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In everyday life, the stream of affect results from the interaction between past experiences, expectations and the unfolding of events. How the brain represents the relationship between time and affect has been hardly explored, as it requires modeling the complexity of everyday life in the laboratory setting. Movies condense into hours a multitude of emotional responses, synchronized across subjects and characterized by temporal dynamics alike real-world experiences. Here, we use time-varying intersubject brain synchronization and real-time behavioral reports to test whether connectivity dynamics track changes in affect during movie watching. The results show that polarity and intensity of experiences relate to the connectivity of the default mode and control networks and converge in the right temporoparietal cortex. We validate these results in two experiments including four independent samples, two movies and alternative analysis workflows. Finally, we reveal chronotopic connectivity maps within the temporoparietal and prefrontal cortex, where adjacent areas preferentially encode affect at specific timescales.

The human face is one of the most salient stimuli in the environment. It has been suggested that even basic face-like configurations (three dots composing a downward pointing triangle) may convey salience. Interestingly, stimulus salience can be signaled by mismatch detection phenomena, characterized by greater amplitudes of event-related potentials (ERPs) in response to relevant novel stimulation as compared to non-relevant repeated events. Here, we investigate whether basic face-like stimuli are salient enough to modulate mismatch detection phenomena. ERPs are elicited by a pair of sequentially presented visual stimuli (S1-S2), delivered at a constant 1-s interval, representing either a face-like stimulus (Upright configuration) or three neutral configurations (Inverted, Leftwards, and Rightwards configurations), that are obtained by rotating the Upright configuration along the three different axes. In pairs including a canonical face-like stimulus, we observe a more effective mismatch detection mechanism, with significantly larger N270 and P300 components when S2 is different from S1 as compared to when S2 is identical to S1. This ERP modulation, not significant in pairs excluding face-like stimuli, reveals that mismatch detection phenomena are significantly affected by basic face-like configurations. Even though further experiments are needed to ascertain whether this effect is specifically elicited by face-like configuration rather than by particular orientation changes, our findings suggest that face essential, structural attributes are salient enough to affect change detection processes.

Recently, a monothematic delusion of body ownership due to brain damage (i.e., the embodiment of someone else's body part within the patient's sensorimotor system) has been extensively investigated. Here we aimed at defining in-depth the clinical features and the neural correlates of the delusion. Ninety-six stroke patients in a sub-acute or chronic phase of the illness were assessed with a full ad-hoc protocol to evaluate the embodiment of an alien arm under different conditions. A sub-group of seventy-five hemiplegic patients was also evaluated for the embodiment of the movements of the alien arm. Fifty-five patients were studied to identify the neural bases of the delusion by means of voxel-based lesion-symptom mapping approach. Our results show that, in forty percent of the whole sample, simply viewing the alien arm triggered the delusion, but only if it was a real human arm and that was seen from a 1st person perspective in an anatomically-correct position. In the hemiplegic sub-group, the presence of the embodiment of the alien arm was always accompanied by the embodiment of its passive and active movements. Furthermore, the delusion was significantly associated to primary proprioceptive deficits and to damages of the corona radiata and the superior longitudinal fasciculus. To conclude, we show that the pathological embodiment of an alien arm is well-characterized by recurrent and specific features and might be explained as a disconnection deficit, mainly involving white matter tracts. The proposed exhaustive protocol can be successfully employed to assess stroke-induced disorders of body awareness, unveiling even their more undetectable or covert clinical forms.

Epithelial ovarian cancer (EOC) is the scariest gynaecological cancer. Many advances have been done with evolving knowledge, leading to the introduction of new drugs, most in maintenance setting. The antiangiogenic Bevacizumab and the three approved PARP-inhibitors—olaparib, niraparib and rucaparib—are gradually improving PFS of patients with EOC, with initial effects on OS too. But recurrence is still a heavy sentence and lethality continues to be high. Ovarian cancer is a complex disease, with different clinical presentation, histological aspect, and molecular expression, leading to disappointing results, when using a single drug. Implementation of biobanking and analysis of patients’ tumour samples, before starting a treatment, could be a promising way to better understand molecular aspects of this disease, to identify markers predictive of response and to allow a better use of experimental drugs, as immunomodulators, targeted therapies, and combinations of these, to fight tumour growth and clinical progression. We reviewed the literature on the updated treatments for recurrent ovarian cancer, summarizing all the available drugs and combinations to treat patients with this diagnosis, and focusing the attention on the new approved molecules and the contemporary Clinical Trials, investigating new target therapies and new associations.

RPL is a very debated condition, in which many issues concerning definition, etiological factors to investigate or therapies to apply are still controversial. ML could help clinicians to reach an objectiveness in RPL classification and access to care. Our aim was to stratify RPL patients in different risk classes by applying an ML algorithm, through a diagnostic work-up to validate it for the appropriate prognosis and potential therapeutic approach. 734 patients were enrolled and divided into 4 risk classes, according to the numbers of miscarriages. ML method, called Support Vector Machine (SVM), was used to analyze data. Using the whole set of 43 features and the set of the most informative 18 features we obtained comparable results: respectively 81.86 ± 0.35% and 81.71 ± 0.37% Unbalanced Accuracy. Applying the same method, introducing the only features recommended by ESHRE, a correct classification was obtained only in 58.52 ± 0.58%. ML approach could provide a Support Decision System tool to stratify RPL patients and address them objectively to the proper clinical management.

Our research focused on the role of vision and proprioception in modulating a defensive reflex (hand blink reflex, HBR) whose magnitude is enhanced when the threatened hand is inside the peripersonal space of the face. We capitalized on virtual reality, which allows dissociating vision and proprioception by presenting a virtual limb in congruent/incongruent positions with respect to the participants' limb. In experiment 1, participants placed their own stimulated hand in far/near positions with respect to their face (postural manipulation task), while observing a virtual empty scenario. Vision was not informative, but the HBR was significantly enhanced in near compared with far position, suggesting that proprioception is sufficient for the HBR modulation to occur. In experiment 2, participants did not perform the postural manipulation but they (passively) observed the avatar's virtual limb performing it. Proprioceptive signals were not informative, but the HBR was significantly enhanced when the observed virtual limb was near to the face, suggesting that visual information plays a role in modulating the HBR. In experiment 3, both participants and avatar performed the postural manipulation, either congruently (both of them far/near) or incongruently (one of them far, the other near). The HBR modulation was present only in congruent conditions. In incongruent conditions, the conflict between vision and proprioception confounded the system, abolishing the difference between far and near positions. Taken together, these findings promote the view that observing a virtual limb modulates the HBR, providing also new evidence on the role of vision and proprioception in modulating this subcortical reflex.

