From asking to observing. Behavioural measures of socio-emotional and motivational skills in large-scale assessments.

Socio-emotional and motivational skills are routinely measured using self-reports in large-scale educational assessments. Measures exploiting test-takers' behaviour during the completion of questionnaires or cognitive tests are increasingly used as alternatives to self-reports in the economics of education literature. We compute behavioural measures of socio-emotional and motivational skills using data from the Programme for International Student Assessment (PISA). We find that these measures capture important aspects of students' academic profiles: some are importantly associated with contemporaneous performance and educational attainment and most measures have a high degree of stability over time. However, these measures are only limitedly correlated among themselves and have low correlations with self-report measures of the same constructs. This is likely a reflection of the fact that behavioural measures are representations of the test taker current 'state', rather than descriptions of the participant view of their own 'trait' like the self-report measures. Moreover, the low correlation across measures suggests that they capture different behavioural responses to the test-taking situation. These differences are still limitedly understood because the measures are constructed ex-post using collateral information collected during the administration of assessments rather than developed ex ante in line with theoretical models of human cognition and affect.

Melanoma secretion of transforming growth factor-ß2 leads to loss of epidermal AMBRA1 threatening epidermal integrity and facilitating tumour ulceration.

BACKGROUND: For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoral epidermis is associated with a significantly increased risk of metastasis. OBJECTIVES: The aim of the present study was to evaluate the potential contribution of melanoma paracrine transforming growth factor (TGF)-ß signalling to the loss of AMBRA1 in the epidermis overlying the primary tumour and disruption of epidermal integrity. METHODS: Immunohistochemistry was used to analyse AMBRA1 and TGF-ß2 in a cohort of 109 AJCC all-stage melanomas, and TGF-ß2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analysed in a cohort of 42 melanomas, with TGF-ß2 signalling evaluated in primary keratinocytes. RESULTS: Increased tumoral TGF-ß2 was significantly associated with loss of peritumoral AMBRA1 (P < 0·05), ulceration (P < 0·001), AMLo high-risk status (P < 0·05) and metastasis (P < 0·01). TGF-ß2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes (P < 0·05). Importantly, we show loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression (P < 0·05), parakeratosis (P < 0·01) and cleft formation in the dermoepidermal junction (P < 0·05). CONCLUSIONS: Collectively, these data suggest a paracrine mechanism whereby TGF-ß2 causes loss of AMBRA1 overlying high-risk AJCC early-stage melanomas and reduced epidermal integrity, thereby facilitating erosion of the epidermis and tumour ulceration.

Assessing motor competence in kicking in individuals with Down syndrome through wearable motion sensors.

BACKGROUND: Kicking a ball is a very frequent action in sport and leisure time activities and a low proficiency in this skill could limit the participation in recreational sport activities. This issue is emphasised in individuals with Down syndrome (IDS) for which data about motor competence in kicking are limited to children. Here, we aim at evaluating the kicking competence of IDS combining a qualitative and a quantitative method. METHODS: Twenty-three adult IDS and 21 typically developed individuals (ITD) volunteered to participate in the study. Peak-to-peak 3D linear acceleration and angular velocity were recorded at 200 samples/s using two inertial measurement units placed on the lower back and lateral malleolus of the dominant limb during kicking. Motor competence in kicking was assessed according to the criteria proposed in the test of gross motor development version 3 (TGMD-3). RESULTS: Individuals with Down syndrome showed lower motor competence (ITD: 5.9 ± 1.2; IDS: 3.2 ± 2.0) and lower angular velocities about the cranio-caudal (ITD: 3.0 ± 1.8; IDS: 2.1 ± 1.1 rad/s) and medio-lateral axes (ITD: 4.5 ± 1.5; IDS: 3.0 ± 1.1 rad/s) of the trunk compared with ITD. Shank angular velocity about the medio-lateral axis was lower in IDS (ITD: 14.3.6 ± 4.0; IDS: 9.9 ± 2.8 rad/s). CONCLUSIONS: The lower trunk angular velocity in IDS may limit the possibility to rely on the proximal-to-distal sequencing commonly observed in kicking and generate high shank angular velocity upon ball impact. The lower trunk angular velocity may result from orthopaedic features of the pelvic girdle and possibly from a poorer neuromuscular control of core muscles.

