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The International Classification of Diseases–11th revision (ICD-11) classification of personality disorders is the official diagnostic system that is used all over the world, and it has recently been renewed. However, as yet very few data are available on its performance. This study examines the Personality Inventory for ICD-11 (PiCD), which assesses the personality domains of the system, and the Standardized Assessment of Severity of Personality Disorder (SASPD), which determines severity. The Spanish versions of the questionnaires were administered to a community (n = 2,522) and a clinical sample (n = 797). Internal consistency was adequate in the PiCD (α =.75 to.84) but less so in the SASPD (α =.64 and.73). Factor analyses suggested a unidimensional or bidimensional structure for severity, while revealing that the personality trait qualifiers are organized into four factors: negative affectivity, detachment, dissociality, and a bipolar domain of disinhibition–anankastia. The mutual relationships between traits and severity were analyzed, as well as the ability of the whole system to identify clinical subjects. Although further improvements are required, the results generally support the use of the PiCD and the SASPD and help substantiate the new ICD-11 taxonomy that underlies them., This work was supported by project PI15/00536, part of the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016, financed by the ISCIII Subdirección General de Evaluación and the cofinanced by the European Regional Development Fund (ERDF, “A way to build Europe”; PI: F. Gutiérrez)

The Personality Inventory for ICD-11 (PiCD) was recently developed to assess the ICD-11 model of personality disorders. The purpose of this study was to examine the construct validity of the PiCD using the Minnesota Multiphasic Personality Inventory (MMPI)-2-Restructured Form (MMPI-2-RF) and the Computerized Adaptive Test of Personality Disorders Static Form (CAT-PD-SF). We administered these tests to 328 college students (150 males, 178 females). We found that the PiCD had adequate internal consistency reliability. Correlations between scores from the PiCD scales and the criterion measures generally indicated adequate discriminant validity. Along the same lines, convergent validity was adequate for the PiCD Negative Affective, Disinhibition, and Dissocial scales. However, the evidence was more mixed for the PiCD Detachment and Anankastic domains, which may be due to limitations with the content domains for these scales. Consistent with other research and theoretical expectations, a conjoint exploratory factor analysis utilizing the PiCD and MMPI-2-RF PSY-5 scales also indicated that anankastic and disinhibition may be more appropriately conceptualized as measuring opposite poles of one construct. Implications of these findings for the PiCD and the ICD-11 model are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

To assess the psychometric properties of the Personality Inventory for ICD-11 (PiCD, where ICD-11 is the International Classification of Diseases, 11th Revision), a sample of Italian community-dwelling adult participants (N = 1,122) was administered the PiCD, the Five-Factor Model Rating Form, the Big Five Inventory, the Personality Inventory for DSM-5 Short Form (where DSM-5 is the Diagnostic and Statistical Manual of Mental Disorders, fifth edition), and the Measure of Disordered Personality Functioning. Our findings supported the unidimensionality hypothesis for the PiCD Negative Affectivity, Detachment, and Dissocial scale items, whereas adequate fit indices were observed for the bifactor model of the PiCD Disinhibition and Anankastic item joint polychoric correlation matrix. The PiCD scales showed adequate internal consistency, test-retest reliability (n = 262), and meaningful relationships with five-factor model domains and their maladaptive variants. A four-factor model of the joint correlation matrix of the PiCD, Personality Inventory for DSM-5 Short Form, and the five-factor model composite score was provided with adequate fit. All PiCD scales were significantly associated with the impairment in personality functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Dig Dis Sci DOI 10.1007/s10620-016-4248-5 EDITORIAL Prevention of the Paracentesis-Induced Circulatory Dysfunction (PICD) in Cirrhosis: Is the SPA Treatment Worthwhile? John Carl Hoefs 1 Received: 3 July 2016 / Accepted: 5 July 2016 O Springer Science+Business Media New York 2016 The older leading concept concerning ascites formation postulates an imbalance of oncotic and hydrostatic forces, with portal pressure pushing fluid into the peritoneal cavity opposed by the serum colloid osmotic pressure generated by albumin. When hydrostatic exceed oncotic forces, the abdominal cavity fills with fluid until a counterbalancing increase in abdominal pressure prevents further ascites formation. Furthermore, patients with ascites are almost perfectly separated from those without ascites on the basis of portal pressure (relative to the cardiac pressure) and serum albumin concentration [1] seeming to support this concept. According to this model, decreased intra-abdom- inal pressure due to fluid removal by paracentesis promotes fluid movement into the peritoneal cavity at the expense of the intravascular compartment, potentially resulting in catastrophic hypotension and renal failure. Since these events were thought to occur soon after paracentesis, the prevailing recommendation was for \2 L to be removed at any one time. Harmful effects from paracentesis were considered likely despite a large global clinical experience that had not identified a high incidence of hypotension or renal failure due to a common and routine clinical procedure. Two factors changed this view. The first was the description of oncotic-hydrostatic balance between serum and ascites [2–7] documenting an ‘‘abnormal balance’’ between colloid osmotic and hydrostatic pressure rather than an outright imbalance. In this model, the portal pres- sure gradient (portal pressure relative to intra-abdominal & John Carl Hoefs jchoefs@uci.edu Emeritus Professor, University of California, Irvine, Irvine, CA, USA pressure) was the major cause of ascites, as reflected in the serum to ascites albumin gradient (SAAG) both of which are unchanged after removing peritoneal fluid, during diuresis, or following albumin infusions [4, 5]. Thus, rapid formation of ascitic fluid was an unlikely consequence of paracentesis in this model although a fragile system sen- sitive to changes in intravascular volume might be pre- dicted. Furthermore, the model predicted the importance of the SAAG in the differential diagnosis of ascites, a widely accepted finding [4, 5] supporting the validity of this model. The second was data obtained from controlled trials that failed to document a major decrease in systemic blood pressure or an increased incidence of renal failure follow- ing paracentesis [7]. Indeed, control of ascites with para- centesis appeared safer than with diuretics [7]. Nevertheless, carefully controlled trials using sensitive hemodynamic measures did document statistically signifi- cant mild subclinical abnormalities such as alterations in plasma renin activity (PRA) and creatinine in some patients with tense ascites following complete fluid drainage or ‘‘total’’ paracentesis, usually days after the procedure and this is termed paracentesis-induced circulatory dysfunction (PICD) [8, 9]. Progressive renal failure or vascular collapse was not reported in these studies. Nonetheless, the concept of PICD became firmly established, with data supporting the concept that PICD could be prevented by salt-poor albumin (SPA) infusions [9]. The concern remained that some patients with PICD would deteriorate to the point that severe adverse clinical events occurred, justifying the expense of SPA infusions in all patients undergoing para- centesis. Furthermore, similar, but more pronounced alterations were present in the context of this fragile hemodynamic system such as spontaneous bacterial peri- tonitis, with hemodynamic improvement and increased survival attributed to concurrent SPA infusions [10]. Thus

An imbalance in apoptosis or survival of immune cells plays an essential role in the pathophysiology of sepsis. Phagocytosis-induced cell death (PICD) is a common result of the pathogen-host cell interaction mediated by reactive oxygen species (ROS). Neonatal sepsis is frequently characterized by hyperinflammation. Cord blood monocytes (CBMO) are equivalent to monocytes of adults [peripheral blood monocytes (PBMO)], both in terms of phagocytosis and killing of Escherichia coli. We investigated whether CBMO are less sensitive toward PICD compared with PBMO. Monocytes were infected with green fluorescent protein (GFP)-labeled E. coli. Phagocytic activity, cell-count, Annexin V staining, hypoploid DNA content, CD95 and CD95L expression, and caspase-8 and -9 activities were analyzed by flow cytometry, ROS production by chemiluminescence, and CD95L mRNA expression by reverse-transcriptase polymerase chain reaction. With equal phagocytic activity and ROS production, PBMO cell count was decreased by 82 +/- 6% versus 28 +/- 8% for CBMO after infection. Annexin V binding was enhanced fivefold on PBMO; 56 +/- 15% of PBMO showed a hypodiploid DNA content compared with 9 +/- 6% of CBMO. Caspases CD95L and CD95L mRNA were up-regulated in PBMO. Our results indicate that CBMO are less sensitive toward E. coli-mediated PICD than PBMO. Modifying monocyte apoptosis may be a target for future interventions in sepsis.

