BPSD Patterns in Patients With Severe Neuropsychiatric Disturbances: Insight From the RECAGE Study.

OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) profiles vary depending on etiology in patients with mild-to-moderate BPSD. It is not known if similar differences exist in patients with severe BPSD. METHODS: We analyzed data collected at baseline in 398 patients with severe BPSD (NPI ≥ 32) and defined diagnosis of dementia (Alzheimer's disease [AD] 297; frontotemporal dementia [FTD] 39; Lewy body disease/Parkinsonian dementia [LBD/PD] 31; and vascular dementia [VD] 31) included in the European multicenter cohort RECAGE. RESULTS: Mean total NPI was 52.11 (18.55). LBD/PD patients demonstrated more hallucinations, more anxiety and more delusions than patients with other dementia. FTD patients had less delusions and more disinhibition than patients with other neurodegenerative disorders. These profiles overlapped partially with those reported in the literature in patients with less severe symptoms. CONCLUSION: Patients with severe BPSD display different and specific profiles of neuropsychiatric symptoms depending on dementia etiology.

Alzheimer Café: an approach focused on Alzheimer's patients but with remarkable values on the quality of life of their caregivers.

BACKGROUND: Alzheimer's disease (AD) affects the global quality of life of persons who suffer from it and their caregivers, because of the behavioral and psychological consequences associated with the pathology and its caring. The Alzheimer Café (AC) is one example of approach aimed to help persons and caregivers deal with their disease. AIM: This is a pilot study focusing on the efficacy of AC in relieving caregivers' and persons' burdens due to dementia. METHODS: The quality of life of both caregivers and persons who attended the AC was compared with the quality of life of those who did not. Basic and instrumental daily activities and neuropsychiatric functioning were assessed. Caregivers also answered to general well-being and caregiving burden questionnaires. The evaluation took place at the beginning of the intervention and after 1, 3, 6, 9 and 12 months. RESULTS: Caregivers who joined the AC with their persons with dementia showed to have significantly benefited in the daily care of persons with dementia, in terms of total well-being, vitality, and emotional burden. DISCUSSION: Although improvements were not observed in persons with dementia who attended the AC, significant benefits were reported by their caregivers, suggesting that the intervention may produce better management of social and economic problems and lead to better emotional support. CONCLUSIONS: The AC seems to help families of AD persons to better manage the disease, and also delay the institutionalization of these persons, which is certainly an ambitious goal for an incurable disorder such as Alzheimer's disease.

XIAP: inhibitor of two worlds.

Autophagy is a catabolic mechanism that selectively eliminates long-lived proteins, aggregates and damaged organelles and is thereby fundamental in maintaining cellular homeostasis. As a prosurvival mechanism, autophagy is carefully regulated and its dysfunction is associated with cancer development. Work of Huang et al (2013) in this issue of The EMBO Journal identifies the apoptosis inhibitor XIAP as a novel repressor of autophagy--a function that significantly contributes to its tumorigenecity.

Cognitive and motor reaction times in obstructive sleep apnea syndrome: A study based on computerized measures.

Obstructive Sleep Apnea Syndrome (OSAS) is mainly associated with executive dysfunction. Although delayed reaction times (RTs) in patients with OSAS have been reported, sensitivity of processing speed has not been adequately assessed. This study suggests sensitive and reliable measures to clarify whether different components of information processing speed, i.e. cognitive and motor responses, are equally impaired in OSAS. Thirty-three patients with OSAS were compared with thirty healthy controls. The MoCA test was administered to assess participants' global neuropsychological profile. Cognitive and motor reaction times were measured using a detector panel which allows to distinguish between stimulus encoding, decision processing, and selection of the appropriate motor response. Logistic regression models highlighted both MoCA test and motor RTs as the best predictors differentiating patients from healthy participants. Results support the hypothesis of a slight decline in the cognitive profile of patients with OSAS and identify significant slowing down in the motor component of responses. It could be hypothesized that slower motor responsiveness is the cause of the global cognitive profile of these patients. With aging, motor movements and RTs usually become impaired and hypoxia might accelerate the aging process by compromising first of all the motor component of RTs.

p53 prevents neurodegeneration by regulating synaptic genes.

