Time to put aside the false dichotomy between personality disorders and psychotic symptoms.

Unlike internalizing and externalizing symptoms, psychotic symptoms (e.g., hallucinations, delusions) are manifestations of personality disorders (PDs) that are more controversial and poorly understood. This leaves clinicians with very little guidance for clinical practice, especially for diagnosis. What is more, most reviews have focused strictly on the links between psychotic symptoms and the categorically defined borderline PD, which contrasts with the growing movement that emphasizes a dimensional perspective (especially in psychology). Thus, the objectives of this critical review will be to (a) expose typical cases where PDs and psychotic symptoms might cooccur; (b) assess the state of scientific knowledge surrounding PD and psychotic symptoms; and (c) provide clinicians and researchers with recommendations to keep the field moving forward. We conclude that researchers and clinicians should move past the false "PD or psychosis" dichotomy since they often cooccur, avoid (as far as possible) making psychotic symptoms an exclusion criterion in PD research to enhance ecological validity, and consider dimensional PD diagnosis as a potential unifying solution to the dilemma posed by this cooccurrence.

Oral levofloxacin: population pharmacokinetics model and pharmacodynamics study in bone and joint infections.

OBJECTIVES: This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs). METHODS: From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio >100). RESULTS: One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio >100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa). CONCLUSIONS: Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.

Associations between the Personality Inventory for DSM-5 trait facets and aggression among outpatients with personality disorder: A multimethod study.

BACKGROUND: Most research on the Personality Inventory for DSM-5 (PID-5) was conducted with self-reports. One of the specific areas for which a multimethod design has yet to be implemented is for the PID-5's associations with aggression. The main objectives of this study were to (a) compare the PID-5 associations with self-reported and file-rated aggression, (b) compare these associations between women and men, and (c) identify the relative importance of PID-5 facet predictors. METHODS: A sample of outpatients with personality disorder (N = 285) was recruited in a specialized public clinic to complete questionnaires, and a subsample was assessed for file-rated aggression (n = 227). Multiple regression analyses were performed with PID-5 facets as statistical predictors but using distinct operationalizations of aggression (self-reported vs. file-rated). Moderation analyses were performed to identify the moderating effect of biological sex. Dominance analyses were computed to identify the relative importance of predictors. RESULTS: PID-5 facet predictors of self-reported and file-rated aggression were very consistent in both conditions. However, the amount of explained variance was reduced in the latter case (from 39% to 14%), especially for women (from 40% to 2%). The most important predictors were Hostility, Risk Taking, and Callousness. CONCLUSION: Pertaining to the statistically significant facets associated with aggression, strong evidence of multimethod replication was found. The women-men discrepancies were not most obvious in their specific associations with aggression, but rather in their amount of explained variance, maybe reflecting examiners' or patients' implicit biases, and/or different manifestations of aggression between women and men.

Ankle CT scan allows better management of posterior malleolus fractures than X-rays.

PURPOSE: Undiagnosed and undertreated posterior malleolus fractures lead to early ankle instability and arthritis. A preoperative CT scan could improve the management of those fractures. This study assessed the benefits of a systematic ankle CT scanner to diagnose and manage posterior malleolus fracture. METHODS: A monocentric retrospective cohort study was conducted. Sixty consecutive patients with bimalleolar fractures were operated and underwent a preoperative CT scan. The mean age was 50.0 years old (18.6 years old) with a mean body mass index of 20.3 (kg/m2) (11.4 kg/m2) and 71.7% (43/60) of women. The primary outcome was the rate of posterior malleolus fragment diagnosed on X-rays and on CT scan. Secondly, interobserver and interobserver's agreement were compared between conventional X-rays and CT scan. RESULTS: Thirty-five (58.3%) posterior fragment fractures were observed on X-rays and 53 (88.3%) on the preoperative CT scan (p < 0.01). The intraobserver reproducibility for X-rays was low (0.02 [- 0.23; 0.27]) and moderate for CT scan (0.45 [0.0; 0.84]). The interobserver reproducibility for X-rays was moderate (0.39 [0.15; 0.60]) and excellent for CT scan (0.78 [0.0; 1.0]). CONCLUSION: A wide proportion of bimalleolar fractures are associated with posterior malleolus fractures and undiagnosed with standard X-rays. We advocate a systematic preoperative CT scan in the management of bimalleolar fractures. LEVEL OF EVIDENCE: Level IV, retrospective cohort study. TRIAL REGISTRATION NUMBER: 2218999v0, date of registration: 11/08/2020 (retrospectively registered).