Breast reconstruction plays a fundamental role in the therapeutic process of breast cancer treatment and breast implants represents the leading breast reconstruction strategy. Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL), locoregional recurrence in the skin flap, and skin flap necrosis are well-known complications following mastectomy and immediate breast reconstruction (IBR). We report a case of locoregional cancer recurrence in the mastectomy flap mimicking BIA-ALCL, in a patient who underwent 6 breast procedures in four facilities across 15 years including immediate breast reconstruction with macrotextured breast implants. Despite the rate and onset of the disease, clinicians should be aware of BIA-ALCL. Due to the risk of false negative results of fine needle aspiration, clinical suspicion of BIA-ALCL should drive clinicians' choices, aside from cytological results. In the present case, surgical capsulectomy of the abnormal periprosthesic tissue revealed locoregional recurrence.

The ability to identify our own body and its boundaries is crucial for survival. Ideally, the sooner we learn to discriminate external stimuli occurring close to our body from those occurring far from it, the better (and safer) we may interact with the sensory environment. However, when this mechanism emerges within ontogeny is unknown. Is it something acquired throughout infancy, or is it already present soon after birth? The presence of a spatial modulation of multisensory integration (MSI) is considered a hallmark of a functioning representation of the body position in space. Here, we investigated whether MSI is present and spatially organized in 18- to 92-h-old newborns. We compared electrophysiological responses to tactile stimulation when concurrent auditory events were delivered close to, as opposed to far from, the body in healthy newborns and in a control group of adult participants. In accordance with previous studies, adult controls showed a clear spatial modulation of MSI, with greater superadditive responses for multisensory stimuli close to the body. In newborns, we demonstrated the presence of a genuine electrophysiological pattern of MSI, with older newborns showing a larger MSI effect. Importantly, as for adults, multisensory superadditive responses were modulated by the proximity to the body. This finding may represent the electrophysiological mechanism responsible for a primitive coding of bodily self boundaries, thus suggesting that even just a few hours after birth, human newborns identify their own body as a distinct entity from the environment.

The clinical effects of the Covid-19 pandemic are now the subject of numerous studies worldwide. But what are the effects of the quarantine imposed by the states that implemented the measures of lockdown? The present research aims to explore, in a preliminary way, the major stress-related symptoms during the lockdown, due to Covid-19, in the Italian population. Subjects were asked to fill out a survey, that traced a line identifying the most relevant psychophysiological symptoms that took into account factors such as perceived stress, body perception, perceived pain, quality of sleep, perceptive variations (i.e., olfactory, gustatory, visual, acoustic, and haptic perception). A network approach formulating a hypothesis-generating exploratory analysis was adopted. Main results of the network analysis showed that the beliefs of having had the Covid-19 was related to individual variables (i.e., gender, working in presence, sleep quality, anxiety symptoms), while the familiarity of Covid-19 disease was related to contextual factors (e.g., number of recorded cases in the Region, working in presence). The self-perception of olfactory and perceptive alterations highlighted a great sensorial cross-modality, additionally, the olfactory impairment was related to the belief of having had the Covid-19. Compared to general network data, BAI, perceived stress, anxiety and chronic pain were in relation to daily sleep disturbance. Main study's results show how the management of the Covid-19 stressful representation, in its cognitive aspects, can modulate the psychophysiological responses.

Highlights • Superficial myofibroblastoma of the Labia Majora. • Differential diagnosis between vulvar superficial myofibroblastoma and cyst/hydrocele of Nuck duct. • Differential diagnosis between vulvar superficial myofibroblastoma and inguinal/crural hernia.

Problem While there are several known causes for recurrent pregnancy loss (RPL), about 50% are unexplained (uRPL), and in these cases, an aberrant immune regulation seems to be involved. Although fetally derived trophoblast cells have a key role in immune regulation, it is difficult to study their immune function during pregnancy, and it is not known whether trophoblast function may be an inherent aberration in uRPL or whether it is associated with the outcome of the current pregnancy. Method of study Chorionic villus sampling (CVS) was performed for clinical indications at 12 weeks of gestation. Superfluous materials, divided in small explants, were cultured for 20-24 hours, and supernatants (conditioned medium) were collected from 36 women with singleton normal pregnancies, of whom 9 women had a history of RPL. The secreted immune protein profile was measured by proximity extension assay, and the conditioned medium was further used in functional ex vivo models to assess ability to polarize blood monocytes and CD4(+)T cells into immune regulatory phenotypes, as detected by flow cytometry. Results Conditioned medium from chorionic villi, human fetally derived placental tissue, was able to induce a decidual-type of M2-like macrophages, as well as an expansion of Treg cells ex vivo, both in women with uRPL and in control women. The preserved immunological properties were confirmed by a maintained immune protein profile in RPL compared with controls. Conclusion Trophoblasts in an ex vivo model maintain tolerogenic and proteomic profile features in successful pregnancies, despite a previous history of RPL. Funding Agencies|Swedish Research CouncilSwedish Research Council [2018-02776]; Linkoping University; Tor Vergata University; ALF Grants

Background/aim Coronavirus disease is spreading worldwide. Due to fast transmission and high fatality rate drastic emergency restrictions were issued. During the lockdown, only urgent medical services are guaranteed. All non-urgent services, as breast cancer (BC) screening, are temporarily suspended. The potential of breast cancer screening programs in increasing the survival rate and decreasing the mortality rate has been widely confirmed. Suspension could lead to worse outcomes for breast cancer patients. Our study aimed to analyse the data and provide estimates regarding the temporary BC screening suspension. Patients and methods Data regarding breast cancer and respective screening programs were achieved through literature research and analysis. Results Considering three different scenarios with respect to the lockdown's impact on breast cancer screening, we estimate that approximately 10,000 patients could have a missed diagnosis during these 3 months. Considering a 6-month period, as suggested by the Imperial college model, the number of patients who will not receive a diagnosis will rise to 16,000. Conclusion Breast cancer screening should be resumed as soon as possible in order to avoid further breast cancer missed diagnosis and reduce the impact of delayed diagnosis.

