The paired-pulse TMS paradigm of short intracortical inhibition is mediated by a reduction of repetitive motor neuron discharges.

Transcranial magnetic stimulation (TMS) causes repetitive spinal motoneuron discharges (repMNDs), but the effects of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) on repMNDs remain unknown. Triple stimulation technique (TST) and the extended TST-protocols that include a fourth and fifth stimulation, the Quadruple (QuadS) and Quintuple (QuintS) stimulation, respectively, offer a precise estimate of cortical and spinal motor neuron discharges, including repMNDs. The objective of our study was to explore the effects of SICI and ICF on repMNDs. We explored conventional paired-pulse TMS protocols of SICI and ICF with the TMS, TST, the QuadS, and the QuintS protocols, in a randomized study design in 20 healthy volunteers. We found significantly less repMNDs in the SICI paradigm compared with a single-pulse TMS (SP-TMS). No significant difference was observed in the ICF paradigm. There was a significant inter- and intrasubject variability in both SICI and ICF. We demonstrate a significant reduction of repMNDs in SICI, which may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no increase in repMNDs in ICF suggesting another mechanism underlying facilitation. This study provides the proof that a reduction of repMNDs mediates the inhibition seen in SICI.NEW & NOTEWORTHY Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.

Women in acute forensic psychiatric care: comparison of clinical, sociodemographic, and detention-related characteristics in pretrial detention, sentence execution, and court-ordered treatment.

Compared to men inmates, women display decreased prevalence of severe mental disorder but increased occurrence of substance use disorders (SUD) and higher rates of previous contacts with mental health services. The group of women in detention is highly heterogeneous according to the status of incarceration (pre-trial detention (PTD), sentence execution (SE) and court ordered treatments (COT)). Studies focusing on the comparison of sociodemographic patterns, detention-related and clinical variables between these groups are still lacking. We explored these parameters in 136 women admitted for acute psychiatric care in the sole Geneva forensic unit during a nine year period (2014-2023). Sociodemographic and detention-related data included age, nationality, marital status, presence of children, education attainment, most frequently speaking language, social support, employment before conviction and type of offenses. Clinical variables included the main ICD-10 diagnosis, presence of concomitant SUD, type of personality disorders, presence of suicidal thoughts and attempts at admission, as well as number and mean duration of stays. PTD and SE women had at least 9 years of formal education in 38.9% and 30.3% of cases. Most women in PTD (77.7%), SE (56.6%) and COT (56.2%) groups were Swiss or European citizens. The level of French knowledge was excellent in most of the cases. 43.8% of COT women had at least one child and this percentage is even higher for PTD and SE cases. The employment rate before conviction was also quite high, mainly for PTD and SE (61.1% and 60.6%) and, in a lesser degree, for COT (43.8%) women. Significant social support was present in the vast majority of women without any significant group difference. The distribution of type of offenses did not differ between the three types of detention with a predominance of physical violence, and drug trafficking. The number of stays during the period of reference was significantly higher in COT compared to both SE and PTD women. History of previous inpatient care was also significantly more frequent in COT that SE and PTD women. Adjustment and affective disorders were more often found in SE and PTD cases, these diagnoses were absent in the COT group. In contrast, a main diagnosis of psychotic disorders was found in 62.5% of COT cases compared to only 21.2% in SE and 24.1% in PTD cases. The number of stays, history of inpatient care and diagnosis of psychosis were independent predictors of COT status. In conclusion, the present data reveal the good social integration and emotional support of women needing acute psychiatric care in prison independently of the type of detention. Clinically, women in PTD and SE display more often emotional distress whereas those in COT suffer from acute psychotic symptoms with previous history of psychiatric care and multiple inpatient stays.

CCR5 deficiency: Decreased neuronal resilience to oxidative stress and increased risk of vascular dementia.

