The FreiBurger: a new optotype for P300-based acuity estimation.

PURPOSE: Accurate objective assessment of visual acuity is crucial, particularly in cases of suspected malingering, or when the patient's inability to cooperate makes standard psychophysical acuity tests unreliable. The P300 component of the event-related potentials offers a potential solution and even allows for the use of standard optotypes like the Landolt C. However, low-vision patients with large eccentric visual field defects often struggle to locate the Landolt C gap quickly enough for a P300 to be reliably produced. METHODS: Addressing this challenge, we introduce a novel optotype (the "FreiBurger") with a critical detail that extends through the optotype's center. Two experiments, with 16 and 12 participants, respectively, were conducted. In the first, psychophysical acuity estimates were obtained with both the FreiBurger and the Landolt C. In the second, we tested the performance of the FreiBurger, relative to the Landolt C, in eliciting a P300 with undegraded vision, simulated low vision, and in a simulated combination of low vision and visual field constriction. RESULTS: Comparable psychophysical acuity values (average difference 0.03 logMAR) were obtained for both optotypes. In the P300 recordings, both optotypes produced similar P300 responses under conditions of undegraded vision and low vision. However, with the combination of low vision and constricted visual field, the P300 could only be reliably obtained with the FreiBurger, while the amplitude was drastically reduced with the Landolt C (9.1 µV vs. 2.2 µV; p < 0.0005). CONCLUSION: The new optotype extends the applicability of P300-based acuity estimation to the frequently encountered combination of low vision and constricted visual field, where Landolt C optotypes fail. Although impairments were simulated in the present study, we assume that the advantages of the new optotype will also manifest in patients with such impairments. We furthermore expect the advantages to apply to time-sensitive psychophysical examinations as well.

Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-ADmini randomized controlled trial.

BACKGROUND: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. METHODS: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. RESULTS: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (ßLifestyle×Time = 1.11, P = 0.038; ßLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions. CONCLUSIONS: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03249688.

Autobiographical memory in chronic schizophrenia: A follow-up study.

Chronic schizophrenia is a very disabling disease and patient's social integration remains difficult. One important aspect is autobiographical memory (AM) as it is impaired in schizophrenia and highly correlated to patient's outcome, since its closely linked to self and identity. Reduced specificity and lack of details are characteristics of patients' AM, but its longitudinal course in schizophrenia remains unclear. We examined 21 patients who underwent our protocol twice with an interval of 7 years. AM was assessed using a semi-structured interview, covering four periods of life and addressing semantic knowledge and autobiographical episodes as well as their details. The results can be divided into three parts, separating semantic memories, specific autobiographical memories and details describing the latter. While a significant deterioration of semantic AM over time could be revealed, the specificity of the free recalled autobiographical episodes remained rather stable - albeit on a low level. In contrast, unique events were remembered with significantly less details at follow-up than at the first examination. While floor-effects given a relatively small number of unique events have to be considered, semantic AM and episodic details seem to be a valuable target for AM remediation given their further deterioration over time.

Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study.

OBJECTIVES: To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality. PATIENTS AND METHODS: We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis. RESULTS: Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8-43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2-4.4)), other haematological malignancies (OR 2.1 (1.2-3.8)), other underlying diseases (OR 4.3 (1.4-13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2-3.0)), fever (OR 2.4 (1.5-4.1)), tracheal intubation (OR 2.6 (1.5-4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1-6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3-3.7) and OR 2.2 (1.2-4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1-1.9), p < 0.01). CONCLUSIONS: Coinfections are frequent in IA patients and are associated with higher mortality.

Neurological soft signs and cognition in the late course of chronic schizophrenia: a longitudinal study.