The ability to identify our own body is considered a pivotal marker of self-awareness. Previous research demonstrated that subjects are more efficient in the recognition of images representing self rather than others' body effectors (self-advantage). Here, we verified whether, at an electrophysiological level, bodily-self recognition modulates change detection responses. In a first EEG experiment (discovery sample), event-related potentials (ERPs) were elicited by a pair of sequentially presented visual stimuli (vS1; vS2), representing either the self-hand or other people's hands. In a second EEG experiment (replicating sample), together with the previously described visual stimuli, also a familiar hand was presented. Participants were asked to decide whether vS2 was identical or different from vS1. Accuracy and response times were collected. In both experiments, results confirmed the presence of the self-advantage: participants responded faster and more accurately when the self-hand was presented. ERP results paralleled behavioral findings. Anytime the self-hand was presented, we observed significant change detection responses, with a larger N270 component for vS2 different rather than identical to vS1. Conversely, when the self-hand was not included, and even in response to the familiar hand in Experiment 2, we did not find any significant modulation of the change detection responses. Overall our findings, showing behavioral self-advantage and the selective modulation of N270 for the self-hand, support the existence of a specific mechanism devoted to bodily-self recognition, likely relying on the multimodal (visual and sensorimotor) dimension of the bodily-self representation. We propose that such a multimodal self-representation may activate the salience network, boosting change detection effects specifically for the self-hand.

Surgery in suspected/confirmed COVID-19 patients is a high-risk venture. In infected patients, COVID-19 is present in the body cavity. During surgery it could be nebulized in the spray generated by surgical instruments and could theoretically infect members of the surgical team. Nevertheless, some surgical gynecologic pathologies cannot be postponed. We present a list of the most frequent gynecologic diseases and recommendations on their surgical management during the COVID-19 pandemic, based on expert opinion, current available information, and international scientific society recommendations to support the work of gynecologists worldwide. In brief, any kind of surgical treatment should be scrutinized and postponed if possible. Nonoperative conservative treatment including pharmacological therapies for hormone-sensitive pathologies should be implemented. Health risk assessment by patient history and COVID-19 test before elective surgery are pivotal to protect both patients and healthcare providers. In confirmed COVID-19 patients or highly suspected cases, elective surgery should be postponed until full recovery.

Objective: The objective of this study is to assess whether the subpubic arch angle (SPA) changes throughout pregnancy. Materials and Methods: We recruited a group of nulliparous women in the first trimester of pregnancy. Each woman was assessed 3 times throughout pregnancy, once per each trimester, by measuring SPA using a recently described highly reproducible three-dimensional transperineal ultrasound (linear reconstruction with contrast enhancement technique; OmniView-volume contrast imaging). Repeated measures analysis of variance was used to study SPA changes during pregnancy. Results: Overall, 97 women were included in the final analysis. SPA increased progressively and significantly (F = 27.824, p < 0.001) from the first to the second trimester (121.8 ± 8.7 vs. 123.5 ± 8.4°, p = 0.01) and from the second to the third trimester (123.5 ± 8.4 vs. 125.3 ± 8.1°, p = 0.01). Conclusion: SPA width increases progressively but slightly during pregnancy. Although this finding is interesting, the extremely small difference detected is unlikely to be clinically significant.

ObjectiveSince vulvar cancer is such a rare disease, the international experience with electrochemotherapy has been derived from only a few centers. The aim of this study was to evaluate clinical outcome and side effects profile with the use of electrochemotherapy in patients with primary or recurrent vulvar cancer.MethodsData were retrospectively collected from November 2017 to November 2019 in two major Italian oncologic institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Electrochemotherapy was offered in a palliative setting to patients with a primary or recurrent vulvar cancer who were not candidates for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anesthesia. Electrical pulses were delivered using a pulse generator. Intravenous bleomycin was administered in conjunction with electrochemotherapy. Follow-up examinations were performed at 1, 3, and 6 months. Primary endpoint was to assess the response rate of electrochemotherapy as palliative treatment in patients with vulvar cancer.ResultsA total of 15 patients were included in the study. Fourteen patients (93.3%) had a squamous cell carcinoma and one patient had vulvar carcinosarcoma. Ten patients (66.7 %) had a single lesion and 5 patients (33.3%) had multiple lesions. Median number of electrical pulses was 22 (range 3–42) and median operative time was 13 (range 7–20) min. No intra-procedure complications occurred. One patient had pneumonia during their post-operative stay. Overall response rate after 1 month was 80%. At the 3-month follow-up, 3 patients (20%) had disease progression, 3 patients (20%) had died from ongoing disease, 1 patient (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. A total of 8/13 patients (61.5%) were alive at 6-month follow-up, whereas 6/12 patients (50%) were alive at 1-year follow-up.ConclusionsElectrochemotherapy is a feasible, easy to perform, and reproducible procedure in patients with primary or recurrent vulvar cancer who are unable to undergo surgery. Survival after 1 year in this population was 50%. Electrochemotherapy may have a role in the management of vulvar cancer, especially as palliative treatment when other therapies are no longer applicable.

The immune escape mechanisms at the base of tumor progression in endometrial cancer mimic immune tolerance mechanisms occurring at the maternal–fetal interface. The biological and immunological processes behind the maternal–fetal interface are finely tuned in time and space during embryo implantation and subsequent pregnancy stages; conversely, those behind cancer progression are often aberrant. The environment composition at the maternal–fetal interface parallels the pro-tumor microenvironment identified in many cancers, pointing to the possibility for the use of the maternal–fetal interface as a model to depict immune therapeutic targets in cancer. The framework of cancer environment signatures involved in immune adaptations, precisely timed in cancer progression, could reveal a specific “immune clock” in endometrial cancer, which might guide clinicians in patient risk class assessment, diagnostic workup, management, surgical and therapeutic approach, and surveillance strategies. Here, we review studies approaching this hypothesis, focusing on what is known so far about oncofetal similarities in immunity with the idea to individualize personalized immunotherapy targets, through the downregulation of the immune escape stage or the reactivation of the pro-inflammatory processes suppressed by the tumor.