INTRODUCTION: As the chemokine receptor5 (CCR5) may play a role in ischemia, we studied the links between CCR5 deficiency, the sensitivity of neurons to oxidative stress, and the development of dementia. METHODS: Logistic regression models with CCR5/apolipoprotein E (ApoE) polymorphisms were applied on a sample of 205 cognitively normal individuals and 189 dementia patients from Geneva. The impact of oxidative stress on Ccr5 expression and cell death was assessed in mice neurons. RESULTS: CCR5-Δ32 allele synergized with ApoEε4 as risk factor for dementia and specifically for dementia with a vascular component. We confirmed these results in an independent cohort from Italy (157 cognitively normal and 620 dementia). Carriers of the ApoEε4/CCR5-Δ32 genotype aged ≥80 years have an 11-fold greater risk of vascular-and-mixed dementia. Oxidative stress-induced cell death in Ccr5-/- mice neurons. DISCUSSION: We propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia.

[Court-ordered inpatient psychiatric care in Switzerland. Length of stay and treatment outcome]. / Thérapies sous mandat pénal en Suisse. Population clinique, durées de séjour et destinations de sortie.

Mentally disordered offenders may be convicted to court-ordered psychiatric-psychotherapeutic inpatient care. Based on the concept of a forensic therapeutic community, the treatments of 204 inmates of a medium-security hospital, who presented with psychosis, personality disorders or substance-use disorders, have been assessed. After a median stay of 2.5 years, 56% of the offenders had been transferred to a sheltered educational housing or to an open low-security psychiatric ward. Length of stay was independent of psychiatric diagnosis, yet dependent on the nature of the offense. Having a cluster B personality disorder or a conviction for a sexual offense increased the risk of return to prison. Younger age and offenses without interpersonal violence increased the chances to enter sheltered educational housing.

Les auteurs d'infractions atteints d'un trouble mental sévère peuvent être soumis à un traitement psychiatrique-psychothérapeutique par ordonnance pénale. Basés sur le concept de la communauté thérapeutique forensique, les suivis de 204 détenus-patients atteints d'un trouble psychotique ou de la personnalité ou encore d'une dépendance aux substances ont été évalués. Après un séjour médian de 2,5 ans, 56 % ont été transférés dans un foyer socioéducatif ou une unité psychiatrique hors prison. La durée de séjour est indépendante du diagnostic psychiatrique mais dépend du type de délit. Un diagnostic de trouble de la personnalité cluster B ou une infraction sexuelle augmentent la probabilité de retourner en prison. Un jeune âge et un délit sans violence interpersonnelle favorisent une sortie en foyer.

Determinants of clinical outcome and length of stay in acute care forensic psychiatry units.

Criminological and sociodemographic variables, such as previous criminal convictions, increased risk of violence, early onset of mental disorder, antisocial personality, psychosis and low social support, have all been related to longer length of stay (LoS) and poorer outcome in long stay forensic services. The factors impacting on LoS and clinical response in acute care specialized units are poorly documented. To address this issue, we examined the psychiatric records of all cases admitted between January 1st and December 31th 2020 in the sole acute ward for detained persons located in the central prison of the Geneva County, Switzerland. Information on judicial status included pre-trial versus sentence execution, previous incarcerations, and age of the first incarceration. Sociodemographic data included age, gender, marital status, and education attainment. Previous inpatient stays prior to incarceration were recorded. All of the ICD-10 clinical diagnoses were made by two independent, board-certified psychiatrists blind to the scope of the study. The standardized assessment was based on the HoNOS (Health of Nation Outcome Scales) at admission and discharge, HONOS-secure at admission, HCR-20 (Historical Clinical Risk 20) version 2, PCL-R (Psychopathy Checklist Revised), and SAPROF (Structured Assessment of Protective Factors). Stepwise forward multiple linear regression models predicting the LoS and delta HONOS respectively were built with the above mentioned parameters. The selected variables were then used in univariate and multivariable regression models. Higher HCR-scores (mainly on clinical items), and longer LoS were related to higher delta HONOS scores. In contrast, cases in pre-trial detention showed a worst clinical outcome. In multivariable models, all three variables remained independent predictors of the clinical outcome and explained 30.7% of its variance. Only education and diagnosis of borderline personality were related to the LoS and explained 12.6% of its variance in multivariable models. Our results suggest that the use of acute wards specialized in forensic psychiatry are mainly useful for patients with prior inpatient care experience, and higher violence risk during sentence execution. In contrast, they seem to be less performant for persons in pre-trial detention that could benefit from less restrictive clinical settings.