Neurological soft signs (NSS) are minor ('soft') neurological abnormalities in sensory and motor performances, which are frequently reported in patients with schizophrenia at any stage of their illness. It has been demonstrated that NSS vary in the clinical course of the disorder: longitudinally NSS decrease in parallel with remission of psychopathological symptoms, an effect which mainly applies to patients with a remitting course. These findings are primarily based on patients with a first episode of the disorder, while the course of NSS in patients with chronic schizophrenia and persisting symptoms is rather unknown. Therefore, we investigated NSS twice in 21 patients with chronic schizophrenia (initial mean duration of illness: 23 ± 11 years) with a mean follow-up interval of 7 years. NSS were evaluated by the Heidelberg Scale, established instruments were used to rate neuropsychological performance and psychopathological symptoms. NSS showed significant increases on the subscales "motor coordination" and "integrative functions", while positive and negative symptoms, including apathy, showed only minor, non-significant changes. Verbal memory, verbal fluency, and cognitive flexibility along with severity of global cognitive deficits demonstrated a significant deterioration. Regression analyses identified executive dysfunction (cognitive flexibility and verbal fluency) at baseline as significant predictors of NSS increase at follow-up. Our findings indicate that NSS deteriorate in the long-term course of chronic schizophrenia. This effect may be accounted for by a decrease of executive functions and logical memory, which can be attributed to premature brain aging.

Neurological soft signs (NSS) and cognitive impairment in chronic schizophrenia.

Recent studies indicate that neurological soft signs (NSS) in schizophrenia are associated with generalized cognitive impairments rather than changes in specific neuropsychological domains. However, the majority of studies solely included first-episode patients or patients with a remitting course and did not consider age, course, education or severity of global cognitive deficits as potential confounding variables. Therefore, we examined NSS with respect to cognitive deficits in chronic schizophrenia, i.e. patients who are particularly vulnerable to both, NSS and cognitive impairments. Eighty patients with chronic schizophrenia (43.36 ±â€¯15a) and 60 healthy controls (47.52 ±â€¯14.8a) matched for age, sex and years of education were examined on the Heidelberg NSS scale and a broad neuropsychological battery including short term, working, logical and autobiographic memory (AM), theory of mind (ToM), psychomotor speed and cognitive flexibility. When contrasted with the controls, patients showed significantly higher NSS scores and impairments in all neuropsychological domains but short-term memory. NSS were significantly associated with all neuropsychological domains considered but short-term memory and semantic AM. Except for episodic AM (which was significantly correlated with NSS in patients only) these correlations applied to both groups and were confirmed when age, years of education and severity of global cognitive deficits (Mini Mental State Examination) were controlled for. Results demonstrate that NSS reflect a rather wide range of cognitive impairments in schizophrenia, which also involves episodic AM and ToM. These associations were not accounted for by age, education or severity of global cognitive deficits and facilitate the clinical usage of NSS as a screening instrument.

Tuberculosis and atypical mycobacterial infections in ruxolitinib-treated patients with primary or secondary myelofibrosis or polycythemia vera.

Ruxolitinib is a JAK-1/JAK-2 inhibitor indicated for the treatment of polycythemia vera and primary or secondary myelofibrosis. Only one patient (0.2%) was diagnosed with tuberculosis among the 485 patients receiving ruxolitinib in the four pivotal trials. Fourteen cases of tuberculosis have since been reported. We observed two (3%) mycobacterial infections (one due to Mycobacterium tuberculosis and one due to Mycobacterium avium complex) in our cohort of 65 patients receiving ruxolitinib. This observation suggests that the rate of mycobacterial infection might be higher than that observed in the pivotal trials and that atypical mycobacterial infections can also occur.

Contribution of 1p, 19q, 9p and 10q Automated Analysis by FISH to the Diagnosis and Prognosis of Oligodendroglial Tumors According to WHO 2016 Guidelines.

