Self-face representation is fundamentally important for self-identity and self-consciousness. Given its role in preserving identity over time, self-face processing is considered as a robust and ...stable process. Yet, recent studies indicate that simple psychophysics manipulations may change how we process our own face. Specifically, experiencing tactile facial stimulation while seeing similar synchronous stimuli delivered to the face of another individual seen as in a mirror, induces 'enfacement' illusion, i.e. the subjective experience of ownership of the other's face and a bias in attributing to the self, facial features of the other person. Here we recorded visual Event-Related Potentials elicited by the presentation of self, other and morphed faces during a self-other discrimination task performed immediately after participants received synchronous and control asynchronous Interpersonal Multisensory Stimulation (IMS). We found that self-face presentation after synchronous as compared to asynchronous stimulation significantly reduced the late positive potential (LPP; 450-750 ms), a reliable electrophysiological marker of self-identification processes. Additionally, enfacement cancelled out the differences in LPP amplitudes produced by self- and other-face during the control condition. These findings represent the first direct neurophysiological evidence that enfacement may affect self-face processing and pave the way to novel paradigms for exploring defective self-representation and self-other interactions.
There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used.
To assess the potential DDIs of DAAs in ...HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study.
Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org).
Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI.
Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To describe clinical and imaging findings in a group of patients affected by nonsyndromic deafness A9 (DFNA9), using advanced magnetic resonance imaging (MRI) with 3-dimensional (3D) fluid-attenuated ...inversion recovery (FLAIR) sequence.
A retrospective case review was conducted in a tertiary referral center in Italy. Four sequential adult DFNA9-affected patients, who had undergone MRI at our Department between January 2017 and June 2018, were enrolled (male = 2, female = 2; median age: 65.6 years; 8 diseased ears analyzed). Three patients were relatives; the fourth was unrelated. The main outcome measures - age, sex, records of audiological and vestibular testing, genetic assessment, MRI findings - were analyzed.
All subjects suffered from bilateral progressive sensorineural hearing loss, more severely at the high frequencies and with a typical clinical pattern of bilateral chronic degenerative cochleovestibular deficit. Aural fullness was reported at the onset of the disease. All patients revealed a pathogenic heterozygous mutation in the Limulus factor C, Coch-5b2 and Lgl1 domain of cochlin. None of the patients showed a significant vestibular and cochlear endolymphatic hydrops at MRI, while high bilateral contrast enhancement on 4-h delayed postcontrast 3D FLAIR sequence was observed in all ears.
Increased perilymph enhancement on 4-h delayed postcontrast 3D FLAIR sequence is the common imaging feature of DFNA9 ears, suggesting that blood-labyrinthine barrier breakdown may play the main role in the pathophysiology of this disease. Significant hydrops has been excluded by MRI. This finding might be clinically useful in differentiating DFNA9 disease from other pathologies with similar clinical findings like Ménière's disease.
Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment ...where it arises-advanced chronic liver disease-to its heterogeneous clinical and biological behaviour. The advent, and good results, of immunotherapy for cancer called for the evaluation of its potential application also in HCC, where there is evidence of intra-hepatic immune response activation. Several studies advanced our knowledge of immune checkpoints expression in HCC, thus suggesting that immune checkpoint blockade may have a strong rationale even in the treatment of HCC. According to this background, initial studies with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, and nivolumab, a programmed cell death protein 1 (PD-1) antibody, showed promising results, and further studies exploring the effects of other immune checkpoint inhibitors, alone or with other drugs, are currently underway. However, we are still far from the identification of the correct setting, and sequence, where these drugs might be used in clinical practice, and their actual applicability in real-life is unknown. This review focuses on HCC immunobiology and on the potential of immune checkpoint blockade therapy for this tumour, with a critical evaluation of the available trials on immune checkpoint blocking antibodies treatment for HCC. Moreover, it assesses the potential applicability of immune checkpoint inhibitors in the real-life setting, by analysing a large, multicentre cohort of Italian patients with HCC.