PLoS one 12(8), e0182415 (2017). doi:10.1371/journal.pone.0182415, Published by PLoS, Lawrence, Kan.

PLoS one 11(11), e0166648 (2016). doi:10.1371/journal.pone.0166648, Published by PLoS, Lawrence, Kan.

Human PICD was identified by homology probing the data base of expressed sequence tags with the protein sequence of Saccharomyces cerevisiae Idp3p, a peroxisomal NADP(+)-dependent isocitrate dehydrogenase. The human PICD cDNA contains a 1242-base pair open reading frame, and its deduced protein sequence is 59% identical to yeast Idp3p. Expression of PICD partially rescued the fatty acid growth defect of the yeast idp3 deletion mutant suggesting that PICD is functionally homologous to Idp3p. Kinetic studies on bacterially expressed PICD demonstrated that this enzyme catalyzed the oxidative decarboxylation of isocitrate to 2-oxoglutarate with a specific activity of 22.5 units/mg and that PICD displayed K(M) values of 76 microM for isocitrate and 112 microM for NADP(+). In subcellular fractionation experiments, we found PICD in both peroxisomes and cytoplasm of human and rat liver cells, with approximately 27% of total PICD protein associated with peroxisomes. The presence of PICD in mammalian peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. As for cytoplasmic PICD, the phenotypes of patients with glucose-6-phosphate dehydrogenase deficiency (Luzzatto, L., and Mehta, A. (1995) in The Metabolic and Molecular Bases of Inherited Disease (Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D., eds) Vol. 3, 7th Ed., pp. 3367-3398, McGraw-Hill Inc., New York) suggest that PICD serves a significant role in cytoplasmic NADPH production, particularly under conditions that do not favor the use of the hexose monophosphate shunt (Luzzatto et al.).

The International Classification of Diseases-11th Edition (ICD-11) Classification of Personality Disorders provides the option of coding 5 trait domain qualifiers that contribute to the individual expression of personality dysfunction (i.e., Negative Affectivity, Detachment, Dissociality, Disinhibition, and Anankastia). Previous investigations of these trait domains are based on self-reported data, and so is much of the research literature from which the ICD-11 trait model has evolved. However, the ICD-11 itself involves judgments made by clinicians about their patients. Thus, it is important to examine whether the trait domains identified in self-report studies can also be obtained from clinician-reported data. A sample of 238 mental health patients were characterized by clinicians using an informant-report form of the Personality Inventory for ICD-11 (PiCD-IRF). As expected, exploratory factor analysis (EFA) indicated that clinician-reported ICD-11 trait domains could be captured by both 4- and 5-factor structures, of which the 5-factor solution seemed less conceptually sound relative to the 4-factor solution. The 4-factor model captured the unipolar domains of Negative Affectivity, Detachment, Dissociality, along with a bipolar domain of Disinhibition versus Anankastia, whereas the 5-factor model furthermore captured features of Disinhibition and Anankastia as 2 separate factors. The hierarchical structure from 1 to 5 factors partially resembled previously reported trait structures and models of psychopathology. These findings overall support the multimethod robustness of ICD-11 trait domain qualifiers and the potential for their valid ratings by mental health clinicians. The PiCD-IRF is provided in the online supplementary material - for clinical or research purposes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully.A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient.Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.

Background The International Classification of Diseases 11th Revision (ICD-11) personality disorder model comprises, among other elements, five maladaptive personality trait domains (negative affectivity, detachment, dissociality, disinhibition, anankastia). Recently, the personality inventory for ICD-11 (PiCD) has emerged as one of the most widely used measures of these ICD-11 personality trait domains. Methods The current study contributed to the validation of the PiCD validation by exploring its stability and predictive links with psychological distress over 6 months in a sample of 206 German community adults. Results The PiCD trait domain scales displayed strong differential (all r ≥ .80) and absolute stability (all |d| ≤ .09). Additionally, PiCD negative affectivity predicted depression, anxiety, and stress, and PiCD detachment predicted depression over 6 months beyond baseline. Conclusion In sum, this study demonstrated the stability of the PiCD trait domain scores, supporting their utility for capturing relatively stable traits as described in the ICD-11. Additionally, we provided the first evidence for the predictive validity of some of the PiCD trait domain scores.

PURPOSE: This study aimed to describe the frequency of colostomy and ileostomy complications and types of nursing interventions as well as to examine patient and ostomy variables associated with early and late complications. METHODS: The records of 572 patients who received ostomy care from a wound ostomy care (WOC) nurse between 2013 and 2017 were abstracted. Patient demographic and ostomy variables, early period (< 30 days after surgery) and late period (> 30 days after surgery) complications, as well as documented nursing interventions were retrieved. Percentages and rates, chi-square statistics, and logistic regression were used to analyze the data. RESULTS: The mean patient age was 59.1 years (standard deviation [SD], 13.86), and the majority of patients were male (302 patients; 52.8%), married (454; 79.4%), and had a temporary (438; 76.6%) end colostomy (253; 44.2%). One (1) or more complications developed in 323 patients (56.5%) in the early period and in 207 patients (36.2%) in the late period. The most common complications in the early period were peristomal irritant contact dermatitis (PICD) (181; 31.6%) and mucocutaneous separation (135; 23.6%). PICD was also the most common complication in the late period (149; 26%). The risk of PICD was significantly higher in patients with a body mass index > 24.9 kg/m(2) (odds ratio [OR] = 1.547), who had an ileostomy (OR = 1.654), or a temporary ostomy (OR = 1.728). Variables associated with an increased risk of mucocutaneous separation included obstacles to ostomy care (OR = 2.222), having an end ostomy (OR = 2.171), and ostomy height < 10 mm (OR = 1.964). Complications were treated by the WOC nurse in 67.5% of patients, and the most common intervention was application of skin barrier powder and wipe layers. CONCLUSIONS: The rate of ostomy complications, especially PICD and mucocutaneous separation, in this study was high. Results confirm that patient and ostomy characteristics might significantly affect the risk of complications. The findings support the importance of outpatient follow-up by a WOC nurse. Explorative or randomized controlled studies are needed to identify optimal nursing strategies to decrease complication rates.

A central innovation in the International Classification of Diseases 11th Revision (ICD-11) is a dimensional personality disorder model differentiating five personality trait domains. The Personality Inventory for ICD-11 (PiCD) is a frequently used measure to assess these components of the ICD-11 personality disorder model. Conceptually, the ICD-11 personality trait domains correspond to trait domains from the five-factor model (FFM) of personality. However, empirically, it is unclear how the PiCD scales align with the FFM. In this questionnaire study with 480 German community adults, we assessed the joint factor structure of the PiCD trait domain scales and the FFM personality facets (assessed with the Big Five Inventory-2 [BFI-2]). A principal axis factor analysis revealed a joint five-factorial structure. The PiCD trait domain scales and the BFI-2 facet scales of the respectively corresponding FFM trait domains were almost perfectly aligned, including a bipolar anankastia-disinhibition factor along the conscientiousness dimension. Facets of openness to experience formed a fifth factor, separate from the PiCD scales. Together, these findings demonstrate structural correspondences of the PiCD trait domain scales and the respective BFI-2 facet scales, mirroring conceptual analogies between the ICD-11 and FFM personality models. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

