The WHO Adult ADHD self-report Scale used in a clinical sample of patients with overlapping symptoms - psychometric properties of and scoring methods for the Swedish translation.

BACKGROUND: The WHO Adult ADHD Self-report Scale (ASRSv1.1 and ASRS-S) is used for screening for attention-deficit/hyperactivity disorder (ADHD). The capacity of the Swedish version of the scale to discriminate ADHD from borderline personality disorder (BPD) and bipolar disorder (BP) has not been tested. AIM: Evaluate scoring methods, psychometric properties, and diagnostic accuracy of the Swedish versions of ASRSv1.1/ASRS-S in a group of patients with ADHD and/or BPD and/or BP. METHOD: A total of 151 young adult psychiatric patients diagnosed with ADHD, BPD and/or BD completed ASRSv1.1 and the Wender Utah Rating Scale (WURS) for ADHD symptoms, and the Sheehan Disability Scale (SDS) for functional impairment. ADHD diagnoses were assessed with the Schedule for Affective Disorders and Schizophrenia (K-SADS) interview. Both versions of the scale were analysed through dichotomised and non-dichotomised scoring for diagnostic accuracy analysis. RESULTS: The internal consistency for ASRSv1.1/ASRS-S was satisfactory with α 0.913 and 0.743, respectively. The two-factor structure of the ASRSv1.1 and the one factor structure of ASRS-S were supported by the confirmatory factor analyses. A strong positive correlation was found between ASRSv1.1 and WURS and a moderate level of correlation was found between ASRSv1.1 and SDS. The area under the curve for both scoring methods were excellent with an area under the curve (AUC) of 0.808 and 0.817, respectively. Optimal cut-off scores were in line with the original recommendations. CONCLUSION: The Swedish translation of ASRSv1.1/ASRS-S has psychometric properties comparable to other populations and the capacity to screen for ADHD in patients with overlapping symptoms.

Changes in patterns of alcohol consumption in young psychiatric outpatients: two comparable samples assessed with 10 years apart.

AIMS: Over the past 20 years, a trend towards non-drinking and less use of alcohol has been reported among young adults. This study aimed to investigate if a similar trend in alcohol consumption can be seen among young adult psychiatric outpatients. METHODS: This was a cross-sectional study based on two comparable samples of young adult (18-25 years) psychiatric outpatients recruited approximately 10 years apart in 2002-2003 (N = 197) and 2012-2016 (N = 380). The Swedish version of the Alcohol Use Disorders Identification Test (AUDIT) was used to assess alcohol consumption. Psychiatric diagnoses were based on diagnostic interviews. Differences between the two samples in alcohol consumption and a number of alcohol-use disorder diagnoses were analysed. Cramer's V was chosen as the effect size measure. RESULTS: Mean AUDIT scores and prevalence of diagnosed alcohol-use disorder in the two samples did not differ significantly. The number of non-drinkers was larger among patients in the mid-2010s (15.8% vs. 8.1%; χ2 = 6.76, p < 0.01, Φ = 0.11), but when non-drinkers were excluded, the alcohol consumption was higher among females in the later sample. CONCLUSION: The mean level of alcohol consumption seems not to have changed to the same extent among young psychiatric patients as in the general population. However, some young psychiatric patients have followed the trend of non-drinking, while others consume more alcohol. Further studies on both non-drinking and high alcohol consumption in psychiatric patients are needed to understand their mechanisms.

Brief internet-delivered skills training based on DBT for adults with borderline personality disorder - a feasibility study.

OBJECTIVE: Borderline personality disorder (BPD) is characterized by instability in emotions, relationships, and behaviors, such as self-injury and suicidal behavior. Dialectical Behavioral Therapy (DBT) is an established intervention for BPD, but there are long waiting times for treatment. This study aimed to explore if a brief internet-delivered DBT skills training program with minimal therapist support is acceptable, that it can be administered, useful, and does not do harm for patients with BPD. METHODS: Acceptability was measured through data on recruitment and attrition, utilization of the intervention, reported impulses to drop out, and through ratings on self-injury and suicidality. Participants were interviewed about their experiences of the intervention; analyzed with content analysis. RESULTS: Twenty patients on the waiting list for treatment at a DBT-clinic were invited and nine female patients (age 19-37 years) volunteered. The participants completed a large part of the intervention, which did not appear harmful since ratings of suicidal and self-harming behavior were similar before and after the intervention. In the interviews, participants stated that they had gained new knowledge and skills to manage situations, e.g. to stop and think before acting. Some even reported decreased levels of self-injury. The time spent on patient contact was short, and some patients reported difficulties to practice on their own and requested more support. CONCLUSIONS: The intervention seems to be acceptable. Future studies should investigate in what ways some BPD patients are more susceptible to internet-delivered skills training than others, and if this intervention could be delivered within a stepped-care model.

