Exploring neurocognitive features in adolescents and young adults with anorexia nervosa: Evidence from a longitudinal study.

OBJECTIVE: We aimed to evaluate longitudinal changes in set-shifting and central coherence in a predominantly adolescent cohort with anorexia nervosa (AN) and to explore whether these factors predict long-term eating disorder outcomes. METHOD: Ninety-two female patients with AN (mean age: 16.2, range: 13-21 years) completed neurocognitive tests (Rey Complex Figure Test, Adapted Version of the Wisconsin Card Sorting Test) before and after 12 months of psychotherapeutic treatment (n = 45 Maudsley AN Treatment, MANTRa; n = 47 standard psychotherapy; groups not randomised). Eating disorder severity was assessed at baseline, after 6, 12 and 18 months. RESULTS: Central coherence (indicated by an increase in the Rey Figure Style Index) and set-shifting (indicated by a reduction in the percentage of perseverative errors) significantly improved over the course of treatment, with similar outcomes across groups. Lower central coherence was associated with higher eating disorder severity. Individuals with lower baseline set-shifting ability tended to have worse eating disorder outcomes in the long-term. However, this trend did not reach statistical significance in a multilevel linear mixed model. CONCLUSIONS: Neurocognitive difficulties in adolescents and young adults with AN can improve after treatment. Interventions specifically addressing flexibility in thinking and behaviour may contribute to treatment success.

Development of phenyl-urea-based small molecules that target penicillin-binding protein 4.

Staphylococcus aureus has the ability to invade cortical bone osteocyte lacuno-canalicular networks (OLCNs) and cause osteomyelitis. It was recently established that the cell wall transpeptidase, penicillin-binding protein 4 (PBP4), is crucial for this function, with pbp4 deletion strains unable to invade OLCNs and cause bone pathogenesis in a murine model of S. aureus osteomyelitis. Moreover, PBP4 has recently been found to modulate S. aureus resistance to ß-lactam antibiotics. As such, small molecule inhibitors of S. aureus PBP4 may represent dual functional antimicrobial agents that limit osteomyelitis and/or reverse antibiotic resistance. A high throughput screen recently revealed that the phenyl-urea 1 targets PBP4. Herein, we describe a structure-activity relationship (SAR) study on 1. Leveraging in silico docking and modeling, a set of analogs was synthesized and assessed for PBP4 inhibitory activities. Results revealed a preliminary SAR and identified lead compounds with enhanced binding to PBP4, more potent antibiotic resistance reversal, and diminished PBP4 cell wall transpeptidase activity in comparison to 1.

Evaluation of a Digital Dementia Registry's IT Architecture After a Three-Year Period in Practice: digiDEM Bayern.

INTRODUCTION: The project "digiDEM Bayern" aims to set up a registry with long-term follow-up data on people with dementia and their family caregivers. For that purpose an Electronic Data Capture (EDC) system linked with a Participant Management (PM) system has been established. This study evaluates the acceptance and usability of the IT tools supporting all data management processes in order to further improve the system and associated processes. METHODS: For this purpose we collected the key numbers of the registry, and used the System Usability Scale (SUS) to evaluate the interactions of the data management systems in a wide area. RESULTS: Thirty-six research partners (RP) and six study team (ST) members completed the anonymous online survey. The EDC system overall reached an average SUS score of 73.42 and the PM system of 77.92. DISCUSSION: The two systems fulfil their required task and, therefore, simplify the work of the RP in the data collection process and of the ST during the data quality checks. CONCLUSION: Integrating the used systems is therefore recommended for registry studies in other medical areas.

Acceptability and feasibility of SUCCEAT, an intervention for parents of adolescents with anorexia nervosa.