Performance decline in a low-stakes test at age 15 and educational attainment at age 25: Cross-country longitudinal evidence.

INTRODUCTION: Educational attainment is associated with important life outcomes including labour market performance, health status, well-being, civic and political participation. An important question is whether it is possible to identify early those students who lack the achievement motivation that is needed to complete a higher education degree. METHODS: Longitudinal follow-ups of representative samples of participants in the 2000 and 2003 Programme for International Student Assessment (PISA) from Australia, Denmark and Switzerland (N = 3110; 1130; and 1962; age = 15 to 27; % females 51%, 51%, 49%; ethnicity/race unknown) were used to identify the association between a measure of effort on a cognitively demanding low-stake task at age 15 - performance decline during the test - and educational attainment at age 25-27. RESULTS: A one SD difference in performance decline was associated with a 5-6 percentage point difference in the probability of obtaining tertiary-level qualifications (r = -0.15 in Australia; -0.11 in Denmark and -0.11 in Switzerland). We find no evidence of differences in this relationship across genders, socio-economic status and baseline levels of ability in the three countries. The association between performance decline and educational attainment is homogeneous across these groups. Self-reported measures of achievement motivation were not predictive of educational attainment in the three countries. CONCLUSIONS: Our work contributes new longitudinal evidence to the body of research in education employing behavioural measures of motivation and engagement. It can be used to understand the potential long-term consequences of disparities in students' preparation to sustain effort over cognitively demanding tasks.

Transglutaminase Type 2 is Involved in the Hematopoietic Stem Cells Homeostasis.

Type 2 transglutaminase (TG2) is a multifunctional protein involved in various biological processes playing a key regulatory role in cell homeostasis such as cell death and autophagy. New evidence is emerging that support an important role of autophagy in regulating normal hematopoiesis. Prompted by these findings, in this study we investigated in vivo involvement of TG2 in mouse hematopoiesis under normal or nutrient deprivation conditions. We found that the number and rate of differentiation of bone marrow hematopoietic stem cell was decreased in the TG2 knockout mice. We present evidence showing that these effects on hematopoietic system are very likely due to the TG2-dependent impairment of autophagy. In fact, stimulation of autophagy by starvation is able to rescue the block of the differentiation of stem cells progenitors in the TG2 KO mice. It was also shown that the RhoA/ERK½ pathway, known to be essential for regulation of the bone marrow progenitor cells homeostasis, was significantly impaired in the absence of TG2. Hence, this study expanded our knowledge about TG2 discovering a role of this enzyme in regulation of hematopoiesis.

Transglutaminase type 2 plays a key role in the pathogenesis of Mycobacterium tuberculosis infection.

BACKGROUND: Mycobacterium tuberculosis (MTB), the aetiological agent of tuberculosis (TB), is capable of interfering with the phagosome maturation pathway, by inhibiting phagosome-lysosome fusion and the autophagic process to ensure survival and replication in macrophages. Thus, it has been proposed that the modulation of autophagy may represent a therapeutic approach to reduce MTB viability by enhancing its clearance. OBJECTIVE: The aim of this study was to investigate whether transglutaminase type 2 (TG2) is involved in the pathogenesis of MTB. RESULTS: We have shown that either genetic or pharmacological inhibition of TG2 leads to a marked reduction in MTB replicative capacity. Infection of TG2 knockout mice demonstrated that TG2 is required for MTB intracellular survival in macrophages and host tissues. The same inhibitory effect can be reproduced in vitro using Z-DON, a specific inhibitor of the transamidating activity of TG2. Massive cell death observed in macrophages that properly express TG2 is hampered by the absence of the enzyme and can be largely reduced by the treatment of wild-type macrophages with the TG2 inhibitor. Our data suggest that reduced MTB replication in cells lacking TG2 is due to the impairment of LC3/autophagy homeostasis. Finally, we have shown that treatment of MTB-infected murine and human primary macrophages with cystamine, a TG2 inhibitor already tested in clinical studies, causes a reduction in intracellular colony-forming units in human macrophages similar to that achieved by the anti-TB drug capreomycin. CONCLUSION: These results suggest that inhibition of TG2 activity is a potential novel approach for the treatment of TB.

