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.

Evaluation of a structured skills training group for adolescents with attention-deficit/hyperactivity disorder: a randomised controlled trial.

Attention-deficit/hyperactivity disorder (ADHD) in adolescence is associated with behavioural, emotional and interpersonal problems, and non-pharmacological treatments targeting these difficulties have been requested. The objective of this study was to evaluate the effectiveness and acceptance of an age-adapted structured skills training group (SSTG) for adolescents with ADHD. Adolescents (n = 184, ages 15-18 years) with a diagnosis of ADHD were randomly assigned to either the SSTG, which is based on dialectical behavioural therapy, or an active control group based on psychoeducation. Symptoms of ADHD, behavioural and emotional problems, functional impairment, and health-related outcomes were assessed with self-ratings and parental ratings two weeks before, two weeks after, and six months after treatment. All participants who completed the pre-treatment measurements (n = 164) were included in the main analyses, which were conducted using a linear mixed model. Our results demonstrated no significant group differences in favour of the SSTG for any of the study outcomes. A majority of the participants in both groups reported that they had increased their knowledge about ADHD, improved their ability to manage problems related to the diagnosis, and would recommend the treatment to others. We conclude that the SSTG seems to be acceptable for adolescents with ADHD in a clinical context. However, the treatment was not proved to be more effective or more acceptable than the psychoeducational control intervention.Trial registration: http://www.isrctn.com/ISRCTN17366720,11/05/2016 , retrospectively registered.

Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines.

Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. These compounds where screened for antibacterial- and antifungal activity, antibiofilm formation and anti-cell proliferation activity. Additionally, apoptosis-, cell cycle-, kinase binding- and docking studies were performed to evaluate the mechanism-of-action. None of the compounds showed activity in antibacterial-, antibiofilm- or antifungal assays. However, one of the isolated compounds, purpuroine K, showed activity against two cell lines, MV-4-11 and MOLM-13, two AML cell lines both carrying the FTL3-ITD mutation. In MV-4-11 cells, purpuroine K was found to increase apoptosis and arrest cells cycle in G1/G0, which is a common feature of FLT3 inhibitors. Interactions between purpuroine K and the FLT3 wild type or FLT3 ITD mutant proteins could however not be elucidated in our kinase binding and docking studies. In conclusion, we have isolated three novel molecules, purpuroine K-M, one of which (purpuroine K) shows a potent activity against FLT3-ITD mutated AML cell lines, however, the molecular target(s) of purpuroine K still need to be further investigated.

Liquid biopsy as an option for predictive testing and prognosis in patients with lung cancer.

BACKGROUND: The aim of this study was to investigate the clinical value of liquid biopsy as a primary source for variant analysis in lung cancer. In addition, we sought to characterize liquid biopsy variants and to correlate mutational load to clinical data. METHODS: Circulating cell-free DNA was extracted from plasma from patients with lung cancer (n = 60) and controls with benign lung disease (n = 16). Variant analysis was performed using the AVENIO ctDNA Surveillance kit and the results were correlated to clinical and variant analysis data from tumor tissue or cytology retrieved from clinical routine diagnostics. RESULTS: There were significantly more variants detected in lung cancer cases compared to controls (p = 0.011), but no difference between the histological subgroups of lung cancer was found (p = 0.465). Furthermore, significantly more variants were detected in patients with stage IIIb-IV disease compared to patients with stage I-IIIa (median 7 vs 4, p = 0.017). Plasma cfDNA mutational load was significantly associated with overall survival (p = 0.010). The association persisted when adjusted for stage and ECOG performance status (HR: 3.64, 95% CI 1.37-9.67, p = 0.009). Agreement between tumor and plasma samples significantly differed with stage; patients with stage IIIb-IV disease showed agreement in 88.2% of the cases with clinically relevant variants, compared to zero cases in stage I-IIIa (p = 0.004). Furthermore, one variant in EGFR, two in KRAS, and one in BRAF were detected in plasma but not in tumor samples. CONCLUSION: This study concludes that in the vast majority of advanced NSCLC patients a reliable variant analysis can be performed using liquid biopsy from plasma. Furthermore, we found that the number of variants in plasma is associated with prognosis, possibly indicating a strategy for closer follow up on this crucial patient group.

Chlovalicin B, a Chlorinated Sesquiterpene Isolated from the Marine Mushroom Digitatispora marina.