Digastric olecranon osteotomy a new approach to the elbow: retrospective study of 24 Coonrad-Morrey® total elbow arthroplasty at 30-month follow-up.

BACKGROUND: Digastric olecranon osteotomy approach allows an excellent articular exposure and preserves principal vascular supply and the continuity of the extensor apparatus. The aim of this study was to assess the early clinical and radiological outcome after total elbow arthroplasty implanted from a digastric olecranon osteotomy approach. METHODS: We retrospectively enrolled 22 patients (two men and twenty women) treated with 24 Coonrad-Morrey® total elbow arthroplasty implanted from a digastric olecranon osteotomy approach in Island of France (Paris, Argenteuil and Saint-Denis). The mean age was 80 years (50-96). We treated 20 fractures; according to AO classification, seven patients suffered from a C1 fracture, seven from a C3 and C2, two from malunions, and four from rheumatoid arthritis. The mean time of follow-up was 30 months (6-132). Clinical outcomes were assessed with the Mayo elbow performance score. We evaluated triceps strength and radiographic healing. RESULTS: At the latest follow-up, the average flexion arc was 23° (5°-50°) to 112° (95°-130°). The Mayo elbow performance score averaged 92 points (75-100). The mean strength of the triceps in extension and flexion was, respectively, 1.9 and 4.7 kgs. All elbows were stable. A single immediate post-operative wound infection was reported and did not require any surgical revision. Radiological consolidation of the olecranon osteotomy was assessed in sixteen patients between 8 and 16 weeks. Heterotopic ossifications were noted in one elbow. One patient had an elbow dislocation by fracture of the axe's component. CONCLUSION: The early clinical and radiological outcomes are promising and support the use of digastric olecranon osteotomy for the implantation of total elbow arthroplasty. LEVEL OF EVIDENCE: Treatment study, level IV.

Generation of functional cholangiocyte-like cells from human pluripotent stem cells and HepaRG cells.

UNLABELLED: Cholangiocytes are biliary epithelial cells, which, like hepatocytes, originate from hepatoblasts during embryonic development. In this study we investigated the potential of human embryonic stem cells (hESCs) to differentiate into cholangiocytes and we report a new approach, which drives differentiation of hESCs toward the cholangiocytic lineage using feeder-free and defined culture conditions. After differentiation into hepatic progenitors, hESCs were differentiated further into cholangiocytes using growth hormone, epidermal growth factor, interleukin-6, and then sodium taurocholate. These conditions also allowed us to generate cholangiocytes from HepaRG-derived hepatoblasts. hESC- and HepaRG-derived cholangiocyte-like cells expressed markers of cholangiocytes including cytokeratin 7 and osteopontin, and the transcription factors SOX9 and hepatocyte nuclear factor 6. The cells also displayed specific proteins important for cholangiocyte functions including cystic fibrosis transmembrane conductance regulator, secretin receptor, and nuclear receptors. They formed primary cilia and also responded to hormonal stimulation by increase of intracellular Ca(2+) . We demonstrated by integrative genomics that the expression of genes, which signed hESC- or HepaRG-cholangiocytes, separates hepatocytic lineage from cholangiocyte lineage. When grown in a 3D matrix, cholangiocytes developed epithelial/apicobasal polarity and formed functional cysts and biliary ducts. In addition, we showed that cholangiocyte-like cells could also be generated from human induced pluripotent stem cells, demonstrating the efficacy of our approach with stem/progenitor cells of diverse origins. CONCLUSION: We have developed a robust and efficient method for differentiating pluripotent stem cells into cholangiocyte-like cells, which display structural and functional similarities to bile duct cells in normal liver. These cells will be useful for the in vitro study of the molecular mechanisms of bile duct development and have important potential for therapeutic strategies, including bioengineered liver approaches.

