. Physical exercise induces satellite cell activation in muscle. Currently, C2C12 murine myoblast cells are used to study myogenic differentiation. Herein, we evaluated whether human LHCN-M2 myoblasts can differentiate into mature myotubes and express early (myotube formation, creatine kinase activity and myogenin) and late (MyHC-ß) muscle-specific markers when cultured in differentiation medium (DM) for 2, 4 and 7 days. We demonstrate that treatment of LHCN-M2 cells with DM supplemented with 0.5% serum from long-term (3 years) differently exercised subjects for 4 days induced myotube formation and significantly increased the early (creatine kinase activity and myogenin) and late (MyHC-ß expression) differentiation markers versus cells treated with serum from untrained subjects. Interestingly, serum from aerobic exercised subjects (swimming) had a greater positive effect on late-differentiation marker (MyHC-ß) expression than serum from anaerobic (body building) or from mixed exercised (soccer and volleyball) subjects. Moreover, p62and anti-apoptotic Bcl-2 protein expression was lower in LHCN-M2 cells cultured with human sera from differently exercised subjectst han in cells cultured with DM. In conclusion, LHCN-M2 human myoblasts represent a species-specific system with which to study human myogenic differentiation induced by serum from differently exercised subjects.

Determination of spermatic vein reflux after varicocele repair helps to define the efficacy of treatment in improving sperm parameters of subfertile men.

PURPOSE: A continuous spermatic venous reflux (SVR) at colour Doppler ultrasound (CDU) is an evidence for varicocele, a frequent correlate for male subfertility. We explored whether SVR after left varicocele repair is predictive for changes in semen quality in subfertile men. METHODS: Blood hormones (FSH, LH, and total testosterone) and scrotal CDU were obtained in subfertile patients with left grade II or grade III varicocele on physical evaluation and a poor sperm quality. Semen analysis and CDU were re-evaluated 6 months after a retrograde internal spermatic vein scleroembolisation. RESULTS: The retrospective study included 100 men with a baseline SVR >3 cm/s; 60 men showed a disappearance (group 1) and 40 men (group 2) showed a reduced SVR after varicocele repair. Total motile sperm count (TMC) was markedly increased after treatment (p < 0.0001; F = 35.79) and the increase was more relevant in group 1 compared to group 2 (p = 0.04; F = 4.20). TMC and left SVR values after varicocele repair were negatively correlated (R = -0.218; p = 0.035). Multivariate analysis showed that adjusted SVR after repair negatively predicted TMC change (TMC after repair minus baseline TMC) (ß = -2.56; p = 0.022). Disappearance of a continuous left SVR at CDU after varicocele repair was associated to a better improvement of semen parameters in subfertile men. CONCLUSION: Recording of a continuous left spermatic vein reflux is an objective method to assess a successful varicocele repair aimed to improve sperm parameters in subfertile men.

Effect of lifelong football training on the expression of muscle molecular markers involved in healthy longevity.

PURPOSE: We investigated whether lifelong football training affects the expression of healthy longevity-related muscle molecular markers. METHODS: Biopsies were collected from the vastus lateralis muscle of 10 lifelong football-trained men (68.2 ± 3.0 years) and of 10 active untrained healthy men (66.7 ± 1.3 years). Gene and protein expression was measured by RTqPCR on RNA and by western blotting on protein extracts from muscle biopsies, respectively. RESULTS: The expression of AMPKα1/α2, NAMPT, TFAM and PGC1α, which are markers of oxidative metabolism, and MyHC ß isoform expression was higher in the muscle of football-trained men vs untrained men. Also citrate synthase activity was higher in trained than in untrained men (109.3 ± 9.2 vs 75.1 ± 9.2 mU/mg). These findings were associated with a healthier body composition in trained than in untrained men [body weight: 78.2 ± 6.5 vs 91.2 ± 11.2 kg; body mass index BMI: 24.4 ± 1.6 vs 28.8 ± 4.0 kg m-2; fat%: 22.6 ± 8.0 vs 31.4 ± 5.0%)] and with a higher maximal oxygen uptake (VO2max: 34.7 ± 3.8 vs 27.3 ± 4.0 ml/min/kg). Also the expression of proteins involved in DNA repair and in senescence suppression (Erk1/2, Akt and FoxM1) was higher in trained than in untrained men. At BMI- and age-adjusted multiple linear regression analysis, fat percentage was independently associated with Akt protein expression, and VO2max was independently associated with TFAM mRNA and with Erk1/2 protein expression. CONCLUSIONS: Lifelong football training increases the expression of key markers involved in muscle oxidative metabolism, and in the DNA repair and senescence suppression pathways, thus providing the molecular basis for healthy longevity.

