Further Evidence for Embedded Performance Validity Tests in Children within the Conners’ Continuous Performance Test – Second Edition

Objective: To replicate previous research on Conners’ Continuous Performance Test – Second Edition subscales as performance validity tests (PVTs) in children.

Method: Classification accuracy for the Omissions (OMI), Hit Reaction Time (HRT), and Perseverations (PER) subscales was computed for 414 children and adolescents.

Results: Overall, OMI, HRT, and PER demonstrated good specificity but low and variable sensitivity across cutoffs.

Conclusions: Results suggest that OMI, HRT, and PER can function as embedded PVTs in mixed clinical samples of children, although their clinical utility is limited by their low sensitivity. Implications for the use of these PVTs in the context of attention-deficit/hyperactivity disorder evaluations, medication-seeking patients, and sports concussion clinics are discussed.     

Forensic characteristics and phylogenetic analysis of 23 Y-STR loci in the Miao population from Guizhou province,southwest China

Background: Investigation of haplotype/allele frequency data of Y-STR loci in ethnically diverse populations is essential for forensic reference database construction and genetic application. However, the population genetic characteristics of the Chinese Miao minority from Guizhou Province remain uncharacterised.

Aim: To assess forensic characteristics for 23 Y-Chromosomal STR loci in Guizhou Miao and explore population genetic relationships with geographically neighbouring populations.

Subjects and methods: Twenty-three Y-Chromosomal STRs were genotyped using the Powerplex^® Y23 system in 103 unrelated Chinese Miao males from Guizhou Province, southwest China. Haplotypes and forensic parameters were obtained. Population relationships of Guizhou Miao with others were revealed using AMOVA and an MDS plot.

Results: A total of 96 haplotypes were identified with overall haplotype diversity (HD) and discrimination capacity (DC) of 0.9985 and 0.9320, respectively. Genetic differentiation was observed with most of the comparison populations, prominently for Guizhou Shui.

Conclusion: The 23 Y-STR loci were highly polymorphic and discriminating in the Guizhou Miao population and could be used for forensic practice and population genetic studies. Population relationship analysis revealed Guizhou Miao had a close genetic relationship with geographically close Guizhou Gelao, as well as Han majorities derived from different regions.     

Pharmacological basis for use of madecassoside in gouty arthritis: anti-inflammatory,anti-hyperuricemic,and NLRP3 inhibition

Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia.

Methods: DBA/1 mice were intradermally injected with MSU to stimulate joint inflammation or intraperitoneally injected with MSU to trigger peritonitis. Moreover, ICR mice were exposed to potassium oxonate to stimulate hyperuricemia.

Results: Madecassoside repressed MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation in DBA/1 mice with gouty arthritis. Neutrophil infiltration and IL-1β & IL-6 & MCP-1 secretion was also alleviated in lavage fluids from DBA/1 mice with peritonitis due to Madecassoside treatment. Furthermore, Madecassoside decreased MSU-induced neutrophil cytosolic factor 1, caspase-1 and NLRP3 expression in mice with peritoneal inflammation. In hyperuricemic mice, Madecassoside improved renal dysfunction. Serum uric acid, BUN, and creatinine were down-regulated by Madecassoside.

Conclusion: These findings indicate that Madecassoside has potential to ameliorate inflammation in both acute gouty arthritis model and peritonitis model, probably via regulating IL-1β and NLRP3 expression.

Practical point: Madecassoside also exhibited a urate-lowering effect and a renal protective effect in hyperuricemic mice.     

Sex-dependent effect of post-migration adaptation on height and relative lower leg length in Polish youth

Background: Growth in tibia length is considered to be particularly sensitive to environmental stress.

Aim: To estimate the effect of parental migration status on the relative length of the tibia in their school-age children.

Subjects and methods: Data included a nationwide random sample of 17,155 schoolchildren, 7–18?years of age, examined between 1966 and 1969 in Poland who provided information on anthropometric measurements and demographic and social characteristics. Parental migration status was based on paternal migration history. After standardisation by LMS method, z-scores of relative tibia length and z-scores of height were used for analysis. Three-way ANOVA was used to evaluate the influence of migration on tibia length-to-height ratio.

Results: Sons of migrants have a significantly higher tibia length-to-height ratio compared to sons of non-migrants. Children of non-migrants were taller than children of migrants among boys in medium SES and among girls in high and low SES. Relative tibia length indicated significant effects of migration among boys in all age categories and in late adolescent girls: sons of migrants had a higher ratio and daughters of migrants had a lower tibia length-to-height ratio.