Stalking perpetration through the lens of the alternative DSM-5 model for personality disorders.

Emerging dimensional models of personality disorders such as the Alternative DSM-5 Model for Personality Disorders (AMPD) provide new opportunities to explore the associations between personality pathology and harmful interpersonal behaviours such as stalking perpetration. Two goals are pursued by this study: (a) To document associations between stalking, level of personality pathology, and pathological personality domains/facets; and (b) to determine the relative importance of maladaptive personality facets in the statistical prediction of stalking. Data from 1489 young adults (18-30 years old) from a community sample were analysed. Moderate positive significant correlations were found between stalking, level of personality pathology, and maladaptive personality domains. A clear gradient of severity of stalking behaviours was found across five severity degrees of personality pathology. Dominance analyses revealed that Deceitfulness was the most dominant statistical predictor in women. Unusual Beliefs and Experiences, a facet from the Psychoticism domain, made an important contribution in the prediction of stalking in men only. Impulsivity was a key predictor in both genders but more markedly in men. Results suggest that the AMPD represents a useful framework to study stalking perpetration. Identification of key personality predictors might prove relevant for identifying risk factors, underlying motives, and treatment targets for stalking perpetrators.

Restoration of hip anatomy using computer modelling prior to total hip arthroplasty and its potential consequences in terms of lower limb-length difference.

BACKGROUND: Restoring hip anatomy during total hip arthroplasty (THA) is the gold standard. The general goal is for hips to be symmetrical in terms of height. This study aimed to analyse the effect of simulating hip length (HL) equalisation on leg-length difference (LLD) before and after THA with a computerised plan. METHODS: 141 consecutive patients were enrolled following THA. Outcomes of interest were preoperative hip-length difference (HLD) and LLD as determined on CT and final LLD as determined by simulating HL equalisation. We divided patients into 3 groups: no LLD, LLD >5 mm and LLD ⩾10 mm. RESULTS: The rate of preoperative LLD >5 mm and LLD ⩾10 mm was 37.5% and 14.8%, respectively. HL equalisation did not change LLD distribution in the overall cohort. Among patients with smaller preoperative HLs and LLDs, HL equalisation changed the rate of LLD >5 mm from 100% (n = 24) to 41.7% (n = 10) (p < 0.0001) and of LLD ⩾10 mm from 100% (n = 12) to 16.7% (n = 2) (p < 0.0001). Among patients with no preoperative LLD, HL equalisation changed the rate of LLD ⩽5 mm from 100% (n = 64) to 59.3% (n = 38) (p < 0.0001) and of LLD<10 mm from 100% (n = 76) to 89.5% (n = 68) (p = 0.006). CONCLUSIONS: Restoring biomechanical hip anatomy by HL equalisation may not be the correct goal for all patients. In patients with no LLD and shorter HLs, equalisation could result in LLD >5 mm in 40% of patients and LLD >10 mm in 10%, demonstrating the necessity to further analyse individuals and propose a personalised stem position.

Monitoring the one year postoperative infection rate after primary total hip replacement.

PURPOSE: Infection of a total hip replacement is potentially a devastating complication. Statistical process control methods have been generating interest as a means of improving the quality of healthcare, and we report our experience with the implementation of such a method to monitor the one year infection rate after primary total hip replacement. METHOD: Infection was defined as the growth of the same organism in cultures of at least two aspirates or intra-operative specimens, or growth of one pathogen in a patient with local signs of infection such as erythema, abscess or draining sinus tract. The cumulative summation test (CUSUM test) was used to continuously monitor the one year postoperative infection rate. The target performance was 0.5% and the test was set to detect twice that rate. RESULTS: Over the three year study period, 2006 primary total hip replacements were performed. Infection developed within one year after surgery in eight (0.4%) hips. The CUSUM test generated no alarms during the study period, indicating that there was no evidence that the process was out of control. CONCLUSION: The one year infection rate after primary total hip replacement was in control. The CUSUM test is a useful method to continuously ensure that performance is maintained at an adequate level.

Preliminary Steps Toward Extracting the Specific Alternative Model for Personality Disorders Diagnoses From Criteria A and B Self-Reports.