A novel prosthesis presentation test to screen for cognitive and functional decline.

OBJECTIVES AND BACKGROUND: To validate a novel screening test for cognitive and functional decline in older patients rehabilitated with complete removable dental prostheses (CRDPs). MATERIALS AND METHODS: Edentate old in-patients rehabilitated with CRDPs were included in this study. Participants were requested to remove their prostheses before their intraoral examinations. The prostheses were then presented in an inverted orientation. Participants had to correct the orientation of the prostheses and insert them in the appropriate jaws. The test was repeated after the intraoral exam. Appropriate statistical models were used (⍺ = .05) to associate the test results with the participants' mini-mental state examination (MMSE) score, functional independence measure (FIM), age and sex. RESULTS: Among the 86 participants (mean-age: 85.4 ± 6.4 years; mean MMSE: 19.8 ± 5.5; mean FIM: 77.9 ± 20.8), 21 (24.4%) failed to correctly insert the prosthesis. The prosthesis presentation test (PPT) was associated with the FIM but not the MMSE. Regression models further confirmed an association with age (P = .043), but not sex. Additional analyses revealed the PPT test is associated with the FIM's cognitive sub-sets of memory, problem solving and social interaction. CONCLUSION: The PPT is a novel, simple and quick screening tool that can help detect functional difficulties in older people. It can easily be performed during an oral examination. Future studies are needed to determine whether the PPT can be used to detect deficits in executive function, as a complement to the MMSE and also as a first assessment of a patient's ability to manage dentures independently.

Alzheimer resemblance atrophy index, BrainAGE, and normal pressure hydrocephalus score in the prediction of subtle cognitive decline: added value compared to existing MR imaging markers.

OBJECTIVES: Established visual brain MRI markers for dementia include hippocampal atrophy (mesio-temporal atrophy MTA), white matter lesions (Fazekas score), and number of cerebral microbleeds (CMBs). We assessed whether novel quantitative, artificial intelligence (AI)-based volumetric scores provide additional value in predicting subsequent cognitive decline in elderly controls. METHODS: A prospective study including 80 individuals (46 females, mean age 73.4 ± 3.5 years). 3T MR imaging was performed at baseline. Extensive neuropsychological assessment was performed at baseline and at 4.5-year follow-up. AI-based volumetric scores were derived from 3DT1: Alzheimer Disease Resemblance Atrophy Index (AD-RAI), Brain Age Gap Estimate (BrainAGE), and normal pressure hydrocephalus (NPH) index. Analyses included regression models between cognitive scores and imaging markers. RESULTS: AD-RAI score at baseline was associated with Corsi (visuospatial memory) decline (10.6% of cognitive variability in multiple regression models). After inclusion of MTA, CMB, and Fazekas scores simultaneously, the AD-RAI score remained as the sole valid predictor of the cognitive outcome explaining 16.7% of its variability. Its percentage reached 21.4% when amyloid positivity was considered an additional explanatory factor. BrainAGE score was associated with Trail Making B (executive functions) decrease (8.5% of cognitive variability). Among the conventional MRI markers, only the Fazekas score at baseline was positively related to the cognitive outcome (8.7% of cognitive variability). The addition of the BrainAGE score as an independent variable significantly increased the percentage of cognitive variability explained by the regression model (from 8.7 to 14%). The addition of amyloid positivity led to a further increase in this percentage reaching 21.8%. CONCLUSIONS: The AI-based AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs. KEY POINTS: • AD-RAI score at baseline was associated with Corsi score (visuospatial memory) decline. • BrainAGE score was associated with Trail Making B (executive functions) decrease. • AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs.