When body ownership is impaired after brain-damage, the capacity to discriminate between one's own and others' body-parts is lost. Delusional body-ownership has been recently described in patients who misidentify someone else's limb as their own (pathological embodiment) whenever it is positioned in a body congruent position. This delusion can be frequently associated with somatosensory and attentional deficits. Here, we leveraged the phenomenon of tactile extinction, as this clinical sign can be substantially ameliorated when contralesional touches are combined with proximal visual stimulation. Is body ownership a necessary prerequisite to modulate cross-modal processing and thus reducing tactile extinction? Fourteen patients with tactile extinction (TE+) took part in the study: eight of them with pathological embodiment (E+, experimental group) and six of them without pathological embodiment (E-, control group). In two different paradigms, differing for the nature of visuo-tactile stimuli, bilateral tactile stimulation of the patients' hands was combined with visual stimuli occurring on A) their own contralesional (affected) hand, B) the examiner's hand (embodied in E+), or C) a neutral object. In both groups, visual stimuli proximal to the own hand significantly improved contralesional tactile detection, while visual stimuli occurring on the neutral object did not. Crucially, only in E+TE+ patients did visual stimuli on the examiner's (embodied) hand improve contralesional tactile detection. This finding shows that cross-modal visuo-tactile integration is conditional to body-ownership, so that it ameliorates tactile extinction when visual stimuli occur on what is believed to be one's own body. From a clinical point of view, this study suggests that the effectiveness of cross-modal rehabilitative intervention can benefit from a careful evaluation of the patients' sense of body-ownership, so often impaired after brain-damage.

Anatomo-clinical evidence from motor-awareness disorders after brain-damages suggests that the premotor cortex (PMC) is involved in motor-monitoring of voluntary actions. Indeed, PMC lesions prevent patients from detecting the mismatch between intended, but not executed, movements with the paralyzed limb. This functional magnetic resonance imaging study compared, in healthy subjects, free movements against blocked movements, precluded by a cast. Cast-related corticospinal excitability changes were investigated by using transcranial magnetic stimulation. Immediately after the immobilization, when the cast prevented the execution of left-hand movements, the contralateral right (ventral) vPMC showed both increased hemodynamic activity and increased functional connectivity with the hand area in the right somatosensory cortex, suggesting a vPMC involvement in detecting the mismatch between planned and executed movements. Crucially, after 1 week of immobilization, when the motor system had likely learned that no movement could be executed and, therefore, predictions about motor consequences were changed, vPMC did not show the enhanced activity as if no incongruence has to be detected. This can be interpreted as a consequence of the plastic changes induced by long-lasting immobilization, as also proved by the cast-related corticospinal excitability modulation in our subjects. The present findings highlight the crucial role of vPMC in the anatomo-functional network generating the human motor-awareness.

Aim The aim of this study was to investigate the possible association between recurrent miscarriage (RM) and ectopic pregnancy (EP). Methods In this case-control retrospective study, the clinical cards of women followed as outpatients in the RM and low-risk pregnancy offices of the Obstetrics and Gynecology Unit at the Policlinico Tor Vergata University Hospital were carefully reviewed for the occurrence of EP. Results Overall, 598 women with RM and 2043 normal women without RM (controls) were included in the study. Among these women, 4974 pregnancies were analyzed, in which 2028 miscarriages occurred. The EP rate (3.51%) was significantly higher in RM than in control women (1.51%) [odds ratio = 2.31 (95% confidence interval: 2.3-2.4)]; it was particularly high in women with primary RM (5.11%). However, when EP rates were calculated not by women but by overall pregnancies, no differences could be found between RM and control women. In control women, the absence of a miscarriage in the reproductive history was associated with a lower rate of EP. Conclusions Women with RM, particularly primary RM, are at increased risk of EP. This increased risk seems to be dependent on the high number of pregnancies occurring in women with RM rather than to specific characteristics of these women.

There is no consensus on whether, and to what extent, actions contribute to constructing awareness of one's own body. Here we investigated at both physiological and behavioral level whether a prolonged limb immobilization affects body ownership. We tested a group of healthy participants, whose left-hand movements were prevented by a cast for one week, and a control group without any movement restriction. In both groups, we measured the strength of the rubber hand illusion (i.e., proprioceptive shift and questionnaire on ownership) and the physiological parameters known to be modulated by short-term arm immobilization (i.e., resting motor threshold, motor evoked potentials and force parameters) before and after the week of immobilization. Our results showed stronger illusory effects on the immobilized hand on both behavioral indexes and weaker illusory effects on the non-immobilized hand on the questionnaire. Additionally, the increased proprioceptive shift was positively correlated to the motor threshold of the contralateral hemisphere. Our findings show at both behavioral and physiological level that altering those movement-related signals which constantly stem from our own body parts, modulates the experience of those body parts as mine. This, in turn, supports the view of a direct role of actions in the developing and maintaining a coherent body ownership.

Background The direct role of antiphospholipid antibodies (aPL) at maternal-fetal interface has not been fully investigated, especially whether they are involved in physiological and pathological implantation conditions, in an antiphospholipid syndrome (APS)-independent manner. In fact, trophoblast cells and placental endothelial cells at the implantation site express potential aPL targeted-phospholipid antigens (PL Ags); thus, the local production and presence of their specific antibodies, not related to APS (characterized by aPL presence in the peripheral blood), could be a potential marker of aberrant invasion, implantation and fetal-maternal immune tolerance processes. Methods Anti-Beta2glycoprotein I (anti-β2GPI) and anticardiolipin (aCL Ab) antibodies (the most clinically relevant aPL) were detected by immunoenzymatic assay (ELISA), in the amniotic fluid (AF) of 167 women with physiological and complicated common pregnancy conditions, sharing an aberrant implantation process, such as recurrent pregnancy loss (RPL), autoimmune hypothyroidism (ahT) and smoking. All women included in the study were negative to peripheral blood aPL. Results aCL and anti-β2GPI antibodies were detectable in all the AF samples. RPL, ahT and smoking patients had higher level of anti-β2GPI Abs (IgM) compared to women with physiological pregnancies (p stimuli, could be hypothesized. Conclusions The presence of aPL in the AF (not related to APS) could reveal a potential clinical significance at maternal-fetal interface in selected pregnancy complications, in which an aberrant implantation process, and in turn an impaired fetal-maternal immune tolerance cross-talk, could occur.

Endometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule.758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate.Higher recurrence rate (RR) was significantly detected (p 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01).To identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.

The effect of long-term immobilization on the motor system has been described during motor preparation, imagination or execution, when the movement has to be performed. But, what happens when the movement has to be suppressed? Does long-term limb immobilization modulate physiological responses underlying motor inhibition? Event-related potentials (ERPs) were recorded in healthy participants performing a Go/Nogo task, either with both hands free to respond (T1/T4: before/after the immobilization) or when left-hand movements were prevented by a cast (T2: as soon as the cast was positioned; T3: after one week of immobilization). In the right (control) side, N140, N2, and P3 components showed the expected greater amplitude in Nogo than in Go trials, irrespective of the timepoint. On the contrary, in the left (manipulated) side, each component of the ERP responses to Nogo trials showed specific differences across timepoints, suggesting that the inhibition-related EEG activity is significantly reduced by the presence of the cast and the duration of the immobilization. Furthermore, inhibition-related theta band activity to Nogo stimuli decreased at post-immobilization blocked session (T3-blocked). Altogether these findings can be interpreted as a consequence of the plastic changes induced by the immobilization, as also demonstrated by the cast-related corticospinal excitability modulation (investigated by using TMS) and by the decreased beta band in response to Go and Nogo trials. Thus, only if we are free to move, then inhibitory responses are fully implemented. After one week of immobilization, the amount of inhibition necessary to block the movement is lower and, consequently, inhibitory-related responses are reduced.

Low-molecular-weight heparin (LMWH) is widely used to treat recurrent pregnancy loss (RPL) because of its anti-coagulant effects. Although in vitro studies have suggested additional immunological effects, these are debated. We therefore investigated whether LMWH could modulate immune responses in vivo during pregnancy of women with unexplained RPL. A Swedish open multi-centre randomised controlled trial included 45 women treated with tinzaparin and 42 untreated women. Longitudinally collected plasma samples were obtained at gestational weeks (gw) 6, 18, 28 and 34 and analysed by multiplex bead technology for levels of 11 cytokines and chemokines, chosen to represent inflammation and T-helper subset-associated immunity. Mixed linear models test on LMWH-treated and untreated women showed differences during pregnancy of the Th1-associated chemokines CXCL10 (p = 0.01), CXCL11 (p amp;lt; 0.001) and the Th17-associated chemokine CCL20 (p = 0.04), while CCL2, CCL17, CCL22, CXCL1, CXCL8, CXCL12, CXCL13 and IL-6 did not differ. Subsequent Students t-test showed significantly higher plasma levels of CXCL10 and CXCL11 in treated than untreated women at gw 28 and 34. The consistent increase in the two Th1-associated chemokines suggests a potential proinflammatory and unfavourable effect of LMWH treatment during later stages of pregnancy, when Th1 immunity is known to disrupt immunological tolerance. Funding Agencies|Stig and Ragna Gorthon foundation, Helsingborg; Thelma Zoegas foundation for medical research, Lund; Medical Research Council of Southeast Sweden [FORSS-159721]; ALF grants, Region Ostergotland, Linkoping University; Skane County Councils Research and Development

Background The potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, although some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients. A hypothesized mechanism is through changes in uterine flow in pre-conceptional stage, by modifying endometrial receptivity in RPL. However, scant data are available, in pregnancy, about their role in RPL placental perfusion, also in relation to its potential treatments, such as low molecular weight heparin (LMWH). The aim of this study is to retrospectively further investigate the correlation between two-dimensional (2D) and three-dimensional (3D) uterine and placental flow indexes and the presence or the absence of ANA in women with unexplained RPL (uRPL), treated or not treated with LMWH. Methods 2D Doppler measurement of pulsatility index (PI) of the uterine arteries and 3D ultrasonography determination of vascularization index (VI), flow index (FI) and vascularization flow index (VFI) was carried out with the aid of the virtual organ computer-aided analysis (VOCAL) technique in LMWH treated (n 24) and not treated-uRPL patients (n 20) and in the relative control group (n 27), each group divided in ANA+ and ANA- subgroups. Serum assay for the presence of ANA was performed in all women. Results No differences were found in PI, VFI and VI values, by comparing the different groups. A difference in VI values was found for ANA- patients between RPL women not treated with LMWH and the treated ones (p = 0,01), which have lower VI values and similar to controls. By considering only ANA- treated and not treated RPL patients, the ROC curve shows an area of 0,80 and at the VI cut-off of 11,08 a sensitivity of 85% and a specificity of 67%. Conclusions LMWH could exert a potential beneficial effect in restoring the physiological blood flow supply in terms of VI in uRPL ANA- status, suggesting to include ANA and VI investigations in the RPL diagnostic algorithm in a research context, since further studies are needed to clarify this challenging hypothesis in order to try to ameliorate ANA and abnormal placental vascularization negative influence on RPL pregnancy outcome .

Previous evidence has shown that tool-use can reshape one's own body schema, extending peripersonal space and modulating the representation of related body parts. Here, we investigated the role of tool action in shaping the body metric representation, by contrasting two different views. According to a first view, the shaping would rely on the mere execution of tool action, while the second view suggests that the shaping induced by tool action on body representation would primarily depend on the representation of the action goals to be accomplished. To this aim, we contrasted a condition in which participants voluntarily accomplish the movement by representing the program and goal of a tool action (i.e., active tool-use training) with a condition in which the tool-use training was produced without any prior goal representation (i.e., passive tool-use training by means of robotic assistance). If the body metric representation primarily depends on the coexistence between goal representation and bodily movements, we would expect an increase of the perceived forearm length in the post- with respect to the pre-training phase after the active training phase only. Healthy participants were asked to estimate the midpoint of their right forearm before and after 20 min of tool-use training. In the active condition, subjects performed "enfold-and-push" movements using a rake to prolong their arm. In the passive condition, subjects were asked to be completely relaxed while the movements were performed with robotic assistance. Results showed a significant increase in the perceived arm length in the post- with respect to the pre-training phase only in the active task. Interestingly, only in the post-training phase, a significant difference was found between active and passive conditions, with a higher perceived arm length in the former than in the latter. From a theoretical perspective, these findings suggest that tool-use may shape body metric representation only when action programs are motorically represented and not merely produced. From a clinical perspective, these results support the use of robots for the rehabilitation of brain-damaged hemiplegic patients, provided that robot assistance during the exercises is present only "as-needed" and that patients' motor representation is actively involved.