OBJECTIVE: "Supporting Carers of Children and Adolescents with Eating Disorders in Austria" (SUCCEAT), a skills training for parents, delivered via workshops (WS) or online modules (ONL), has been proven to be effective in terms of parental distress, caregiver skills, and adolescents' outcome. This study examined the adherence to and the acceptability and feasibility of SUCCEAT. METHOD: One-hundred parents (86% mothers) of adolescents with anorexia nervosa participated in the 8-week training. Parents were assigned to the WS (n = 50) or ONL (n = 50) format using a quasi-randomised design. Adherence, acceptability, and feasibility were assessed using self-report questionnaires. RESULTS: Adherence to the sessions was high (66%-98%) for both groups. The usage of the material was comparable between the groups. However, in the WS group, participants actively approached the coaches (71.8% vs. 48.9% often/very often) or other parents (63% vs. 4.4% often/very often) more often. Perceived helpfulness was high in both groups, overall satisfaction and practicability were higher in the WS group. CONCLUSIONS: Good adherence, acceptability, and feasibility were confirmed for both formats of SUCCEAT, with minimal advantages of the WS regarding satisfaction and contact with other parents and coaches. Thus, both formats can be recommended for implementation in clinical routine.

Therapeutic drug monitoring in adolescents with anorexia nervosa for safe treatment with adjunct olanzapine.

OBJECTIVE: Medication is commonly used in anorexia nervosa (AN) despite largely missing high grade evidence. Olanzapine (OLZ) is the best-evidenced substance used off-label in this group, with conflicting outcome regarding BMI, clinical and safety parameters. Therefore, it is important to strictly assure quality of treatment with OLZ in AN by using 'Therapeutic Drug Monitoring' according to AGNP-guidelines, including serum levels and adverse drug reactions (ADRs) to support safety for adolescents with AN and attempt to generate an initial age- and disorder-specific therapeutic reference range. METHOD: Sixty-five adolescents with AN (aged 10-18) treated with OLZ (98% female; 97.5% AN-restricting-type) were prospectively observed, ADRs reported, and correlations between dosage and serum levels measured at trough level were calculated, a preliminary therapeutic range defined. RESULTS: Mean dosage of OLZ was 8.15 (SD: 2.91) mg and 0.19 (SD: 0.07) mg/kg respectively, average concentration was 26.57 (SD: 13.46) ng/mL. Correlation between daily dosage/dosage per kg and serum level was 0.72 (**p < 0.001)/0.65 (**p < 0.001), respectively. ADRs with impairment were rare (6.3%). 75% improved clinically (CGI). BMI increased significantly by 1.5 kg/m2 (t = 10.6, p < 0.001). A preliminary therapeutic reference range is 11.9 and 39.9 ng/mL. CONCLUSIONS: OLZ in the hands of specialists is a well-tolerated and safe treatment adjunct for adolescents with AN.

Fathers in the spotlight: parental burden and the effectiveness of a parental skills training for anorexia nervosa in mother-father dyads.

PURPOSE: Research on the engagement of fathers in the treatment of childhood psychiatric disorders is scarce. This study aims to investigate differences between mothers and fathers of adolescents with anorexia nervosa regarding parental burden and effectiveness of a parental skills training. METHODS: Ninety-one mother-father dyads caring for a child with anorexia nervosa participated in an 8-week parental skills training and completed a set of questionnaires assessing parental psychopathology, eating disorder related burden, caregiver skills and expressed emotion at baseline and post-intervention. RESULTS: Fathers showed lower levels of general psychological distress, depression, anxiety and eating disorder related burden as well as lower emotional overinvolvement compared to mothers. The skills training was effective in reducing parental psychopathology, eating disorder-related burden and emotional overinvolvement as well as in increasing caregiver skills with no differences between mothers and fathers. However, session adherence and the willingness to practice skills between the sessions were slightly lower in fathers. CONCLUSIONS: These findings show that fathers are a great resource for the child's eating disorder treatment as they may counterbalance maternal emotional overinvolvement and over-protection. Furthermore, this is the first study demonstrating that fathers can profit from a parental skills training for anorexia nervosa in a similar way as mothers. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.

