Clinical distinction between cognitive disengagement syndrome and ADHD presentations in a nationally representative sample of Spanish children and adolescents.

BACKGROUND: This study sought to determine whether cognitive disengagement syndrome (CDS, formerly sluggish cognitive tempo) has different external correlates relative to ADHD-inattentive presentation (INP), ADHD-hyperactive/impulsive presentation (HIP), and ADHD-combined presentation (CP). METHODS: Parents of a nationally representative sample of 5,525 Spanish youth (ages: 5-16, 56.1% boys) completed measures of CDS, ADHD-inattention (IN), and ADHD-hyperactivity/impulsivity (HI) and other measures. Scores greater/less than the top 5% on CDS, ADHD-IN, and ADHD-HI were used to create control (n = 5,013, 90.73%), CDS-only (n = 131, 2.37%), ADHD-INP-only (n = 83, 1.50%), ADHD-HIP-only (n = 113, 2.05%), ADHD-CP-only (n = 48, 0.97%), CDS + ADHD-INP (n = 44, 0.80%), CDS + ADHD-HIP (n = 25, 0.45%), and CDS + ADHD-CP (n = 68, 1.23%) groups. RESULTS: Forty-nine percent of youth with clinically elevated CDS did not qualify for any ADHD presentation, whereas 64% of youth with clinically elevated ADHD did not qualify for CDS. The CDS-only group was higher than the ADHD-INP-only, ADHD-HIP-only, and ADHD-CP-only groups on anxiety, depression, somatization, daytime sleep-related impairment, nighttime sleep disturbance, and peer withdrawal, whereas the CDS-only and ADHD-INP-only groups did not differ on ODD (ADHD-HIP-only and ADHD-CP-only higher) and academic impairment (ADHD-CP-only higher than CDS-only and ADHD-HIP-only lower than CDS-only). The CDS-only group also had higher rates of anxiety, depression, and bipolar disorder diagnoses than the ADHD-only group. CONCLUSIONS: A distinction was found between CDS and each ADHD presentation, thus providing support for CDS as a syndrome that frequently co-occurs with yet is distinct from each ADHD presentation.

Predictors and Mechanisms of Resilience for High School Students with ADHD: A Prospective Longitudinal Study.

Attention-deficit/hyperactivity disorder (ADHD) has primarily been studied from a deficit-focused perspective. However, there are individuals with ADHD who exhibit resilience or a pattern of positive adaptation despite the risks associated with their diagnosis. The present study evaluated whether peer acceptance predicted resilience for adolescents with ADHD and if self-efficacy or a stress-is-enhancing mindset served as mechanisms of those relations. Participants included 113 comprehensively evaluated adolescents with ADHD (67% male) across three time-points (10th-12th grade). Mediation analyses revealed higher T1 peer acceptance significantly predicted higher resilience (ß = 0.24) 1.5-2 years later, with higher T2 self-efficacy (ß = 0.08) demonstrating a significant indirect effect of the association. A stress-is-enhancing mindset directly predicted resilience (ß = 0.15) but was not associated with peer acceptance nor mediated the association between peer acceptance and resilience. Present results are the first to provide longitudinal evidence for peer acceptance, self-efficacy, and a stress-is-enhancing mindset as important for promoting resilience among adolescents with ADHD.

Optimization of array encoding for ultrasound imaging.

OBJECTIVE: The transmit encoding model for synthetic aperture imaging is a robust and flexible framework for understanding the effects of acoustic transmission on ultrasound image reconstruction. Our objective is to use machine learning (ML) to construct scanning sequences, parameterized by time delays and apodization weights, that produce high-quality B-mode images. Approach: We use a custom ML model in PyTorch with simulated RF data from Field II to probe the space of possible encoding sequences for those that minimize a loss function that describes image quality. This approach is made computationally feasible by a novel formulation of the derivative for delay-and-sum beamforming. Main Results: When trained for a specified experimental setting (imaging domain, hardware restrictions, etc.), our ML model produces optimized encoding sequences that, when deployed in the REFoCUS imaging framework, improve a number of standard quality metrics over conventional sequences including resolution, field of view, and contrast. We demonstrate these results experimentally on both wire targets and a tissue-mimicking phantom. Significance: This work demonstrates that the set of commonly used encoding schemes represent only a narrow subset of those available. Additionally, it demonstrates the value for ML tasks in synthetic transmit aperture imaging to consider the beamformer within the model, instead of purely as a post-processing step.