Thyroid Function and its Implications in Oxidative Stress Influencing the Pathogenesis of Osteoporosis in Adults with Down Syndrome: A Cohort Study.

People with Down syndrome (DS) show lower bone mass density (BMD) and a higher prevalence of hypothyroidism compared to general population. Furthermore, DS is a well-known high oxidative stress (OS) condition because genes involved in OS map on chromosome 21. Thyroid function too is involved in OS. Since both thyroid function and OS lead to lower BMD and osteoporotic fractures, we have explored correlations among BMD, thyroid hormones, and parameters of OS in DS adults. A total of 105 DS patients (48 males; 21-71 years; mean BMI 28.88±7.12 kg/m(2)) were enrolled in a cohort study, 48 of them undergoing thyroid replacement therapy. We evaluated thyroid function, BMD, and total antioxidant capacity (TAC) in blood plasma. TAC was assayed by H2O2-metmyoglobin system, as source of radicals, and by the chromogenous ABTS, with a latency time (LAG) in the appearance of its cation ABTS+proportional to antioxidant concentration. BMD was evaluated with DEXA, using WHO criteria to classify osteoporosis. Low BMD was found in 83.78% of patients. TSH and LAG did not correlate with BMD. Nevertheless, LAG significantly correlates to Z-scores estimated at the lumbar spine (r(2)=0.558; p=0.03) in hypothyroid patients. Our data show that low TAC could be more associated with reduced BMD rather than TSH itself in DS patients and that the OS could have a role in the pathogenesis of osteoporosis regarding the hypothyroid subgroup.

Effect of rMnSOD on survival signaling in pediatric high risk T-cell acute lymphoblastic leukaemia.

Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that defends against oxidative damage due to reactive oxygen species (ROS). A new isoform of MnSOD with cytotoxic activity was recently discovered in liposarcoma cells. Here, we tested the effectiveness of a recombinant form of this isoform (rMnSOD) on leukemic T cells, Jurkat cells, and lymphocytes. Our results confirm that leukemic T cells can internalize rMnSOD and that rMnSOD causes apoptosis of 99% of leukemic cells without showing toxic effects on healthy cells. Using light and electron microscopy, we determined that an rMnSOD concentration of 0.067 µM most effective on apoptosis induction. Western blot analysis showed that treatment with 0.067 µM rMnSOD resulted in high expression of the pro-apoptotic protein Bax and low expression of the anti-apoptotic protein Bcl-2 in leukemia cells. Concerning signal transduction pathway no influence was observed after treatment except for Jurkat cells showing a slightly decreased expression of ERK phosphorylation. These results suggest that rMnSOD may be an effective and non-toxic treatment option for T-cell leukemia.

GPR40 agonists for the treatment of type 2 diabetes: life after 'TAKing' a hit.

The free fatty acid receptor GPR40 has been proposed as a potential target for type 2 diabetes (T2D) pharmacotherapy. This idea has been validated in both preclinical and clinical studies, in which activation of GPR40 was shown to improve glycaemic control by stimulating glucose-dependent insulin secretion; however, the recent termination of phase III clinical trials using the GPR40 agonist TAK-875 (fasiglifam) has raised important questions regarding the long-term safety and viability of targeting GPR40 and, more specifically, about our understanding of this receptor's basic biology. In the present review, we provide a summary of established and novel concepts related to GPR40's pharmacobiology and discuss the current status and future outlook for GPR40-based drug development for the treatment of T2D.

Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism.