OBJECTIVE: To study the feasibility and the diagnostic and prognostic interest of automated analysis of 1p, 19q, 9p and 10q status by FISH technique in oligodendroglial tumors. METHODS: We analyzed a retrospective series of 33 consecutive gliomas with oligodendroglial histology (originally diagnosed as 24 oligodendrogliomas and 9 oligoastrocytomas). For all cases, automated FISH analysis of 1p, 19q, 9p and 10q status were performed and compared to clinical and histological data, ATRX, IDH1R132H and alpha-internexin status (studied by immunohistochemistry) and overall survival (OS). Manual analysis of 9p and 10q status were also performed and compared to automated analysis to verify the concordance of the two methods. RESULTS: The 33 gliomas were reclassified into 13 low-grade oligodendrogliomas (OII), 10 anaplastic oligodendrogliomas (OIII), 3 diffuse astrocytomas (AII), 3 anaplastic astrocytomas (AIII) and 4 glioblastomas (GBM) according to the WHO 2016 histological criteria. The 1p and/or 19q imbalanced status were restricted to astrocytomas with no correlation to their grade or their OS. Chromosome 9p deletion was restricted to OIII (70%) and GBM (100%) and was correlated with a shorter OS in the total cohort (p = 0.0007), the oligodendroglioma cohort (p = 0.03) and the astrocytoma cohort (p = 0.001). Concordance between 9p manual and automated analysis was satisfactory (81%, κ = 0.69). Chromosome 10q deletion was restricted to GBMs (50%) and was correlated with a poor OS in both the total cohort (p = 0.003) and the astrocytoma (AS) cohort (p = 0.04). Concordance between manual and automated analysis was satisfactory (79%, κ = 0.62). CONCLUSION: Automated analysis of 1p, 19q, 9p and 10q status by FISH is a reliable technique which allows for refined classification of oligodendroglial tumors. 1p and/or 19q imbalanced status is evidence of astrocytic differentiation. 9p deletion is found in high grade oligodendrogliomas and astrocytomas with a poor OS. 10q is related to GBM status and a poor OS.

Neurophysiological responses to unpleasant stimuli (acute electrical stimulations and emotional pictures) are increased in patients with schizophrenia.

Patients with schizophrenia have often been described as insensitive to nociceptive signals, but objective evidence is sparse. We address this question by combining subjective behavioral and objective neurochemical and neurophysiological measures. The present study involved 21 stabilized and mildly symptomatic patients with schizophrenia and 21 control subjects. We applied electrical stimulations below the pain threshold and assessed sensations of pain and unpleasantness with rating scales, and Somatosensory Evoked Potentials (SEPs/EEG). We also measured attention, two neurochemical stress indices (ACTH/cortisol), and subjective VEPs/EEG responses to visual emotional stimuli. Our results revealed that, subjectively, patients' evaluations do not differ from controls. However, the amplitude of EEG evoked potentials was greater in patients than controls as early as 50 ms after electrical stimulations and beyond one second after visual processing of emotional pictures. Such responses could not be linked to the stress induced by the stimulations, since stress hormone levels were stable. Nor was there a difference between patients and controls in respect of attention performance and tactile sensitivity. Taken together, all indices measured in patients in our study were either heightened or equivalent relative to healthy volunteers.

Automated Analysis of 1p/19q Status by FISH in Oligodendroglial Tumors: Rationale and Proposal of an Algorithm.

OBJECTIVE: To propose a new algorithm facilitating automated analysis of 1p and 19q status by FISH technique in oligodendroglial tumors with software packages available in the majority of institutions using this technique. METHODS: We documented all green/red (G/R) probe signal combinations in a retrospective series of 53 oligodendroglial tumors according to literature guidelines (Algorithm 1) and selected only the most significant combinations for a new algorithm (Algorithm 2). This second algorithm was then validated on a prospective internal series of 45 oligodendroglial tumors and on an external series of 36 gliomas. RESULTS: Algorithm 2 utilizes 24 G/R combinations which represent less than 40% of combinations observed with Algorithm 1. The new algorithm excludes some common G/R combinations (1/1, 3/2) and redefines the place of others (defining 1/2 as compatible with normal and 3/3, 4/4 and 5/5 as compatible with imbalanced chromosomal status). The new algorithm uses the combination + ratio method of signal probe analysis to give the best concordance between manual and automated analysis on samples of 100 tumor cells (91% concordance for 1p and 89% concordance for 19q) and full concordance on samples of 200 tumor cells. This highlights the value of automated analysis as a means to identify cases in which a larger number of tumor cells should be studied by manual analysis. Validation of this algorithm on a second series from another institution showed a satisfactory concordance (89%, κ = 0.8). CONCLUSION: Our algorithm can be easily implemented on all existing FISH analysis software platforms and should facilitate multicentric evaluation and standardization of 1p/19q assessment in gliomas with reduction of the professional and technical time required.