The Role of Comorbid Symptoms in Perceived Stress and Sleep Problems in Adolescent ADHD.

We examined perceived stress and sleep problems in adolescent ADHD and whether this varies as a function of ADHD presentation and sex. Further, we mapped structural associations between ADHD symptoms, comorbid symptoms, perceived stress, and sleep problems. Participants were 306 adolescents aged 13-19 years (66.8% females, 193 had an ADHD diagnosis, 113 were controls). Parents rated ADHD symptoms, all other constructs were self-rated. Adolescents with ADHD had elevated levels of perceived stress and sleep problems. Girls with ADHD reported the highest levels of perceived stress. Emotional symptoms mediated the effect of inattention whereas conduct problems mediated the effect of hyperactivity/impulsivity on stress and sleep. Perceived stress and sleep problems should be considered when mapping ADHD-related problems. Comorbid symptoms are potential intervention targets that may increase treatment response.

Community Violence Exposure and Eating Disorder Symptoms among Belgian, Russian and US Adolescents: Cross-Country and Gender Perspectives.

Community violence exposure (CVE) is one of the most common adverse childhood experiences worldwide. Despite this, its potential effect on disordered eating in adolescents from different cultures is underexplored. In the present cross-sectional study, self-reported data were collected from 9751 students (Mean age = 14.27) from Belgium, Russia and the US on CVE (witnessing violence and violence victimization), eating disorder (ED) symptoms (ED thoughts with associated compensatory behaviors), and comorbid symptoms of posttraumatic stress, depression and anxiety. Increased CVE (from no exposure to witnessing to victimization) was associated with more ED symptoms, and the associations remained significant after adjusting for comorbid conditions. The associations were similar for adolescents across the three countries. No gender differences were observed in the association between CVE and ED symptoms, even though girls in general reported more ED symptoms than boys. We conclude that CVE appears to be associated with ED symptoms in three culturally different samples of adolescents.

Are older patients with non-small cell lung cancer receiving optimal care? A population-based study.

BACKGROUND: Results from studies addressing age-related patterns of cancer care have found evidence of unjustified differences in management between younger and older patients. METHODS: We examined associations between age and clinical presentation, management and mortality in patients diagnosed with non-small cell lung cancer (NSCLC) between 2002 and 2016. Analyses were adjusted for comorbidity and other factors that may have affected management decisions and outcomes. RESULTS: The study population encompassed 40,026 patients with NSCLC. Stage at diagnosis did not differ between age groups ≤ 84. The diagnostic intensity was similar in age groups <80 years. In patients with stage IA-IIB disease and PS 0-2, surgery was more common in the youngest age groups and decreased with increasing age, and was rarely performed in those ≥ 85 years. The use of stereotactic body radiotherapy (SBRT) increased with age (≤69 years 5.4%; ≥85 years 35.8%). In patients with stage IIIA disease and PS 0-2, concurrent chemoradiotherapy was more common in younger patients (≤69 years 55.3%; ≥85 years 2.2%). In stage IA-IIIA disease, no major differences in treatment-related mortality was observed. In stage IIIB-IV and PS 0-2, chemotherapy was more common in patients <80 years. However, 58.1% of patients 80-84 years and 30.3% ≥ 85 years received treatment. In stage IA-IIIA, overall and cause-specific survival decreased with increasing age. No age-differences in survival were observed in patients with stage IIIB-IV NSCLC. CONCLUSION: Treatments were readily given to older patients with metastatic disease, but to a lesser degree to those with early stage disease. Significant differences in cause specific survival were observed in early, but not late stage disease. Our findings underscore the importance of individualized assessment of health status and life expectancy. Our results indicate that older patients with early stage lung cancer to a higher extent should be considered for curative treatment.

Infiltration of NK and plasma cells is associated with a distinct immune subset in non-small cell lung cancer.

Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Moderators of long-term treatment outcome when comparing two group interventions for adolescents with ADHD: who benefits more from DBT-based skills training?