Role of autophagy in HIV infection and pathogenesis.

The aim of autophagy is to re-establish homeostasis in response to a variety of stress conditions. By forming double-membrane vesicles, autophagy engulfs damaged or superfluous cytoplasmic material and recycles degradation products for new synthesis or energy production. Of note, the same mechanism is used to capture pathogens and has important implications in both innate and adaptive immunity. To establish a chronic infection, pathogens have therefore evolved multiple mechanisms to evade autophagy-mediated degradation. HIV infection represents one of the best characterized systems in which autophagy is disarmed by a virus using multiple strategies to prevent the sequestration and degradation of its proteins and to establish a chronic infection. HIV alters autophagy at various stages of the process in both infected and bystander cells. In particular, the HIV proteins TAT, NEF and ENV are involved in this regulation by either blocking or stimulating autophagy through direct interaction with autophagy proteins and/or modulation of the mTOR pathway. Although the roles of autophagy during HIV infection are multiple and vary amongst the different cell types, several lines of evidence point to a potential beneficial effect of stimulating autophagy-mediated lysosomal degradation to potentiate the immune response to HIV. Characterization of the molecular mechanisms regulating selective autophagy is expected to be valuable for developing new drugs able to specifically enhance the anti-HIV response.

Analysis of session-RPE and profile of mood states during a triathlon training camp.

AIM: The aim of the present study was to monitor the internal training load and profile of mood states (POMS) during a training camp in junior-elite triathletes. METHODS: Sixteen (10 male and 6 female) young triathlon athletes (junior-elite: 18±1 yrs) were included in this study. All triathletes had been training for 7±3 years, and regularly trained 4 times a week 3h per session, throughout the year. The training camp (5 days) included two daily supervised training sessions. The CR-10RPE scale was used 30 minutes after every training session to evaluate session-RPE. POMS was administered 3 times during the training camp: at the beginning, on the 3rd day, and at the end of training camp. RESULTS: Session-RPE throughout the different training days showed significant differences (P<0.001). POMS scores showed a significant increase (P<0.001) in fatigue from the first (7.8±1.4), to the third (10.5±2.2) and to the last day of training (14.2±3.4). At the end of the camp, lower (P<0.01) vigour values (12.7±2.8) emerged with respect to the first day (15.8±3.0), whereas anger decreased (P=0.015) the last day (8.6±2.2) with respect to the intermediate evaluation (9.6±2.7). CONCLUSION: The 45% increase in fatigue, the 24% decrease in vigour, and the intraindividual variability in session RPE that emerged, indicates that young triathletes need to be monitored closely during training camps in order to individualize training to avoid training maladaptation such as non-functional overreaching.

Stress related changes during a half marathon in master endurance athletes.