We investigated whether long-term recreational football training affects the expression of health-related biochemical and molecular markers in healthy untrained subjects. Five untrained healthy men trained for 1 h 2.4 times/week for 12 weeks and 1.3 times/week for another 52 weeks. Blood samples and a muscle biopsy from the vastus lateralis were collected at T0 (pre intervention) and at T1 (post intervention). Gene expression was measured by RTqPCR on RNA extracted from muscle biopsies. The expression levels of the genes principally involved in energy metabolism (PPARγ, adiponectin, AMPKα1/α2, TFAM, NAMPT, PGC1α and SIRT1) were measured at T0 and T1. Up-regulation of PPARγ (p < 0.0005), AMPKα1 (p < 0.01), AMPKα2 (p < 0.0005) and adiponectin was observed at T1 vs T0. Increases were also found in the expression of TFAM (p < 0.001), NAMPT (p < 0.01), PGC1α (p < 0.01) and SIRT1 (p < 0.01), which are directly or indirectly involved in the glucose and lipid oxidative metabolism. Multiple linear regression analysis revealed that fat percentage was independently associated with NAMPT, PPARγ and adiponectin expression. In conclusion, long-term recreational football training could be a useful tool to improve the expression of muscle molecular biomarkers that are correlated to oxidative metabolism in healthy males.

The kidney in Fabry's disease.

Fabry disease (FD) is an X-linked disease in which mutations of the GLA gene result in a deficiency of the enzyme α-galactosidase A and subsequent progressive, intralysosomal deposition of undegraded glycosphingolipid products, primarily globotriaosylceramide, in multiple organs. Progressive nephropathy is one of the main features of FD and is marked by an insidious development, with an overall rate of progression of chronic kidney disease (CKD) very similar to diabetic nephropathy. Untreated patients usually develop end stage renal disease in their 50s. The decline in renal function in FD is adversely affected by male gender, advanced CKD, hypertension and, in particular, severe proteinuria. Enzyme replacement therapy (ERT) has been shown to slow the progression of Fabry nephropathy. The current consensus is that ERT should be started in all men and women with signs of renal involvement.

Coenzyme Q10 supplementation in infertile men with low-grade varicocele: an open, uncontrolled pilot study.

Many conditions associated with male infertility are inducers of oxidative stress, including varicocele. Antioxidants, such as coenzyme Q10, may be useful in this case. To evaluate the antioxidant capacity of seminal plasma of infertile men with varicocele before and after an oral supplementation with coenzyme Q10 , 38 patients were recruited from a pilot clinical trial. A standard semen analysis was also performed at baseline and 3 months after an oral supplementation with exogenous coenzyme Q10 100 mg per die. Seminal plasma antioxidant capacity was measured using a spectroscopic method. Coenzyme Q10 therapy improved semen parameters and antioxidant status. This study highlights the importance of oxidative stress in the pathogenesis of male infertility, namely in varicocele, and strengthens the possibility of the usefulness of the antioxidant therapy.

The experience of the rigid lockdown in the dental emergency room and urgency care during COVID-19 pandemic: a transnational multicenter observational study.

OBJECTIVE: The COVID-19 pandemic had a major impact on our lives all over the world. Changes have occurred in daily life as well as in all medical services. The aim of the present study was to evaluate the emergency accesses in four universities' emergency services during the lockdown period from March to June 2020 during the COVID-19 pandemic. SUBJECTS AND METHODS: A cross-sectional study was carried out on 44,787 patients to evaluate the emergency services of university centers. The medical data of Medical Emergency Service Data (MESD) were assessed by five independent operators considering the epidemiological findings for statistics methods. RESULTS: A lower level of emergency access was reported in March-July compared to the pre-COVID period. The epidemiological data confirmed that female pathologies were more frequent compared to male patients. A fluctuation for almost all urgent healthcare centers was detected, showing one/two peaks per year during the years 2017-2019. The COVID-19 pandemic period did not influence the variety of pathology detected. CONCLUSIONS: After the lockdown period, the emergency services slowly increased in cases. The pre-COVID period showed an overlapping of the most frequent pathologies compared to the post-COVID period: periodontitis (Bari and Tirana), dental fractures (Bari and Bucharest), odontogenic abscess (Bari, Cluj and Tirana).

DHT and IGF-1 in peripheral blood lymphocytes: new markers for the biological passport of athletes.