Conclusion: It is possible that migration experiences of the parents may have influenced the growth of their offspring. The results emphasise the potential importance of research addressing the impact of different types of migration on growth of children.     

Timing of puberty and reserve capacity in adolescence as pathways to educational level in adulthood—a longitudinal study

Background: Family socioeconomic status (SES) is related to a child’s educational success. Intermediate pathways for this relationship, such as through pubertal timing and reserve capacity, occur in adolescence.

Aim: To study whether family SES affects a child’s adult education through a psychosocial and behavioural pathway (reserve capacity) and/or a biological pathway (pubertal timing) or only through school achievement in adolescence.

Subjects and methods: Finnish adolescents sampled in five cross-sectional surveys from 1985 to 1995 (n?=?37,876) were followed through the Registry of Completed Education and Degrees until 2009, when they were 29–43?years old. Family SES data also came from this registry. Structural equation modelling adjusted for ages at baseline and follow-up was used.

Results: Low family SES increased the probability of low adult education, delayed pubertal timing (in boys), weak reserve capacity and low school achievement. Reserve capacity and school achievement directly affected adult education and mediated the relationship of family SES with the outcome. Delayed pubertal timing predicted low adult education, except when school achievement was added to the model.

Conclusions: The results show that family SES affects the child’s adult education level through psychosocial and biobehavioural pathways, but the biological pathway is mediated by school achievement.     

Y chromosome genetic data defined by 23 short tandem repeats in a Serbian population on the Balkan Peninsula

Background: Serbs mainly live in the territory of the recently re-established state of Serbia. However, the turbulent history in the Balkan Peninsula has led to settlement of Serbs not only within present day Serbia, but also in different parts of neighbouring countries.

Aim: To define polymorphisms of 23 Y-chromosomal short tandem repeat (STR) loci in a modern Serbian population from the central part of the Balkan Peninsula.

Subjects and methods: The reference sample consisted of 303 men declared as Serbs over three generations. Localities of the collected materials include the territories of Serbia, Bosnia and Herzegovina, Croatia and Montenegro. DNA samples were typed using the PowerPlex^®Y23 amplification kit.

Results: The highest locus diversity was observed for DYS385 and DYS481. In this study the most abundant haplogroups were I2a, E1b1b, R1a and I1. The largest genetic distances between the Serbs and other close Southern Slavs were for the Macedonians and Slovenians.

Conclusion: This study is the first one to define STR polymorphism of Serbian people not only from Serbia but also from other parts of the Balkan Peninsula. The presented genetic data may be useful in further examinations of the genesis and genetic structuring of the present-day Serbian gene pool.     

Fluconazole induces genotoxicity in cultured human peripheral blood mononuclear cells via immunomodulation of TNF-α, IL-6, and IL-10: new challenges for safe therapeutic regimens

Context: Fluconazole (FNZ) is a drug used in antifungal therapy. However, the minimum FNZ dose to interfering with immune responses or inducing DNA damage is still unknown.

Objective: This study investigated the toxicological profile of FNZ on cultured human peripheral blood mononuclear cells (PBMCs) treated with different concentrations of this azole.

Materials and methods: Cultured PBMCs were exposed to FNZ (6, 12, 30, 60 and 120?μg/mL) and the toxicological profile was assessed by the following parameters: cytotoxic and nuclear division index (necrotic, apoptotic and viable cells), DNA damage (alkaline comet test), mutagenic potential (micronucleus test), cytokine modulation (IL-1, IL-6, IL-10, TNF-α, IFN-γ), and predictive toxicity (Osiris^® and LAZAR^® programs).

Results: Our results demonstrated that FNZ induced cellular DNA damage and mutagenicity at concentrations above the plasma peak (>30?μg/mL) and 6?μg/mL, respectively, which was associated with increased TNF-α, and decrease IL-6 and IL-10 concentrations. These effects may be related to increased apoptosis and cytotoxic nuclear division index in the cultured PBMCs. In silico results indicated potential mutagenic, tumorigenic, irritant, and carcinogenic effects, which were partially confirmed by the above assays.

Discussion and conclusions: Together, these findings suggest the need to rationalize the use of FNZ, especially if it is used for long periods or with concomitant pathologies requiring azole therapy that may increase FNZ's plasma concentration.     