Editorial: New Insights Into the Complexities and Neurocognitive Correlates of Sleep in Adolescents with Attention-Deficit/Hyperactivity Disorder.

Despite decades-long interest in sleep in individuals with attention-deficit/hyperactivity disorder (ADHD)-"restless sleep" was a symptom for diagnosing attention deficit disorder in the Third Edition of the DSM-our understanding of its role in the pathophysiology, trajectories, and functional outcomes of ADHD remains far from complete. This is perhaps no more so the case than in the developmental period of adolescence. The oft-described "perfect storm" of short and ill-timed sleep coinciding with bioregulatory maturation during adolescence1 may be further intensified for adolescents with ADHD, who often experience wide-ranging and intensifying functional impairments.2 Almost a decade ago, Lunsford-Avery and colleagues3 provided a systematic review and research roadmap to guide future research on sleep in adolescents with ADHD, casting a much-needed spotlight on this understudied topic.

Examining Cognitive Disengagement Syndrome in Relation to Social Problem Solving in Young Adults.

OBJECTIVE: Cognitive disengagement syndrome (CDS), previously referred to as sluggish cognitive tempo (SCT), is characterized by symptoms such as excessive daydreaming, mental confusion, and hypoactivity. CDS symptoms are associated with emotional, social, and daily life impairments. The way in which one solves problems in their daily life is associated with experiences of further problems, such that maladaptive problem-solving can lead to further physical and psychological problems. However, there is limited information on how CDS symptoms are associated with problem solving. The current study examined CDS symptoms in relation to different social problem solving approaches. METHOD: A total of 280 college students (ages 18-23 years; 77.9% female) completed measures of psychopathology symptoms and social problem solving. RESULTS: Above and beyond ADHD and internalizing symptoms, CDS symptoms were independently associated with negative problem orientation and avoidance style domains of maladaptive problem solving. CONCLUSION: Findings indicate that CDS symptoms are related to specific difficulties with social problem solving. CDS symptoms may lead to difficulties attending to problems or working through relevant steps needed to identify solutions for the problem, which may then lead to avoidance and social withdrawal. Longitudinal research is needed to evaluate maladaptive problem solving as a potential mechanism in the association between CDS, social withdrawal, and internalizing symptoms.

Examining cognitive disengagement syndrome in a psychiatric outpatient sample: Psychometric support and associations with internalizing symptoms and sleep problems.

OBJECTIVE: The internal (structural) and external validity of a self-report measure of cognitive disengagement syndrome (CDS, formerly sluggish cognitive tempo) relative to a self-report measure of attention-deficit/hyperactivity disorder-inattention (ADHD-IN) was evaluated with adults from university outpatient psychiatric clinics in Turkey. METHODS: A total of 274 outpatients (75.9% women; ages 18-64 years; Mage = 31.06; SDage = 10.84; 50.4% anxiety disorders; 41.6% depressive disorders; 2.9% ADHD; 1.5% sleep disorders; 0.7% eating disorders; 2.9% no mental disorder) completed self-report measures of CDS, ADHD-IN, ADHD-hyperactivity/impulsivity (HI), sleep problems, depression, and stress. RESULTS: All 15 CDS symptoms measured by the Adult Concentration Inventory (ACI) showed convergent (moderate to high loadings on the CDS factor) and discriminant (loading close to zero on the ADHD-IN factor) validity. CDS also showed stronger first-order and unique associations than ADHD-IN with sleep problems, depression, anxiety, and stress, whereas ADHD-IN showed stronger first-order and unique associations than CDS with ADHD-HI. CONCLUSION: This is the first study to provide support for the scores from this 15 item self-report measure of CDS by the ACI in a clinical sample of adults, with findings consistent with previous studies examining parent and teacher rating scale measures with the same 15 CDS symptoms. These findings provide additional support for usefulness of these 15 CDS symptoms as measured by the ACI to study CDS across various cultures.