Phantom limb is a common sensation in amputees, who often report vivid experiences of voluntarily moving their phantom. Previous studies showed that phantom movement can be functionally disentangled from imagined movement comparable to the actual movement of an intact limb. How and to what extent phantom movement and real movement share similar physiological mechanisms? Here, we focused on a specific aspect of motor control, the motor inhibition, and we asked whether inhibitory physiological responses are implemented when a phantom movement has to be suppressed. Sixteen two-handed controls and two left upper-limb amputees (with and without phantom movement) underwent a Go/Nogo paradigm, while event-related potentials (ERPs) were recorded. The task was performed with both the right (intact) and the left (phantom) hand, either in real or imagery conditions. Opposite results between the moving-phantom case and the static-phantom case were found. In the real condition, moving-phantom case showed the classical motor-inhibition related ERP pattern, with large P300 inhibitory wave when the movements of both (right) intact and (left) phantom limbs have to be suppressed. This inhibitory response was not different from that found in controls (who performed the task with an existing hand; real condition), but, crucially, it was significantly different from the imagery condition of controls. Contrariwise, in the static-phantom case, the ERP responses to Nogo trials during the real condition were different from the real condition in controls, but were not different from their imagery condition. Importantly, in the real condition, Nogo-ERP responses were significantly different between the two phantom cases. Taken together, these findings provide compelling evidence that phantom movements share the same neurophysiological correlates of real movements, not only when an action has to be executed, but also when it should be inhibited.

Congenital Muscular Dystrophies (CMDs) are a heterogeneous group of autosomal recessive disorders presenting at birth with psychomotor delay, cognitive impairment, muscle weakness and hypotonia. Here we described an alteration of mitochondrial inner membrane potential and mitochondrial network in cells derived from Italian patients carrying three novel mutations in CHKB gene, recently associated with "megaconial CMD". On the bases of our findings, we hypothesize that the mitochondrial membrane potential alteration, presumably as a consequence of the altered biosynthesis of phosphatidylcholine, could be responsible for the peculiar morphological aspect of mitochondria in this disease and might be involved in the disease pathogenesis.

The ability to know where our body parts are located in space (proprioception) is fundamental for both successfully interacting with the external world and monitoring potential threats. In this case-control study, we investigated whether the absence of proprioceptive signals may affect physiological defensive responses. To this aim, a right brain-damaged patient with a left upper-limb proprioceptive deficit (P+ patient) and age-matched healthy controls, underwent the recording of the Hand-Blink Reflex (HBR). This defensive response, elicited by electrical stimulation of the median nerve and recorded from the orbicularis oculi, is modulated by the hand position: it is enhanced when the threatened hand is near to the face, inside the defensive peripersonal-space (DPPS). According to the classical neuropsychological perspective, we used P+ patient as a model to investigate the role of proprioception in HBR modulation, by manipulating the congruity/incongruity between the intended and actual positions of the stimulated hand. P+ patient, with his eyes closed, had to voluntarily place his left hand either far from or near to his face and to relieve the arm’s weight over a supporting device. Then, in congruent conditions, the hand was stimulated in the actual (intended) position. In incongruent conditions, the patient’s hand was moved by the examiner from the intended to the opposite (not-intended) position and then stimulated. We observed an inverse response pattern between congruent and incongruent conditions. In congruent conditions, P+ patient showed an HBR enhancement in near compared to far position, comparable to that found in healthy controls. This suggests that, even in absence of proprioceptive and visual information, the HBR modulation was still present. Conversely, in incongruent conditions, P+ patient showed a greater HBR magnitude for far position (when the hand was actually far, but the patient intended it to be near) than for near position (when the hand was actually near, but the patient intended it to be far). This result suggests that proprioceptive signals are not necessary for HBR modulation to occur. It relies more on the intended than on the actual position of the hand. The role of motor intention and planning in shaping the DPPS is discussed.

Introduction Evidence about altered bimanual coordination has been reported in Parkinson's Disease. However, no previous study has explored such an alteration quantifying the interference effect that the trajectory of each hand might impose on the other one. Thus, in the present research, we applied the traditional Circles-Lines Coupling Task, which allowed assessing the motor coordination of the two hands, in the context of Parkinson's Disease. Methods Thirty-six individuals affected by Parkinson's Disease were consecutively recruited and assigned to two groups according to their symptoms' lateralization. Moreover, eighteen age-matched healthy controls participated in the study. We capitalized on the Circles-Lines Coupling Task, in which the performance during incongruent movements (drawing lines with one hand and circles with the other hand) was compared with the performance during congruent movements (drawing lines with both hands). A bimanual coupling index was computed to compare the interference effect of each hand on the other one. Results In healthy controls, the bimanual coupling index did not differ between the two hands. Crucially, in both groups of individuals affected by Parkinson's Disease, the less affected hand showed a significantly higher bimanual coupling index, due to the abnormal interference exerted by the most affected one, than vice versa. Conclusions Our results highlighted an altered spatial bimanual coupling in Parkinson's disease, depending on the symptoms' lateralization. We offered different explanations of our results according to the theoretical frameworks about the mechanisms subserving bimanual coordination.

Problem To investigate whether antinuclear autoantibodies (ANA) could be related to the outcome of the successive pregnancy in women with unexplained recurrent miscarriage (uRM). Methods Circulating ANA were measured by indirect immunofluorescence in 86 women with uRM before pregnancy, repeated in the first trimester of the successive gestation and correlated with pregnancy outcome. Results Forty-one women were ANA− and 45 were ANA+ before pregnancy. No relation was found between pre-pregnancy ANA status and the outcome of the successive pregnancy. However, when these women were monitored at 7th week during their pregnancy for ANA, of the 22 ANA+ women who remained ANA+ seven miscarriages (31.8%) were observed, whereas all of the 23 ANA+ women who became ANA− had pregnancies ongoing beyond the 20th week without miscarriage. Conclusions ANA status could have a role in uRM. Disappearance of ANA in early pregnancy could have a favorable prognostic value in the successive pregnancy.

