The Frontal Assessment Battery 20 years later: normative data for a shortened version (FAB15).

OBJECTIVE: The Frontal Assessment Battery (FAB) is a neuropsychological tool largely used to assess executive functions. Prior studies found a marked ceiling effect for the prehension behavior subtest (PBT) in healthy and clinical populations. Aims of the present study were (i) to examine the psychometric properties of the FAB without the contribution of PBT and (ii) to provide normative data for a revised version of the FAB after exclusion of PBT (FAB15). METHODS: The normative sample included 1,187 healthy participants. PBT had near-zero variance, poor content validity, and no discrimination power. Internal consistency increased when PBT was excluded. We assessed the FAB15 factorial structure, interrater, and test-retest reliabilities. Normative data  for the FAB15 were extracted through a regression-based procedure according to sex, age, and education. RESULTS: The principal component analysis revealed a single "executive factor" or alternatively a bifactorial solution reflecting the different degree of discriminative capability vs. difficulty of the subtests. The FAB15 demonstrated excellent interrater and test-retest reliabilities. Regression analysis showed that sex (lowly educated women < lowly educated men), higher age, and lower education affected FAB15 score. Accordingly, three grids for adjustment of raw scores (men, women, and both) were constructed. The cut-off was fixed at the non-parametric outer tolerance limit on the fifth centile (9.36, 95% CI). CONCLUSION: The observation of a ceiling effect in healthy subjects makes PBT not suitable for inclusion in a neuropsychological battery. The FAB15 may successfully replace the conventional FAB as a more severe and valid short screening tool to assess executive functioning.

Neuropsychology of posteromedial parietal cortex and conversion factors from Mild Cognitive Impairment to Alzheimer's disease: systematic search and state-of-the-art review.

In the present review, we discuss the rationale and the clinical implications of assessing visuospatial working memory (VSWM), awareness of memory deficits, and visuomotor control in patients with mild cognitive impairment (MCI). These three domains are related to neural activity in the posteromedial parietal cortex (PMC) whose hypoactivation seems to be a significant predictor of conversion from MCI to Alzheimer's disease (AD) as indicated by recent neuroimaging evidence. A systematic literature search was performed up to May 2021. Forty-eight studies were included: 42 studies provided analytical cross-sectional data and 6 studies longitudinal data on conversion rates. Overall, these studies showed that patients with MCI performed worse than healthy controls in tasks assessing VSWM, awareness of memory deficits, and visuomotor control; in some cases, MCI patients' performance was comparable to that of patients with overt dementia. Deficits in VSWM and metamemory appear to be significant predictors of conversion. No study explored the relationship between visuomotor control and conversion. Nevertheless, it has been speculated that the assessment of visuomotor abilities in subjects at high AD risk might be useful to discriminate patients who are likely to convert from those who are not. Being able to indirectly estimate PMC functioning through quick and easy neuropsychological tasks in outpatient settings may improve diagnostic and prognostic accuracy, and therefore, the quality of the MCI patient's management.

Hand movements in Mild Cognitive Impairment: clinical implications and insights for future research.

Decreased upper-extremity/visuomotor abilities are frequently encountered in healthy aging. However, few studies have assessed hand movements in the prodromal stage of dementia. The evaluation of visuomotor skills in patients with Mild Cognitive Impairment (PwMCI) may have non-negligible clinical relevance both in diagnostic and prognostic terms, given the strong relationships with executive functioning and functional autonomies. In the present review paper, these issues will be disclosed by describing general pathophysiological and neuropsychological mechanisms responsible for visuomotor deficits, and by reporting the available experimental results on differences in visuomotor functioning between PwMCI, healthy controls and/or patients with dementia. Moreover, the relationships binding visuomotor and executive domains to functional autonomies will be then addressed. Finally, we will propose insights for future research.

Italian version of the Starkstein Apathy Scale (SAS-I) and a shortened version (SAS-6) to assess "pure apathy" symptoms: normative study on 392 individuals.