Anti-inflammatory potential of pyocyanin in LPS-stimulated murine macrophages

Context: Pyocyanin is a typical Pseudomonas aeruginosa virulence factor, a common Gram-negative rod responsible for a wide range of severe nosocomial infections. There is evidence indicating that pyocyanin has multiple biological activities, but little is known about anti-inflammatory properties.

Objective: This study investigated pyocyanin effect on nitric oxide and cytokine production in lipopolysaccharide (LPS)-activated murine peritoneal macrophages.

Materials and methods: Macrophages were incubated in the presence and absence of pyocyanin (1, 5, 10, 50, and 100 µM) with and without LPS (1 µg/mL). Nitric oxide production was determined by Griess reagent and tumor necrosis factor (TNF)-α and interleukin (IL)-1β production was assessed by enzyme-linked immunosorbent assay. In addition, pyocyanin effects on zymosan A-induced peritonitis in mice were evaluated.

Results: Pyocyanin (5 and 10 µM) decreased nitric oxide, TNF-α, and IL-1β production independent of macrophage death. On the other hand, in vivo, pyocyanin (5 mg/kg) was not able to affect leukocyte migration into the site of inflammation.

Discussion and conclusion: Thus, our findings suggest that pyocyanin exerts anti-inflammatory effects on murine peritoneal macrophages, downregulating nitric oxide, TNF-α, and IL-1β levels, which seems to be independent of cell migration. These effects may represent a mechanism of immune evasion; nevertheless more detailed studies should be performed to confirm this hypothesis.     

Climate change,uncertainty and allostatic load

Context: Humans constantly respond to environmental stressors challenging their somatic stability. Allostasis, an evolved neuroendocrine/physiological stressor response system, is our main pathway for doing so. Effective allostasis returns somatic systems to their current optima; over a lifetime of stressor responses, related systems fail, effectiveness declines, and physiological dysregulation (i.e. allostatic load) increases. Global Climate Change (GCC) multiplies environmental stressors on human populations and is likely to increase allostatic load.

Objectives: As a population-level stressor, GCC increases risks for multiple stressors, including sociocultural instability and food and water insecurity, while also motivating migration. We predict GCC increases risk for elevated allostatic load. Here, we review pathways by which GCC increases climatic and social stressors contributing to greater stress and allostatic load.

Methods: Based upon published sources and primary ethnographic case studies, this review examines how GCC, by multiplying climate-related stressors, likely increases social instability, food and water insecurity, and migration. Thereby, it is proposed that GCC contributes to allostatic load.

Results: GCC multiplies stressors on local populations. Those experiencing social insecurity related to GCC during growth and development are expected to show the largest influences on their lifetime allostatic load. Similarly, as GCC increases food and water insecurity, it likely will increase allostatic load in those affected and is likely to propel migrants to seek improved living circumstances. These stressors may be continued among their descendants via historical trauma or epigenetic responses.

Conclusion: GCC accentuates effects of environmental and sociocultural stressors on human populations. Those exposed to GCC are likely to show lifelong elevated allostatic load.     

Disengagement and reengagement of HIV continuum of care in a single center cohort in northern Italy

Background: Despite the progress in HIV care, adherence to follow up remains critical. Disengagement impairs the benefit of HIV care and the increasing number of data that associates failed retention with worse outcomes has led public health institutions to consider retention in care as a new tool to fight against HIV pandemic.

Objective: The aim of this retrospective, observational study was to estimate the burden of disengagement and reengagement in care in our HIV cohort and to identify the characteristics of our LTFU and reengaged patients. Moreover, we build our cascade of care to explore how closely our center aligned with the “90–90–90” targets.

Methods: From the local electronic database we extracted all HIV-infected patients with at least one contact with HIV Clinic between 2012 and 2018 excluding deceased and transferred patients.

Our definition of LTFU was based on the lack of any visit during at least 1 year after the last visit. Patients re-engaged were defined as those firstly considered as LTFU patients who subsequently were newly linked to HIV care.

Results: About 8% of patients were lost to follow up during the period of study, with a rate of less than 2% per year and 14.1% of them were re-engaged in care. The cascade of care shows, among HIV cases diagnosed between 2011 and 2018, 86.7% patients retained in care, 94.1% of whom were on cART and 95.6% of whom were virologically suppressed.

A higher attrition was found among infections diagnosed since 2011 than before 2011, such as women, patients coming from foreign countries and those with poor virological control.

Conclusions: The retention rate found in our cohort is high and is in accordance with the 90–90–90 strategy. Nevertheless, understanding disengagement and re-engagement determinants is important to strengthen retention in care in the most fragile population.     