AIM: The aim of the present study was to investigate heart rate (HR), salivary cortisol (sC) alpha-amylase (sAA) and rating of perceived exertion (RPE) in relation to competition outcome during a half marathon. METHODS: HR was monitored and salivary samples were collected during an official half marathon in five Master endurance runners (age 47 ± 7 years). RPE was collected using a 100-mm Visual Analogue Scale (VAS) 30 minutes after the end of competition. RESULTS: Performance corresponded to 94% of their personal best (PB). Athletes spent 53.7% of total race time at intensities above 95% HRmax. RPE showed values of 68 ± 8 mm. With respect to pre-competition values (25.54 ± 6.39 nmol/L), sC concentrations significantly increased (P=0.043) by 59% immediately after the race (40.54 ± 3.95 nmol/L) and remained elevated until 1 h post exercise. Pre-competition sAA concentrations (90.59 ± 42.86 U/mL) were 118% higher (P=0.043) with respect to time-matched baseline values (197.92 ± 132 U/mL). sAA increased (192%; P=0.043) immediately after the race and was higher than time-matched resting samples. The better each athlete performed the greater cortisol increase during exercise (P<0.001). Performance was not correlated to the anticipatory sAA (the percent difference between pre-competition values and time-matched baseline ones) or to the sAA increase during exercise. CONCLUSION: This is the first attempt to study the stress-related responses during official endurance competitions in master runners. Although the strict criteria of inclusion might have limited the statistical significance, the present findings indicate that endurance competition is a remarkable stressor for psycho-physiological aspects of master athletes.

Does the junior IAAF athletic world championship represent a springboard for the success in the throwing events? A retrospective study.

AIM: The aim of the present study was to analyze how many finalists of the IAAF World Junior Championships (WJC) in the throwing events were present in the senior IAAF ranking at the end of 2012. METHODS: The results of the 8 male and the 8 female finalists of all throwing events of the last 5 editions of the WJC from the 2002 edition were gathered. We analyzed how many athletes were missing from the IAAF ranking in 2012. For those athletes that did not drop out we monitored their progression in performance comparing their WJC and their 2012 performance. Moreover, we evaluated if the relative age effects (RAE) influenced drop out rate. RESULTS: Drop out rate was 58% in 2002, 59% in 2004, 39% in 2006, and 28% in 2008 and in 2010. The female javelin throwers showed the highest drop out rate (100%) in 2002, while the female hammer throwers showed the lowest drop out rate (0%) in 2008. Performance decreased for all male shot putters, discus and hammer throwers (P<0.001). For females and for male javelin throwers, performance increased (P<0.001). RAEs showed no significant influence on drop out rate CONCLUSION: Even if 8 of the finalists won a medal at the Olympic Games or at the World Championships, it is still not clear if participation at the WJC is a prerequisite to success at a senior level, given the elevated drop out rate observed in the present study.

Transglutaminases: future perspectives.

This is the third special issue focused on "Transglutaminases" that is now available on this journal and dedicated to one of the pioneers of these enzymes, John Edward Folk, who died December 2010 [see in this issue Beninati et al. 2012a]. The first edition, "Polyamines and Transglutaminases" was published in Amino Acids, vol 26, no. 4, 2004, with the contribution of two prestigious Guest Editors as Alberto Abbruzzese and Mauro Piacentini. This editorial initiative was followed by the second special issue published in occasion of the 50th years of the discovery of transglutaminase. Indeed, "Transglutaminase 2: 50th Anniversary of the Discovery" Amino Acids, vol 36, no. 4, 2009, was published with the valuable collaboration of Carlo Maria Bergamini and Mauro Piacentini (Beninati et al. 2009). To continue with this editorial tradition, on this occasion, an outstanding board of Guest Editors composed by Francesco Facchiano and Mauro Piacentini has also been invited to promote this initiative and recruit a selected panel of Authors, many of who participated in the first and second edition of the Gordon Conference on Transglutaminases: "Transglutaminases in Human Diseases Processes" chaired by Rickard L Eckert and Kapil Mehta on July 18-23, 2010, and by Kapil Mehta and Mauro Piacentini on July 15-20, 2012, held at Davidson College, NC, USA. In this Amino Acids special issue, the manuscripts were selected to reflect the progress and the future perspectives of transglutaminases.

Cardiovascular responses during an indoor race walking competition.