OBJECTIVES: The present normative study aimed to (1) develop the Italian version of the Starkstein Apathy Scale (SAS-I) and (2) construct a shortened version including only the most sensitive items to "pure apathy" experiences. METHODS: The normative sample included 392 healthy subjects. A regression-based procedure was used to explore the effects of sex, age, and education on the raw SAS-I score. A correction grid was designed for adjusting raw scores by adding or subtracting the contribution of any significant variable and net of sociodemographic interindividual differences. Cutoff scores were also calculated and fixed at the external tolerance limit on the ninety-fifth centile. To obtain the shortened version, each SAS-I item was correlated with the Beck's Depression Inventory (BDI) score. The only items showing no correlation with BDI were implemented to bypass the well-known overlap between apathetic and depressive symptoms. RESULTS: The mean raw SAS-I score was 11.27 (SD = 4.42). A significant education effect was observed, with highly educated subjects obtaining lower scores than lowly educated ones. The proposed general cutoff score was 20.68. The SAS-I had fair internal consistency and discriminant validity. Internal consistency increased by removing item 3. The new SAS-6 included items 1, 2, 4, 10, 11, and 13 of the original scale. CONCLUSION: The SAS-I is a reliable assessment tool to support the diagnosis of apathy. The SAS-6, instead, is a brief questionnaire useful for quickly screening apathetic symptoms in outpatient practice, addressing or not the clinician to further investigations.

Psychometric properties of the STAI-Y scales and normative data in an Italian elderly population.

BACKGROUND: Early detection of anxiety symptoms in older people is capital as it may be linked to increased physical/functional disabilities, onset and progression of neurodegenerative disorders, and poor cognitive functioning. Nonetheless, there is a paucity of psychometrically validated anxiety measures in the elderly. AIMS: This study aimed at assessing the psychometric properties of the State-Trait Anxiety Inventory-Form Y (STAI-Y) and providing the first normative data for the Italian elderly population. METHODS: The sample included 361 individuals aged 65-94. All subjects underwent the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the state (S-Anxiety) and trait anxiety (T-anxiety) scales of the STAI-Y. RESULTS: The S-Anxiety and T-Anxiety scales showed reliable internal consistency and, overall, good item characteristics. Divergent validity was "apparently" threatened, with S-Anxiety scale correlating with MMSE and GDS, and T-Anxiety scale only with GDS. The principal component analysis revealed a three-factor solution for both scales, i.e., presence and absence of state (or trait) anxiety, and performance anxiety. Since no effect of sociodemographic variables was found, unadjusted cutoffs were provided. CONCLUSIONS: Although some questions on the psychometric properties of the STAI-Y remain unanswered, this normative study can help clinicians and researchers to monitor anxiety levels in the Italian elderly population.

Daily exposure to digital displays may affect the clock-drawing test: from psychometrics to serendipity.

BACKGROUND: The clock-drawing test (CDT) is a neuropsychological screening tool largely used to explore cognitive functioning. It requires participants to draw an analog clock face. Many studies have reported a good correlation between the CDT and the Mini-Mental State Examination (MMSE). The CDT has also showed a variable specificity. There are, however, some inconsistencies concerning the effect of sociodemographic variables (sex, age, education) on clock-drawing abilities. The present study aimed at examining these issues in a sample of middle-aged/young-old healthy adults. METHOD: Participants (n = 97) performed the MMSE and CDT. Clock drawings were assessed by five formal scoring systems (Wolf-Klein, Watson, Freedman, Manos, Shulman). In addition, three naïve raters provided a dichotomous judgment (normal vs. abnormal) for each clock. RESULTS: Sociodemographic variables did not affect CDT performance. Unlike earlier studies, CDT scores did not correlate with MMSE. Moreover, test specificity was appropriate only for Freedman's, Shulman's, and Wolf-Klein's methods. Interestingly, some participants drew clocks with numbers as they appear in digital clocks. By re-running the statistical analyses after removing these atypical clocks, four out of the five formal scores showed a significant correlation with MMSE; furthermore, CDT specificity slightly increased for all scoring systems including naïve ratings. CONCLUSIONS: CDT is not affected by sociodemographic variables. The finding of some clocks with digitally represented numbers suggests the need to align neuropsychological assessments with demands from an increasing digitalized environment. Moreover, the occurrence of high false-positives and possible digital contaminations suggest great caution in interpreting the clinical significance of CDT.

Mini-Mental State Examination: new normative values on subjects in Southern Italy.