The relationship between smoking,psoriasis and psoriatic arthritis

Introduction: Smoking is the single most important cause of preventable mortality worldwide. Besides being associated with major cardiovascular and bronchopulmonary diseases, and several cancers, it has been linked with a number of immune-related conditions, including psoriasis and psoriatic arthritis (PsA)

We aimed to summarize data on the role of smoking in the development and prognosis of psoriasis and PsA, pointing to the consequences in terms of disease management.

Areas covered: Mechanisms, clinical manifestations, and comorbidities associated with smoking in psoriasis and PsA were reviewed by searching Medline, Embase and Cochrane Library databases for papers published between January 2000 and July 2018 using combination of terms. Articles not written in English were excluded.

Expert commentary: Smoking is a risk factor for psoriasis development. As for PsA, smoking is positively associated with the disease at the population level, but it is negatively associated in patients with psoriasis. This phenomenon is referred to as the ‘smoking paradox’ of PsA. Smoking may cause poor response and reduced adherence to treatment of both psorasis and PsA. Physicians need to be aware of the smoking habits of their patients with psoriasis and PsA; whenever possible, smoking cessation programs should be considered.     

Preclinical evidences of safety of a new synthetic adjuvant to formulate with the influenza human vaccine: absence of subchronic toxicity and mutagenicity

Context: Influenza is a severe, life-threatening viral disease that can be prevented by vaccination. However, the anti-influenza human vaccine failed to show the required efficacy both in infants under 5?years old and in the elder population, who are among those with the highest risk of developing severe complications after influenza infection. Therefore, it is of high importance to improve the vaccine efficacy and ensure its safety in these susceptible populations.

GK-1, a novel 18-aa peptide adjuvant, has been proved to increase the immunogenicity of the human influenza vaccine in both young and aged mice.

Objective: A preclinical study of the toxicity profile of GK-1 following the World Health Organization guidelines to support its use was herein conducted.

Material and methods: GK-1 was synthetically produced following Good Manufacturing Practices. The toxicological evaluation of GK-1 peptide was performed in rats after repeated dose-ranging trials by the subcutaneous route. The mutagenic potential of GK-1 was assessed by the micronucleus, chromosomal aberration, and Ames tests, in accordance with OECD Guidelines.

Results: GK-1 did not show toxic effects at doses up to 12.5mg/kg, corresponding to 25 times the dose intended for human use. No indications of mutagenic potential were observed. GK-1 after dermal administration was well tolerated locally.

Conclusion: The efficacy of GK-1 to improve influenza vaccine protection, along with the absence of toxicity and mutagenicity, as reported herein, support the evaluation of this peptide in a clinical trial as a novel adjuvant for human use.     

The role of IL-17 in systemic lupus erythematosus and its potential as a therapeutic target

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies production and immune complex deposition with systemic clinical manifestations. Interleukin (IL)-17-producing cells play a crucial role in disease pathogenesis and represent an attractive therapeutic target.

Areas covered: This review provides an update on the possibility of targeting IL-17 in SLE. The rational for this approach as well as currently available and future targets are discussed.

Expert opinion: Although human expression studies and animal models indicate that IL-17 blocking may be a promising therapeutic strategy for SLE, direct evidence for IL-17 inhibition in SLE patients is unavailable. Biologic therapies and small-molecule drugs that target IL-17 production are required for the achievement of a favorable clinical effect in SLE patients.     

Pulegone inhibits inflammation via suppression of NLRP3 inflammasome and reducing cytokine production in mice

Context: Pulegone, a key compound in Schizonepeta essential oil, has been identified as an anti-inflammatory. However, its underlying molecular mechanisms on NLR family pyrin domain containing 3 (NLRP3) inflammasome have not been elucidated.

Objective: Here, the modulatory effects of pulegone on NLRP3 inflammasome were investigated.

Materials and methods: The C57BL/6J mice were randomly divided into five groups: Normal, Lipopolysaccharides (LPS), Dexamethasone (DEX, 5?mg/kg), Pulegone (0.095 and 0.190?g/kg) groups. All mice were challenged by LPS except for the Normal group.