AIM: This study aims to examine the cardiovascular responses during an indoor race walking competition over the distance of 3-km for female and 5-km for male athletes. METHODS: During the Italian indoor RW Championship heart rate was monitored on eleven well trained race walkers (five men and six women) and then refereed as percentages of individuals' theoretical maximum heart rate (206-0.7·age). To provide a measure of relative intensity, five HR zones were assessed. Alterations in % HRmax both for the five and three 1000-m split distances were determined. RESULTS: During the 5-km race the athletes spent 79.7% (15 min 45 s) at HR5 (i.e., 90-100% of HRmax). Specifically, % HRmax increased by 10% in the last compared to the first 1000-m sector (P=0.006, effect size = 2.47±0.83, very large), with the first 1000-m sector lower than the subsequent ones (P=0.01, effect size=2.17 to 2.47, very large). While, for the 3-km the athletes spent 86.9% (11 min 35 s) at HR5 (i.e., 90-100% of HRmax) with no differences observed in the % HRmax between the three 1000-m sectors (P>0.01). CONCLUSION: The dissemination of performance and physical attributes identified within the present study reveal that the exercise intensity of indoor race walking competitions has a high-intensity profile and will assist coaches and athletes in formulating appropriate training, competition and recovery.

The use of session RPE for interval training in master endurance athletes: should rest be included?

AIM: The aim of this study was to evaluate the effectiveness of the session rate of perceived exertion (RPE) method as a tool to quantify internal training load during interval training in master athletes. In addition, we investigated whether it is appropriate to take into account rest periods when calculating the session-RPE. METHODS: Eight male master endurance athletes (age: 45.3±7.3 years; stature: 1.74±0.06 m; body mass: 64.9±9.1 kg) were monitored during an interval training session consisting of 5 x 1000 m performed at 95% of vVO2max with 5 min rest between bouts. Edwards' summated heart rate zone method was used as a reference measure and the session RPE rating was obtained using the CR10 Borg's scale modified by Foster. RESULTS: High (r: 0.82; R2: 0.67) and significant (P=0.013) correlation was observed between the Edwards' heart rate (HR) and the session-RPE method when rest periods are taken into account; meanwhile a higher significant correlation (r: 0.86; R2: 0.74; P=0.003) was found between Edwards' HR and the session-RPE methods when rest periods were eliminated for the session-RPE computation. CONCLUSION: Despite the rest period exclusion from the computation of session RPE seems more appropriate, the statistical analysis indicates that there is no significant difference between the two correlation coefficients. These findings suggest that the session-RPE can be a useful tool to monitor internal training load during interval training and that the inclusion/exclusion of rest periods in its computation needs further investigation.

Is subareolar intraoperative biopsy still necessary to predict nipple involvement?

OBJECTIVE: To predict the occult tumor involvement of nipple-areola complex (NAC) using preoperative MR imaging and to investigate whether the intraoperative histopathological examination of the subareolar tissue is still necessary. PATIENTS AND METHODS: Out of 712 patients submitted to nipple-sparing mastectomy (NSM) between 2014 and 2019, we selected 188 patients who underwent preoperative breast MRI. Breast MRI and intraoperative histopathological examination of the subareolar tissue were performed to predict NAC involvement at permanent pathology. All parameters were correlated with final pathological NAC assessment by univariate and multivariate analysis. RESULTS: Forty-three patients (22.9%) had tumor involvement of the NAC. At univariate analysis, non-mass enhancement type (p = 0.009), multifocality/multicentricity (p = 0.002), median tumor size (p < 0.001), median tumor-NAC distance measured by MRI (p < 0.001), tumor-NAC distance ≤ 10 mm (p < 0.001) and tumor-NAC distance ≤ 20 mm (p < 0.001), and lymphovascular invasion (p = 0.001) were significantly correlated with NAC involvement. At multivariate analysis, only tumor-NAC distance ≤ 10 mm retained statistical significance. The sensitivity and specificity of MRI tumor-NAC distance ≤ 10 mm were 79.1% and 97.2% and those of intraoperative pathologic assessment were 74,4% and 100%, respectively. CONCLUSIONS: Tumor-NAC distance is the only reliable MRI characteristic that can predict NAC involvement in breast cancer patients. Although several cut-offs showed promising performances, intraoperative pathologic assessment is still mandatory.