DNA damage has been implicated in neurodegenerative disorders, including Alzheimer's disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis, we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, synaptic function, in p53-mediated neuroprotection. We then demonstrate that the control of synaptic genes by p53 is conserved in mammals. Collectively, our results implicate synaptic function as a central target in p53-dependent protection from neurodegeneration.

Speech prosody enhances the neural processing of syntax.

Human language relies on the correct processing of syntactic information, as it is essential for successful communication between speakers. As an abstract level of language, syntax has often been studied separately from the physical form of the speech signal, thus often masking the interactions that can promote better syntactic processing in the human brain. However, behavioral and neural evidence from adults suggests the idea that prosody and syntax interact, and studies in infants support the notion that prosody assists language learning. Here we analyze a MEG dataset to investigate how acoustic cues, specifically prosody, interact with syntactic representations in the brains of native English speakers. More specifically, to examine whether prosody enhances the cortical encoding of syntactic representations, we decode syntactic phrase boundaries directly from brain activity, and evaluate possible modulations of this decoding by the prosodic boundaries. Our findings demonstrate that the presence of prosodic boundaries improves the neural representation of phrase boundaries, indicating the facilitative role of prosodic cues in processing abstract linguistic features. This work has implications for interactive models of how the brain processes different linguistic features. Future research is needed to establish the neural underpinnings of prosody-syntax interactions in languages with different typological characteristics.

Surprisal From Language Models Can Predict ERPs in Processing Predicate-Argument Structures Only if Enriched by an Agent Preference Principle.

Language models based on artificial neural networks increasingly capture key aspects of how humans process sentences. Most notably, model-based surprisals predict event-related potentials such as N400 amplitudes during parsing. Assuming that these models represent realistic estimates of human linguistic experience, their success in modeling language processing raises the possibility that the human processing system relies on no other principles than the general architecture of language models and on sufficient linguistic input. Here, we test this hypothesis on N400 effects observed during the processing of verb-final sentences in German, Basque, and Hindi. By stacking Bayesian generalised additive models, we show that, in each language, N400 amplitudes and topographies in the region of the verb are best predicted when model-based surprisals are complemented by an Agent Preference principle that transiently interprets initial role-ambiguous noun phrases as agents, leading to reanalysis when this interpretation fails. Our findings demonstrate the need for this principle independently of usage frequencies and structural differences between languages. The principle has an unequal force, however. Compared to surprisal, its effect is weakest in German, stronger in Hindi, and still stronger in Basque. This gradient is correlated with the extent to which grammars allow unmarked NPs to be patients, a structural feature that boosts reanalysis effects. We conclude that language models gain more neurobiological plausibility by incorporating an Agent Preference. Conversely, theories of human processing profit from incorporating surprisal estimates in addition to principles like the Agent Preference, which arguably have distinct evolutionary roots.

Predictors of Nursing Home Placement in a Cohort of European People with Alzheimer's Disease and Other Dementia Cases Enrolled in SCU-B or Non SCU-B Centers: The RECage Study.

Background: Nursing home placement (NHP) can be the final step of patients with Alzheimer's disease. Objective: We aimed to identify NHP predictors among 508 people with dementia with a 3-year follow-up. Methods: We analyzed data from the international observational RECage study, involving 508 people with especially Alzheimer's disease and comparing a cohort enrolled by five centers with a Special Care Unit for BPSD (behavioral and psychological symptoms of dementia) and another one enrolled by six centers lacking this facility. The tertiary objective of the study was to assess the possible role of the SCU-B in delaying NHP. We assessed the relationship of the baseline characteristics with NHP by means of univariate analysis followed by Cox's multivariate model. Results: Patients' mean age was 78.1 years, 54.9% were women. Diagnosis mean age was 75.4 (±8.32) years; the main diagnosis was Alzheimer's disease (296; 58.4%). During follow-up, 96 (18.9%) patients died and 153 (30.1%) were institutionalized without a statistically significant difference between the two cohorts (p = 0.9626). The mean NHP time was 902 (95% CI: 870-934). The multivariable analysis without death as a competing risk retained four independent predictors of NHP: age increase (hazard ratio (HR) = 1.023, 95% CI: 1.000-1.046), patient education level increase (HR = 1.062, 95% CI: 1.024-1.101), Neuropsychiatric Inventory total increase (HR = 1.018; 95% CI: 1.011-1.026), and total Mini-Mental State Examination as a favorable factor (HR = 0.948, 95% CI: 0.925-0.971). Gender (females versus males: HR = 1.265, 95% CI: 0.899-1.781) was included in the final Cox's model for adjusting the estimates for. Conclusions: Our data partially agree with the predictors of NHP in literature including the effect of high education level. No caregivers' factors were statistically significant. Clinical trial registration: NCT03507504.