OBJECTIVE: The aims of the present study were: (a) to obtain new normative data of the Italian version of the Mini-Mental Examination State (MMSE) (Measso et al. in Dev Neuropsychol 9:77-85, 1993) by administering the tool to a sample of normal Italian individuals more representative of the current Italian population; (b) to compare the sensitivity of this tool in detecting patients suffering from Alzheimer's disease (AD according to NIA-AA), as compared to the those reported in previous normative Italian studies. METHODS: MMSE was administered to 314 normal subjects recruited among individuals (and/or their relatives) attending the Offices of General Practitioners (GP) or Memory Clinics in Campania (Italy) by convenience sampling. A group of 47 patients with AD were included into the study. The effect of demographic variables on the raw MMSE scores of normal subjects was checked by multiple linear regression assuming MMSE scores as dependent variable and age, gender and education as the independent one(s). Therefore, a simultaneous regression model was constructed to correct the raw scores according the sensitive variables. Correction grid and equivalent scores were devised to classify subject's performance. RESULTS: The mean raw MMSE score was 27.78 (SD = 1.80) (range 22-30/30). There was no significant difference between scores achieved by men or women (p = 0.688). Multiple linear regression analysis showed a significant effect of age and years of school attendance on the MMSE raw score, whereas gender did not show any significant effect. The cutoff score, distinguishing between pathological and normal performances, was fixed at the fifth centile corresponding to 24.9/30, higher than the current score of 23.8/30. The new cutoff value was able to identify 44/47 patients with AD, in contrast to 38/47 subjects detected by currently used norms. CONCLUSIONS: (1) A more updated and representative population sample; (2) a new cutoff threshold able to distinguish between normal and pathological performances; (3) a correction grid that reduces the risk of false-positive and false-negative values due to the influence of the main demographic factors; (4) greater sensitivity, compared to previous Italian normative studies in identifying people with dementia.

Meta-Analysis of Neuropsychological Studies in Panic Disorder Patients: Evidence of Impaired Performance during the Emotional Stroop Task.

BACKGROUND: Recent investigations have highlighted significant differences in verbal recall between patients with panic disorder (PD) and controls. These studies have highlighted that verbal memory and working memory could be impaired in PD. OBJECTIVES: The objective of the present meta-analysis is to confirm this hypothesis, reviewing the studies that have investigated neurocognitive testing in PD. METHODS: We performed a systematic literature search for studies published between 1980 and 2015 that reported cognitive measurements in PD patients and controls. Effect size estimates were computed using the restricted maximum likelihood model. Only case-control studies were selected for this meta-analysis. We included studies that made a direct comparison between PD subjects and healthy controls. The diagnostic group consisted of adult patients aged over 18 years diagnosed with PD. We excluded the studies that did not employ a case-control design. All statistical analyses were carried out on R using the "metafor" package version 1.9-8. The effect size for each study neuropsychological test was calculated using the mean and SD of performance results, and p values < 0.05 were considered significant. RESULTS: We identified few studies that tested verbal memory and executive functions in PD patients and controls, and this difference was not significant. On the other hand, there are several studies that have used the emotional Stroop task to assess cognitive functions in PD. There is no robust evidence of impairment of memory function in PD; however, when considering the emotional Stroop task, it was found that PD patients performed slower (p < 0.01) than healthy controls for all three types of stimuli (neutral, negative, positive). CONCLUSION: This meta-analysis included a small number of studies, which may have introduced bias into the analysis. However, there is some evidence of impairment of neurocognitive functions in PD when performing the emotional Stroop task. Furthermore, the paucity of studies evaluating neurocognition in PD suggests the need for further research in this field in order to draw meaningful conclusions.

Manual asymmetry for temporal and spatial parameters in sensorimotor synchronization.

Previous studies suggest a right hemisphere advantage for temporal processing and a left hemisphere advantage for planning of motor actions. In the present study, we studied sensorimotor synchronization of hand reaching movements with an auditory rhythm. Blindfolded right-handed participants were asked to synchronize left and right hand movements to an auditory rhythm (40 vs. 60 vs. 80 bpm) and simultaneously reproduce the amplitude of a previously shown movement. Constant and variable asynchronies and movement amplitude errors were measured. The results showed that (a) constant asynchrony was lesser with the left hand than the right hand and (b) constant and variable amplitude errors were lesser with the right hand than the left hand. We suggest that when hand reaching movements are synchronized with an auditory rhythm, the left hand/right hemisphere system appears relatively specialized in temporally adhering to the rhythm and the right hand/left hemisphere system in performing spatially accurate movements.