Multiparametric MR imaging of the prostate at 1.5-T without endorectal coil using an 8 channel pelvic phased array: Is it still a viable option?

INTRODUCTION: The purpose of our work was to evaluate the feasibility of prostate multiparametric MR imaging at 1.5-T without endorectal coil using an 8 channel pelvic phased array coil. MATERIAL AND METHODS: A total of 154 patients who underwent mp-MRI were retrospectively included. Patients received a standardized mp-MRI, compliant with 2012 European Society of Uro-Radiology guidelines, with 1·5 T magnetic field strength and an 8 channel pelvic phased-array coil. Two blinded readers graded the image quality of mp-MRI on a three-point scale and they scored the prostate lesions according to PI-RADS v2. All PI-RADS of 4 or 5 underwent biopsy. A third radiologist and a pathologist verified the correspondence between the MRI images and the results of the biopsy. RESULTS: 64 (41.6%) patients showed a Pi-rads of 4 or 5. At biopsy, 79.7% showed a Gleason score ≥7, 12.5% showed a Gleason score of 6 and 7.8% showed a negative biopsy. In the group of Pi-rads ≤ 3, 12 patients underwent a biopsy with the following results: negative biopsy in 33.3%, atypical Small Acinar Proliferation in 16.7%, prostatic intraepithelial neoplasia in 25% and indolent PCa 25%. Mp-MRI in the identification of clinically significant cancer provided a low percentage of false positive (7.8%) while in 79.7% of cases it was capable to detect clinically significant prostate cancer. In 92.2% of patients mp-MRI identified a prostate cancer with a Gleason score ≥6. The inter-reader agreement was excellent in defining both the quality of the examination and the PI-RADS category (k = 0.83 and k = 0.70, respectively). CONCLUSIONS: mp-MRI at 1.5-T without endorectal coil using an 8 channel phased array is an appropriate tool for early detection of clinically significant prostate cancer. IMPLICATIONS FOR PRACTICE: 8 channel pelvic phased array is still an appropriate tool for early detection of clinically significant prostate cancer and for obtaining a reduction in overdiagnosis of indolent PCa.

Human immunodeficiency virus 1 envelope glycoprotein complex-induced apoptosis involves mammalian target of rapamycin/FKBP12-rapamycin-associated protein-mediated p53 phosphorylation.

Syncytia arising from the fusion of cells expressing a lymphotropic human immunodeficiency virus (HIV)-1-encoded envelope glycoprotein complex (Env) gene with cells expressing the CD4/CXCR4 complex undergo apoptosis through a mitochondrion-controlled pathway initiated by the upregulation of Bax. In syncytial apoptosis, phosphorylation of p53 on serine 15 (p53S15) precedes Bax upregulation, the apoptosis-linked conformational change of Bax, the insertion of Bax in mitochondrial membranes, subsequent release of cytochrome c, caspase activation, and apoptosis. p53S15 phosphorylation also occurs in vivo, in HIV-1(+) donors, where it can be detected in preapoptotic and apoptotic syncytia in lymph nodes, as well as in peripheral blood mononuclear cells, correlating with viral load. Syncytium-induced p53S15 phosphorylation is mediated by the upregulation/activation of mammalian target of rapamycin (mTOR), also called FKBP12-rapamycin-associated protein (FRAP), which coimmunoprecipitates with p53. Inhibition of mTOR/FRAP by rapamycin reduces apoptosis in several paradigms of syncytium-dependent death, including in primary CD4(+) lymphoblasts infected by HIV-1. Concomitantly, rapamycin inhibits p53S15 phosphorylation, mitochondrial translocation of Bax, loss of the mitochondrial transmembrane potential, mitochondrial release of cytochrome c, and nuclear chromatin condensation. Transfection with dominant negative p53 has a similar antiapoptotic action as rapamycin, upstream of the Bax upregulation/translocation. In summary, we demonstrate that phosphorylation of p53S15 by mTOR/FRAP plays a critical role in syncytial apoptosis driven by HIV-1 Env.