Personality Traits in Relation to Cognitive Disengagement Syndrome and ADHD Inattention in Two Samples of Children.

OBJECTIVE: Cognitive disengagement syndrome (CDS; previously referred to as sluggish cognitive tempo) is a set of behaviors, including excessive mind-wandering, mental fogginess, and hypoactivity, that are separate from ADHD inattentive (ADHD-IN) symptoms and linked to functional outcomes. However, CDS and ADHD-IN symptoms are strongly associated, and our understanding of whether personality correlates are similarly or differentially linked to CDS and ADHD-IN is limited. The objective of the current study was to examine personality correlates of CDS and ADHD-IN symptoms across two independent samples of school-aged youth. METHOD: Study 1 included 207 school-aged children (ages 7-11; 63% male; 87.9% White) with or without teacher-reported elevations in CDS. Study 2 included 263 school-aged children (ages 8-12; 58% male; 75.3% White) with the full range of CDS symptomatology. Parents and teachers completed ratings of ADHD-IN and CDS, and parents also reported on their child's personality dimensions. RESULTS: Across two samples and controlling for demographic characteristics as well as ADHD-IN symptoms and other personality traits, higher levels of FFFS-fear/shyness were uniquely associated with higher levels of parent- and teacher-reported CDS symptoms. In most models, lower levels of BAS-drive were also uniquely associated with higher levels of CDS. In contrast, when controlling for demographic characteristics and CDS symptoms, higher levels of BAS-impulsivity/fun-seeking were uniquely associated with higher levels of parent- and teacher-reported ADHD-IN symptoms. DISCUSSION: The findings provide the clearest evidence to date that personality dimensions are differentially associated with ADHD-IN and CDS symptoms in children, further underscoring CDS as a distinct construct from ADHD-IN.

Preliminary examination of ADHD inattentive and cognitive disengagement syndrome symptoms in relation to probe-caught mind-wandering during a sustained attention to response task.

OBJECTIVE: The role of mind-wandering- periods of internally-directed distractibility - among patients with attention-deficit/hyperactivity disorder (ADHD) has recently garnered attention, though few studies have assessed mind-wandering using thought probes during a sustained attention to response task (SART) or examined the possible role of cognitive disengagement syndrome (CDS) symptoms. We examined whether parent- and/or teacher-reported ADHD-inattentive (ADHD-IN) or CDS symptoms were independently associated with probe-caught mind-wandering. METHODS: Fifty-four children (ages 9-12; 35.2% female) completed a SART with thought probes inquiring about various on- and off-task thoughts, including mind-wandering and distraction. Questionnaires provided information on demographics, medication treatment, and parent- and teacher-reported ADHD-IN and CDS symptoms. Regression models were estimated separately by informant to examine whether ADHD-IN or CDS symptoms were uniquely associated with mind-wandering or distraction frequency during the SART. RESULTS: Higher teacher-reported CDS ratings, but not ADHD-IN ratings, were uniquely associated with more probe-caught mind-wandering. No significant findings related to parent-reported symptoms or probe-caught distraction were observed. CONCLUSIONS: These preliminary findings add to an emerging body of work pointing to CDS as more consistently or strongly associated than ADHD-IN with mind-wandering. Theoretical and clinical implications are discussed.

A Multi-Method Examination of Peer Functioning in Children with and without Cognitive Disengagement Syndrome.