The aim of this study was to assess the influence of age-related changes in cortical activity related to the motor preparation involved in simple- and discriminative-reaction tasks. To distinguish ...between age effects on motor planning and stimulus processing, both movement- and stimulus-locked event related potentials (ERPs) were investigated in 14 younger, 14 middle-aged, and 14 older adults (mean ages 24.4, 49, and 70years, respectively). The novel results of the present study are the prefrontal over-recruitment observed in older adults in movement-related cortical potentials (MRCPs) and the differential pattern of aging effects observed at behavioral and at electrophysiological level between middle-aged and older adults. Overall, the following results were observed: (i) behavioral results confirmed the well-known slowing of responses in aging people, which were associated with optimal accuracy; (ii) the age-related differences in cortical activity underlying the generation of voluntary movements in response to external stimuli were more pronounced for the motor planning than the stimulus processing stage; (iii) the source and the time-course analysis of the over-recruitment in the older adults indicated tonic involvement of prefrontal areas regardless of task complexity; and (iv) middle-aged adults showed a ‘young adult-like’ behavioral speed, but an ‘older adult-like’ overactivation of prefrontal areas. In summary, to reach the same accuracy, older subjects prepared the action with greater anticipation and higher cost, as indexed by the earlier latency onset and larger prefrontal cortical activation.
► Stimulus processing and motor planning across the adult life span were studied. ► During Go/No-Go task age-related slowing at behavioral and cognitive level was found. ► ERPs and source analyses showed age-related PFC over-recruitment. ► Elderly classify stimuli more slowly and prepare actions with large anticipation. ► The PFC hyperactivity is regardless of task complexity.
Anticipatory event-related potentials (ERPs) precede upcoming events such as stimuli or actions. These ERPs are usually obtained in cued sensory–motor tasks employing a warning stimulus that precedes ...a probe stimulus as in the contingent negative variation (CNV) paradigms. The CNV wave has been widely studied, from clinical to brain–computer interface (BCI) applications, and has been shown to emerge in medial frontoparietal areas, localized in the cingulate and supplementary motor areas. Several dated studies also suggest the existence of a prefrontal CNV, although this component was not confirmed by later studies due to the contamination of ocular artifacts. Another lesser-known anticipatory ERP is the prefrontal negativity (pN) that precedes the uncued probe stimuli in discriminative response tasks and has been localized in the inferior frontal gyrus. This study aimed to characterize the pN by comparing it with the CNV in cued and uncued tasks and test if the pN could be associated with event preparation, temporal preparation, or both. To achieve these aims, high-density electroencephalographic recording and advanced ERP analysis controlling for ocular activity were obtained in 25 volunteers who performed 4 different visuomotor tasks. Our results showed that the pN amplitude was largest in the condition requiring both time and event preparation, medium in the condition requiring event preparation only, and smallest in the condition requiring temporal preparation only. We concluded that the prefrontal CNV could be associated with the pN, and this activity emerges in complex tasks requiring the anticipation of both the category and timing of the upcoming stimulus. The proposed method can be useful in BCI studies investigating the endogenous neural signatures triggered by different sensorimotor paradigms.
The very-low-calorie ketogenic diet (VLCKD) is effective and safe for obese individuals, but limited information exists on its impact on the intestinal barrier. This study analyzed the effects of 8 ...weeks of VLCKD on 24 obese patients (11M/13F). Carbohydrate intake was fixed at 20-50 g/day, while protein and lipid intake varied from 1-1.4 g/kg of ideal body weight and 15-30 g per day, respectively. Daily calorie intake was below 800 kcal. The lactulose-mannitol absorption test assessed small intestinal permeability. Multiple markers, such as serum and fecal zonulin, fatty acid-binding protein, diamine oxidase concentrations, urinary dysbiosis markers (indican and skatole), and circulating lipopolysaccharide levels, were analyzed. Inflammation markers (serum interleukin 6, 8, 10, and tumor necrosis factor-α concentrations) were also evaluated. The results showed significant reductions in weight, BMI, and waist circumference post-diet. However, the lactulose-mannitol ratio increased by 76.5%, and a significant increase in dysbiosis markers at the end of the diet occurred. This trend was particularly evident in a subgroup of patients. Despite initial benefits, the VLCKD might negatively affect the intestinal barrier function in obese patients, potentially worsening their compromised intestinal balance.