At present, there are two models of pathological personality represented in two measurement instruments, the Personality Inventory for DSM-5 (PID-5) and the Personality Inventory for ICD-11 (PiCD). Although both instruments have shown high convergence, the PID-5 has the advantage of including facets that might offer greater predictive capacity. An alternative to the PiCD has recently been proposed to overcome this drawback, namely the Five-Factor Personality Inventory for ICD-11 (FFiCD). The present study aims to explore its internal structure and to offer additional validity evidence. Data were collected for a total of 1,409 community individuals from two populations in Spain. They responded to the FFiCD, PiCD, the PID-5/SF, and measures of personality functioning and personality disorder screening (Level of Personality Functioning Scale Self-Report [LPFS-SR] and International Personality Disorder Examination [IPDE]). The internal structure of the FFiCD was analyzed through exploratory factor analysis with oblique and bifactor rotations. The predictive capacity of the domains and facets was examined. The structure reported in the original study was replicated, as were the convergent validity data with respect to the PID-5/SF and the PiCD. Facets were grouped into four factors corresponding to the theoretical domains, including a bipolar Anankastia/Disinhibition factor. High correlations were found with the LPFS-SR, and the patterns of relationships with the IPDE shed light on which aspects of pathological personality contribute most to the 10 traditional personality disorders. In general, validity evidence is provided to support the use of the FFiCD, though four of the 20 facets merit revision so that a simpler factor structure can be obtained. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Ascites is the most common presentation of decompensated liver cirrhosis. It is treated with therapeutic paracentesis which is associated with several complications. The role of human albumin in patients with cirrhotic ascites remains elusive and has been extensively studied with conflicting results. Thus, in order to fully appraise the available data we sought to perform this systematic review and meta-analysis. Herein we included studies comparing the efficacy and safety of human albumin comparing with other volume expanders and vasoactive agents in patients undergoing paracentesis in cirrhotic ascites. Odds ratio (OR) and mean difference (MD) were used to estimate the outcome with a 95% confidence interval (CI). Albumin use reduced the odds of paracentesis induced circulatory dysfunction (PICD) by 60% (OR 0.40, 95% CI 0.27–0.58). While performing subgroup analysis, albumin use lowered the odds of PICD significantly (OR 0.34, 95% CI 0.22–0.52) in comparison to other colloid volume expanders, but did not lower the odds of PICD in comparison to vasoconstrictor therapy (OR 0.93, 95% CI 0.35–2.45). Albumin was associated with a statistically significant lower incidence of hyponatremia (OR 0.59, 95% CI 0.39–0.88). Albumin did not reduce the overall mortality, readmission rate, recurrence of ascites, mean arterial pressure, incidence of renal impairment, hepatic encephalopathy, and gastrointestinal (GI) bleeding. Thus, treatment with albumin in cirrhotic ascites reduced PICD and hyponatremia although there was no benefit in terms of mortality, readmission rate, recurrence of ascites, hepatic encephalopathy, and GI bleeding.

Proposed for the ICD-11 is a dimensional model of personality disorder that, if approved, would be a paradigm shift in the conceptualization of personality disorder. The proposal consists of a general severity rating, 5 maladaptive personality trait domains, and a borderline pattern qualifier. The general severity rating can be assessed by the Standardized Assessment of Severity of Personality Disorder (SASPD), the trait domains by the Personality Inventory for ICD-11 (PiCD), and the borderline pattern by the Borderline Pattern Scale (BPS), which is developed in the present study. To date, no study has examined the relations among all 3 components, due in part to the absence of direct measures for each component (until recently). The current study develops and provides initial validation evidence for the BPS, and examines the relations among the BPS, SASPD, and PiCD. Also considered is their relationship with the 5-factor model of general personality as well as with 2 other measures of personality disorder severity (including the DSM-5 Level of Personality Functioning Scale [LPFS]). Further, an alternative trait-based coding of the DSM-5 LPFS is examined (modeled after the ICD-11 SASPD), suggesting that its coverage of diverse maladaptivity may not be because it assesses the core of personality disorder, but rather because it has items specific to the different domains of personality. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The International Classification of Diseases-11th Edition (ICD-11) includes a dimensional trait model of personality disorder. The Personality Inventory for ICD-11 (PiCD) was the first self-report measure developed for its assessment. The present study examines the validity of an informant-report version of the PiCD, the Informant-Personality Inventory for ICD-11 (the IPiC), and is the first study to test self-other agreement, ratings from close others, and the criterion validity of both the IPiC and the PiCD for several popular and well-validated measures of life functioning: Life and romantic relationship satisfaction, social support, physical and mental health, depressive symptoms, insomnia symptoms, and cognitive decline. The present study is also the first to examine the IPiC and PiCD in a sample of older adults in the community. Results suggest that the IPiC and the PiCD show moderate self-other agreement, are associated significantly with several important life functioning areas, and have structural validity even at the item level. Further replication and validation are necessary for these instruments, but the IPiC and the PiCD have shown strong validation evidence to date, now including evidence of consensual and criterion validity, in addition to structural validity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

MΦ differentiate from circulating monocytes (Mo). The reduced ability of neonatal Mo to undergo apoptosis after E. coli infection (phagocytosis-induced cell death (PICD)) could contribute to sustained inflammatory processes. The objective of our study was to investigate whether immune metabolism in Mo can be modified to gain access to pro-apoptotic signaling. To this end, we supplemented Mo from neonates and from adults with the branched amino acid leucine. In neonatal Mo, we observed increased energy production via oxidative phosphorylation (Oxphos) after E. coli infection via Seahorse assay. Leucine did not change phagocytic properties. In neonatal Mo, we detected temporal activation of the AKT and mTOR pathways, accompanied with subsequent activation of downstream targets S6 Kinase (S6K) and S6. FACS analyses showed that once mTOR activation was terminated, the level of anti-apoptotic BCL-2 family proteins (BCL-2, BCL-XL) decreased. Release of cytochrome C and cleavage of caspase-3 indicated involvement of the intrinsic apoptotic pathway. Concomitantly, the PICD of neonatal Mo was initiated, as detected by hypodiploid DNA. This process was sensitive to rapamycin and metformin, suggesting a functional link between AKT, mTOR and the control of intrinsic apoptotic signaling. These features were unique to neonatal Mo and could not be observed in adult Mo. Supplementation with leucine therefore could be beneficial to reduce sustained inflammation in septic neonates.

Previous studies suggested that right ventricular pacing was associated with pacing-induced cardiac dysfunction (PICD). The purpose of this study was to investigate the clinical characteristics including the incidence of undiagnosed cardiac sarcoidosis (CS) in patients with atrioventricular block (AVB) who manifest PICD. We retrospectively investigated consecutive patients with permanent pacemaker (PPM) undergoing a first-generator replacement surgery with a new PPM or an upgrade procedure to a cardiac resynchronization therapy (CRT) device between December 1, 2011 and June 30, 2017. Patients with AVB showing normal echocardiographic findings before PPM implantation were included and divided into 2 groups: patients with post-PPM left ventricular ejection fraction (LVEF)

Optimal innate immune response to infection includes eradication of potential pathogens, resolution of associated inflammation, and restitution of homeostasis. Phagocytosing human polymorphonuclear leukocytes (hPMN) undergo accelerated apoptosis, a process referred to as phagocytosis-induced cell death (PICD) and an early step in their clearance from inflammatory sites. Among human pathogens that modulate hPMN apoptosis, Neisseria gonorrhoeae delays PICD, which may contribute to the exuberant neutrophilic inflammation that characterizes gonorrhea. To elucidate the mechanisms underlying delayed PICD, we compared features of hPMN cell death that followed phagocytosis of N. gonorrhoeae FA1090 wild-type (GC) or serum-opsonized zymosan (OPZ), a prototypical stimulus of PICD. Phosphatidylserine externalization required NADPH oxidase activity after ingestion of GC or OPZ, and annexin V staining and DNA fragmentation were less after phagocytosis of GC compared to OPZ. Caspase 3/7 and caspase 9 activities after phagocytosis of GC were less than that seen after ingestion of OPZ, but caspase 8 activity was the same after ingestion of GC or OPZ. When hPMN sequentially ingested GC followed by OPZ, both caspase 3/7 and 9 activities were less than that seen after OPZ alone, and the inhibition was dose dependent for GC, suggesting that ingestion of GC actively inhibited PICD. Sequential phagocytosis did not block caspase 8 activity, mitochondrial depolarization, or annexin V/propidium iodide staining compared to responses of hPMN fed OPZ alone, despite inhibition of caspases 3/7 and 9. Taken together, these data suggest that active inhibition of the intrinsic pathway of apoptosis contributes to the delay in PICD after hPMN ingestion of N. gonorrhoeae.