We performed a pilot study using human peripheral blood lymphocytes (PBL) as a novel system to identify new biomarkers of dihydrotestosterone (DHT) and insulin-like growth factor-1 (IGF-1) abuse in sport. First, to obtain a gene signature, we treated cultures of lymphocytes from sedentary males with three doses of 0.237 microg/ml DHT, each of which is 80-fold the physiological concentration in young adult male serum, at days 0, 2 and 4, or with a single dose of 1.25 microg/ml IGF-1, which is 5-fold the physiological concentration in young adult male serum. We then used the Human Genome U133 Plus 2.0 microarray to identify a gene signature related to DHT or IGF-1 administration. Gene expression was evaluated after 7 and 21 days of DHT treatment, and after 24 h, 72 h and 7 days of IGF-1 treatment. Microarray analysis yielded a list of genes whose expression was altered after DHT or IGF-1 treatment. Among these we selected the genes that are most representative of the pathways associated with skeletal and muscular disorders using the IPA bioinformatics tool. We identified six (IDO1, CXCL13, CCL1, GZMB, VDR and IL2RA) and two (FN1 and RAB31) genes that were up-regulated in lymphocytes from sedentary subjects after 7 days of DHT and IGF-1 treatment, respectively. The expression of these genes in lymphocytes from differently trained athletes was either down-regulated or similar to that in lymphocytes from sedentary subjects. This finding suggests that up-regulation was due to the drug and not to physical exercise. In conclusion, we demonstrate that PBL can be useful in anti-doping checks, and we describe new biomarkers of DHT and IGF-1 abuse which can be included in the Athlete's Biological Passport.

Non-thyroidal illness syndrome in chronic diseases: role of irisin as modulator of antioxidants.

OBJECTIVE: Non-thyroidal-illness syndrome (NTIS) refers to condition found in chronic diseases that is an adaptive mechanism. However, oxidative stress is related to NTIS in a vicious circle, due to deiodinases alteration and negative effects of low T3 on antioxidant levels or activity. Muscle is one of the main targets of thyroid hormones and it can secrete a myokine named irisin, which is able to induce the browning of white adipose tissue, energy expenditure and protect against insulin resistance. Inconclusive data have been reported about irisin role in chronic diseases. Moreover, no correlation with antioxidants has been investigated. Therefore, we performed a case-control study with the primary endpoint to evaluate irisin levels in two models of NTIS, such as chronic heart failure (CHF) and chronic kidney disease (CKD) during haemodialytic treatment. The secondary endpoint was the correlation with total antioxidant capacity (TAC) to establish a possible role of irisin in the modulation of antioxidant systems. PATIENTS AND METHODS: Three groups of subjects were enrolled. Group A included CHF patients (n=18; aged 70.22 ± 2.78 ys; BMI ± 27.75 ± 1.28 kg/m2); Group B included CKD patients (n=29; aged 67.03 ± 2.64; BMI 24.53 ± 1.01); finally, 11 normal subjects (Group C) have been enrolled as controls. Irisin has been evaluated by ELISA method and Total Antioxidant Capacity (TAC) by spectrophotometric method. RESULTS: Irisin was significantly higher in Group B vs. A and C groups (Mean ± SEM: 20.18 ± 0.61 ng/ml vs. 2.77 ± 0.77 and 13.06 ± 0.56, respectively; p<0.05); a significant correlation between irisin and TAC was observed in group B. CONCLUSIONS: These preliminary data suggest a possible role of irisin in the modulation of antioxidants in two chronic syndromes with low T3 (i.e., CHF and CKD) with differential pattern in these two models studied. Further insights are needed to confirm this pilot study, which could be the basis for a longitudinal investigation, to assess a prognostic role of irisin with possible therapeutic implications.

Autologous tooth for bone regeneration: dimensional examination of Tooth Transformer® granules.

OBJECTIVE: Since 1967, when the osteoinduction properties of autogenous demineralized dentin matrix were discovered, autologous tooth grafts have been advocated as a viable option to autologous or heterologous bone graft. Tooth graft materials may be extracted from the patient's whole tooth using a granulating device. The aim of this study was to examine the size of granules obtained by the Tooth Transformer (TT)® device, using a laser instrument with high precision. MATERIALS AND METHODS: The TT® device can obtain bone graft material in a short period from an extracted tooth. The resulting material can act as an osteoconductive scaffold, providing a mineral substrate during resorption, including platelet growth factors and morphogenetic proteins. Different studies have investigated the dimension and behavior of various graft material particles, since the size of the grafted particles may play a role in osteogenesis and bone regeneration. RESULTS: Different dimensions of granules are available: small (< 400 µm), medium (400 µm-1,000 µm) and large (1,000 µm-2,000 µm). From 4.03 µm to 100 µm the percentage of granules was 14.52 ± 1.93%. A larger part of the granules was up to 100 µm, while 85.47 ± 1.93% of the granules were from 100 µm to 1,000 µm. CONCLUSIONS: 85% of the granules produced were in accordance with the dimensions suggested in the literature.