OBJECTIVE: Cognitive disengagement syndrome (CDS) includes excessive daydreaming, mental confusion, and hypoactive behaviors that are distinct from attention-deficit/hyperactivity disorder inattentive (ADHD-IN) symptoms. A growing number of studies indicate that CDS symptoms may be associated with ratings of social withdrawal. However, it is important to examine this association in children specifically recruited for the presence or absence of CDS, and to incorporate multiple methods including direct observations of peer interactions. The current study builds on previous research by recruiting children with and without clinically elevated CDS symptoms and using a multi-method, multi-informant design including recess observations and parent, teacher, and child rating scales. METHOD: Participants were 207 children in grades 2-5 (63.3% male), including 103 with CDS and 104 without CDS, closely matched on grade and sex. RESULTS: Controlling for family income, medication status, internalizing symptoms, and ADHD-IN severity, children with CDS were observed during recess to spend more time alone or engaging in parallel play, as well as less time involved in direct social interactions, than children without CDS. Children with CDS were also rated by teachers as being more asocial, shy, and socially disinterested than children without CDS. Although children with and without CDS did not differ on parent- or self-report ratings of shyness or social disinterest, children with CDS rated themselves as lonelier than children without CDS. CONCLUSIONS: Findings indicate that children with CDS have a distinct profile of peer functioning and point to the potential importance of targeting withdrawal in interventions for youth with elevated CDS symptoms.

[Formula: see text] Neurocognition in children with cognitive disengagement syndrome: accurate but slow.

Cognitive disengagement syndrome (CDS), previously termed sluggish cognitive tempo (SCT), is characterized by excessive daydreaming, mental confusion, and slowed behavior or thinking. Prior research has found inconsistent relations between CDS and neurocognition, though most studies have used small or ADHD-defined samples, non-optimal measures of CDS, and/or examined limited neurocognitive domains. Accordingly, this study examined the association of parent- and teacher-reported CDS symptoms using a comprehensive neurocognitive battery in a sample of 263 children (aged 8-12) selected with a range of CDS symptomatology. Parents and teachers provided ratings of CDS and ADHD inattentive (ADHD-IN) symptoms. Path analyses were conducted to examine CDS and ADHD-IN as unique predictors of neurocognitive functioning after covarying for age, sex, and family income. CDS symptoms were uniquely associated with slower performance across a range of cognitive domains, including verbal inhibition, rapid naming/reading, planning, divided attention, and set shifting. In contrast, ADHD-IN symptoms were uniquely associated with poorer performance on a Go/NoGo task (inhibition/distractibility), visual scanning and discrimination, and interference control. Findings from the current study, amongst the first to recruit children based on levels of CDS symptomatology, provide the strongest evidence to date that the neurocognitive phenotype of CDS is characterized by slowed cognitive processing, and add to its validity as a separate syndrome from ADHD. If replicated, these findings have implications for assessment, treatment, and school accommodations for CDS. Neuroimaging studies exploring the neurobiological basis of CDS are also needed.

ADHD, chronotype, and circadian preference in a multi-site sample of college students.

Attention-deficit/hyperactivity disorder and an evening chronotype are both common among college students, and there is growing interest in understanding the possible link between attention-deficit/hyperactivity disorder and circadian function. However, mixed findings have been reported, and many of the existing studies have used small samples that were unable to examine chronotype across attention-deficit/hyperactivity disorder presentations. Participants were 4751 students (73% female; 80% White), aged 18-29 years (M = 19.28, SD = 1.50), from five universities who completed measures assessing attention-deficit/hyperactivity disorder, depressive and anxiety symptoms, as well as the Morningness-Eveningness Questionnaire to assess chronotype (categorical) and circadian preference (dimensional). Participants with either attention-deficit/hyperactivity disorder predominantly inattentive presentation or attention-deficit/hyperactivity disorder combined presentation had higher rates of being an evening type (47.2% and 41.5%, respectively) than participants without elevated attention-deficit/hyperactivity disorder (28.5%), and participants with attention-deficit/hyperactivity disorder predominantly inattentive presentation also had higher rates of being an evening type than participants with attention-deficit/hyperactivity disorder predominantly hyperactive-impulsive presentation (30.7%). Dimensional analyses indicated that attention-deficit/hyperactivity disorder inattentive symptoms were more strongly associated than hyperactive-impulsive symptoms with eveningness preference. Finally, greater eveningness preference strengthened the association between attention-deficit/hyperactivity disorder inattention and depressive symptoms but not anxiety symptoms. This is the largest study to document that college students with elevated attention-deficit/hyperactivity disorder symptoms are more likely to be evening types than other college students, and inattentive symptoms in particular are associated with later circadian preference.