Results: A reduced expression of Interleukin-18 (IL-18), Interleukin-1β (IL-1β), Interleukin-5 (IL-5), Tumor necrosis factor-α (TNF-α), Interferon-gamma (IFN-γ), Monocyte chemoattratctant protein-1 (MCP-1), Macrophage inflammatory protein-1β (MIP-1β), Monocyte colony stimulating factor (M-CSF) and Granulocyte-macrophage colony stimulating factor (GM-CSF) in serum were detected in the pulegone groups as compared to the LPS group. In addition, a reduced mRNA and protein expression production of ASC, NLRP3, and Caspase-1 were detected in lungs after pulegone administration. Histological analysis results indicated that the histological changes of lungs caused by LPS were ameliorated by pulegone. Immunohistochemical study showed a decreased positive cell numbers of P2X7R in Pulegone (0.095 and 0.190?g/kg) groups.

Conclusion: Pulegone exerts anti-inflammatory effects on LPS-induced sepsis mice via inhibition of the NLRP3 expression.     

Paternal lineages in southern Iberia provide time frames for gene flow from mainland Europe and the Mediterranean world

Background: The geography of southern Iberia and an abundant archaeological record of human occupation are ideal conditions for a full understanding of scenarios of genetic history in the area. Recent advances in the phylogeography of Y-chromosome lineages offer the opportunity to set upper bounds for the appearance of different genetic components.

Aim: To provide a global knowledge on the Y haplogroups observed in Andalusia with their Y microsatellite variation. Preferential attention is given to the vehement debate about the age, origin and expansion of R1b-M269 clade and sub-lineages.

Subject and methods: Four hundred and fourteen male DNA samples from western and eastern autochthonous Andalusians were genotyped for a set of Y-SNPs and Y-STRs. Gene diversity, potential population genetic structures and coalescent times were assessed.

Results: Most of the analysed samples belong to the European haplogroup R1b1a1a2-M269, whereas haplogroups E, J, I, G and T show lower frequencies. A phylogenetic dissection of the R1b-M269 was performed and younger time frames than those previously reported in the literature were obtained for its sub-lineages.

Conclusion: The particular Andalusian R1b-M269 assemblage confirms the shallow topology of the clade. Moreover, the sharing of lineages with the rest of Europe indicates the impact in Iberia of an amount of pre-existing diversity, with the possible exception of R1b-DF27. Lineages such as J2-M172 and G-M201 highlight the importance of maritime travels of early farmers who reached the Iberian Peninsula.     

Assessment of menopausal symptoms in different transition phases using the Greene Climacteric Scale among rural women of North India

Background: Menopause is the universal physiological process of women’s midlife and exhibits a wide variety of symptoms. However, there is little data on the menopausal symptoms and factors associated with their severity among rural Indian women.

Aim: To evaluate the prevalence of menopausal symptoms during the different transition phases of menopause among rural women of North India.

Subjects and methods: This cross-sectional study consisted of 351 women aged 35–55?years (mean age 44.6?years) residing in rural areas of North India. A structured questionnaire was used to collect data regarding menopausal status, demographic profile and reproductive history of the participants. Frequency and severity of menopausal symptoms were evaluated using the Greene Climacteric Scale in different stages of menopause. All statistical procedures were accomplished using SPSS version 19.0.

Results: In the present study the mean ages of attainment of menarche and menopause were 14.3?years and 47.2?years, respectively. Mean score of total Greene Climacteric Scale was highest among perimenopausal women (16.12?±?8.1) over post-menopausal (14.78?±?7.3) and pre-menopausal women (11.08?±?6.1). Logistic regression analysis revealed that advancing age, low educational attainment, low socioeconomic status, menopausal status, later age at menarche and higher BMI were all associated with more severe menopausal symptoms.

Conclusion: The climacteric symptoms were more prevalent among women who were perimenopausal followed by post-menopausal women and were the lowest in pre-menopausal women. Age, menopausal status, socio-economic status, and reproductive factors significantly influenced the severity of menopausal symptoms.     

Clinical presentation and neuropsychological profiles of Functional Cognitive Disorder patients with and without co-morbid depression

Introduction: Functional Cognitive Disorder (FCD) is poorly understood. We sought to better characterise FCD in order to inform future diagnostic criteria and evidence based treatments. Additionally, we compared FCD patients with and without co-morbid depression, including their neuropsychological profiles, to determine whether these two disorders are distinct.

Methods: 47 FCD patients (55% female, mean age: 52 years) attending a tertiary neuropsychiatric clinic over a one year period were included. We evaluated sociodemographic characteristics and clinical features including presentation, medications, the presence and nature of co-morbid psychiatric or physical illnesses, and the results of neuropsychometric testing.