Association between antipsychotic treatment and leptin levels across multiple psychiatric populations: An updated meta-analysis.

OBJECTIVE: Antipsychotics (APs) are associated with metabolic syndrome, with increases in leptin proposed as an underlying mechanism of AP-induced weight gain. Currently available meta-analyses on this topic have limited their populations of interest to those diagnosed with schizophrenia. The purpose of this meta-analysis is to explore the relationship between leptin levels and AP use across multiple psychiatric diagnoses, and also in healthy controls. METHOD: Systematic electronic searches were conducted using PubMed and OVID: Medline. Longitudinal studies were included if showing leptin levels before and after AP use. We included participants with any psychiatric disorders and mentally healthy participants, if exposed to AP use. The differences in leptin levels were evaluated using Hedges' g with a random effects model. RESULTS: Forty-two studies were found (36 schizophrenia, 2 bipolar disorder, 1 anorexia nervosa, and 3 healthy controls), encompassing 66 study arms and 1,156 participants. The meta-analysis showed that regardless of diagnoses, leptin levels increase with AP use (Hedges' g = 0.811, p ≤ .001). CONCLUSION: Leptin increases induced by APs are present across all diagnoses. More comprehensive research is needed to understand the relationship between AP use and leptin levels across multiple diagnoses.

Visual illusion and line bisection: a bias hypothesis revisited.

It is generally accepted that visual illusions affect line bisection in the predicted direction. However, it has been reported an illusionary bias which seems questioning such general view. In a previous study, participants bisected lines flanked at both ends by two pairs of arrows, pointing in the same direction. The medialmost vertices of one pair converged on the line (converging arrows), whereas those of the other pair did not (non-converging arrows). Participants bisected lines toward the base of the arrows, i.e., toward the wider end of the stimulus and in the direction opposite to that predicted by the Baldwin illusion. However, the bisection bias was also directed away from the location of the converging arrows. We investigated what is the main factor affecting line bisection: arrows orientation, as previously suggested, or interference effects related to the location of converging arrows. In experiment 1, participants bisected lines flanked by converging versus non-converging arrows. Results confirmed the presence of a bisection bias directed not only toward the base of the converging arrows but also away from their location. In experiment 2, the arrows were located more internally, so that their medialmost vertices always converged on the line. Results showed that the bisection bias was directed away from the location of the arrows regardless of their orientation. It is suggested that the previously reported bisection bias did not depend on arrows orientation, but rather on interference effects related to converging arrows position. The theoretical implications of the results are discussed.

Qualitative patterns at Raven's colored progressive matrices in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Visuo-spatial and problem-solving abilities are commonly impaired in patients with Alzheimer's disease (AD). Conversely, subjects with amnestic mild cognitive impairment (aMCI) do not exhibit overt involvement of cognitive domains other than memory. Consequently, a detection of an impairment at the Raven's colored progressive matrices (RCPM) could be useful to discriminate aMCI from AD and to mark the progression from one condition to another. AIM OF THE STUDY: To describe the pattern of errors at RCPM in subjects suffering from AD as compared with that of aMCI. METHODS: Fifteen patients with AD, 15 subjects with aMCI and 31 Healthy Controls (HC) received the RCPM. The errors were classified as: (1) difference (D); (2) inadequate individuation (II); (3) repetition of the pattern (RP); (4) incomplete correlation (IC). RESULTS: No difference approached significance between aMCI subjects and HC. AD patients always exhibited a higher number of errors as compared with HC. AD patients showed higher number of errors as compared with aMCI only on RP and IC errors. CONCLUSIONS: The results suggest that the visuo-spatial and problem-solving impairment that characterize AD, and probably subtend the progression from aMCI to dementia, do not affect to the same extent all cognitive dimensions explored by RCPM.

High levels of GPR30 protein in human testicular carcinoma in situ and seminomas correlate with low levels of estrogen receptor-beta and indicate a switch in estrogen responsiveness.