The Maudsley model of anorexia nervosa treatment for adolescents and emerging adults: A multi-centre cohort study.

OBJECTIVE: The aim of this study was examining the efficacy of the Maudsley Model of Anorexia Nervosa Treatment for Adolescents and Young Adults (MANTRa) compared to individual psychotherapy that can be considered as standard in Austria (TAU-O). METHOD: In this cohort study, 92 patients between 13 and 21 years suffering from full-syndrome, atypical or weight-restored anorexia nervosa (AN) received either 24-34 individual MANTRa sessions (n = 45) or TAU-O (n = 47). Outcome variables were age- and sex-related BMI, eating disorder and comorbid psychopathology at 6-, 12- and 18-month post baseline as well as acceptability of treatment and therapeutic alliance. RESULTS: Both treatments resulted in significant improvements in age- and sex related BMI and reductions in eating disorder and comorbid psychopathology over time with significant differences between groups in favour of MANTRa. The percentage of participants with fully remitted AN was significantly higher in the MANTRa group compared to TAU-O at 18-month follow-up (MANTRa: 46% vs. TAU-O: 16%, p = 0.006). Satisfaction with both treatments was high. CONCLUSIONS: MANTRa is an effective treatment programme for adolescents and young adults with AN. Randomised controlled trials comparing MANTRa with existing treatments are necessary. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (Identifier: NCT03535714).

Pyochelin biotransformation by Staphylococcus aureus shapes bacterial competition with Pseudomonas aeruginosa in polymicrobial infections.

Pseudomonas aeruginosa and Staphylococcus aureus are among the most frequently isolated bacterial species from polymicrobial infections of patients with cystic fibrosis and chronic wounds. We apply mass spectrometry guided interaction studies to determine how chemical interaction shapes the fitness and community structure during co-infection of these two pathogens. We demonstrate that S. aureus is equipped with an elegant mechanism to inactivate pyochelin via the yet uncharacterized methyltransferase Spm (staphylococcal pyochelin methyltransferase). Methylation of pyochelin abolishes the siderophore activity of pyochelin and significantly lowers pyochelin-mediated intracellular reactive oxygen species (ROS) production in S. aureus. In a murine wound co-infection model, an S. aureus mutant unable to methylate pyochelin shows significantly lower fitness compared with its parental strain. Thus, Spm-mediated pyochelin methylation is a mechanism to increase S. aureus survival during in vivo competition with P. aeruginosa.

[The Therapeutic Potential of Prebiotics and Probiotics in Child and Adolescent Psychiatric Disorders]. / Zum therapeutischen Potenzial der Gabe von Präbiotika und Probiotika bei kinder- und jugendpsychiatrischen Erkrankungen.

The Therapeutic Potential of Prebiotics and Probiotics in Child and Adolescent Psychiatric Disorders Abstract: This short review summarizes the literature available on therapeutic interventions with prebiotics and probiotics and their potential use in psychiatric disorders in childhood, adolescence, and adulthood. Most studies of children and adolescents are done on ADHD and autism spectrum disorders, whereas single reports exist largely on positive effects on cognitive symptoms and quality of life. Initial studies regarding anorexia nervosa point to a potential effect of weight gain and reduction of gastrointestinal symptoms. To date, the effects of prebiotics and probiotics in depression, bipolar disorder, anxiety disorders, and schizophrenia have been mainly investigated in adults. The best reported evidence exists for depression, whereas the effects on depressive symptomatology are small. Positive effects are seen on gastrointestinal symptoms in these disorders. Given these positive effects, the mixed literature reports may result from very heterogeneous study designs. Nevertheless, the high potential of prebiotics and probiotics may be seen for minors with mental health problems. Further studies that include child and adolescent psychiatric populations and reflect the complexity of the gut-brain axis are urgently needed.

Mental Health and Health-Related Quality of Life in Austrian Adolescents with Chronic Physical Health Conditions: Results from the MHAT Study.