Eye-to-Hand Coordination in Obstructive Sleep APNEA Syndrome: a Descriptive Study.

OBJECTIVE: Psychomotor slowdown was observed in individuals with Obstructive Sleep Apnea Syndrome (OSAS). Previous studies evaluated separately cognitive and motor reaction times, finding that OSAS individuals show a specific impairment in the latter. The present study investigates whether eye-to-hand coordination (EHC), a specific psychomotor ability, is compromised in OSAS. METHOD: The EHC was measured in 30 OSAS individuals who were matched with 30 healthy controls by the Two-Hand Coordination Test analyzing the speed, accuracy, and coordination; the role of these variables was investigated in predicting the group they belonged to. RESULTS: The OSAS participants showed poorer performance in the execution accuracy (t(55) = -3.36, d'Cohen = -0.89, p ≤ .001), which was also found to be the only predictor of the belonging to group (ß = 0.43 (0.18), p < .05). CONCLUSIONS: The OSAS individuals show impairments in EHC and in correcting their error (executive slowdown). This is the first investigation exploring EHC coordination in this population and contributes in understanding the psychomotor slowness characterizing OSAS.

A Confirmatory and an Exploratory Factor Analysis of the Cohen-Mansfield Agitation Inventory (CMAI) in a European Case Series of Patients with Dementia: Results from the RECage Study.

BACKGROUND: One of the most widely used instruments for assessing agitation in dementia patients is the Cohen-Mansfield Agitation Inventory (CMAI), nevertheless no global score has been proposed. The aim of this study is: (a) to conduct a confirmatory (CFA) and exploratory factor analysis (EFA) of CMAI on people with dementia and Psychological and Behavioral Symptoms (BPSD), and (b) to propose an alternative structure, based on clinical criteria including all CMAI items. METHODS: Confirmatory and exploratory factor analyses were carried out on the CMAI 29 items administered at baseline to 505 patients with dementia (PwD) and BPSD enrolled in the international observational RECage study. RESULTS: The three-factor structure has not been confirmed by the CFA, whilst the EFA was carried out respectively on 25 items disregarding 4 items with a prevalence ≤5% and then on 20 items disregarding 9 items with a prevalence ≤10%. The four-factor structure explaining 56% of the variance comprised Physically Aggressive behavior, Verbally Aggressive behavior, Physically non-aggressive behavior, and Physically and verbally aggressive behavior. CONCLUSIONS: A new grouping of all items according to a clinical criterion is proposed, allowing for a more sensible evaluation of the symptoms leading to better differentiation.

Respectful Caring for the Agitated Elderly (ReCAGE): A Multicentre, Prospective, Observational Study to Evaluate the Effectiveness of Special Care Units for People with Dementia.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) bring complexity in the clinical management of people with dementia; therefore, it is important to evaluate different models of care, such as Special Care Units (SCU-B).∥Objective:To evaluate the SCU-B effectiveness toward alleviating BPSD and improving the quality of life (QoL) of patients and their caregivers.∥Methods:ReCAGE was a multicenter, controlled, longitudinal study where 508 patients with BPSD were enrolled in two cohorts: 262 patients from centers endowed with a SCU-B, and 246 from centers without SCU-B. Statistical analyses included factorial ANCOVA for comparison among centers. The primary endpoint was effectiveness of the SCU-B, measured through the Neuropsychiatric Inventory (NPI) changes. Secondary endpoints were change in QoL of patients and caregivers, and the tertiary endpoint was time to nursing home admission.∥Results:The NPI scores decreased in both arms, with a statistically significant difference from baseline to 36 months (p < 0.0001) in both cohorts. Over time, NPI decreased more steeply during the first year in the SCU-B arm, but in the following two years the slope was clearly in favor of the control arm. This different pattern of the two cohorts reached statistical significance at the interaction "cohort by time" (p < 0.0001). Conflicting results were found regarding the outcomes of quality of life, while there were no differences in time to institutionalization in both cohorts.∥Conclusion:The RECage study did not confirm the long-term superiority of the pathway comprising a SCU-B. A post-hoc analysis revealed data supporting their acute effectiveness during behavioral crises.

Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study.

BACKGROUND: Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up. OBJECTIVE: We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine. METHODS: This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed. RESULTS: A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events. CONCLUSIONS: This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified.

Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected With Pre-Omicron Variants.

BACKGROUND AND OBJECTIVES: A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome. METHODS: The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death. RESULTS: Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI 0.05-0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%). DISCUSSION: Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.

Beyond the Benchmarks: Toward Human-Like Lexical Representations.

To process language in a way that is compatible with human expectations in a communicative interaction, we need computational representations of lexical properties that form the basis of human knowledge of words. In this article, we concentrate on word-level semantics. We discuss key concepts and issues that underlie the scientific understanding of the human lexicon: its richly structured semantic representations, their ready and continual adaptability, and their grounding in crosslinguistically valid conceptualization. We assess the state of the art in natural language processing (NLP) in achieving these identified properties, and suggest ways in which the language sciences can inspire new approaches to their computational instantiation.

Persistent trigeminal artery causing "double" neurovascular conflict.

We report the case of a 73-year-old woman who presented with right VI nerve palsy and homolateral atypical trigeminal neuralgia; standard neuroradiological investigation of orbital/retroorbital regions and intracranial arteries excluded the most commonly demonstrable underlying causes while brain magnetic resonance (T1-weighted fat suppression; T2-weighted thin-section) and magnetic resonance angiography disclosed the evidence of "double" neurovascular conflict because of persistent trigeminal artery with aneurysmal dilation. A role of this almost rare vascular condition in causing painful ophthalmoplegia is discussed.

[Mandibular repositioning in adult patients. An alternative to surgery in some patients? A two-year follow-up]. / Le repositionnement mandibulaire : une alternative à la chirurgie chez des patients adultes ? Un suivi sur deux ans.

INTRODUCTION: A number of adult patients with skeletal discrepancies refuse surgical intervention. AIMS: The aim was to assess the reaction to mandibular repositioning in simulating a skeletal correction in such patients. MATERIALS AND METHODS: 32 consecutive patients without any signs of temporo-mandibular dysfunction (TMD) were offered mandibular repositioning, as a non-invasive alternative and it was explained to them that the approach was based on the results described in case reports. Before initiating any treatment initial records, headfilms, study casts and photos were taken (T0) and the mandible was repositioned to camouflage the skeletal discrepancy by means of an occlusal built-up in Triad® Gel. RESULTS: Three months later (T1) 23 patients had adapted to the new occlusion reflected in absence of functional problems and lack of fracture of the built-up. In these patients the mandibular position was maintained by orthodontics adjusting the occlusion to the built-up position (T1). The skeletal changes occurring during repositioning were assessed on sagittal and frontal head films while intra-articular changes occurring during a 2-year follow-up period (T2) were evaluated on images constructed from CBCT images. No significant changes, neither in the direction of a relapse nor in the direction of further normalization of the condylar positioning, were observed during the 2-year observation period. CONCLUSIONS: Repositioning is a non-invasive intervention and may be considered a valid alternative to surgery in some patients. Morphological variables from the radiographs taken at T0 and the results of the initial clinical evaluation of dysfunction yielded only vague and insignificant indications regarding the predictability of adaptation to the repositioning.

Global cognitive profile and different components of reaction times in obstructive sleep apnea syndrome: Effects of continuous positive airway pressure over time.