The ICD-11 model of personality disorder consists of a level of severity, 5 trait domains, and a borderline pattern qualifier. Level of severity is assessed by the Standardized Assessment of Severity of Personality Disorder (SASPD; Olajide et al., 2018), the trait model by the Personality Inventory for ICD-11 (PiCD; Oltmanns & Widiger, 2018), and the borderline pattern qualifier by the Borderline Pattern Specifier inventory (BPS; Oltmanns & Widiger, 2019). The DSM-5 Section III Alternative Model of Personality Disorder includes a level of personality functioning and the five-domain trait model. These two components are assessed by the Level of Personality Functioning Scale (LPFS; Morey, 2017) and the Personality Inventory for DSM-5 (PID-5; Krueger, Derringer, Markon, Watson, & Skodol, 2012). Components of each model have been related to one another, but no study has yet considered all of the components for both models within one study. The current study considers the convergent, discriminant, and structural validity of the relationship of the LPFS and PID-5 with the SASPD, PiCD, and BPS. Also included were multiple measures of borderline personality disorder to determine if the BPS obtains incremental validity in accounting for borderline personality disorder variance above and beyond the trait models. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The 11th edition of the International Classification of Diseases and Related Health Problems (ICD-11), recently approved by the World Health Organization, contains a new diagnostic approach for personality disorders. This approach partly involves the consideration of 5 dimensional trait domain qualifiers-Negative Affectivity, Detachment, Dissocial, Disinhibition, and Anankastia. Oltmanns and Widiger (2018) recently developed a self-report measure, the Personality Inventory for ICD-11 (PiCD), to assess the 5 domains; however, further examination of the psychometric properties of the PiCD is warranted due to its limited research base. The present study aimed to further examine the reliability, structural and concurrent validity, and method variance of the PiCD in an ethnically diverse undergraduate sample (N = 518), who were also administered the Minnesota Multiphasic Personality Inventory-2-Restructured Form. First, results suggested that the PiCD domain scales exhibited adequate internal consistency reliability via coefficient categorical omega (range = .77-.87). Next, exploratory structural equation modeling results suggested support for a 4-factor solution, with the 4th factor thought to represent a bipolar continuum of Anankastia to Disinhibition severity. Random-intercept factor analysis results suggested a small amount of variance in items (4.88%) attributable to idiosyncratic scale usage. Lastly, relations between PiCD domains and Minnesota Multiphasic Personality Inventory-2-Restructured Form scales (Personality Psychopathology-5 and Higher Order scales) provided support for the validity of the Negative Affectivity, Detachment, and Dissocial domains, though relatively less support for the Disinhibition and Anankastia domains. Further examination of other psychometric properties and the nomological network of the PiCD is recommended. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The predominant maladaptive trait models are now provided by Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) Section III, assessed by the Personality Inventory for DSM-5 (PID-5; Krueger, Derringer, Markon, Watson, & Skodol, 2012), and the International Classification of Diseases-11th Revision (ICD-11; assessed by the Personality Inventory for ICD-11 (PiCD; Oltmanns & Widiger, 2018). However, 2 historical precedents are the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ; Livesley & Jackson, 2009) and the Schedule for Nonadaptive and Adaptive Personality (SNAP; Clark, 1993). The current study administered the DAPP-BQ, SNAP, PiCD, and PID-5 to a sample of 323 persons with a history of mental health treatment. The results provided support for the historical precedence of the DAPP-BQ and SNAP, although also suggest that additional traits should perhaps be included in current models. The results also bear on additional ongoing issues, including (but not limited to) the bipolarity of maladaptive personality structure, the conceptualization of identity problems as a trait, and the discriminant validity of maladaptive trait models and their assessment. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

BACKGROUND AND AIMS Paracentesis-induced circulatory dysfunction (PICD) is a serious complication of large-volume (>5 L) paracentesis in cirrhosis and is reduced with albumin infusion. There is a lack of data on PICD in acute-on-chronic liver failure (ACLF). Because ACLF patients have greater hemodynamic derangements than patients with decompensated cirrhosis, we investigated whether PICD could develop with modest-volume paracentesis (MVP) and the role of albumin infusion. APPROACH AND RESULTS A total of 80 ACLF patients undergoing

Objective Apoptotic cells participate in maintenance of homeostasis of the adaptive immune system. Granulocyte/monocyte adsorptive apheresis (GMA) performed with an Adacolumn has been shown to have clinical efficacy together with immunomodulatory effects for immune-mediated disorder cases, such as inflammatory bowel disease (IBD) or psoriatic arthritis. Although induction of apoptosis in neutrophils by GMA has been observed, the detailed mechanism remains unclear. Methods To focus on phagocytosis-induced cell death (PICD) that induces apoptotic neutrophils, a comparative study utilizing a GMA-carrier (leukocyte adsorbing carrier for Adacolumn) and yeast particles was performed with in vitro and in vivo examinations. Results L-selectin was significantly (P = 0.0133) shed, reactive oxygen species (ROS) production was promoted (P = 0.0019), and apoptosis induction was enhanced (P = 0.0087) by peripheral blood co-cultured with the GMA-carrier or yeast particles as compared to incubated blood alone. Furthermore, degranulation of myeloperoxidase, elastase, and lactoferrin was increased by both treatments, while the highest level of interleukin-1 receptor antagonist release was found with GMA-carrier treatment (P = 0.0087) as compared to the yeast particles. Plasma from blood treated with the GMA-carrier showed chemotactic activity, and suppressed neutrophil migration to IL-8 and LTB4. In vivo results demonstrated that neutrophil chemotaxis to IL-8 was desensitized (P = 0.0078) in rabbits following GMA apheresis, while CXCR1 and CXCR2 expressions in neutrophils were reduced by exposing peripheral blood to the GMA-carrier. Conclusions GMA may regulate the immune system in patients with an immune-mediated disorder by inducing a biological response of neutrophils with a PICD-like reaction.

Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli infection mounts for activation of MMP-9 and TACE in monocytes and whether this process regulates PICD. Results: The surface expression of TACE was most prominent on infected adult monocytes. In contrast, surface presentation of MMP-9 was highest on infected neonatal monocytes. Selective blocking of MMP-9 decreased CD95L secretion, while inhibition of TACE left CD95L secretion unaltered. Blocking of MMP-9 increased surface CD95L (memCD95L) expression on infected neonatal monocytes to levels comparable to infected adult monocytes. Moreover, MMP-9 inhibition raised PICD of infected neonatal monocytes to levels observed for infected adult monocytes. In contrast, TACE inhibition decreased PICD in infected monocytes. Addition of extracellular TNF effectively induced memCD95L presentation and PICD of adult monocytes and less of neonatal monocytes. Conclusion: MMP-9 activity is crucial for downregulating cell-contact dependent PICD in E. coli infected neonatal monocytes. By this mechanism, MMP-9 could contribute to reducing sustained inflammation in neonates.