Characterization of the human α9 integrin subunit gene: Promoter analysis and transcriptional regulation in ocular cells.

α9ß1 is the most recent addition to the integrin family of membrane receptors and consequently remains the one that is the least characterized. To better understand how transcription of the human gene encoding the α9 subunit is regulated, we cloned the α9 promoter and characterized the regulatory elements that are required to ensure its transcription. Transfection of α9 promoter/CAT plasmids in primary cultured human corneal epithelial cells (HCECs) and uveal melanoma cell lines demonstrated the presence of both negative and positive regulatory elements along the α9 promoter and positioned the basal α9 promoter to within 118 bp from the α9 mRNA start site. In vitro DNaseI footprinting and in vivo ChIP analyses demonstrated the binding of the transcription factors Sp1, c-Myb and NFI to the most upstream α9 negative regulatory element. The transcription factors Sp1 and NFI were found to bind the basal α9 promoter individually but Sp1 binding clearly predominates when both transcription factors are present in the same extract. Suppression of Sp1 expression through RNAi also caused a dramatic reduction in the expression of the α9 gene. Most of all, addition of tenascin-C (TNC), the ligand of α9ß1, to the tissue culture plates prior to seeding HCECs increased α9 transcription whereas it simultaneously decreased expression of the α5 integrin subunit gene. This dual regulatory action of TNC on the transcription of the α9 and α5 genes suggests that both these integrins must work together to appropriately regulate cell adhesion, migration and differentiation that are hallmarks of tissue wound healing.

[Mecanisms of pharmacokinetic interactions involving oral anticancer agents]. / Mécanismes des interactions pharmacocinétiques impliquant les agents anticancéreux oraux.

Oral anticancer agents and particularly kinase inhibitors are subject to pharmacokinetic drug interactions in relation to absorption and elimination phases. Interacting factors are food, fruit juices, cigarette smoke, acid-reducing agents and inducers/inhibitors. Some anticancer agents are inducers and/or inhibitors and can also perpetrate drug interactions. This review emphasizes the mechanisms of pharmacokinetic drug interactions involving oral anticancer agents.

Disruption of information processing in schizophrenia: The time perspective.

We review studies suggesting time disorders on both automatic and subjective levels in patients with schizophrenia. Patients have difficulty explicitly discriminating between simultaneous and asynchronous events, and ordering events in time. We discuss the relationship between these difficulties and impairments on a more elementary level. We showed that for undetectable stimulus onset asynchronies below 20 ms, neither patients nor controls merge events in time, as previously believed. On the contrary, subjects implicitly distinguish between events even when evaluating them to be simultaneous. Furthermore, controls privilege the last stimulus, whereas patients seem to stay stuck on the first stimulus when asynchronies are sub-threshold. Combining previous results shows this to be true for patients even for asynchronies as short as 8 ms. Moreover, this peculiarity predicts difficulties with detecting asynchronies longer than 50 ms, suggesting an impact on the conscious ability to time events. Difficulties on the subjective level are also correlated with clinical disorganization. The results are interpreted within the framework of predictive coding which can account for an implicit ability to update events. These results complement a range of other results, by suggesting a difficulty with binding information in time as well as space, and by showing that information processing lacks continuity and stability in patients. The time perspective may help bridge the gap between cognitive impairments and clinical symptoms, by showing how the innermost structure of thought and experience is disrupted.

Fatal stimulation of acute myeloid leukemia blasts by pegfilgrastim.