Examining daily stimulant medication use and sleep in adolescents with ADHD.

Research has been inconclusive as to whether stimulant treatment causes or exacerbates sleep problems in adolescents with ADHD. This study examined sleep differences in adolescents with ADHD as a function of stimulant use. Participants were adolescents with ADHD (N = 159, ages 12-14). Parents reported on receipt of stimulant treatment (n = 92, 57.86%; n = 47 amphetamines, n = 45 methylphenidate). Adolescents wore actigraphs and completed daily diaries assessing sleep and daily use of stimulants for 2 weeks. Sleep parameters included daily-reported bedtime, sleep onset latency (SOL), sleep duration, daytime sleepiness, and difficulty waking the following morning; and actigraphy-measured sleep onset time, total time in bed, and sleep efficiency. We estimated between- and within-individual associations between stimulant medication use and sleep indices with all stimulants, after removing adolescents using sleep aids and weekend days, and as a function of stimulant type. Adolescent sleep did not differ between those receiving and not receiving stimulant treatment. Within individuals using stimulants, we largely observed no significant differences between medicated and unmedicated days, though findings were most often significant for school days only. Small effects were found indicating longer SOL, later sleep onset time, and more daytime sleepiness related to medication use. In contrast, there were slight improvements to sleep duration and sleep efficiency related to methylphenidate use, though methylphenidate was also associated with later sleep onset time and more daytime sleepiness. Given the inconsistent and small effects, findings suggest that stimulant medication may impact sleep, but does not appear to be a primary contributor to sleep problems in adolescents with ADHD.

Can lung airway geometry be used to predict autism? A preliminary machine learning-based study.

The goal of this study is to assess the feasibility of airway geometry as a biomarker for autism spectrum disorder (ASD). Chest computed tomography images of children with a documented diagnosis of ASD as well as healthy controls were identified retrospectively. Fifty-four scans were obtained for analysis, including 31 ASD cases and 23 controls. A feature selection and classification procedure using principal component analysis and support vector machine achieved a peak cross validation accuracy of nearly 89% using a feature set of eight airway branching angles. Sensitivity was 94%, but specificity was only 78%. The results suggest a measurable difference in airway branching angles between children with ASD and the control population.

Cognitive Disengagement Syndrome Symptoms from Early Childhood to Adolescence in a Nationally Representative Spanish Sample.

OBJECTIVE: The identification of a common set of symptoms for assessing cognitive disengagement syndrome (CDS, formerly sluggish cognitive tempo) for early childhood (ages 5-8), middle childhood (ages 9-12), and adolescence (ages 13-16) is needed to advance research on the developmental psychopathology of CDS (i.e. a common symptom set with comparable internal and external validity for each age group). METHOD: Parents of a nationally representative sample of 5,525 Spanish children and adolescents (ages 5 to 16, 56.1% boys) completed measures of CDS, attention-deficit/hyperactivity disorder-inattention (ADHD-IN), and other measures. RESULTS: First, the 15 CDS symptoms showed convergent and discriminant validity relative to the ADHD-IN symptoms within each age group. Second, CDS showed stronger first-order and unique associations than ADHD-IN with anxiety, depression, somatization, daytime sleep-related impairment, and nighttime sleep disturbance, whereas ADHD-IN showed stronger first-order and unique associations than CDS with ADHD-hyperactivity/impulsivity, oppositional defiant disorder, and academic impairment. Third, CDS showed stronger first-order and unique associations than ADHD-IN with a history of having an anxiety, depression, or bipolar disorder diagnosis, whereas ADHD-IN showed stronger first-order and unique associations with having an ADHD diagnosis. CONCLUSIONS: The identification of a common set of CDS symptoms spanning early childhood to adolescence allows for the advancement of research on CDS, with a particular need now for longitudinal studies and examination of CDS with other functional outcomes and across other cultural contexts.

Multi-method examination of cognitive disengagement syndrome and ADHD inattentive symptoms in relation to early adolescents' academic functioning.