Background A percutaneous intravascular cardioverter-defibrillator (PICD) has been developed with a right ventricular (RV) single-coil lead and titanium electrodes in the superior vena cava (SVC)–brachiocephalic vein (BCV) region and the inferior vena cava (IVC). Objective To compare defibrillation thresholds (DFTs) of the PICD with those of a conventional ICD in humans. Methods Ten patients with ischemic cardiomyopathy and ejection fraction ≤35% were randomized to initial testing with either PICD or conventional ICD. A standard dual-coil lead was positioned in the RV apex. If randomized to PICD, the device was placed into the vasculature such that 1 titanium electrode was positioned in the SVC-BCV region and the second in the IVC. For PICD DFTs, the RV coil of the conventional ICD lead was connected to the PICD mandrel [shock vector: RV (+) to SVC-BCV (−) + IVC (−)]. When testing the conventional ICD, a subcutaneous pocket was formed in the left pectoralis region and the ICD was connected to the lead system and positioned in the pocket [shock vector: RV (+) to SVC (−) + active can (−)]. Each device was removed before testing with the other. A step-down binary search protocol determined the DFT, with the initial shock being 9 J. Results The mean PICD DFT was 7.6 ± 3.3 J, and the conventional ICD system demonstrated a mean DFT of 9.5 ± 4.7 J (N = 10; paired t test, P = .28). Conclusion The intravascular defibrillator has DFTs similar to those of commercially available ICDs.

Proposed for the 11th edition of the World Health Organization's International Classification of Diseases (ICD-11) is a dimensional trait model for the classification of personality disorder (Tyrer, Reed, & Crawford, 2015). The ICD-11 proposal consists of 5 broad domains: negative affective, detachment, dissocial, disinhibition, and anankastic (Mulder, Horwood, Tyrer, Carter, & Joyce, 2016). Several field trials have examined this proposal, yet none has included a direct measure of the trait model. The purpose of the current study was to develop and provide initial validation for the Personality Inventory for ICD-11 (PiCD), a self-report measure of this proposed 5-domain maladaptive trait model. Item selection and scale construction proceeded through 3 initial data collections assessing potential item performance. Two subsequent studies were conducted for scale validation. In Study 1, the PiCD was evaluated in a sample of 259 MTurk participants (who were or had been receiving mental health treatment) with respect to 2 measures of general personality structure: The Eysenck Personality Questionnaire-Revised and the 5-Dimensional Personality Test. In Study 2, the PiCD was evaluated in an additional sample of 285 participants with respect to 2 measures of maladaptive personality traits: The Personality Inventory for DSM-5 and the Computerized Adaptive Test for Personality Disorders. Study 3 provides an item-level exploratory structural equation model with the combined samples from Studies 1 and 2. The results are discussed with respect to the validity of the measure and the potential benefits for future research in having a direct, self-report measure of the ICD-11 trait proposal. (PsycINFO Database Record

Understanding central mechanisms underlying drug-induced toxicity plays a crucial role in drug development and drug safety. However, a translation of cellular in vitro findings to an actual in vivo context remains challenging. Here, physiologically based pharmacokinetic (PBPK) modeling was used for in vivo contextualization of in vitro toxicity data (PICD) to quantitatively predict in vivo drug response over time by integrating multiple levels of biological organization. Explicitly, in vitro toxicity data at the cellular level were integrated into whole-body PBPK models at the organism level by coupling in vitro drug exposure with in vivo drug concentration–time profiles simulated in the extracellular environment within the organ. PICD was exemplarily applied on the hepatotoxicant azathioprine to quantitatively predict in vivo drug response of perturbed biological pathways and cellular processes in rats and humans. The predictive accuracy of PICD was assessed by comparing in vivo drug response predicted for rats with observed in vivo measurements. To demonstrate clinical applicability of PICD, in vivo drug responses of a critical toxicity-related pathway were predicted for eight patients following acute azathioprine overdoses. Moreover, acute liver failure after multiple dosing of azathioprine was investigated in a patient case study by use of own clinical data. Simulated pharmacokinetic profiles were therefore related to in vivo drug response predicted for genes associated with observed clinical symptoms and to clinical biomarkers measured in vivo. PICD provides a generic platform to investigate drug-induced toxicity at a patient level and thus may facilitate individualized risk assessment during drug development. Electronic supplementary material The online version of this article (doi:10.1007/s00204-016-1723-x) contains supplementary material, which is available to authorized users.

Ascites is a major complication of cirrhosis and is associated with poor prognosis [1]. Large-volume paracentesis (LVP) has become first-line treatment for patients with tense (grade 3) or refractory ascites. However, LVP markedly influences systemic hemodynamics and, in the absence of concomitant plasma volume expansion, >70% of patients undergoing LVP may develop paracentesis-induced circulatory dysfunction (PICD). This is associated with ascites recurrence, hepatic encephalopathy, hepatorenal syndrome, hyponatremia, and reduced survival. Human albumin is a physiological plasma expander used for LVP and can significantly reduce incidence of PICD. Albumin was also shown to be favorable versus alternative treatments (such as plasma expanders or vasoconstrictors) in minimizing PICD, hyponatremia, and mortality among patients with cirrhosis and ascites undergoing LVP in a meta-analysis conducted by our group in 2012. However, these results have been questioned by a recent meta-analysis investigating the effect of albumin on morbidity, performed by Kütting et al. [7]. Here, we critically analyze the evidence from Kütting et al. and other recent metaanalyses assessing use of albumin in LVP.

Background & Aims In patients with cirrhosis and refractory ascites the role of beta-blockers in the development of paracentesis-induced circulatory dysfunction (PICD) is unknown. The aim of this study was to investigate the incidence of PICD before and after discontinuation of beta-blockers in patients with cirrhosis and refractory ascites. A self control cross-over study was performed. Methods Patients with cirrhosis and refractory ascites treated with beta-blockers were selected. Heart rate, arterial pressure, and plasma renin concentrations (PRC) were collected before, immediately after and 1week after large-volume paracentesis associated with intravenous albumin administration. Beta-blocker therapy was progressively discontinued after complete endoscopic eradication of varices. The clinical and biological evaluation was then repeated. The presence of PICD was defined as an increase in PRC of at least 50% above baseline 1week after paracentesis. Results Ten patients were included (nine men, mean age 59.1±10.7years old). The MELD score was 17.7±4.4 and eight patients were Child–Pugh C. When patients were given beta-blockers, the heart rate did not change immediately after paracentesis while mean arterial pressure significantly decreased; PICD developed in eight patients. After beta-blockers were discontinued, the heart rate significantly increased immediately after paracentesis and mean arterial pressure significantly decreased; PICD only developed in one patient; the difference in the incidence of PICD was significant when these same patients were treated with beta-blockers. Conclusions The use of beta-blockers may be associated with a high risk of PICD in patients with cirrhosis and refractory ascites.

Background: Immunoglobulins (IVIG) have been shown to be useful in adults suffering from sepsis. In contrast, prophylactic and curative IVIG trials failed to show beneficial effects in neonates. We tested the hypothesis that IVIG, have different effects on monocytes from cord blood (CBMO) and peripheral blood monocytes from adults (PBMO) with respect to survival, phenotype, and function. Methods: Mononuclear cells, or purified monocytes, were cultured in 5% human serum, incubated with polyvalent IVIG (1 mg/ml), stimulated with green fluorescent protein (GFP)-labeled Escherichia coli (E. Coli-GFP), Interferon-c (IFN-c, 50 U/ml), or the T cell mitogen anti-CD3 monoclonal antibody, aCD3-mAb, (5 lg/ml). Phagocytosis, phenotype, T cell proliferation, and apoptosis were assessed by flow cytometry. Results: IVIG enhanced phagocytosis in PBMO or CBMO when infected directly after isolation, while IVIG had no effect on monocytes cultured 48 h prior to infection. In contrast to PBMO, IVIG inhibited the IFN-c mediated up-regulation of CD80, CD86, and HLA-DR on CBMO. In the presence of IVIG, stimulation with aCD3 in cord blood enhanced deletion, inhibited blast formation and CD28 up-regulation of T cells (P < 0.05 vs. T cells from adults). IVIG induced monocyte apoptosis, associated with up-regulation of Annexin V and loss of nuclear DNA, which was more pronounced in CBMO. Although phagocytosis induced cell death (PICD) was lower in CBMO (P < 0.05 vs. PBMO), the addition of IVIG enhanced PICD levels of CBMO to the extent of PBMO. Conclusions: IVIG inhibits co-stimulatory receptors and functions of CBMO and induces apoptosis. These findings may be of clinical relevance for the failure of IVIG benefit in neonatal sepsis. V C 2011