Preferential Involvement of BRCA1/BARD1, Not Tip60/Fe65, in DNA Double-Strand Break Repair in Presenilin-1 P117L Alzheimer Models.

Recently, we showed that DNA double-strand breaks (DSBs) are increased by the Aß 42-amyloid peptide and decreased by all-trans retinoic acid (RA) in SH-SY5Y cells and C57BL/6J mice. The present work was aimed at investigating DSBs in cells and murine models of Alzheimer's disease carrying the preseniline-1 (PS1) P117L mutation. We observed that DSBs could hardly decrease following RA treatment in the mutated cells compared to the wild-type cells. The activation of the amyloidogenic pathway is proposed in the former case as Aß 42- and RA-dependent DSBs changes were reproduced by an α-secretase and a γ-secretase inhibitions, respectively. Unexpectedly, the PS1 P117L cells showed lower DSB levels than the controls. As the DSB repair proteins Tip60 and Fe65 were less expressed in the mutated cell nuclei, they do not appear to contribute to this difference. On the contrary, full-length BRCA1 and BARD1 proteins were significantly increased in the chromatin compartment of the mutated cells, suggesting that they decrease DSBs in the pathological situation. These Western blot data were corroborated by in situ proximity ligation assays: the numbers of BRCA1-BARD1, not of Fe65-Tip60 heterodimers, were increased only in the mutated cell nuclei. RA also enhanced the expression of BARD1 and of the 90 kDa BRCA1 isoform. The increased BRCA1 expression in the mutated cells can be related to the enhanced difficulty to inhibit this pathway by BRCA1 siRNA in these cells. Overall, our study suggests that at earlier stages of the disease, similarly to PS1 P117L cells, a compensatory mechanism exists that decreases DSB levels via an activation of the BRCA1/BARD1 pathway. This supports the importance of this pathway in neuroprotection against Alzheimer's disease.

Prison inmates with court-ordered treatments: are they really different?

BACKGROUND: Both the frequency of court-ordered treatments (COT) for offenders and prevalence of mental disorders among regular prison inmates steadily increased in most western countries. Whether there are major sociodemographic and clinical differences between these two populations is still matter of debate. METHODS: We compared the sociodemographic and clinical characteristics in a representative sample of 139 regular prison inmates versus 61 offenders with COT admitted during a 5-year period in an acute psychiatric care unit located in the central prison of the Geneva county. Fisher exact, unpaired Student's t and Mann-Whitney U tests were used to compare demographic and clinical variables between COT patients and regular inmates. In addition, univariate and multivariable ordered logistic regression models were built to identify the sociodemographic and clinical determinants of COT. RESULTS: COT patients were significantly older, less frequently married, with better education attainment, predominantly French-speaking, of the Christian religious group and with regular religious practice. History of psychiatric outpatient care was significantly more frequent in this group. Unlike the significantly higher occurrence of adjustment disorders in regular prisoners, psychosis was the main diagnosis in COT patients. When all diagnostic categories were taken into account in multivariable models, the presence of personality and psychotic disorders were the stronger predictors of COT status. CONCLUSIONS: Our data reveal that offenders with COT represent a clinically distinct group with an overrepresentation of personality and psychotic disorders. Moreover, they show that, at least in the Swiss penitentiary system, COT patients are less exposed to acculturation issues compared to regular inmates.

Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test.

Idiopathic Normal Pressure Hydrocephalus (iNPH)-the leading cause of reversible dementia in aging-is characterized by ventriculomegaly and gait, cognitive and urinary impairments. Despite its high prevalence estimated at 6% among the elderlies, iNPH remains underdiagnosed and undertreated due to the lack of iNPH-specific diagnostic markers and limited understanding of pathophysiological mechanisms. INPH diagnosis is also complicated by the frequent occurrence of comorbidities, the most common one being Alzheimer's disease (AD). Here we investigate the resting-state functional magnetic resonance imaging dynamics of 26 iNPH patients before and after a CSF tap test, and of 48 normal older adults. Alzheimer's pathology was evaluated by CSF biomarkers. We show that the interactions between the default mode, and the executive-control, salience and attention networks are impaired in iNPH, explain gait and executive disturbances in patients, and are not driven by AD-pathology. In particular, AD molecular biomarkers are associated with functional changes distinct from iNPH functional alterations. Finally, we demonstrate a partial normalization of brain dynamics 24 hr after a CSF tap test, indicating functional plasticity mechanisms. We conclude that functional changes involving the default mode cross-network interactions reflect iNPH pathophysiological mechanisms and track treatment response, possibly contributing to iNPH differential diagnosis and better clinical management.