Chronic physical health conditions (CPHC) are on the rise in younger age groups and might have a negative impact on children and adolescents. In a representative sample of Austrian adolescents aged 10-18 years, internalizing, externalizing, and behavioral problems were assessed cross-sectionally using the Youth Self-Report and health-related quality of life (HrQoL) using the KIDSCREEN questionnaire. Sociodemographic variables, life events, and chronic illness specific parameters were considered as associated variables with mental health problems in individuals with CPHC. Of 3469 adolescents, 9.4% of girls and 7.1% of boys suffered from a chronic pediatric illness. Of these individuals, 31.7% and 11.9% had clinically relevant levels of internalizing and externalizing mental health problems, respectively, compared to 16.3% and 7.1% adolescents without a CPHC. Anxiety, depression, and social problems were twice as high in this population. Medication intake due to CPHC and any traumatic life-event were related to mental health problems. All HrQoL domains were deteriorated in adolescents with a double burden of mental and CPHC, whereas adolescents with a CPHC without mental health problems did not differ significantly from adolescents without a chronic illness. Targeted prevention programs for adolescents with a CPHC are urgently needed to prevent mental health problems in the long term.

[Scientific evidence and user quality in mobile health applications for people with cognitive impairments and their caregivers]. / Wissenschaftliche Evidenz und Nutzerqualität von Mobile-Health-Anwendungen für Menschen mit kognitiven Beeinträchtigungen und deren Angehörige.

INTRODUCTION: The range of health-related apps is large, but the scientific evidence for them is uncertain. The aim of this study is to evaluate the methodological quality of German-language mobile health apps for people with dementia and their caregivers. METHODS: The app search was conducted according to the PRISMA-P guidelines in the application stores (Google Play Store and Apple App Store) using the terms "Demenz", "Alzheimer", "Kognition" and "Kognitive Beeinträchtigung". A systematic literature search with subsequent assessment of the scientific evidence was performed. The user quality assessment was conducted using "The German Version of the Mobile App Rating Scale" (MARS-G). RESULTS: Scientific studies have been published for only 6 of the 20 apps identified. A total of 13 studies were included in the evaluation, whereby the app itself was the subject of investigation in only two publications. In addition, methodological weaknesses were often observed such as small group sizes, short study duration and/or insufficient comparative treatment. The overall quality of the apps can be rated as acceptable with a mean MARS rating of 3.38. Seven apps were able to achieve a score of over 4.0 and thus a good rating, but just as many apps fell below the acceptable limit of 3.0. DISCUSSION: The contents of most apps have not been scientifically tested. This identified lack of evidence is consistent with the information in the literature in other indication areas. A systematic and transparent evaluation of health applications is necessary to protect end-users and better support their selection process.

Psychological distress and caregiving experience during the first two years of the COVID-19 pandemic among parents of an offspring with anorexia nervosa.

OBJECTIVE: To compare different aspects of caregiving distress and experience in parents of patients with anorexia nervosa (AN) before and during the COVID-19 pandemic. METHODS: Three cohorts of parents of AN patients (cohort 1-pre-pandemic: N = 78, cohort 2-first pandemic year: N = 51, cohort 3-second pandemic year: N = 119) were recruited from child and adolescent psychiatry wards and cross-sectionally assessed as part of the clinical routine. Quantitative measures of psychological distress, psychopathology, eating disorder (ED)-related burden, expressed emotion and caregiver skills were obtained at the beginning of the child's inpatient or outpatient treatment. RESULTS: Cohort 2 showed lower levels of anxiety and a tendency of lower emotional overinvolvement and higher caregiving skills compared to the pre-pandemic cohort. In contrast, the levels of general psychological distress, depression, ED-related burden and criticism observed in cohort 3 significantly exceeded pre-pandemic levels. The prevalence of clinically relevant depression was higher in cohort 3 (41.5%) compared to cohorts 1 (24.4%) and 2 (21.6%). DISCUSSION: The pandemic effects on parents seem to be time-specific. Lower distress in the early phase of the pandemic may be associated with improvements in parent-child-relationships reported in previous studies. However, the pandemic may has negative consequences in the long-term emphasising the need of ongoing parental support.