As part of our search for bioactive metabolites from understudied marine microorganisms, the new chlorinated metabolite chlovalicin B (1) was isolated from liquid cultures of the marine basidiomycete Digitatispora marina, which was collected and isolated from driftwood found at Vannøya, Norway. The structure of the novel compound was elucidated by spectroscopic methods including 1D and 2D NMR and analysis of HRMS data, revealing that 1 shares its molecular scaffold with a previously isolated compound, chlovalicin. This represents the first compound isolated from the Digitatispora genus, and the first reported fumagillin/ovalicin-like compound isolated from Basidiomycota. Compound 1 was evaluated for antibacterial activities against a panel of five bacteria, its ability to inhibit bacterial biofilm formation, for antifungal activity against Candida albicans, and for cytotoxic activities against malignant and non-malignant human cell lines. Compound 1 displayed weak cytotoxic activity against the human melanoma cell line A2058 (~50% survival at 50 µM). No activity was detected against biofilm formation or C. albicans at 50 µM, or against bacterial growth at 100 µM nor against the production of cytokines by the human acute monocytic leukemia cell line THP-1 at 50 µM.

Two Novel Lyso-Ornithine Lipids Isolated from an Arctic Marine Lacinutrix sp. Bacterium.

The Lacinutrix genus was discovered in 2005 and includes 12 Gram-negative bacterial species. To the best of our knowledge, the secondary metabolite production potential of this genus has not been explored before, and examination of Lacinutrix species may reveal novel chemistry. As part of a screening project of Arctic marine bacteria, the Lacinutrix sp. strain M09B143 was cultivated, extracted, fractionated and tested for antibacterial and cytotoxic activities. One fraction had antibacterial activity and was subjected to mass spectrometry analysis, which revealed two compounds with elemental composition that did not match any known compounds in databases. This resulted in the identification and isolation of two novel isobranched lyso-ornithine lipids, whose structures were elucidated by mass spectrometry and NMR spectroscopy. Lyso-ornithine lipids consist of a 3-hydroxy fatty acid linked to the alpha amino group of an ornithine amino acid through an amide bond. The fatty acid chains were determined to be iso-C15:0 (1) and iso-C16:0 (2). Compound 1 was active against the Gram-positive S. agalactiae, while 2 showed cytotoxic activity against A2058 human melanoma cells.

SKILLS - A psychoeducational group programme for children with ADHD.

Psychoeducation is regarded as a first line of intervention for attention-deficit/hyperactivity disorder (ADHD). Previous studies have been limited to psychoeducation for adult patients or parents of children with ADHD. Therefore, the aim of the present study was to investigate the acceptability and effectiveness of a psychoeducational group intervention for children with ADHD. The two-session psychoeducational intervention, SKILLS, was completed by 125 children (6-12 years) with ADHD and their parents. Self-ratings and parental ratings of ADHD symptoms, functional impairment and attitudes to diagnosis and treatment were collected before and after treatment. Post-treatment client satisfaction and parental responses to an open question about SKILLS were assessed. The data were analyzed using a combination of quantitative and qualitative (content analysis) methods. A majority of the participants expressed satisfaction with the group intervention. The intervention had no effect on symptoms and level of function, although the parents were more positive to their child's diagnosis after the intervention. The parents were positive to the group format and to the opportunity for their children to meet other children with similar symptoms. Parents wished for more interactive elements and more opportunities for children to share experiences. We concluded that the group intervention was accepted by most participants, although more activating exercises and opportunities for interaction between participants should be included. Since the intervention group was not compared with a control group, the results should be interpreted with caution. Future studies should use a randomized control treatment design and investigate the effect on adherence to later treatment.

The Role of Gender in the Associations Among Posttraumatic Stress Symptoms, Anger, and Aggression in Russian Adolescents.

Symptoms of posttraumatic stress disorder (PTSD) have been linked to anger and aggressive behavior in adult and veteran populations. However, research on the associations among anger, aggression, and PTSD in adolescents is lacking, particularly regarding differences between the sexes. To address this research gap, we used self-report data from Russian adolescents (N = 2,810; age range: 13-17 years) to perform a full path analysis examining the associations between PTSD symptoms and the emotional (anger traits) and cognitive (rumination) components of anger as well as physical/verbal and social aggression, after adjusting for depressive symptoms. We also examined the interaction effects between PTSD symptoms and sex on anger and aggression. The results indicated that girls scored higher on measures of anger and PTSD symptoms, ds = 0.20-0.32, whereas boys scored higher on measures of physical and verbal aggression, d = 0.54. Clinical levels of PTSD symptoms were associated with anger rumination, ß = .16, and trait anger, ß = .06, and an interaction effect for PTSD symptoms and sex was found for aggression, whereby boys with clinical levels of PTSD symptoms reported more physical/verbal and social aggression, ßs = .05 and .20, respectively. Our findings suggest that PTSD symptoms may have an important impact on anger, anger rumination, and aggression during adolescence. In particular, boys seem to have an increased risk for aggressive behavior in the presence of PTSD symptoms. The present results highlight the importance of taking anger and aggression into account when evaluating PTSD.