COVID-19 encephalopathy: Clinical and neurobiological features.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has been associated with neurological complications, including acute encephalopathy. To better understand the neuropathogenesis of this acute encephalopathy, we describe a series of patients with coronavirus disease 2019 (COVID-19) encephalopathy, highlighting its phenomenology and its neurobiological features. On May 10, 2020, 707 patients infected by SARS-CoV-2 were hospitalized at the Geneva University Hospitals; 31 (4.4%) consecutive patients with an acute encephalopathy (64.6 ± 12.1 years; 6.5% female) were included in this series, after exclusion of comorbid neurological conditions, such as stroke or meningitis. The severity of the COVID-19 encephalopathy was divided into severe and mild based on the Richmond Agitation Sedation Scale (RASS): severe cases (n = 14, 45.2%) were defined on a RASS < -3 at worst presentation. The severe form of this so-called COVID-19 encephalopathy presented more often a headache. The severity of the pneumonia was not associated with the severity of the COVID-19 encephalopathy: 28 of 31 (90%) patients did develop an acute respiratory distress syndrome, without any difference between groups (p = .665). Magnetic resonance imaging abnormalities were found in 92.0% (23 of 25 patients) with an intracranial vessel gadolinium enhancement in 85.0% (17 of 20 patients), while an increased cerebrospinal fluid/serum quotient of albumin suggestive of blood-brain barrier disruption was reported in 85.7% (6 of 7 patients). Reverse transcription-polymerase chain reaction for SARS-CoV-2 was negative for all patients in the cerebrospinal fluid. Although different pathophysiological mechanisms may contribute to this acute encephalopathy, our findings suggest the hypothesis of disturbed brain homeostasis and vascular dysfunction consistent with a SARS-CoV-2-induced endotheliitis.

Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats.

BACKGROUND: Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. METHODS: We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. RESULTS: We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. CONCLUSIONS: Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

Incidence, characteristics and clinical relevance of acute stroke in old patients hospitalized with COVID-19.

BACKGROUND: Stroke in the course of coronavirus disease (COVID-19) has been shown to be associated with more severe respiratory symptoms and higher mortality, but little knowledge in this regard exists on older populations. We aimed to investigate the incidence, characteristics, and prognosis of acute stroke in geriatric patients hospitalized with COVID-19. METHODS: A monocentric cross-sectional retrospective study of 265 older patients hospitalized with COVID-19 on acute geriatric wards. 11/265 presented a stroke episode during hospitalization. Mortality rates and two-group comparisons (stroke vs non-stroke patients) were calculated and significant variables added in logistic regression models to investigate stroke risk factors. RESULTS: Combined ischemic and hemorrhagic stroke incidence was 4.15%. 72.7% of events occurred during acute care. Strokes presented with altered state of consciousness and/or delirium in 81.8%, followed by a focal neurological deficit in 45.5%. Ischemic stroke was more frequently unilateral (88.8%) and localized in the middle cerebral artery territory (55.5%). Smoking and a history of previous stroke increased by more than seven (OR 7.44; 95% CI 1.75-31.64; p = 0.007) and five times (OR 5.19; 95% CI 1.50-17.92; p = 0.009), respectively, the risk of stroke. Each additional point in body mass index (BMI) reduced the risk of stroke by 14% (OR 0.86; 95% CI 0.74-0.98; p = 0.03). In-hospital mortality (32.1% vs. 27.3%; p > 0.999) and institutionalization at discharge (36.4% vs. 21.1%; p = 0.258) were similar between patients with and without stroke. CONCLUSION: Incident stroke complicating COVID-19 in old patients was associated with active smoking, previous history of stroke, and low BMI. Acute stroke did not influence early mortality or institutionalization rate at discharge.