Personality Disorder in Adolescent Patients with Anorexia Nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a highly debilitating disease which frequently results in chronification and often originates in adolescence. Personality traits have been associated with the onset and maintenance of AN; moreover, study results indicated a worse treatment outcome in patients with AN and comorbid personality disorder (PD). However, research on PD in adolescent AN is scarce. METHODS: The sample consists of 73 female adolescent patients with AN. We investigated comorbid PD and AN symptom severity performing the International Personality Disorder Examination (IPDE) and the Eating Disorder Inventory 2 (EDI-2). RESULTS: Almost a third (27.4%) of all participants were diagnosed with comorbid PD. They had significantly higher EDI-2 total scores reflecting overall stronger symptom severity, as well as significantly higher scores in the subscales "ineffectiveness," "interpersonal distrust," "interoceptive awareness," "asceticism," "impulse regulation," and "social insecurity." CONCLUSION: PD is an important and frequent comorbid condition in adolescent AN and should be addressed in diagnostic and treatment planning. Early diagnosis of comorbidity could have an impact on choosing specialized treatment for adolescents with AN and PD in order to enhance the outcome.

Psychosocial impact of the COVID-19 pandemic for adolescents with type-1-diabetes: a qualitative interview study involving adolescents and parents.

This study aims to investigate the psychosocial impact of the COVID-19 pandemic on adolescents with type-1-diabetes (T1D). We conducted 18 semi-structured interviews including adolescents with T1D (n = 10, 50% female, 15-18 years) and their parents (n = 8, 88% mothers). The main topics addressed were experiences during confinement regarding everyday life, lifestyle behaviors, diabetes management and treatment. We applied thematic analysis to identify common patterns of meanings. Being aware of belonging to a potential COVID-19 risk group caused worries especially in parents which resulted in strict adherence to preventive measures. Information from trustworthy sources regarding the actual risk mitigated the concerns. Digital diabetes treatment was well accepted and experienced as highly usable. The pandemic situation either facilitated or hindered the transition from parental control to diabetes self-management. While some patients managed to improve healthy lifestyle behaviors as their everyday lives seemed more predictable, others had difficulties in adapting to changed daily routines resulting in increased sedentary behavior and snacking. The perceived level of stress was directly associated with blood glucose levels. In conclusion, the implementation of psychological interventions (both for adolescents with T1D and their parents) addressing mental health literacy and media literacy seems to be important to promote positive coping skills for dealing with the pandemic situation.

An investigation of the factor structure of a German version of the Eating Disorder Symptom Impact Scale (EDSIS) among parents of adolescents and young adults with anorexia nervosa.

The aim of this study was to explore the factor structure, scale characteristics and convergent validity of a German version of the Eating Disorder Symptom Impact Scale (EDSIS). A total of 335 parents of adolescents and young adults with anorexia nervosa in inpatient or outpatient treatment completed the 24-item German translation of the EDSIS and other measures of caregiving burden and psychological distress. We tested a 4 vs. 6-factor model of the EDSIS using confirmatory factor analyses. The 6-factor model treating items as ordinal variables showed the best fit to the data (CFI = 0.949, RMSEA = 0.064). Strong invariance of this model was shown between the sample of mothers and fathers. Internal consistencies of the EDSIS scales were in the acceptable-to-good range. Bottom effects were observed for the 'Binge-Purge-Impacts' subscale only. Mothers had significantly higher EDSIS scores compared to fathers. The EDSIS total score and most of the subscores showed substantial positive correlations with caregivers' psychological distress, level of depression, anxiety and expressed emotion as well as negative associations with the level of perceived caregiving skills. The German version of the EDSIS is a useful tool to assess caregiving burden in mothers and fathers of patients with anorexia nervosa.