Isolation and Characterization of Antimicrobial Peptides with Unusual Disulfide Connectivity from the Colonial Ascidian Synoicum turgens.

This study reports the isolation of two novel cysteine-rich antibacterial peptides, turgencin A and turgencin B, along with their oxidized derivatives, from the Arctic marine colonial ascidian Synoicum turgens. The peptides are post-translationally modified, containing six cysteines with an unusual disulfide connectivity of Cys1-Cys6, Cys2-Cys5, and Cys3-Cys4 and an amidated C-terminus. Furthermore, the peptides contain methionine residues resulting in the isolation of peptides with different degrees of oxidation. The most potent peptide, turgencin AMox1 with one oxidized methionine, displayed antimicrobial activity against both Gram-negative and Gram-positive bacteria with a minimum inhibitory concentration (MIC) as low as 0.4 µM against selected bacterial strains. In addition, the peptide inhibited the growth of the melanoma cancer cell line A2058 (IC50 = 1.4 µM) and the human fibroblast cell line MRC-5 (IC50 = 4.8 µM). The results from this study show that natural peptides isolated from marine tunicates have the potential to be promising drug leads.

Risk Factors Associated with Alcohol Use in Early Adolescence among American Inner-City Youth: A Longitudinal Study.

Background: Early alcohol use is associated with an increased risk for later alcohol dependence, as well as social and mental health problems. In this study, we investigate the risk factors (internalizing and externalizing behaviors) associated with early alcohol consumption over a period of 1 year, and examine whether the association is sex-specific. Methods: U.S. inner-city adolescents (N = 1785, Mean age = 12.11) were assessed and reassessed in the sixth and seventh grades (Mean age = 13.10). Self-reported information was obtained on the lifetime level of alcohol consumption, internalizing (depression, anxiety and posttraumatic stress [PTS]), and externalizing behaviors (sensation seeking, conduct problems and affiliation with delinquent peers). Associations between the variables were examined using structural equation modeling (SEM). Results: In an adjusted SEM analysis drinking by the sixth grade was primarily associated with externalizing behaviors, whereas PTS was linked to lower levels of alcohol consumption. In addition, alcohol consumption and greater externalizing behaviors by the sixth grade predicted higher alcohol consumption by the seventh grade, whereas anxiety and African American ethnicity were associated with less alcohol consumption. No sex differences were found in the association between internalizing and externalizing behaviors and drinking. However, in the adjusted SEM analysis female sex predicted higher lifetime consumption by the seventh grade. Conclusion: Sensation seeking behavior, conduct problems and affiliation with delinquent peers should be regarded as risk factors and taken into consideration when planning prevention efforts in order to decrease alcohol use in early adolescence.

How do adolescents with ADHD perceive and experience stress? An interview study.

Background: Attention-deficit/hyperactivity disorder (ADHD) is linked to high levels of perceived stress in adult populations. Thus, it is not surprising that stress managing techniques are being included in treatment protocols for adults with ADHD. There is, however, a paucity of studies on perceived stress in adolescents with ADHD.Aims: This study aims to explore how adolescents with ADHD perceive and experience stress (and stressors) using a qualitative approach.Methods: Explorative interviews were conducted with 20 adolescents (Mean age: 16.30) diagnosed with ADHD in conjunction with group treatment therapy. Data were analysed using qualitative content analysis.Results: Stress and ADHD, as well as stress, anxiety and ill-health, were described as closely intertwined. The result is presented in four categories: stress is often present, triggers of stress, stress affects daily life, and stress can be handled and prevented. A relation was found between stress and feelings of helplessness, ill-health and anxiety. Stress was viewed as being out of proportion with reality and was driven by such factors as ADHD symptoms, school demands, unpredictable situations and relational problems. Several negative consequences of stress were reported, including postponing schoolwork and the tendency to give up. Some participants also reported performing better when stressed. Accepting help from others, practising acceptance, settling down and controlling oneself, and planning in advance were seen as helpful stress managing techniques.Conclusions: Stress should be considered among other problems related to ADHD. Psychoeducation about stress, stress managing techniques and coaching should be included in the treatment of adolescents with ADHD.