The Alternative DSM-5 Model for Personality Disorders (AMPD) retains six specific personality disorders (PDs) that can be diagnosed based on Criterion A level of impairment and Criterion B maladaptive facets. Those specific diagnoses are still underresearched, despite the preference expressed by most PD scholars for a mixed/hybrid classification. This study explores the possibility of using Criterion A and B self-report questionnaires to extract the specific AMPD diagnoses. Plausible prevalence estimates were found in three samples (outpatient PD, private practice, community; N = 766) using the facet score ≥ 2 and t score > 65 methods for determining the presence of a Criterion B facet; diagnoses had meaningful correlations with external variables. This study provides evidence-albeit preliminary-that the extraction of the specific AMPD PDs from self-report questionnaires might be a viable avenue. Ultimately, it could promote the use and dissemination of those diagnoses for screening purposes in clinical and research settings.

Analysis of the interaction between personality dysfunction and traits in the statistical prediction of physical aggression: Results from outpatient and community samples.

The Alternative Model for Personality Disorders (AMPD), included in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) and the World Health Organization's International Classification of Diseases (11th ed.; ICD-11) are, respectively, hybrid categorical-dimensional and dimensional frameworks for personality disorders (PDs). Both models emphasize personality dysfunction and personality traits. Previous studies investigating the links between the AMPD and ICD-11, and self-reported physical aggression have mostly focused on traits and did not take into account the potential interaction between personality dysfunction and traits. Thus, the aim of this study is to identify dysfunction*trait interactions using regression-based analysis. Outpatients with personality disorder from a specialized public clinic (N = 285) and community participants (N = 995) were recruited to complete self-report questionnaires. Some small-size, albeit significant and clinically/conceptually meaningful personality dysfunction*trait interactions were found to predict physical aggression in both samples. Interaction analyses might further inform, to some degree, about the current discussion pertaining to the potential redundancy between dysfunction and traits, the optimal personality dysfunction structure (in the case of the AMPD), as well as clinical assessment based on AMPD/ICD-11 PD frameworks.

Does delayed weight bearing in the surgical management of fractures of the upper end of the femur in the elderly lead to more complications? A prospective study.

INTRODUCTION: Fractures of the upper end of the femur (FUEF) lead to increased mortality and dependence in the elderly. However, mechanical complications after surgery persist in up to 20% of cases, which may justify a delayed resumption of full weight bearing to protect the osteosynthesis during consolidation. HYPOTHESIS: Our hypothesis was that the late resumption of weight bearing in an elderly population after a FUEF would be limited by a higher frequency of medical complications. METHODS: This was a prospective monocentric study including patients aged 80 or over with an isolated FUEF requiring osteosynthesis. The operator decided on the discharge. The primary endpoint was to show a difference in a medical complication score created for this study (APRETAR), between a group with, and a group without, weight bearing delayed by 45 days. RESULTS: Between 2016 and 2019, 254 patients (88±5.6 years, 77.6% women) were included, and of these, 70 (27.6%) had delayed weight bearing. The mean APRETAR at 45 days was greater in the delayed weight bearing group (5.9±8.6 vs. 5.7±11.0; p<0.001). One-year mortality was 12.6% (32 patients), with no difference between the two groups (p=0.51). The level of dependence was significant (IADL at 2.2±1.7), with some comorbidities (Charlson at 2.9±2.2 and CIRS-G at 6.5±4.3) and all comparable across the two groups but with low cognitive levels, especially in the group with delayed weight bearing (MMSE 15.9±10.7 vs. 21±6.9; p<0.001). CONCLUSION: This prospective study shows that delaying weight bearing in the elderly population, even for mechanical problems with FUEF, statistically increases medical complications but in a clinically acceptable manner. LEVEL OF EVIDENCE: II, Prospective cohort study.

Greener reactants, renewable energies and environmental impact mitigation strategies in pyrometallurgical processes: A review.