UNLABELLED: We herein report the case of a male patient with acute myeloid leukemia with fatal outcome attributable to pharmacokinetics of pegfilgrastim. CASE REPORT: An unexplained blast proliferation in a patient with acute myeloid leukemia following cytotoxic induction chemotherapy was investigated in depth. Myeloblast hyperstimulation was likely related to pegfilgrastim, the long half-life of which extended the duration of side-effects, resulting in massive and rapidly fatal leukemia cell proliferation. CONCLUSION: Pegfilgrastim can cause unexpected deleterious effects in acute myeloid leukemia. We, thus, recommend administering drugs with a shorter half-life, such as filgrastim or lenograstim, to reduce infection incidence in patients receiving myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia.

ImmunoFISH is a reliable technique for the assessment of 1p and 19q status in oligodendrogliomas.

OBJECTIVE: To develop a new ImmunoFISH technique for the study of oligodendrogliomas by combining a standard immunohistochemical stain using MIB-1 antibody with a standard FISH technique using commercial 1p36 and 19q13 chromosomal probes. METHODS: Validation was performed by two observers on a series of 36 pre-selected oligodendrogliomas and compared to the results previously determined by FISH alone. RESULTS: The ImFISH technique is easy to perform and to analyze and is no more time-consuming than the usual FISH technique. Our results show that the inter-observer reliability of ImFISH is high (κ = 0.86 and 0.95 respectively for 1p and 19q). Compared to FISH, the ImFISH exhibits a very high sensitivity (∼100%) and specificity (∼90%) for 1p and/or 19q deleted cases. The sensitivity is high for normal cases (∼85%) and imbalanced cases (∼90%) with a specificity ranging between 50 and 85%. Finally, there were no significant differences between FISH and ImFISH results calculated on 60, 40 or 20 cells. CONCLUSION: Our study demonstrates the reliability of the ImFISH technique in oligodendrogliomas and emphasizes its advantage in poorly cellular tumoral specimen.

Patients with schizophrenia selectively impaired in temporal order judgments.

The ability to order events in time plays a pervasive role in cognitive functions, but has only rarely been explored in patients with schizophrenia. Results we obtained recently suggested that patients have difficulties following events over time. However, this impairment concerned implicit responses at very short asynchronies, and it is not known whether it generalizes to subjective temporal order judgments. Here, we make a direct comparison between temporal order judgments and simultaneity/asynchrony discrimination in the same patients. Two squares were displayed on the screen either simultaneously or with an asynchrony of 24 to 96ms. In one session 20 patients and 20 controls made a temporal order judgment and in the other they discriminated between simultaneous and asynchronous stimuli. Controls recorded similar performances in the two tasks at asynchronies above 50ms, whereas patients displayed a sizeable impairment in temporal order judgment selectively. This impairment occurred in the easiest conditions, with the largest SOAs (Stimulus Onset Asynchronies) and only in the temporal order judgment. The results are the first evidence that patients with schizophrenia have a selective difficulty determining temporal order, even for asynchronies producing a clear perception of asynchrony. This impairment may mediate difficulties engaging oneself in everyday life events.

Functional independence within the self-memory system: new insights from two cases of developmental amnesia.