Results: 23/47 (49%) patients had co-morbid depression. Six had cognitive difficulties greater than expected from their co-morbid conditions suggesting “functional overlay”. 34 patients had formal neuropsychological testing; 12 demonstrated less than full subjective effort. 16/22 (73%) of the remaining patients had non-specific cognitive impairment in at least one domain. There were no significant differences between those with and without co-morbid depression.

Conclusions: Our study informs future diagnostic criteria. For example, they should not exclude patients with co-morbid psychiatric illness or abnormal neuropsychometric testing and clinicians should remain open to the possibility of “functional overlay”. Furthermore, FCD and depression are distinct disorders that can exist co-morbidly.     

A discussion of statistical methods to characterise early growth and its impact on bone mineral content later in childhood

Background: Many statistical methods are available to model longitudinal growth data and relate derived summary measures to later outcomes.

Aim: To apply and compare commonly used methods to a realistic scenario including pre- and postnatal data, missing data, and confounders.

Subjects and methods: Data were collected from 753 offspring in the Southampton Women’s Survey with measurements of bone mineral content (BMC) at age 6?years. Ultrasound measures included crown-rump length (11 weeks’ gestation) and femur length (19 and 34 weeks’ gestation); postnatally, infant length (birth, 6 and 12?months) and height (2 and 3?years) were measured. A residual growth model, two-stage multilevel linear spline model, joint multilevel linear spline model, SITAR and a growth mixture model were used to relate growth to 6-year BMC.

Results: Results from the residual growth, two-stage and joint multilevel linear spline models were most comparable: an increase in length at all ages was positively associated with BMC, the strongest association being with later growth. Both SITAR and the growth mixture model demonstrated that length was positively associated with BMC.

Conclusions: Similarities and differences in results from a variety of analytic strategies need to be understood in the context of each statistical methodology.     

XAV939, a Wnt/β-catenin pathway modulator,has inhibitory effects on LPS-induced inflammatory response

Aim: In this study, we report the anti-inflammatory activity of XAV939, a modulator of the Wnt/β-catenin pathway.

Methods: WNT/β-catenin pathway and NF-κB signaling pathway were examined in LPS-stimulated human bronchial epithelial cells and effects of XAV939 on these pathways were analyzed. The effect of XAV939 was confirmed in human umbilical vein endothelial cells.

Results: LPS-induced expressions of pro-inflammatory genes IL-6, IL-8, TNF-α, IL-1β, MCP-1, MMP-9, iNOS and COX-2 were significantly and dose-dependently suppressed by XAV939. LPS-induced NF-κB signaling, such as IκB phosphorylation and degradation as well as nuclear translocation of NF-κB, was also suppressed by XAV939. Target DNA binding of NF-κB was significantly and dose-dependently suppressed by XAV939 during LPS-induced inflammatory response. The suppressive effects of XAV939 on NF-κB signaling, target DNA binding of NF-κB and pro-inflammatory gene expression were all rescued by over expression of β-catenin, which shows that the anti-inflammatory effect of XAV939 is mediated by the modulation of β-catenin, a central component of the WNT/β-catenin pathway.

Conclusion: The findings of this study showed that XAV939 exerts anti-inflammatory effects through the modulation of the Wnt/β-catenin pathway.     

Impaired introspective accuracy in schizophrenia: an independent predictor of functional outcomes

Introduction: Individuals with schizophrenia present across a spectrum of symptomatology. Disability remains a debilitating reality across varying disease presentations and remains pervasive despite psychiatric medications. Cognition (neuro/social cognition) and negative symptoms have emerged as the strongest predictors of real-world disability, but account for <50% of the variance in outcomes.

Methods: Our attempts to determine what accounts for the remaining 50% of variance has shown that poor introspective accuracy (IA) may be the most potent predictor of functional outcomes 25% of individuals with schizophrenia. We define IA as the adequacy of self-assessments of ability, skills, performance, or decisions. We suggest that IA is a progression of metacognition and can extend beyond cognition to include misestimation of prior and likely future performance in social or other adaptively relevant situations.

Results: Additionally, IA is bidirectional and self-orientated. Emerging research has found that IA of neurocognitive ability better predicts everyday functional deficits than scores on performance-based measures or neurocognitive skills and has found that IA of social cognition accounts unique variance in real-world disability above social cognitive performance.

Discussion: We argue that impaired IA, affecting 25–50% of patients with schizophrenia, in the absence or minimal presence of other impairments might be the most powerful predictor of functional outcomes.