Validation of the Perform-FES: a new fear of falling scale for hospitalized geriatric patients.

BACKGROUND: Fear of falling is highly prevalent in older adults and associated with numerous negative health events. The main objective of this study was to validate a scale to assess fear of falling, based on performance in real situation (Perform-FES), in a hospitalized geriatric population. METHODS: In this cross-sectional study, 55 patients (mean age: 85.3 years; 58% women) hospitalized in a geriatric hospital in Geneva (Switzerland) were enrolled. The Perform-FES scale was administered to all patients in conjunction with four other fear of falling scales. We determined the floor and ceiling effects, internal consistency, reliability, construct validity, and discriminative power of the Perform-FES scale. RESULTS: The Perform-FES scale did not demonstrate any significant floor or ceiling effect. It had a good internal consistency (Cronbach's alpha = 0.78) and an excellent reliability (intraclass correlation coefficient = 0.94). Regarding convergent validity, good correlations were shown between the score obtained on the Perform-FES scale and those obtained on other fear of falling scales. Also, the Perform-FES scale was able to discriminate patients with severe functional impairments (area under the ROC curve = 0.81) and had significantly better discriminating performance than other fear of falling scales. CONCLUSION: Findings suggest that the Perform-FES scale has good psychometric properties and may be a relevant tool to assess fear of falling in a geriatric hospitalized population. Future research should focus in particular on assessing the sensitivity to change and the predictive value of this scale in longitudinal studies, and its validity in other populations.

Disruption of gamma-delta relationship related to working memory deficits in first-episode psychosis.

Working memory (WM) deficits constitute a core symptom of schizophrenia. Inadequacy of WM maintenance in schizophrenia has been reported to reflect abnormalities in the excitation/inhibition (E/I) balance between pyramidal neurons and parvalbumin basket cells, which may explain alterations of the dynamics of gamma and delta oscillations. To address this issue, we assessed event-related gamma (35-45 Hz) and delta (0.5-4 Hz) oscillatory responses in a visual n-back WM task in patients with first-episode psychosis (FEP) and healthy controls (HC). Periodicity analyses of oscillations were computed to explore the relationship between the psychiatric status and the WM load-related processes reflected by each frequency range. The correspondence between nested delta-gamma oscillations was estimated to assess the strength of the frontal E/I balance. In HC, gamma oscillations were synchronized by the stimulus in a 50-150 ms time range for all tasks, and periodicity of the delta cycle was comparable between the tasks. In addition, synchronization of gamma oscillations in HC occurred at the maximal descending phase of the delta cycle half-period, supporting the coexistence of delta-nested gamma oscillations. Compared with controls, FEP patients showed a lack of gamma synchronization independently of the nature of the task, and the period of delta oscillation increased significantly with the difficulty of the WM task. We thus demonstrated in FEP an inability to encode multiple items in short-term memory associated with abnormalities in the relationship between oscillations related to the difficulty of the WM task. These results argue in favor of a dysfunction of the E/I balance in psychosis.

Mandibular two-implant overdentures with CAD-CAM milled bars with distal extensions or retentive anchors: A randomized controlled trial.