Purpose The purpose of this study was to characterize the pulsatile motion of trabecular meshwork (TM) in normal subjects and demonstrate its changes in accommodation with phase-sensitive optical coherence tomography (PhS-OCT). Methods A new PhS-OCT laboratory prototype was designed to measure pulsatile TM motion in 13 healthy humans. Two sets of images were captured in 10 subjects, first with best corrective refraction and the other with an additional 3.0 diopters of accommodation. In each image, both maximum velocity (MV) and cumulative displacement (CD) in two selected regions of TM, the internal (IMV and ICD) and external (EMV and ECD) region, were measured. Results For all parameters the intraclass correlation coefficient was >0.75. Neither MV nor CD was significantly different between eyes in individual subjects (PIMV = 0.967, PEMV = 0.391, PICD = 0.603, PECD = 0.482). In 26 eyes, with best corrective refraction, the EMV was higher than the IMV (23.9 ± 9.8 vs. 18.9 ± 8.08 μm/s; P = 0.0001), as was the ECD compared with the ICD (0.340 ±0.125 vs. 0.264 ± 0.111 μm; P = 0.000004). With accommodation, MV and CD significantly increased (PIMV = 0.0003, PEMV = 0.0003, PICD = 0.019, and PECD = 0.007), whereas MV and CD in the external region were still larger than those in the internal area (PEMV vs. IMV = 0.009, PECD vs. ICD = 0.023). Conclusions This study demonstrates the differences in TM motion between the internal and external regions of TM and displays its change with accommodation. The findings and good reproducibility suggest PhS-OCT helps to understand TM function in regulation of IOP, and, with further refinements, it may be useful in clinical management of glaucoma.

Background: Neonatal sepsis is characterized by an excessive inflammatory response induced by immune cells (monocytes). We investigated the initial stage of monocyte-pathogen interaction, i.e. bacterial ingestion and degradation at the single-cell level, by comparing a new flow cytometric procedure with culture methods. We also examined the hypothesis that, in terms of phagocytosis-induced cell death (PICD), phenotype, or cytokine production, cord blood monocytes (CBMO) differ from monocytes derived from adults (peripheral blood monocytes, PBMO). Methods: Phagocytosis and intracellular degradation were assessed by means of flow cytometry and bacterial cultures of green fluorescent protein-labeled group B Streptococci (GBS) and Escherichia coli. The production of reactive oxygen species (ROS) was measured through luminol-enhanced chemiluminescence. Apoptosis, phenotype, and cytokine production were assessed through flow cytometry. Results: Flow cytometry and bacterial cultures showed no difference between phagocytosis and degradation of GBS and E. coli by PBMO and CBMO. A high correlation between both methods was observed. No difference in ROS production was evident. In comparison with PBMO, CBMO apoptosis was lower after exposure to GBS and E. coli. Similarities were found between nonapoptotic monocytes and pro-inflammatory monocytes. Conclusions: PICD is lower in CBMO during the early stages of monocyte-pathogen interaction. Our results emphasize that monocyte apoptosis has a potential role in tailoring the immune response in neonatal sepsis. © 2009 Clinical Cytometry Society

See Article on Page 365 Ascites is the most common complication in liver cirrhosis (LC), occurring in 60% of the patients with compensated LC within 10 years.1 Therapeutic paracentesis is an effective treatment for tension-type ascites, because it relieves the symptom more quickly than diuretics and shortens hospitalization.2 Refractory ascites is defined as fluid overload that is not controlled despite restriction of sodium intake and the maximum dose of diuretics, and recurs rapidly after paracentesis.3 Large volume paracentesis (LVP) has become the first line of treatment for patients with severe and refractory ascites.4 Paracentesis-induced circulatory dysfunction (PICD) occurs as a complication of LVP. Though PICD remains clinically silent, it is an important predictor of mortality in patients with severe ascites treated by LVP.5 A recent meta-analysis concluded that PICD is associated with a high rate of ascites recurrence, development of hepatorenal syndrome, dilutional hyponatremia, and high mortality.6 PICD is definitively diagnosed through laboratory results, with increases of more than 50% of baseline plasma rennin activity to > 4 ng/mL/h on the 5th to 6th days after paracentesis.5,7 The exact pathophysiology of PICD is not entirely understood. PICD was initially thought to occur secondary to fluid shifting after paracentesis, resulting in decreased circulating volume.8 Additional studies demonstrated that decreased systemic vascular resistance also plays an essential role in PICD.7,9,10 The resulting effective hypovolemia due to arteriolar vasodilation in turn leads to a prolonged activation of the sympathetic nervous system and the rennin-angiotensin-aldosterone pathway. Increased plasma rennin activity in particular is characteristic of PICD, however general hyporesponsiveness to vasoconstrictors in the setting of cirrhosis decreases the ability to compensate for the accentuated vasodilation.11 One of the simplest ways to prevent PICD is to limit the volume of fluid removed to 5 to 6 L at a time.5,12,13 The incidence of PICD approaches 80% when a LVP is performed without additional therapeutic management; the incidence is reduced to 15 to 35% when volume expanders are used.14 Of all the plasma expanders, human albumin infusion is considered as the best option due to its long half-life of 21 days. In addition to its oncotic value, albumin has antioxidant, detoxification, immunoprotective, drug binding and delivery properties.15,16 One recent meta-analysis concluded that albumin was superior to other volume expanders and alternative treatments in decreasing the risk of PICD, hyponatremia, and mortality.6 A separate recent meta-analysis demonstrated the benefit of albumin administration in decreasing the incidence of PICD after paracentesis as well as morbidity and mortality in patients with any type of infection.17 Current guidelines recommend albumin infusion when LVP > 5 liter is removed as it prevents 85% of cirrhotic patients from developing PICD.18,19 Albumin therapy has also been shown to improve survival in cirrhotic patients with spontaneous bacterial peritonitis by reducing incidence of renal impairment.20 The American Association for the Study of Liver Diseases guidelines state that it is reasonable but not mandatory to give 6 to 8 g of albumin per liter of ascites removed when more than 5 L are removed.19 Reducing the flow rate of fluid removed during the paracentesis is also theorized to decrease the incidence of PICD.21 Some physicians have tried this method to prevent PICD in real clinical practice. However, clinical evidence of this approach is lacking. In the current issue, Elsabaawy et al.22 evaluated the impact of paracentesis flow rate on PICD. Sixty patients with refractory ascites underwent LVP randomized into 3 groups and controlled with different flow rate extraction each. Results showed flow rate was not significant factor of PICD development and only female was a predictor of PICD. Authors concluded that paracentesis flow rate did not correlate with PICD development. Although there is limitation of small scale, this study has strength of prospective design. In addition to need of larger scale study, author did not reveal the reason why female was only significant predictor of PICD development. In the era of albumin infusion during LVP, flow rate of parecentesis may do not matter. In this point of view, one question is still remained. Will flow rate not impact on PICD development even without albumin infusion during LVP? In conclusion, this study showed that flow rate of paracentesis did not correlate with PICD development. To date, there is little data about this correlation. Therefore, such information may be useful to clinician. Further well designed larger research is needed to confirm this result.