Type 2 transglutaminase in Huntington's disease: a double-edged sword with clinical potential.

Huntington's disease (HD) is a dominant genetic neurodegenerative disorder. The pathology affects principally neurons in the basal ganglia circuits and terminates invariably in death. There is compelling necessity for safe and effective therapeutic strategies to arrest, or even retard the progression of the pathogenesis. Recent findings indicate the autophagy-lysosome systems as appealing targets for pharmacological intervention. Autophagy exerts a critical role in controlling neuronal protein homeostasis, which is perturbed in HD, and is compromised in the pathogenesis of several neurodegenerative diseases. Type 2 transglutaminase (TG2) plays an important role both in apoptosis and autophagy regulation, and accumulates at high levels in cells under stressful conditions. TG2 inhibition, achieved either via drug treatments or genetic approaches, has been shown to be beneficial for the treatment of HD in animal models. In this review we will discuss the relevance of TG2 to the pathogenesis of HD, in an effort to define novel therapeutic avenues.

Diagnosing overtraining in athletes using the two-bout exercise protocol.

OBJECTIVE: In this work, whether a two-bout exercise protocol can be used to make an objective, immediately available distinction between non-functional over reaching (NFO) and overtraining syndrome (OTS) was studied. DESIGN: Underperforming athletes who were diagnosed with the suspicion of NFO or OTS were included in the study. Recovery of the athletes was monitored by a sports physician to retrospectively distinguish NFO from OTS. SETTING: Sports medicine laboratory PARTICIPANTS: The protocol was started and completed by 10 underperforming athletes. NFO was retrospectively diagnosed in five athletes, and OTS was diagnosed in five athletes. INTERVENTIONS: A two-bout maximal exercise protocol was used to measure physical performance and stressinduced hormonal reactions. MAIN OUTCOME MEASUREMENTS: Exercise duration, heart rate and blood lactate concentration were measured at the end of both exercise tests. Venous concentrations cortisol, adrenocorticotrophic hormone (ACTH), prolactin and growth hormone were measured both before and after both exercise tests. RESULTS: Maximal blood lactate concentration was lower in OTS compared with NFO, while resting concentrations of cortisol, ACTH and prolactin concentrations were higher. However, sensitivity of these measures was low. The ACTH and prolactin reactions to the second exercise bout were much higher in NFO athletes compared with OTS and showed the highest sensitivity for making the distinction. CONCLUSIONS: NFO might be distinguished from OTS based on ACTH and prolactin reactions to a two-bout exercise protocol. This protocol could be a useful tool for diagnosing NFO and OTS; however, more data should be collected before this test can be used as the gold standard.

The involvement of cell death and survival in neural tube defects: a distinct role for apoptosis and autophagy?

Neural tube defects (NTDs), such as spina bifida (SB) or exencephaly, are common congenital malformations leading to infant mortality or severe disability. The etiology of NTDs is multifactorial with a strong genetic component. More than 70 NTD mouse models have been reported, suggesting the involvement of distinct pathogenetic mechanisms, including faulty cell death regulation. In this review, we focus on the contribution of functional genomics in elucidating the role of apoptosis and autophagy genes in neurodevelopment. On the basis of compared phenotypical analysis, here we discuss the relative importance of a tuned control of both apoptosome-mediated cell death and basal autophagy for regulating the correct morphogenesis and cell number in developing central nervous system (CNS). The pharmacological modulation of genes involved in these processes may thus represent a novel strategy for interfering with the occurrence of NTDs.