The G protein-coupled estrogen receptor (GPR30) is suggested to be involved in non-nuclear estrogen signalling and is expressed in a variety of hormone dependent cancer entities. It is well established that oestrogens are involved in pathological germ cell proliferation including testicular germ cell tumours. This study was performed to further elucidate the role of this receptor and the possible correlation with the estrogen receptor ß in human testicular carcinoma in situ (CIS), seminomas and in GC1 and TCam-2 germ cell lines; in addition, a Tissue Micro-Array was built using the most representative areas from 25 cases of human testicular seminomas and 20 cases of CIS. The expression of ERß and GPR30 were observed by using Western blot analysis in combination with immunocytochemistry and immunofluorescence analyses. Here, we show that down regulation of ERß associates with GPR30 over-expression both in human testicular CIS and seminomas. In addition, we show that 17ß-oestradiol induces the ERK1/2 activation and increases c-Fos expression through GPR30 associated with ERß down-regulation in TCam-2 cell line. The present results suggest that exposure to oestrogens or oestrogen-mimics, in some as of yet undefined manner, diminishes the ERß-mediated growth restraint in CIS and in human testicular seminoma, probably due to ERß down-regulation associated to GPR30 increased expression indicating that GPR30 could be a potential therapeutic target to design specific inhibitors.

Flanker interference effects in a line bisection task.

Previous studies have shown that flanking distractors influence line bisection. In the present study, we examined if reaching the flanker after bisecting the line resulted in a variation of flanker interference on line bisection. Right- and left-handed participants were asked to bisect a horizontal line flanked by a dot (bisection task, B-task) or to bisect the line and then to reach the dot (bisection plus reaching task, BR-task). The dot was placed laterally to, and above or below, the line edge. The results showed that in both tasks the subjective midpoint was shifted away from the position of the dot. However, this effect was greater in the BR-task than in the B-task. We suggest that the requirement to perform an action to the flanker in the BR-task induced participants to pay more attention to the dot, enhancing its salience and distorting effects on line bisection.

Age-related differences in distractor interference on line bisection.

Using a bisection paradigm, we investigated age-related differences in susceptibility to distractor interference. Older and younger participants were asked to bisect a horizontal line flanked by a pair of distractors, placed in either left or right hemispace. The results showed that (1) in both groups the distractors interfered with line bisection so that the localization of subjective midpoint was selectively shifted away from their position; (2) the shifting of subjective midpoint was greater in the older than in the younger group when the distractors were placed in the left hemispace. We suggest that the increase of the bisection bias in the older group depends on changes in attentional mechanisms involved in inhibiting irrelevant information.

Laterality of a second player position affects lateral deviation of basketball shooting.

Asymmetrically placed visual distractors are known to cause a lateral bias in the execution of a movement directed toward a target. The aim of the present experiment was to verify if the trajectory of the ball and the trajectory of the jump for a basket-shot can be affected by the sole position of a second player, who stays in front of the shooting player in one of three possible positions (centre, left or right) but too far to physically interfere with the shot. Young basketball players were asked to perform 60 shots at 6.25 m from a regular basket, with or without a second player staying in front of them in, alternately, a centre, left or right position. A computerised system measured the angular deviation of the jump direction from the vertical direction and the lateral deviation of the ball trajectory from the midline. The results showed that both the jump direction and the entry position of the ball deviated toward the opposite side from the second player's side; however, these effects were too small to significantly affect the mean goal percentage. This result confirms that some placements of the players can have an effect as visual distractors. Further studies are necessary to find what game conditions can make such distractors harmful for the athletic performance.

Low-FODMAP diet and hidradenitis suppurativa: the role of nutritionists in the management of dermato-endocrine disorders.

Hidradenitis suppurativa (HS) is a chronic inflammatory, immune-mediated, debilitating skin disease, characterized by subcutaneous nodules, with a still not clear pathophysiology. Although the prevalence is rather low (about 1% in Europe), its clinical complications, as well as the disabling symptomatology, make it necessary multidisciplinary therapeutic approaches. Not recently several authors described the involvement of the well-known gut-skin axis in both pathogenesis and progression of dermatological diseases. In particular, a high frequency of intestinal disorders (such as irritable bowel syndrome and inflammatory bowel disease) has been reported in HS patients, leading to speculate the existence of a relationship between such gut and skin diseases. The keystone in this relationship seems to be an impairment of the physiological gut mucosal barrier structure, resulting in the so-called leaky gut. The leaky gut, thus, might be responsible for a dietary compound-caused activation of the local immune system, with consequent trigging of both local and systemic inflammation, resulting in exacerbation of skin symptoms in HS patients. The current literature suggests the use of a low fermentable, oligo-, di, mono-saccharides and polyols (FODMAP) diet as a valid nutritional strategy in leaky gut. In light of this, we want to evaluate and consider the potential use of low-FODMAP diet in HS patient.