OBJECTIVE: This randomized controlled trial (RCT) aimed to demonstrate the non-inferiority of mandibular 2-implant overdentures (IODs) on a CAD-CAM milled bar with long distal extensions (MBDE) against IODs on retentive anchors (RA). METHODS: Forty edentulous participants rehabilitated with a maxillary conventional denture and a mandibular 2-IOD participated in this trial. They were randomized into two groups [Control group (CG): RA + gold matrices; Experimental group (EG): MBDE + gold clip]. The outcomes included implant survival rate (ISR), chewing efficiency [quantitative (VoH) and subjective (SA) assessments], peri-implant marginal bone levels (PI-MBL), maximum bite force (MBF), and patient-reported outcomes [oral health impact profile (OHIP-EDENT), and denture satisfaction index (DSI)]. Outcomes were recorded at baseline (BL), two weeks (T0 ), 6 months (T1 ), and at 1 year (T2 ) after the intervention. Intra- and inter-group analyses were performed using regression models with ⍺=0.05. RESULTS: 38 participants completed the T2 visit (CG: n = 19, age = 74.7 ± 7.8 years; EG: n = 19, age = 70.3 ± 10.7 years). At T2 , there was no implant loss in either of the groups (ISR = 100%). There were no significant differences between the groups for the PI-MBL changes (p = .754). Improvements occurred faster in the EG than in the CG, but over the observation time, there were no differences between the trial groups for VoH, MBF, OHIP-EDENT, and the DSI, except for SA being significantly better in the EG group (p = .022). CONCLUSIONS: The results of this RCT confirm that mandibular 2-IODs with a CAD-CAM milled bar with long distal extensions are not an inferior treatment to the conventional IODs on retentive anchors in the short term (1 year).

In vitro retention force changes during cyclic dislodging of three novel attachment systems for implant overdentures with different implant angulations.

OBJECTIVES: This in vitro study aimed to compare changes in retentive force due to cyclic dislodging of three novel un-splinted attachments. MATERIALS AND METHODS: Experimental models simulating a mandibular two-implant overdenture situation, with implants positioned with various interimplant discrepancies (0°, 20°, 40°, and 60°) were fabricated. Three attachment systems were tested, "N": a straight or 15°-angulated stud; "L": a sole straight stud; and "C": a straight or individually angulated stud. All models underwent wet testing and were subjected to 10,000 insertion-removal cycles in a universal testing machine. The mean retentive forces were calculated for cycles 10, 100, 1,000, 5,000, and 10,000. Multiple mixed-effects linear regression models were applied for statistical analyses (⍺ < 0.05). RESULTS: "N" demonstrated an increasing retention until 1,000 cycles, which subsequently diminished back to its initial retention at 10,000 cycles, showing no significant loss during the entire experiment. Statistical models demonstrated no effect of implant angulation on retention, except for 60° after 10,000 cycles (p < .05). "L" showed an early peak at 100 cycles and did not significantly lose retentive force before 5,000 cycles. Angulations of 40° or higher were shown to lead to lower retentive forces (0° vs. 40° cycle 5,000: p < .05; 0° vs. 60° cycle 100: p < .05, ≥cycle 1,000: p < .001). "C" showed stable retentive forces with no significant loss only at 10,000 cycles (all angles: p < .001) or 5,000 cycles (0° vs. 60°: p < .05). CONCLUSIONS: All systems showed retentive forces promising successful clinical use in implant overdentures, even in situations with extremely angulated implants. Specific abutments compensating interimplant angulation maintain retention longer in situations with high axe divergencies.

Neuroprotection against Amyloid-ß-Induced DNA Double-Strand Breaks Is Mediated by Multiple Retinoic Acid-Dependent Pathways.

In this study, we have investigated the role of all-trans-retinoic acid (RA) as a neuroprotective agent against Aß 1-42-induced DNA double-strand breaks (DSBs) in neuronal SH-SY5Y and astrocytic DI TNC1 cell lines and in murine brain tissues, by single-cell gel electrophoresis. We showed that RA does not only repair Aß 1-42-induced DSBs, as already known, but also prevents their occurrence. This effect is independent of that of other antioxidants studied, such as vitamin C, and appears to be mediated, at least in part, by changes in expression, not of the RARα, but of the PPARß/δ and of antiamyloidogenic proteins, such as ADAM10, implying a decreased production of endogenous Aß. Whereas Aß 1-42 needs transcription and translation for DSB production, RA protects against Aß 1-42-induced DSBs at the posttranslational level through both the RARα/ß/γ and PPARß/δ receptors as demonstrated by using specific antagonists. Furthermore, it could be shown by a proximity ligation assay that the PPARß/δ-RXR interactions, not the RARα/ß/γ-RXR interactions, increased in the cells when a 10 min RA treatment was followed by a 20 min Aß 1-42 treatment. Thus, the PPARß/δ receptor, known for its antiapoptotic function, might for these short-time treatments play a role in neuroprotection via PPARß/δ-RXR heterodimerization and possibly expression of antiamyloidogenic genes. Overall, this study shows that RA can not only repair Aß 1-42-induced DSBs but also prevent them via the RARα/ß/γ and PPARß/δ receptors. It suggests that the RA-dependent pathways belong to an anti-DSB Adaptative Gene Expression (DSB-AGE) system that can be targeted by prevention strategies to preserve memory in Alzheimer's disease and aging.