Neuropsychological and neuroimaging data suggest that the self-memory system can be fractionated into three functionally independent systems processing personal information at several levels of abstraction, including episodic memories of one's life (episodic autobiographical memory, EAM), semantic knowledge of facts about one's life (semantic autobiographical memory, SAM), and semantic knowledge of one's personality [conceptual self, (CS)]. Through the study of two developmental amnesic patients suffering of neonatal brain injuries, we explored how the different facets of the self-memory system develop when growing up with bilateral hippocampal atrophy. Neuropsychological evaluations showed that both of them suffered from dramatic episodic learning disability with no sense of recollection (Remember/Know procedure), whereas their semantic abilities differed, being completely preserved (Valentine) or not (Jocelyn). Magnetic resonance imaging, including quantitative volumetric measurements of the hippocampus and adjacent (entorhinal, perirhinal, and temporopolar) cortex, showed severe bilateral atrophy of the hippocampus in both patients, with additional atrophy of adjacent cortex in Jocelyn. Exploration of EAM and SAM according to lifetime periods covering the entire lifespan (TEMPAu task, Piolino et al., 2009) showed that both patients had marked impairments in EAM, as they lacked specificity, details and sense of recollection, whereas SAM was completely normal in Valentine, but impaired in Jocelyn. Finally, measures of patients' CS (Tennessee Self-Concept Scale, Fitts and Warren, 1996), checked by their mothers, were generally within normal range, but both patients showed a more positive self-concept than healthy controls. These two new cases support a modular account of the medial-temporal lobe with episodic memory and recollection depending on the hippocampus, and semantic memory and familiarity on adjacent cortices. Furthermore, they highlight developmental episodic and semantic functional independence within the self-memory system suggesting that SAM and CS may be acquired without episodic memories.

Rescue of the transcription factors Sp1 and NFI in human skin keratinocytes through a feeder-layer-dependent suppression of the proteasome activity.

Co-culturing human skin keratinocytes along with a feeder layer has proven to considerably improve their proliferative properties by delaying massive induction of terminal differentiation. Through a yet unclear mechanism, we recently reported that irradiated 3T3 (i3T3) fibroblasts used as a feeder layer increase the nuclear content of Sp1, a positive transcription factor (TF) that plays a critical role in many cellular functions including cell proliferation, into both adult skin keratinocytes and newborn skin keratinocytes. In this study, we examined the influence of i3T3 on the expression and DNA binding of NFI, another TF important for cell proliferation and cell cycle progression, and attempted to decipher the mechanism by which the feeder layer contributes at maintaining higher levels of these TFs in skin keratinocytes. Our results indicate that co-culturing both adult skin keratinocytes and newborn skin keratinocytes along with a feeder layer dramatically increases glycosylation of NFI and may prevent it from being degraded by the proteasome.

[What about the mental time travel and age-related effects?]. / Quid du voyage mental dans le temps subjectif et effets de l'âge ?

According to Tulving, episodic memory allows humans to travel mentally through subjective time into either the past or the future, this ability being at the origin of adaptation, organization and planning of future behavior. The main aim of this review is to present a state of art of episodic mental time travel and a lifespan perspective from children to elderly people. We examine the numerous similarities between remembering the past and envisioning the future which have been highlighted in cognitive, neuroimaging, and neuropsychological studies. We also present studies that have given evidence that remembering the past and imagining the future differ somewhat. We focus on demonstrating that hippocampal dysfunction is associated with disturbances in the recall of episodic autobiographical details in past memories, but also in the imagining of episodic detailed future events. More specifically, we discuss that the future seems to involve higher semantic processes mediated by the inferior frontal and lateral temporal gyri. We propose that the study of mental travel in personal time could be undertaken in line with the distinction between the memory of (episodic) experiences and (semantic) personal knowledge of one's life, which constitutes a major part of the self and constraints what we have been, what we are now, and what we might yet become.

Theory of mind impairments in patients with semantic dementia.

Semantic dementia is characterized by semantic deficits and behavioural abnormalities that occur in the wake of bilateral inferolateral and predominantly left-sided anterior temporal lobe atrophy. The temporal poles have been shown to be involved in theory of mind, namely the ability to ascribe cognitive and affective mental states to others that regulates social interactions by predicting and interpreting human behaviour. However, very few studies have examined theory of mind in semantic dementia. In this study, we investigated both cognitive and affective theory of mind in a group of patients with semantic dementia, using separate objective and subjective assessment tasks. Results provided objective evidence of an impact of semantic dementia on cognitive and affective theory of mind, consistent with the patients' atrophy in the left temporal lobe and hypometabolism in the temporal lobes and the medial frontal cortex. However, the subjective assessment of theory of mind suggested that awareness of the affective but not cognitive theory of mind deficit persists into the moderate stage of the disease.