The Relationship between Executive Functions and Body Weight: Sex as a Moderating Variable.

This study explores the interplay between executive functions and body weight, examining both the influence of biological factors, specifically sex, and methodological issues, such as the choice between Body Mass Index (BMI) and waist circumference (WC) as the primary anthropometric measure. A total of 386 participants (222 females, mean age = 45.98 years, SD = 17.70) were enrolled, from whom sociodemographic (sex, age, years of formal education) and anthropometric (BMI and WC) data were collected. Executive functions were evaluated using the Frontal Assessment Battery-15 (FAB15). The results showed the increased effectiveness of WC over BMI in examining the relationships between executive functions, sex differences, and body weight. In particular, this study revealed that there was a significant moderating effect of sex at comparable levels of executive functioning. Specifically, women with higher executive performance had lower WCs than their male counterparts, suggesting that executive function has a greater impact on WC in women than in men. Our findings highlight the importance of conducting more in-depth investigations of the complex relationship between cognitive deficits and weight gain, considering confounding variables of behavioral, psychobiological, and neurophysiological origin.

Functional Characteristics and Coping Strategies among Rugby Athletes: A Cluster Analysis Approach.

The developing domain of mental health in sports has gained much interest, acknowledging its pivotal role in athlete performance and well-being. The aim of this research is to provide a quantitative description concerning the levels of mental health, physical activity, cognitive fusion, cognitive flexibility, and coping strategies that characterize rugby athletes by using a data-driven approach. A total of 92 rugby athletes took part in this study and filled out a set of self-administered questionnaires. A correlational analysis showed that general well-being was positively associated with years spent playing rugby (r = 0.23) and coping mechanisms (r = 0.29). Athletes' well-being was also negatively correlated with cognitive inflexibility (r = -0.41) and cognitive fusion (r = -0.39). A k-means cluster analysis identified two unique groups: group 1, characterized by higher levels of psychological well-being, lower levels of physical activity, greater cognitive flexibility, improved coping techniques, and reduced cognitive fusion, and group 2, which exhibits opposite characteristics. The discrepancies observed in psychological characteristics such as coping strategies, cognitive fusion, and cognitive inflexibility highlight their potential impact on the general health of rugby players. To comprehend the complex interplay between psychological and physical elements in rugby athletes, long-term studies with larger samples are crucial.

Molecular biomarkers as potential targets for therapeutic strategies in human testicular germ cell tumors: an overview.

Testicular germ cell tumors (TGCTs), the most common malignancy in males between 15 and 34 years of age and the most frequent cause of death from solid tumors in this age group. TGCTs can be subdivided into seminoma and non-seminoma germ cell tumors (NSGCTs), including embryonal cell carcinoma, choriocarcinoma, yolk sac tumor, and teratoma. Seminomas and NSGCTs do not only present distinctive clinical features, but they also show significant differences as far as therapy and prognosis are concerned. Seminomas are highly sensitive to both radiation and chemotherapy, with a good prognosis, non-seminomas are sensitive to platinum-based combination chemotherapy and are less susceptible to radiation, with the exception of teratomas. The different therapeutic outcome might be explained by inherent properties of the cells from which testicular neoplasia originate. The unique treatment sensitivity of TGCTs is unexplained so far, but it is likely to be related to intrinsic molecular characteristics of the PGCs/gonocytes, from which these tumors originate. Many discovered bio-markers including OCT3/4, SOX2, SOX17, HMGA1, HMGA2, PATZ1, GPR30, Aurora B, estrogen receptor ß, and others have given further advantages to discriminate between histological subgroups. In addition, therapeutic approaches for the treatment of TGCTs have been proposed: humanized antibodies against receptors/surface molecules on cancer cells, inhibitors of serine-threonine, and tyrosine kinases, and others. The mini-review will be an overview on the molecular alterations identified in TGCTs and on novel targeted antineoplastic strategies that might help to treat chemotherapy resistant TGCTs.