Photocontact dermatitis is not a common condition, but neither is it rare. Both photo-irritant contact dermatitis (PICD) and photoallergic contact dermatitis (PACD) are seen by most dermatologists in general practice. PICD is diagnosed on clinical grounds and is usually caused by furocoumarins in plants like limes and celery. PACD is caused primarily by sunscreens but can also be the result of fragrances and antibacterial agents. PACD can only be diagnosed by photo-patch testing that most dermatologists, even those who patch test and give phototherapy in their office, do not perform. The procedure as outlined in this manuscript is relatively simple and can easily be accomplished in the dermatologist's office.

Paracentesis-induced circulatory dysfunction (PICD) is a recently described complication that can be prevented with the administration of plasma expanders. The aim of this study was to compare the efficacy of saline versus albumin in the prevention of PICD. Patients were randomized to receive albumin or saline after total paracentesis. Patients readmitted as a consequence of a second episode of tense ascites were treated with total paracentesis and the alternative plasma expander. After randomization, 35 patients received saline and 37 received albumin. Twenty-one patients were readmitted for tense ascites and treated with the alternative expander. Significant increases in plasma renin activity (PRA) were found 24 hours and 6 days after paracentesis when saline was used (baseline, 5.6 +/- 5.7; 24 hours, 7.6 +/- 6.9; 6 days, 8.5 +/- 8.0 ng x mL(-1). hr(-1); P

Podoplanin (PDPN) is a mucin-like transmembrane glycoprotein that plays an important role in development and cancer. Here, we provide evidence that the intracellular domain (ICD) of podoplanin is released into the cytosol following a sequential proteolytic processing by a metalloprotease and γ-secretase. Western blotting and cell fractionation studies revealed that HEK293T and MDCK cells transfected with an eGFP-tagged podoplanin construct (PDPNeGFP, 50-63 kDa) constitutively express two C-terminal fragments (CTFs): a ∼33 kDa membrane-bound PCTF33, and a ∼29 kDa cytosolic podoplanin ICD (PICD). While pharmacological inhibition of metalloproteases reduced the expression of PCTF33, treatment of cells with γ-secretase inhibitors resulted in enhanced PCTF33 levels. PCTF33 processing by γ-secretase depends on presenilin-1 (PS1) function: cells expressing a dominant negative form of PS1 (PS1 D385N), and mouse embryonic fibroblasts (MEFs) genetically deficient in PS1, but not in PS2, show higher levels of PCTF33 expression with respect to wild-type MEFs. Furthermore, transfection of PS1 deficient MEFs with wild-type PS1 (PS1 wt) decreased PCTF33 levels. N-terminal amino acid sequencing of the affinity purified PICD revealed that the γ-secretase cleavage site was located between valines 150 and 151, but these residues are not critical for proteolysis. We found that podoplanin CTFs are also generated in cells expressing podoplanin mutants harboring heterologous transmembrane regions. Taken together, these results indicate that podoplanin is a novel substrate for PS1/γ-secretase. © 2013 Elsevier Ltd. All rights reserved., This work was supported by grants SAF2010-19152 from the Spanish Ministry of Economy and Competitiveness and S2010/BMD-2359 (Skin Model-CM) from the Community of Madrid. M.M.Y. and G.d.C. were funded during part of this work by the Formación de Personal Investigador and Juan de la Cierva programs, respectively. EMV is funded by the Spanish Association for Cancer Research Foundation (AECC).

Neonates show sustained inflammation after a bacterial infection, which is associated with inflammatory diseases like bronchopulmonary dysplasia or periventricular leucomalacia. Physiologically, inflammation is terminated early after the removal of the invading pathogens by phagocytosis-induced cell death (PICD) of immune effector cells. Earlier results showed reduced PICD in neonatal monocytes. The underlying molecular mechanisms are unknown. We hypothesize that the reduced PICD in neonatal monocytes is regulated through the proteins of the B-cell lymphoma 2 (Bcl-2) protein family.mRNA and protein expression of Bcl-2 family proteins in cord blood and adult peripheral blood monocytes infected with Escherichia coli were analyzed by quantitative real-time PCR and flow cytometry and cytochrome c release by fluorescence microscopy.mRNA expression of antiapopototic Bcl-xL was upregulated in cord blood monocytes (CBMO), whereas proapoptotic Bim tended to be higher in peripheral blood monocytes (PBMO). Upon infection, Bax was more strongly expressed in PBMO compared with CBMO. The pro/antiapoptotic balance was skewed toward survival in CBMO and apoptosis in PBMO. Cytochome c release into the cytosol was enhanced in PBMO compared with CBMO.Bcl-2 proteins are involved in reduced PICD in neonatal monocytes. These findings are another step toward the understanding of sustained inflammation in neonates.

The propensity for sustained inflammation after bacterial infection in neonates, resulting in inflammatory sequelae such as bronchopulmonary dysplasia and periventricular leucomalacia, is well known, but its molecular mechanisms remain elusive. Termination of inflammatory reactions physiologically occurs early after removal of bacteria by phagocytosis-induced cell death (PICD) of immune effector cells such as monocytes. PICD from cord blood monocytes (CBMOs) was shown to be reduced as compared with that of peripheral blood monocytes (PBMOs) from adult donors in vitro.PBMOs, CBMOs, and Fas (CD95)-deficient (lpr) mouse monocytes were analyzed in an in vitro infection model using green fluorescence protein-labeled Escherichia coli (E. coli-GFP). Phagocytosis and apoptosis were quantified by flow cytometry and CD95L secretion was quantified by enzyme-linked immunosorbent assay.We demonstrate the involvement of the CD95/CD95 ligand pathway (CD95/CD95L) in PICD and provide evidence that diminished CD95L secretion by CBMOs may result in prolonged activation of neonatal immune effector cells.These in vitro results offer for the first time a molecular mechanism accounting for sustained inflammation seen in neonates.

For many cardiac clinics, list-mode PET is impractical. Therefore, separate dynamic and ECG-gated acquisitions are needed to detect harmful stenoses, indicate affected coronary arteries, and estimate stenosis severity. However, physicians usually order gated studies only because of dose, time, and cost limitations. These gated studies are limited to detection. In an effort to remove these limitations, we developed a novel curve-fitting algorithm [incomplete data (ICD)] to accurately calculate coronary flow reserve (CFR) from a combined dynamic-ECG protocol of a length equal to a typical gated scan.We selected several retrospective dynamic studies to simulate shortened dynamic acquisitions of the combined protocol and compared (a) the accuracy of ICD and a nominal method in extrapolating the complete functional form of arterial input functions (AIFs); and (b) the accuracy of ICD and ICD-AP (ICD with a-posteriori knowledge of complete-data AIFs) in predicting CFRs.According to the Akaike information criterion, AIFs predicted by ICD were more accurate than those predicted by the nominal method in 11 out of 12 studies. CFRs predicted by ICD and ICD-AP were similar to complete-data predictions (PICD=0.94 and PICD-AP=0.91) and had similar average errors (eICD=2.82% and eICD-AP=2.79%).According to a nuclear cardiologist and an expert analyst of PET data, both ICD and ICD-AP predicted CFR values with sufficient accuracy for the clinic. Therefore, by using our method, physicians in cardiac clinics would have access to the necessary amount of information to differentiate between single-vessel and triple-vessel disease for treatment decision making.

To the Editor:We read with great interest the paper by Serste et al. regardingeffects of non-selective beta-blockers (BB) and paracentesisinduced circulatory dysfunction (PICD) [1]. This is the first studyto explore the background for potential deleterious effects of BBin refractory ascites, as suggested in a previous study by theauthors [2]. The high risk of PICD after BB treatment seemsrelated to an inability to increase heart rate during a circulatorychallenge. BB bind to b

Postinterventional cognitive dysfunction (PICD) is a known complication of coronary artery bypass grafting (CABG). However, it is largely unknown whether PICD occurs after coronary catheterization.Neuropsychologic data were obtained from 37 patients who received coronary catheterization and 47 patients who underwent elective CABG at baseline and 3 months after the interventions. The outcomes were contrasted to 33 healthy volunteers, using analysis of covariance with baseline scores as covariates. Cerebral magnetic resonance imaging with diffusion-weighted imaging (DWI) sequences was performed in 30 catheter and 39 CABG patients 2 to 4 days after the procedures.The rate of acute ischemic lesions amounted to 3.3% in the catheter group and to 17.9% in the CABG group. Postinterventional cognitive dysfunction was detected in 2 (of 10) tests in the catheter group as compared with the healthy controls (verbal memory: total recall, t = -2.61 (P = .005) and nonverbal memory, t = -2.60 [P = .005]). The CABG group showed PICD in 7 of 10 tests as compared with the healthy controls (statistics ranging from t = -1.95 [P = .027] to t = -5.14 [P.001]). Scores of depression/anxiety and health-related quality of life were not associated with PICD (P.05).As compared with CABG, PICD and cerebral lesions appear to be substantially milder after coronary catheter intervention, but not negligible.