Pathological embodiment (E+) is a specific contralesional delusion of body ownership, observed following brain damage, in which patients embody someone else's arm and its movements within their own body schema whenever the contralesional 'alien' arm is presented in a body-congruent position (i.e., 1st person perspective and aligned with the patient's shoulder). This disorder is often associated with spatial neglect, a neurological syndrome in which patients are unaware of stimuli presented in the contralesional (often the left) space. Capitalizing on previous evidence demonstrating that prismatic adaptation of the ipsilesional arm to right-deviating prisms is effective in ameliorating neglect symptoms, here we investigated whether such amelioration also occurs in E+ patients with neglect when prismatic training is performed by the 'alien' embodied arm. Four left neglect patients (one with and three without pathological embodiment) underwent visuomotor prismatic training performed by an 'alien' arm. Specifically, while patients were wearing prismatic goggles shifting the visual field rightward, a co-experimenter's left arm presented in a body-congruent perspective was repeatedly moved toward visual targets by another examiner. In a control condition, the co-experimenter's arm was moved toward the targets from a body-incongruent position (i.e., 3rd person perspective). Neglect symptoms were assessed before and after training through paper-and-pencil tasks. In the E+ patient, neglect improved significantly more in 1st than in 3rd person perspective training, suggesting that prismatic adaptation of the 'alien' embodied arm is effective in modulating spatial representation. Conversely, for control E- patients (not embodying the 'alien' arm), we observed more limited improvements following training. These findings indicate that the 'alien' embodied arm is so deeply embedded in the patient body and motor schema that adaptation to prismatic lenses can affect multiple processing stages, from low level sensory-motor correspondences, to higher level body, motor and spatial maps, similarly as it occurs in normal subjects and neglect patients without pathological embodiment.

Mutual adaptive timing (MAT), the capacity to adapt one's timing to the timing of a partner, is a form of interpersonal entrainment necessary to play music in ensemble. To this respect, two questions can be advanced. First, whether MAT can be seen also in non-musician populations. This might imply interesting theoretical consequences with respect to the hypothesis of an innate inter-subjective musicality. Second, whether subject's MAT can be influenced by the position of the partner's body. This might imply that MAT modulation is guided by changes in the feeling of body ownership and agency, which in turn would affect subject's cortico-spinal excitability patterns. In order to test these hypotheses, we employed an alternate joint finger tapping task (which can be easily carried out without being expert performers), while single-pulse TMS was delivered on M1. This experimental design allowed us to test MAT in non-musicians and to study cortico-spinal excitability patterns while manipulating partners' body position. Ownership and agency were tested by ad hoc questionnaires. We first found that MAT was present also in a non-musicians population and was not affected by the position of the partner, thus pointing to the universality of such a joint proto-musical competence. Moreover, cortico-spinal excitability was similar when the subject tapped alone ('solo condition') and when the subject tapped with the partner in a position congruent with the subject's body (the 'egocentric condition'). On the contrary, when the subject tapped with the partner placed in front of him (the 'allocentric' condition') cortico-spinal excitability was higher with respect to the solo and egocentric conditions. These results show that, despite the fact that the partner was present both in the egocentric and in the allocentric position, only the allocentric condition was treated as a social ensemble. Interestingly, in the egocentric condition the partner's body seemed to be treated as the subject's 'own' body. The subjective feeling of ownership and agency were coherent with the physiological data.

Objective: To evaluate the effects of chorionic villus sampling (CVS) on placental volume (PV), perfusion, and vasculature in the first trimester of pregnancy. Method: Uterine artery pulsatility index (PI), PV, vascularization index (VI), flow index (FI), and Vascularization Flow Index (VFI) were serially measured in 38 pregnant women who underwent CVS. Thirty-eight women who did not undergo invasive prenatal diagnosis were recruited as controls. Results: CVS was associated with a mild reduction of PI, a reduction of placental VI, FI, and VFI and with an increase in PV detected one week after the procedure. The outcome of pregnancy was similar between women of the two groups. Conclusion: Our findings showed that CVS is associated with mild placental vascular and morphological changes. However, these changes do not seem to be associated with adverse outcome.

A fundamental component of the self-awareness is the sensation that we are acting with our own body. Thus, a coherent sense of self implies the existence of a tight link between the sense of body ownership and the motor system. Here, we investigated this issue by taking advantage of a well-known experimental manipulation of body ownership, i.e., the rubber hand illusion (RHI), during which the subjects perceive a fake hand as part of their own body. To test the effect of the motor system down-regulation on the RHI susceptibility, we designed a sham-controlled study, where the primary motor cortex (M1) excitability was modulated by off-line low-frequency repetitive transcranial magnetic stimulation (rTMS). After rTMS (real or sham), subjects underwent the RHI either on the right hand, contralateral to the inhibited hemisphere (Experiment 1), or on the left hand, ipsilateral to the inhibited hemisphere (Experiment 2). Only in Experiment 1, the procedure strengthened the illusory experience, as proved by a significant increase, in rTMS compared to Sham, of both subjective (Embodiment/Disembodiment Questionnaires) and objective (Proprioceptive Drift) RHI measures. This evidence demonstrates that, when the M1 activity is down-regulated, the sense of body ownership is attenuated and the subjects become more prone to incorporate an alien body part. This, in turn, supports the existence of a mutual interaction between the sense of body ownership and the motor system, shedding new light on the construction of a coherent sense of self as an acting body.