Abstract: Metals and alloys are among the most technologically important materials for our industrialized societies. They are the most common structural materials used in cars, airplanes and buildings, and constitute the technological core of most electronic devices. They allow the transportation of energy over great distances and are exploited in critical parts of renewable energy technologies. Even though primary metal production industries are mature and operate optimized pyrometallurgical processes, they extensively rely on cheap and abundant carbonaceous reactants (fossil fuels, coke), require high power heating units (which are also typically powered by fossil fuels) to calcine, roast, smelt and refine, and they generate many output streams with high residual energy content. Many unit operations also generate hazardous gaseous species on top of large CO2 emissions which require gas-scrubbing and capture strategies for the future. Therefore, there are still many opportunities to lower the environmental footprint of key pyrometallurgical operations. This paper explores the possibility to use greener reactants such as bio-fuels, bio-char, hydrogen and ammonia in different pyrometallurgical units. It also identifies all recycled streams that are available (such as steel and aluminum scraps, electronic waste and Li-ion batteries) as well as the technological challenges associated with their integration in primary metal processes. A complete discussion about the alternatives to carbon-based reduction is constructed around the use of hydrogen, metallo-reduction as well as inert anode electrometallurgy. The review work is completed with an overview of the different approaches to use renewable energies and valorize residual heat in pyrometallurgical units. Finally, strategies to mitigate environmental impacts of pyrometallurgical operations such as CO2 capture utilization and storage as well as gas scrubbing technologies are detailed. This original review paper brings together for the first time all potential strategies and efforts that could be deployed in the future to decrease the environmental footprint of the pyrometallurgical industry. It is primarily intended to favour collaborative work and establish synergies between academia, the pyrometallurgical industry, decision-makers and equipment providers. Highlights: A more sustainable production of metals using greener reactants, green electricity or carbon capture is possible and sometimes already underway. More investments and pressure are required to hasten change. Discussion: Is there enough pressure on the aluminum and steel industries to meet the set climate targets?The greenhouse gas emissions of existing facilities can often be partly mitigated by retrofitting them with green technologies, should we close plants prematurely to build new plants using greener technologies?Since green or renewable resources presently have limited availability, in which sector should we use them to maximize their benefits?

[Validation of a screening procedure for borderline personality disorder based on the Alternative DSM-5 Model for Personality Disorders]. / Validation d'une procédure de dépistage du trouble de personnalité limite selon le Modèle alternatif pour les troubles de la personnalité du DSM-5.

Objectives The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) includes an Alternative Model for Personality Disorders (DSM-5), which defines personality disorders based on two dimensional criteria. Criterion A corresponds to the severity of personality dysfunction in the areas of self and interpersonal functioning, while Criterion B comprises five pathological domains including a total of 25 facets. Six specific disorders, including borderline personality disorder (BPD), are defined in the AMPD based on Criteria A and B. However, there is currently very little data on these diagnoses as they are operationalized in the MATP. This study aims to present data on this recent operationalization of BPD. More specifically, we will first introduce a procedure, based on self-reported questionnaires covering the two main MATP criteria, implemented to generate the BPD diagnosis from the AMPD. Then, we will assess its validity (a) by documenting its prevalence in a clinical sample; (b) by determining its degree of correspondence with the "traditional" BPD categorical diagnosis and with a dimensional measure of borderline symptomatology; (c) by presenting convergent validity data with constructs relevant to the study of BPD (impulsivity, aggression); and (d) by determining the incremental validity of the proposed procedure in contrast with a simplified approach where only Criterion B would be considered. Method Data from 287 patients recruited as part of the admission process at the Centre de traitement le Faubourg Saint-Jean of the CIUSSS-Capitale-Nationale were analyzed. The BPD diagnosis from the MATP was generated based on two validated self-report questionnaires, in their French version, namely the Self and Interpersonal Functioning Scale (Criterion A) and the Personality Inventory for DSM-5-Faceted Brief Form (Criterion B). Results The BPD diagnosis, as operationalized in the AMPD, had a prevalence of 39.7% in the sample. A moderate fit with the clinician's diagnosis of BPD according to the traditional DSM-5 categorical model was observed, as well as a strong correlation with a dimensional measure of borderline symptomatology. Nomological network analysis revealed high and theoretically expected correlations between the disorder and measures of aggression and impulsivity. The proposed diagnostic extraction procedure, which uses Criteria A and B, showed incremental validity in the statistical prediction of external variables (borderline symptomatology, aggression, impulsivity) compared to a simplified procedure using only Criterion B. Conclusions The proposed procedure for generating the BPD diagnosis according to the MATP definition yields promising results and could allow screening for the disorder based on this contemporary conceptualization of personality pathologies.