Intravenous albumin has been used to prevent paracentesis-induced circulatory dysfunction (PICD) in cirrhotics; however, its use is costly and controversial. Splanchnic arterial vasodilatation is primarily responsible for PICD. There are no reports of use of midodrine in the prevention of PICD. In this pilot study, we evaluated midodrine and albumin in the prevention of PICD.Forty patients with cirrhosis underwent therapeutic paracentesis with midodrine or albumin in a randomized controlled trial at a tertiary center. Effective arterial blood volume was assessed by plasma renin activity.Plasma renin activity at baseline and at 6 days after paracentesis did not differ in the two groups (43.18 +/- 10.73 to 45.90 +/- 8.59 ng/mL/h, P= 0.273 in the albumin group and 44.44 +/- 8.44 to 41.39 +/- 10.21 ng/mL/h, P= 0.115 in the midodrine group). Two patients had an increase in plasma renin activity of more than 50% from baseline in the albumin group, and none in the midodrine group. A significant increase in 24-h urine volume and urine sodium excretion was noted in the midodrine group. Midodrine therapy was cheaper than albumin therapy.The study suggests that midodrine may be as effective as albumin in preventing PICD in cirrhotics, but at a fraction of the cost, and can be administered orally. Midodrine also resulted in an increase in 24-h urine volume and sodium excretion.

Large-volume paracentesis in patients with cirrhosis and ascites induces arterial vasodilatation and decreases effective arterial blood volume, termed paracentesis-induced circulatory dysfunction (PICD), which can be prevented by costly intravenous albumin. Vasoconstrictors, e.g. terlipressin, may also prevent PICD. The aim was to compare the less expensive vasoconstrictor midodrine, an alpha-adrenoceptor agonist, with albumin in preventing PICD.Twenty-four patients with cirrhosis and ascites were randomly assigned to be treated with either midodrine (n=11) (12.5 mg three times per day; over 2 days) or albumin (n=13) (8 g/L of removed ascites) after large-volume paracentesis. Effective arterial blood volume was assessed indirectly by measuring plasma renin and aldosterone concentration on days 0 and 6 after paracentesis; renal function and haemodynamic changes were also measured. PICD was defined as an increase in plasma renin concentration on day 6 by more than 50% of the baseline value.PICD developed in six patients of the midodrine group (60%) and in only four patients (31%) of the albumin group. Six days after paracentesis, the aldosterone concentration increased significantly in the midodrine group, but not in the albumin group.This pilot study suggests that midodrine is not as effective as albumin in preventing circulatory dysfunction after large-volume paracentesis in patients with cirrhosis and ascites.

Protection from physical noxae must include multiple approaches; physical irritant contact dermatitis develops most likely when the cumulative exposure to several physical factors, such as climatic environmental conditions and friction, pressure or occlusion is given. The additive effect of these conditions, frequently found in modern working environments, not only provokes barrier disturbances, but also inflammatory reactions of the deeper layers of the skin. This review reflects on some examples of occupational physical irritant contact dermatitis (PICD) and the current understanding of its possible pathomechanism. On the one hand, the literature reveals epidemiological studies and case reports and on the other hand murine studies. The combination of both views may permit new insights into the pathogenic mechanisms of PICD and its prevention.

Phagocytosis of complement-opsonized targets is a primary function of neutrophils at sites of inflammation, and the clearance of neutrophils that have phagocytosed microbes is important for the resolution of inflammation. Our previous work suggests that phagocytosis leads to rapid neutrophil apoptosis that is inhibited by antibody to the beta2 integrin, Mac-1, and requires NADPH oxidase-derived reactive oxygen species (ROS) generated during phagocytosis. Here we report that phagocytosis-induced cell death (PICD) does not occur in Mac-1-deficient murine neutrophils, suggesting that PICD proceeds through a bona fide Mac-1-dependent pathway. A sustained, intracellular oxidative burst is associated with PICD. Furthermore, PICD does not require traditional death receptors, Fas, or tumor necrosis factor (TNF) receptor. TNF but not Fas synergizes with phagocytosis to enhance significantly PICD by increasing the oxidative burst, and this is Mac-1-dependent. Phagocytosis-induced ROS promote cleavage/activation of caspases 8 and 3, key players in most extrinsic ("death receptor") mediated pathways of apoptosis, and caspases 8 and 3 but not caspase 9/mitochondria, are required for PICD. This suggests that ROS target the extrinsic versus the intrinsic ("stress stimulus") apoptotic pathway. Phagocytosis also triggers a competing MAPK/ERK-dependent survival pathway that provides resistance to PICD likely by down-regulating caspase 8 activation. The anti-apoptotic factor granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly enhances ROS generation associated with phagocytosis. Despite this, it completely suppresses PICD by sustaining ERK activation and inhibiting caspase 8 activation in phagocytosing neutrophils. Together, these studies suggest that Mac-1-mediated phagocytosis promotes apoptosis through a caspase 8/3-dependent pathway that is modulated by NADPH oxidase-generated ROS and MAPK/ERK. Moreover, TNF and GM-CSF, likely encountered by phagocytosing neutrophils at inflammatory sites, exploit pro-(ROS) and anti-apoptotic (ERK) signals triggered by phagocytosis to promote or suppress PICD, respectively, and thus modulate the fate of phagocytosing neutrophils.

SummaryBackground Although physical irritant contact dermatitis (PICD) is a common occupational dermatosis, it is one of the least well understood because of its multiple types, lack of diagnostic test, and the many mechanisms involved in its production. Objectives To characterize the materials and mechanisms of physical irritation of the skin. Methods We did a retrospective analysis over the past 20 years of all patients with a diagnosis of PICD at St John's Institute of Dermatology Contact Dermatitis Clinic. Results Of the 29 000 patients who attended the clinic over the study period, 392 patients were diagnosed with PICD and of these, 335 files were analysed. Conclusions Our findings show that PICD accounted for 1·15% of all patients attending the contact clinic over the study period. Diverse occupations and materials were implicated. The most common cause of PICD was low humidity due to air-conditioning, which caused dermatitis of the face and neck in office workers due to drying out of the skin.

Early diagnosis of presenile Alzheimer's disease (AD), which would serve for prognosis and for guiding choices of treatment, is still an important, difficult task for the clinical neurologist. We studied 24 patients, 12 of whom had minor cognitive impairment or questionable dementia (PICD) and 12 who met NINCDS-ADRDA criteria for presenile AD (PAD). Using clinical, neuropsychological, neurophysiological and neuroradiological methods, we followed the patients up to two disease end-points: death or untestable condition. This paper concentrates on the main clinical and neuropsychological findings relative to these two end-points. All PAD patients evolved into clinically evident Alzheimer-type dementia, became untestable within 60 months and died within 72 months. Only 3 of the PICD patients became demented; 2 of them died during the follow-up and 1 died eight months later. The other 9 PICD patients showed only moderate cognitive decline, compatible with normal aging processes. Neurophysiological and neuroradiological findings might be an important tool for arriving at a correct early diagnosis, when they are assessed with clinical neuropsychological data.