Several robotic devices have been developed for the rehabilitation of treadmill walking in patients with movement disorders due to injuries or diseases of the central nervous system. These robots induce coordinated multi-joint movements aimed at reproducing the physiological walking or stepping patterns. Control strategies developed for robotic locomotor training need a set of predefined lower limb joint angular trajectories as reference input for the control algorithm. Such trajectories are typically taken from normative database of overground unassisted walking. However, it has been demonstrated that gait speed and the amount of body weight support significantly influence joint trajectories during walking. Moreover, both the speed and the level of body weight support must be individually adjusted according to the rehabilitation phase and the residual locomotor abilities of the patient. In this work, 10 healthy participants (age range: 23–48 years) were asked to walk in movement analysis laboratory on a treadmill at five different speeds and four different levels of body weight support; besides, a trial with full body weight support, that is, with the subject suspended on air, was performed at two different cadences. The results confirm that lower limb kinematics during walking is affected by gait speed and by the amount of body weight support, and that on-air stepping is radically different from treadmill walking. Importantly, the results provide normative data in a numerical form to be used as reference trajectories for controlling robot-assisted body weight support walking training. An electronic addendum is provided to easily access to such reference data for different combinations of gait speeds and body weight support levels.

Motor imagery (MI) is the mental simulation of an action without any overt movement. Functional evidences show that brain activity during MI and motor execution (ME) largely overlaps. However, the role of the primary motor cortex (M1) during MI is controversial. Effective connectivity techniques show a facilitation on M1 during ME and an inhibition during MI, depending on whether an action should be performed or suppressed. Conversely, Transcranial Magnetic Stimulation (TMS) studies report facilitatory effects during both ME and MI. The present TMS study shed light on MI mechanisms, by manipulating the instructions given to the participants. In both Experimental and Control groups, participants were asked to mentally simulate a finger-thumb opposition task, but only the Experimental group received the explicit instruction to avoid any unwanted fingers movements. The amplitude of motor evoked potentials (MEPs) to TMS during MI was compared between the two groups. If the M1 facilitation actually pertains to MI per se, we should have expected to find it, irrespective of the instructions. Contrariwise, we found opposite results, showing facilitatory effects (increased MEPs amplitude) in the Control group and inhibitory effects (decreased MEPs amplitude) in the Experimental group. Control experiments demonstrated that the inhibitory effect was specific for the M1 contralateral to the hand performing the MI task and that the given instructions did not compromise the subjects' MI abilities. The present findings suggest a crucial role of motor inhibition when a "pure" MI task is performed and the subjects are explicitly instructed to avoid overt movements.

The sense of body ownership, i.e., the belief that a specific body part belongs to us, can be selectively impaired in brain-damaged patients. Recently, a pathological form of embodiment has been described in patients who, when the examiner's hand is located in a body-congruent position, systematically claim that it is their own hand (E+ patients). This paradoxical behavior suggests that, in these patients, the altered sense of body ownership also affects their capacity of visually discriminating the body-identity details of the own and the alien hand, even when both hands are clearly visible on the table. Here, we investigated whether, in E+ patients with spared tactile sensibility, a coherent body ownership could be restored by introducing a multisensory conflict between what the patients feel on the own hand and what they see on the alien hand. To this aim, we asked the patients to rate their sense of body ownership over the alien hand, either after segregated tactile stimulations of the own hand (out of view) and of the alien hand (visible) or after synchronous and asynchronous tactile stimulations of both hands, as in the rubber hand illusion set-up. Our results show that, when the tactile sensation perceived on the patient's own hand was in conflict with visual stimuli observed on the examiner's hand, E+ patients noticed the conflict and spontaneously described visual details of the (visible) examiner's hand (e.g., the fingers length, the nails shape, the skin color…), to conclude that it was not their own hand. These data represent the first evidence that, in E+ patients, an incongruent visual-tactile stimulation of the own and of the alien hand reduces, at least transitorily, the delusional body ownership over the alien hand, by restoring the access to the perceptual self-identity system, where visual body identity details are stored.

Converging evidence on voluntary actions underlays the existence of a motor monitoring system able to compare the predicted and the actual consequences of our movements. In this context, both the premotor cortex (PMC) and the posterior parietal cortex (PPC) play a role in action monitoring and awareness. The present study explores the role of PMC and PPC in monitoring involuntary muscle contractions induced by transcranial magnetic stimulation (TMS) over the hand motor area. To this aim, the effects of transcranial direct current stimulation (tDCS) over PMC and PPC were examined. Thirty-six healthy subjects were asked to perform a motor monitoring task (i.e., to verbally report hand twitches induced by TMS) after 10 min of tDCS. Through three experiments, the effects of cathodal, anodal and sham tDCS over the left and the right hemispheres were compared. Our results show that cathodal tDCS over the right PMC does not affect the monitoring of involuntary movements. By contrast, tDCS over both the right and the left PPC affects motor monitoring, depending on the current polarity: while cathodal tDCS increases the feeling of phantom-like movements (which actually did not occur), anodal tDCS impairs the ability to detect involuntary hand twitches (which actually took place). These findings show that the PMC is not involved in motor monitoring of involuntary movements; rather, the PPC, where multisensory stimuli converge and are processed, seems to play a crucial role.

Background The knowledge of the individual genetic “status” in the prenatal era is particularly relevant in the case of positive family history for genetic diseases, in advanced maternal age and in the general screening for foetal abnormalities. In this context, here, we report an innovative molecular assay which utilizes the cell-free foetal DNA (cffDNA) as a source for the early and fast detection of the foetal sex. The study involved 132 pregnant women in their first 3 months of pregnancy, who agreed to give a blood sample. All the collected samples were immediately subjected to the separation of the plasma, which was utilized for the extraction of the cffDNA. Successively, the extracted cffDNA was analysed by a quantitative PCR (qPCR) method based on Plexor-HY chemistry, which is able to simultaneously identify, quantify and discriminate the autosomal DNA from the sex-linked DNA. Results Overall, the Plexor-HY assay demonstrated to be sensitive and specific for the determination of low-template DNA, such as the cffDNA. In fact, the Plexor-HY assay has been successfully performed in all the samples, identifying 70 males and 62 females. As the foetal sex can be provided in 120 min just by utilizing a maternal blood sample as cffDNA source, the assay represents a very fast, safe and non-invasive prenatal method. Conclusions The possibility of determining the foetal sex in the early prenatal life consents the application of our assay as a helpful screening test for subjects and families at risk of sex-linked disorders. Moreover, the early knowledge of the foetal sex may be of great help even for the specialist, who might promptly advise the patients concerning the foetal risk of inheriting sex-linked disorders and the clinical utility of performing an invasive prenatal diagnosis. Electronic supplementary material The online version of this article (doi:10.1186/s40246-016-0066-2) contains supplementary material, which is available to authorized users.