Latent profiles of patients with borderline pathology based on the alternative DSM-5 model for personality disorders.

BACKGROUND: There have been multiple attempts to try to parse out heterogeneity within borderline pathology by identifying patient subtypes; thus far, these works have yielded few consistent results. Recent developments in the operationalization of borderline pathology may provide new opportunities to identify clinically and conceptually meaningful subgroups of patients. The Alternative DSM-5 Model for Personality Disorders (AMPD) offers a categorical-dimensional operationalization of Borderline personality disorder (BPD) that has yet to be tested for identification of patient subgroups. The purpose of the present study is to test whether the combination of the Criterion A elements (pertaining to level of severity) and the seven pathological facets from Criterion B that define BPD in the AMPD can yield meaningful patient profiles. METHODS: A total of 211 outpatients from a specialized PD treatment program (133 women, Mage = 33.66, SD = 10.97) were selected based on the presence of at least moderate borderline pathology according to cutoffs recently proposed for the Borderline Symptom List-23. Valid Criterion A (Self and Interpersonal Functioning Scale) and B (Personality Inventory for DSM-5 Faceted Brief Form) self-reports were administered to measure elements and facets that define BPD in the AMPD model; these variables were used as indicators in a latent profile analysis (LPA). RESULTS: The optimal solution generated by LPA yielded four distinct profiles: (a) Borderline traits; (b) Moderate pathology with Impulsivity; (c) Moderate pathology with Identity problems and Depressivity; and (d) Severe pathology. Clinically meaningful distinctions emerged among profiles on AMPD indicators and external variables relevant to PD, especially aggression and impulsivity. CONCLUSIONS: Profiles reflected both the "severity" and "style" components imbedded within Criterion A and B of the AMPD, as they were mainly distinguished by a continuum of severity but also by some meaningful qualitative differences that may have important clinical implications for treatment planning and contracting. Results also suggest that the four Criterion A elements have independent value to identify important differences in patients with borderline pathology. They also highlight that some Criterion B facets that define BPD in the AMPD may be especially important to identify subgroups of patients, mainly Impulsivity and Depressivity.

A Proposed Classification of ICD-11 Severity Degrees of Personality Pathology Using the Self and Interpersonal Functioning Scale.

Background: The 11th version of the World Health Organization's International Classification of Diseases (ICD-11) has adopted a dimensional approach to personality disorder (PD) nosology. Notably, it includes an assessment of PD degree of severity, which can be classified according to five categories. To date, there is no gold standard measure for assessing degree of PD severity based on the ICD-11 model, and there are no empirically-based anchor points to delineate the proposed categories. With the operationalization of PD degrees of severity in the ICD-11 PD model now being closely aligned with Criterion A of the DSM-5 Alternative Model for Personality Disorders (AMPD), sharing a focus on self and interpersonal dysfunction, self-report instruments developed for the latter model might prove useful as screening tools to determine degrees of severity in the former. Methods: The Self and Interpersonal Functioning Scale, a brief validated self-report questionnaire originally designed to assess level of personality pathology according to the AMPD framework, was used to derive anchor points to delineate the five severity degrees from the ICD-11 PD model. Data from five clinical and non-clinical samples (total N = 2,240) allowed identifying anchor points for classification, based on Receiver Operating Characteristic curve analysis, Latent Class Analysis, and data distribution statistics. Categories were validated using multiple indices pertaining to externalizing and internalizing symptoms relevant to PD. Results: Analyses yielded the following anchor points for PD degrees of severity: No PD = 0-1.04; Personality Difficulty = 1.05-1.29; Mild PD = 1.30-1.89; Moderate PD = 1.90-2.49; and Severe PD = 2.50 and above. A clear gradient of severity across the five categories was observed in all samples. A high number of significant contrasts among PD categories were also observed on external variables, consistent with the ICD-11 PD degree of severity operationalization. Conclusions: The present study provides potentially useful guidelines to determine severity of personality pathology based on the ICD-11 model. The use of a brief self-report questionnaire as a screening tool for assessing PD degrees of severity should be seen as a time-efficient support for clinical decision and treatment planning.