Exploring the link between eating disorders and persistent genital arousal disorder/genito-pelvic dysesthesia: first description and a systematic review of the literature.

BACKGROUND: Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD) characterized by recurrent physiological genital without corresponding psychological arousal is a poorly understood and researched condition. Based on the first two case descriptions of eating disorders directly linked to PGAD/GPD the aim of this paper was to systematically review the literature on possible associations between eating disorders and PGAD/GPD. METHOD: A systematic literature search on eating disorders and PGAD/GPD was conducted in PubMed, PsycINFO, and Scopus, complemented by Google Scholar. We included case reports, case series, cross-sectional studies and review articles published in peer-reviewed journals written in English or German-language. RESULTS: The included original papers described a total of 2078 cases with PGAD/GPD symptomatology. Of these, 892 participants fulfilled all five PGAD/GPD core criteria. The aetiology of PGAD/GPD is unknown. Multifactorial genesis of PGAD/GPD is presumed including neurological, pharmacological, hormonal, vascular and psychological causes. A high degree of psychological comorbidity is reported. No study was found that drew a direct link between eating disorders and PGAD/GPD. Although PGAD/GPD symptoms also occur in adolescents, there are no findings in this regard. However, we found a gap in data collection: eating disorders as potential psychiatric comorbidities were systematically recorded in only a few studies. CONCLUSION: The existing literature have not yet considered a possible link between eating disorders and PGAD/GPD so far. According to the authors' knowledge, this work is the first review to systematically explore the associations. We suspect underreporting of PGAD/GPD cases in eating disorders and particularly during adolescence. We argue that there are several common factors that appear to be important in the etiology, course, and treatment of both disorders (e.g. hormonal dysregulation or sensory sensitivity and avoidance), warranting future research on the possible comorbidity of these disorders.

Persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD) is characterized by recurrent physiological genital arousal without corresponding psychological arousal. PGAD/GPD is a poorly understood and researched disorder. It is often associated with significant psychological impairment and distress.Eating disorders are severe psychological illnesses that predominantly affect the female sex. They have a high psychological comorbidity and are often associated with severe physical consequences.We treated two female patients in whom there was a direct association between PGAD/GPD and eating disorder. In our systematic review of the literature, we found no study that further investigated the co-occurrence between PGADPGAD/GPD and eating disorders. This paper is the first to describe and investigate a relationship between PGAD/GPD and eating disorders.In previous literature, several factors have been hypothesized for the development of PGAD/GPD but also eating disorders. We argue that there are several common factors that appear to be important in the etiology, course, and treatment of both disorders (e.g. hormonal dysregulation or sensory sensitivity and avoidance), warranting future research on the possible comorbidity of these disorders.

The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation. In previous studies, the administration of polyunsaturated fatty acids (PUFA) resulted in effects that might be beneficial in the treatment of AN, affecting the microbiome, body weight and executive functions. Therefore, the MiGBAN study aims to examine the effects of a nutritional supplementation with PUFA on the gut microbiome and body mass index (BMI) in patients with AN. METHODS: This is a longitudinal, double-blind, randomized, placebo-controlled trial. Within 2 years, 60 adolescent patients aged 12 to 19 years with AN will receive either PUFA or placebo for 6 months additional to treatment as usual. After 1 year, the long-term effect of PUFA on the gut microbiome and consecutively on BMI will be determined. Secondary outcomes include improvement of gastrointestinal symptoms, eating disorder psychopathology, and comorbidities. Additionally, the interaction of the gut microbiome with the brain (microbiome-gut-brain axis) will be studied by conducting MRI measurements to assess functional and morphological changes and neuropsychological assessments to describe cognitive functioning. Anti-inflammatory effects of PUFA in AN will be examined via serum inflammation and gut permeability markers. Our hypothesis is that PUFA administration will have positive effects on the gut microbiota and thus the treatment of AN by leading to a faster weight gain and a reduction of gastrointestinal problems and eating disorder psychopathology. DISCUSSION: Due to previously heterogeneous results, a systematic and longitudinal investigation of the microbiome-gut-brain axis in AN is essential. The current trial aims to further analyse this promising research field to identify new, effective therapeutic tools that could help improve the treatment and quality of life of patients. If this trial is successful and PUFA supplementation contributes to beneficial microbiome changes and a better treatment outcome, their administration would be a readily applicable additional component of multimodal AN treatment. TRIAL REGISTRATION: German Clinical Trials Register DRKS00017130 . Registered on 12 November 2019.