Obstructive sleep apnea syndrome (OSAS) has been recurrently associated with cognitive and psychomotor impairments. However, the occurrence and possible reversibility of these deficits are still extremely controversial, also as a result of different methodologies adopted used by scholars. The aim of the present study was to compare over time the global cognitive profile of patients with OSAS undergoing the continuous positive airway pressure treatment (CPAP; N=23) with that of patients with OSAS who were not (N=10). A group of healthy participants (N=30) was also included. This study adopted a specific methodological approach allowing the researchers to distinguish between the cognitive and the motor component of reaction times (RTs). After baseline assessment, the same tests were administered after three and six months. No significant differences emerged between groups at each time point. On the other hand, the analysis of cognitive score trajectory over time revealed differences between groups. While healthy controls and OSAS patients undergoing CPAP showed increased MoCA test scores after three months, patients not undergoing CPAP improved their scores only after six months. In addition, patients treated with CPAP also showed significantly faster psychomotor response in motor RTs over time. Results seem to conceivably support a global cognitive vulnerability of non-treated OSAS patients. Conversely, the RT response of treated patients can be increased over time by CPAP, at least in the motor component of RTs. Therefore, our study suggests that CPAP may play an important role by slowing down the negative effects of OSAS, and by fostering sufficient cognitive functioning and adequate psychomotor speed.

Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1.

The circadian clock coordinates behavioral and circadian cues with availability and utilization of nutrients. Proteasomal degradation of clock repressors, such as cryptochrome (CRY)1, maintains periodicity. Whether macroautophagy, a quality control pathway, degrades circadian proteins remains unknown. Here we show that circadian proteins BMAL1, CLOCK, REV-ERBα, and CRY1 are lysosomal targets, and that macroautophagy affects the circadian clock by selectively degrading CRY1. Autophagic degradation of CRY1, an inhibitor of gluconeogenesis, occurs in a diurnal window when rodents rely on gluconeogenesis, suggesting that CRY1 degradation is time-imprinted to maintenance of blood glucose. High-fat feeding accelerates autophagic CRY1 degradation and contributes to obesity-associated hyperglycemia. CRY1 contains several light chain 3 (LC3)-interacting region (LIR) motifs, which facilitate the interaction of cargo proteins with the autophagosome marker LC3. Using mutational analyses, we identified two distinct LIRs on CRY1 that exert circadian glycemic control by regulating CRY1 degradation, revealing LIRs as potential targets for controlling hyperglycemia.

Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver.

The integrative physiology of inter-organ communication in lipophagy regulation is not well understood. Lipophagy and the cytosolic lipases ATGL and HSL contribute to lipid droplet (LD) mobilization; however, whether autophagy proteins engage with lipases to promote lipid utilization remains unknown. Here, we show that cold induces autophagy in proopiomelanocortin (POMC) neurons and activates lipophagy in brown adipose tissue (BAT) and liver in mice. Targeted activation of autophagy in POMC neurons via intra-hypothalamic rapamycin is sufficient to trigger lipid utilization in room temperature-housed mice. Conversely, inhibiting autophagy in POMC neurons or in peripheral tissues or denervating BAT blocks lipid utilization. Unexpectedly, the autophagosome marker LC3 is mechanistically coupled to ATGL-mediated lipolysis. ATGL exhibits LC3-interacting region (LIR) motifs, and mutating a single LIR motif on ATGL displaces ATGL from LD and disrupts lipolysis. Thus, cold-induced activation of central autophagy activates lipophagy and cytosolic lipases in a complementary manner to mediate lipolysis in peripheral tissues.

Physical and functional interaction between HCV core protein and the different p73 isoforms.

Hepatitis C virus (HCV) core protein is a structural viral protein that packages the viral genomic RNA. In addition to this function, HCV core also modulates a number of cellular regulatory functions. In fact, HCV core protein has been found to modulate the expression of the cyclin-dependent inhibitor p21(WAF1/CIP1) and to promote both apoptosis and cell proliferation through its physical interaction with p53. Here, we studied the ability of HCV core to bind the p53-related p73 protein, its isoforms and its deletion mutants. We found that HCV core co-immunoprecipitated with p73 in HepG2 and SAOS-2 cells. Deletion mutational analysis of p73 indicates that the domain involved in HCV core binding is located between amino-acid residues 321-353. We also demonstrate that p73/core interaction results in the nuclear translocation of HCV core protein either in the presence of the p73 alpha or p73 beta tumor-suppressor proteins. In addition, the interaction with HCV core protein prevents p73 alpha, but not p73 beta dependent cell growth arrest in a p53-dependent manner. Our findings demonstrate that HCV core protein may directly influence the various p73 functions, thus playing a role in HCV pathogenesis.