The role of HGF on invasive properties and repopulation potential of human fetal hepatic progenitor cells.

UNLABELLED: The success of hepatocyte transplantation has been limited by the low efficiency of transplanted cell integration into liver parenchyma. Human fetal hepatic progenitor cells (hepatoblasts) engraft more effectively than adult hepatocytes in mouse livers. However, the signals required for their integration are not yet fully understood. We investigated the role of HGF on the migration and invasive ability of human hepatic progenitors in vitro and in vivo. Hepatoblasts were isolated from the livers of human fetuses between 10 and 12 weeks of gestation. Their invasive ability was assessed in the presence or absence of HGF. These cells were also transplanted into immunodeficient mice and analyzed by immunohistochemistry. In contrast to TNF-alpha, HGF increased the motogenesis and invasiveness of hepatoblasts, but not of human adult hepatocytes, via phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. The invasive ability of human hepatoblasts correlated with the expression and secretion of matrix metalloproteinases (MMPs). Hepatoblasts stimulated with HGF prior transplantation into newborn mice migrated from the portal area into the hepatic parenchyma. CONCLUSIONS: In contrast to adult hepatocytes, hepatoblasts display invasive ability that can be modulated by HGF in vitro and in vivo.

Stemmed acetabular cup as a salvage implant for revision total hip arthroplasty with Paprosky type IIIA and IIIB acetabular bone loss.

INTRODUCTION: Certain cases of repeated acetabular loosening with severe bone loss are hardly amenable to reconstruction using a Kerboull-type plate with allograft. This limitation is more likely when the severe bone loss occurs in older adults with significant comorbidities that may require a faster procedure. In these indications, a stemmed acetabular cup may be an alternative, although the outcomes have not been well defined, especially for a version where the peg is coated with porous material and additional screws can be added. This led us to conduct a retrospective study to determine: (1) whether a stemmed cup anchored in the iliac isthmus is a viable alternative in these situations, (2) the complication rate and (3) the revision rate for any reason. HYPOTHESIS: A stemmed cup anchored in the iliac isthmus is a viable alternative in cases of repeated revision with severe acetabular bone loss. MATERIALS AND METHODS: We performed a retrospective single-center study. Sixteen Integra™ cups were implanted in 14 patients (mean age 72.8±10.4 years, minimum-maximum: 58-95) who had aseptic acetabular loosening combined with severe acetabular bone loss graded as Paprosky IIIA in 7 hips and IIIB in 9 hips. The patients had undergone a mean of 2.7±1.8 (minimum-maximum: 1-6) procedures (i.e. primary and/or revision arthroplasty) before this cup was implanted. The cup's survivorship at the time of review and the complication rate were determined. RESULTS: At a mean follow-up of 48.8±23.4 months (minimum-maximum: 7-85), two patients had died and two were lost to follow-up. Six hips experienced one or more complications (37.5%): three infections (18.8%), two mechanical failures (12.5%) and one dislocation (6.7%). The cup had to be removed in three patients (18.8%). These complications required reoperation, thus the cumulative incidence of revision for any reason at 5 years was 31% (95% CI: 11-55%). CONCLUSION: Despite the high complication and revision rates, we believe the stemmed acetabular cup is a viable alternative in salvage reconstruction procedures. LEVEL OF EVIDENCE: IV, Retrospective case study.

Analysis of human histone H2AZ deposition in vivo argues against its direct role in epigenetic templating mechanisms.

Chromatin is considered to be a principal carrier of epigenetic information due to the ability of alternative chromatin states to persist through generations of cell divisions and to spread on DNA. Replacement histone variants are novel candidates for epigenetic marking of chromatin. We developed a novel approach to analyze the chromatin environment of nucleosomes containing a particular replacement histone. We applied it to human H2AZ, one of the most studied alternative histones. We find that neither H2AZ itself nor other features of the H2AZ-containing nucleosome spread to the neighboring nucleosomes in vivo, arguing against a role for H2AZ as a self-perpetuating epigenetic mark.