Of differing methods, disputed estimates and discordant interpretations: the meta-analytical multiverse of brain volume and IQ associations.

Brain size and IQ are positively correlated. However, multiple meta-analyses have led to considerable differences in summary effect estimations, thus failing to provide a plausible effect estimate. Here we aim at resolving this issue by providing the largest meta-analysis and systematic review so far of the brain volume and IQ association (86 studies; 454 effect sizes from k = 194 independent samples; N = 26 000+) in three cognitive ability domains (full-scale, verbal, performance IQ). By means of competing meta-analytical approaches as well as combinatorial and specification curve analyses, we show that most reasonable estimates for the brain size and IQ link yield r-values in the mid-0.20s, with the most extreme specifications yielding rs of 0.10 and 0.37. Summary effects appeared to be somewhat inflated due to selective reporting, and cross-temporally decreasing effect sizes indicated a confounding decline effect, with three quarters of the summary effect estimations according to any reasonable specification not exceeding r = 0.26, thus contrasting effect sizes were observed in some prior related, but individual, meta-analytical specifications. Brain size and IQ associations yielded r = 0.24, with the strongest effects observed for more g-loaded tests and in healthy samples that generalize across participant sex and age bands.

2-Aminoimidazoles Inhibit Mycobacterium abscessus Biofilms in a Zinc-Dependent Manner.

Biofilm growth is thought to be a significant obstacle to the successful treatment of Mycobacterium abscessus infections. A search for agents capable of inhibiting M. abscessus biofilms led to our interest in 2-aminoimidazoles and related scaffolds, which have proven to display antibiofilm properties against a number of Gram-negative and Gram-positive bacteria, including Mycobacterium tuberculosis and Mycobacterium smegmatis. The screening of a library of 30 compounds led to the identification of a compound, AB-2-29, which inhibits the formation of M. abscessus biofilms with an IC50 (the concentration required to inhibit 50% of biofilm formation) in the range of 12.5 to 25 µM. Interestingly, AB-2-29 appears to chelate zinc, and its antibiofilm activity is potentiated by the addition of zinc to the culture medium. Preliminary mechanistic studies indicate that AB-2-29 acts through a distinct mechanism from those reported to date for 2-aminoimidazole compounds.

Synthesis, Stereochemical Confirmation, and Derivatization of 12(S),16ϵ-Dihydroxycleroda-3,13-dien-15,16-olide, a Clerodane Diterpene That Sensitizes Methicillin-Resistant Staphylococcus aureus to ß-Lactam Antibiotics.

Over the past decades, antibiotic resistance has grown to a point where orthogonal approaches to combating infections caused by resistant bacteria are needed. One such approach is the development of non-microbicidal small molecules that potentiate the activity of conventional antibiotics, termed adjuvants. The diterpene natural product 12(S),16ϵ-dihydroxycleroda-3,13-dien-15,16-olide, which we refer to as (-)-LZ-2112, is known to synergize with oxacillin against methicillin-resistant Staphylococcus aureus (MRSA). To explore this activity, (-)-LZ-2112 was synthesized and the structure confirmed through X-ray analysis. Preliminary structure-activity relationship studies following the synthesis of several analogs identified key structural elements responsible for activity and indicate that scaffold simplification is possible. A preliminary mode of action study suggests mecA plays a role in the adjuvant activity of (-)-LZ-2112.