BACKGROUND: Psychosocial interventions for adolescents with attention-deficit/hyperactivity disorder (ADHD), targeting emotional dysregulation and impulsive behaviors, have been requested, but the heterogeneity within this group makes it unlikely that there is one treatment that fits all. The aim of this study was to identify which adolescents with ADHD might have an effect from a structured skills training group (SSTG) based on dialectical behavioral therapy, by exploring pre-treatment characteristics as potential moderators of long-term treatment outcome. METHODS: This study was based on follow-up data from a randomized controlled trial comparing the SSTG (n = 71) to a psychoeducational control intervention (n = 57) for adolescents with ADHD (15-18 years old). Clinical characteristics (sex, age, medication status, ADHD presentation, severity of ADHD symptom, psychiatric comorbidity, impairment of emotional dysregulation and functional impairment) were explored as potential moderators of pre-treatment to follow-up change in ADHD symptoms and functional impairment. Moderation analyses were performed using the PROCESS macro for SPSS. RESULTS: Three moderators (severity of hyperactivity/impulsivity, conduct problems and impairment of emotional dysregulation) were identified in regard to the outcome self-rated change in ADHD symptoms. Participants with elevated pre-scores on these variables had a better effect of the SSTG than of the psychoeducational control intervention. No moderators were found in regard to the parental-rated outcomes. CONCLUSIONS: The SSTG seems to be beneficial for adolescents with ADHD who perceive pronounced symptoms of hyperactivity/impulsivity, conduct problems and emotional dysregulation. Our findings need to be confirmed in future trials evaluating dialectical behavioral therapy-based skills training for adolescents with ADHD, where these moderators could be used as criteria for inclusion or stratification. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN17366720 , retrospectively registered.

Lulworthinone: In Vitro Mode of Action Investigation of an Antibacterial Dimeric Naphthopyrone Isolated from a Marine Fungus.

Treatment options for infections caused by antimicrobial-resistant bacteria are rendered ineffective, and drug alternatives are needed-either from new chemical classes or drugs with new modes of action. Historically, natural products have been important contributors to drug discovery. In a recent study, the dimeric naphthopyrone lulworthinone produced by an obligate marine fungus in the family Lulworthiaceae was discovered. The observed potent antibacterial activity against Gram-positive bacteria, including several clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, prompted this follow-up mode of action investigation. This paper aimed to characterize the antibacterial mode of action (MOA) of lulworthinone by combining in vitro assays, NMR experiments and microscopy. The results point to a MOA targeting the bacterial membrane, leading to improper cell division. Treatment with lulworthinone induced an upregulation of genes responding to cell envelope stress in Bacillus subtilis. Analysis of the membrane integrity and membrane potential indicated that lulworthinone targets the bacterial membrane without destroying it. This was supported by NMR experiments using artificial lipid bilayers. Fluorescence microscopy revealed that lulworthinone affects cell morphology and impedes the localization of the cell division protein FtsZ. Surface plasmon resonance and dynamic light scattering assays showed that this activity is linked with the compound's ability to form colloidal aggregates. Antibacterial agents acting at cell membranes are of special interest, as the development of bacterial resistance to such compounds is deemed more difficult to occur.

Bioassay-Guided Fractionation Leads to the Detection of Cholic Acid Generated by the Rare Thalassomonas sp.

Bacterial symbionts of marine invertebrates are rich sources of novel, pharmaceutically relevant natural products that could become leads in combatting multidrug-resistant pathogens and treating disease. In this study, the bioactive potential of the marine invertebrate symbiont Thalassomonas actiniarum was investigated. Bioactivity screening of the strain revealed Gram-positive specific antibacterial activity as well as cytotoxic activity against a human melanoma cell line (A2058). The dereplication of the active fraction using HPLC-MS led to the isolation and structural elucidation of cholic acid and 3-oxo cholic acid. T. actiniarum is one of three type species belonging to the genus Thalassomonas. The ability to generate cholic acid was assessed for all three species using thin-layer chromatography and was confirmed by LC-MS. The re-sequencing of all three Thalassomonas type species using long-read Oxford Nanopore Technology (ONT) and Illumina data produced complete genomes, enabling the bioinformatic assessment of the ability of the strains to produce cholic acid. Although a complete biosynthetic pathway for cholic acid synthesis in this genus could not be determined based on sequence-based homology searches, the identification of putative penicillin or homoserine lactone acylases in all three species suggests a mechanism for the hydrolysis of conjugated bile acids present in the growth medium, resulting in the generation of cholic acid and 3-oxo cholic acid. With little known currently about the bioactivities of this genus, this study serves as the foundation for future investigations into their bioactive potential as well as the potential ecological role of bile acid transformation, sterol modification and quorum quenching by Thalassomonas sp. in the marine environment.