MRI detection of cerebral microbleeds: size matters.

PURPOSE: Cerebral microbleeds (CMB) play an important role as an imaging biomarker notably in vascular and neurodegenerative diseases. Current clinical brain MRI underestimates the number of CMB with respect to histopathology. It is expected that small CMBs are more likely to be false-negatives, yet this has not been demonstrated and the average size of false-negative and true-positive CMBs have not been established. METHODS: The radiologic-histopathologic correlation study was approved by the local review board and included 42 consecutive cases (mean age at death, 80.7 ± 10.0 years; 23 females and 19 men) between 12 January 2012 and 10 December 2012 having undergone brain autopsy. Postmortem SWI (susceptibility-weighted imaging) images were acquired on a clinical 3T system using parameters similar to clinical routine. The detection of CMB on postmortem MRI was compared with corresponding histopathological slices. RESULTS: Postmortem MRI detected 23 true-positive CMB. Histopathology additionally detected 68 CMBs (false-negative MRI CMBs). The average size true-positive MRI CMBs had on histopathology was 3.6 ± 7.1 mm3. The average size false-negative MRI CMBs was significantly smaller (p < 0.05), measuring 0.3 ± 1.2 mm3 on histopathology. CONCLUSION: Size matters. As expected, the average size of true-positive MRI CMB was around 10 times larger as compared with false-negative MRI CMB. Evidently, in addition to size, other factors will influence the detectability of CMB, including iron content, ratio of Fe2+/Fe3+, spatial configuration, and location, yet this remains to be elucidated in future studies.

Can Early Introduction of Palliative Care Limit Intensive Care, Emergency and Hospital Admissions in Patients with Severe Chronic Obstructive Pulmonary Disease? A Pilot Randomized Study.

BACKGROUND: Despite their poor prognosis, patients with severe chronic obstructive pulmonary disease (COPD) have little access to palliative care and tend to have a high rate of hospital and intensive care unit (ICU) admissions during their last year of life. OBJECTIVES: To determine the feasibility of a home palliative care intervention during 1 year versus usual care, and the possible impact of this intervention on emergency, hospital and ICU admissions, survival, mood, and health-related quality of life (HRQL). METHODS: Prospective controlled study of patients with severe COPD (GOLD stage III or IV) and long-term oxygen therapy and/or home noninvasive ventilation and/or one or more hospital admissions in the previous year for acute exacerbation, randomized to usual care versus usual care with add-on monthly intervention by palliative care specialists at home for 12 months. RESULTS: Of 315 patients screened, 49 (15.5%) were randomized (26 to early palliative care; 23 to the control group); aged (mean ± SD) 71 ± 8 years; FEV1 was 37 ± 14% predicted; 88% with a COPD assessment test score > 10; 69% on long-term oxygen therapy or home noninvasive ventilation. The patients accepted the intervention and completed the assessment scales. After 1 year, there was no difference between groups in symptoms, HRQL and mood, and there was a nonsignificant trend for higher admission rates to hospital and emergency wards in the intervention group. CONCLUSION: Although this pilot study was underpowered to formally exclude a benefit from palliative care in severe COPD, it raises several questions as to patient selection, reluctance to palliative care in this group, and modalities of future trials.