Colorectal cancer (CRC) is one of the leading causes of mortality for cancer in industrialized countries. The link between diet and CRC is well-known, and presumably CRC is the type of cancer which ...is most influenced by dietary habits. In Western countries, an inadequate dietary intake of fibers is endemic, and this could be a driving factor in the increase of CRC incidence. Indeed, several epidemiologic studies have elucidated an inverse relationship between daily fiber intake and risk of CRC. Long-term prognosis in CRC survivors is also dependent on dietary fibers. Several pathogenetic mechanisms may be hypothesized. Fibers may interfere with the metabolism of bile acids, which may promote colon carcinogenesis. Further, fibers are often contained in vegetables which, in turn, contain large amounts of antioxidant agents like resveratrol, polyphenols, or phytoestrogens. Moreover, fibers can be digested by commensal flora, thus producing compounds such as butyrate, which exerts an antiproliferative effect. Finally, fibers may modulate gut microbiota, whose composition has shown to be associated with CRC onset. In this regard, dietary interventions based on high-fiber-containing diets are ongoing to prevent CRC development, especially in patients with high potential for this type of tumor. Despite the fact that outcomes are preliminary, encouraging results have been observed.
Dysfunction of the masseter muscle may cause pathological kinking of the parotid duct leading to parotitis; MR sialography is a non-invasive radiological examination that allows to evaluate ...dynamically the ductal system of the parotid glands. In the present study we aimed to assess the relationships between Stensen’s duct and masseter muscle and their implications in the aetiopathogenesis of recurrent parotitis secondary to masseter muscle dysfunction. Forty-one patients with recurrent unilateral parotitis and nine with bilateral recurrent parotitis, all with a clinical suspicious of masseter muscle hypertrophy due to bruxism were enrolled. They underwent ultrasonography as a first line examination and then MR sialography and sialendoscopy. Different anatomical features were studied. Involved parotid glands had a wider duct compared to contralateral unaffected parotid glands of patients with recurrent parotitis (
p
= 0.00134); male subjects with parotitis had a longer duct compared to the salivary glands of healthy patients (
p
= 0.00943 for affected glands and
p
= 0.00629 for the contralateral). A concordance between the evidence of an acute duct angle during sialendoscopy and a wider duct in patients with parotitis was observed although not statistically significant. These initial findings suggest that the masticatory muscle dysfunction related to bruxism seems to condition alteration of parotid duct course and anatomy thus favouring the occurrence of recurrent parotitis. A specific diagnostic iter based on clinical evaluation, dynamic ultrasonography and MR sialography, is therefore, mandatory to confirm the relationship between masseter muscle anatomy and parotid duct anomalies; this is the premise for an adequate therapeutic approach to underlying masticatory muscle disorder.
A healthy intestinal permeability facilitates the selective transport of nutrients, metabolites, water, and bacterial products, involving cellular, neural, hormonal, and immune factors. An altered ...intestinal permeability indicates pathologic phenotypes and is associated with the exacerbation of obesity and related comorbidities. To investigate the impact of altered permeability in obese patients undergoing a calorie-restrictive dietary regimen (VLCKD), we collected urinary and fecal samples from obese patients with both normal and altered permeability (determined based on the lactulose/mannitol ratio) before and after treatment. The analysis of volatile organic compounds (VOCs) aids in understanding the metabolites produced by the intestinal microbiota in this unique ecological niche. Furthermore, we examined clinical and anthropometric variables from the cohort and compared them to significant VOC panels. Consequently, we identified specific markers in the metabolomics data that differentiated between normal and altered profiles before and after the diet. These markers indicated how the variable contribution specifically accounted for interleukins and lipopolysaccharides (LPS). The targeted metabolomics experiment detected no differences in measured short-chain fatty acids (SCFA). In summary, our study evaluated metabolomic markers capable of distinguishing low-grade inflammation conditions, exacerbated in more advanced stages of obesity with altered intestinal permeability.
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