Cognitive disengagement syndrome (CDS), previously referred to as sluggish cognitive tempo, is a set of symptoms characterized by excessive daydreaming, mental fogginess, and slowed behavior/thinking. Studies examining the association between CDS and academic functioning have reported mixed findings and have relied upon limited measures of CDS, broad ratings of academic impairment, and/or focused only on elementary-aged children. The current study examined the relationship between CDS and academic functioning in adolescents using a comprehensive, multi-informant, multi-method design. Participants were 302 adolescents (Mage = 13.17 years; 44.7% female; 81.8% White; 52% with ADHD) recruited in the fall of their 8th grade. Above and beyond ADHD inattentive symptoms, CDS symptoms were related to poorer homework performance, lower math fluency, and lower daily academic motivation across multiple informants, and teacher-reported CDS symptoms were related to lower grades. Findings were not moderated by ADHD diagnosis, suggesting that associations between CDS and academic outcomes do not differ for adolescents with and without ADHD. Findings demonstrate that CDS symptoms are uniquely associated with daily academic difficulties as well as global indices of academic performance. These findings have implications for assessing and monitoring CDS symptoms in interventions aiming to improve the academic functioning in adolescents with and without ADHD.

Cognitive disengagement syndrome (sluggish cognitive tempo) and medical conditions: a systematic review and call for future research.

Cognitive disengagement syndrome (CDS, previously referred to as sluggish cognitive tempo) is a unique set of symptoms distinct from ADHD inattentive symptoms that appear to be independently associated with neuropsychological and psychosocial outcomes in community and ADHD-specific samples of youth. However, our understanding of CDS in individuals with chronic or complex medical conditions is limited. The current systematic review is the first to summarize the literature on CDS prevalence rates and associations with neurocognitive and functional outcomes in youth with medical conditions, and to discuss areas of future research to guide clinical intervention. We conducted literature searches across four major databases and included studies assessing prevalence estimates, associations with neuropsychological and/or psychosocial functioning, or predictors of CDS in individuals with chronic or complex medical conditions. Twenty-five studies were identified and retained. Fifteen of sixteen studies reported elevations in CDS symptoms, though findings were mixed in studies comparing mean differences to typically developing youth. Seven studies provided inconsistent evidence for CDS being associated with neuropsychological or academic functioning, with six studies demonstrating consistent effects on psychosocial functioning. Finally, nine studies identified biological and sociodemographic factors associated with CDS, though almost all await replication. CDS symptoms are significantly elevated in youth with medical conditions and appear to be particularly linked with psychosocial functioning. Future research is needed to identify prevalence of CDS across a range of medical conditions, examine associations with neuropsychological and psychosocial functioning, and examine whether CDS impacts self-management.

Examining bidirectional associations between sleep and behavior among children with attention-deficit/hyperactivity disorder.

Background: Children with attention-deficit/hyperactivity disorder (ADHD) have more sleep problems than their peers which contribute to behavioral and functional impairments. This study examines the bidirectional relationship between nightly sleep (i.e., total sleep time and sleep efficiency) and daily behavior of children with ADHD. Method: Forty-three children (ages 6-13 [mean = 9.05, 54% male, 77% medicated]) participated in a 2-week study during an ADHD Summer Treatment Program (STP). Sleep was measured with actigraphy. Behavior was assessed using STP clinical data and daily parent and counselor ratings of ADHD symptoms, oppositional defiant disorder behaviors, and emotion regulation (e.g., difficulty regulating emotional disposition and controlling emotions). We hypothesized that healthier night's sleep measured by actigraphy (i.e., sleep efficiency and total sleep time [TST]) would relate to less ADHD symptoms, less emotional dysregulation, and better academic performance the next day. Additionally, we hypothesized that less ADHD symptoms, less emotional dysregulation, and greater academic performance would relate to healthier sleep that night. Results: Higher nightly sleep efficiency was related to improved parent-ratings of ADHD the next day (R 2 = 0.04, p = 0.04) and improved parent-ratings of ADHD during the day lead to higher sleep efficiency that night (R 2 = 0.002, p = 0.02). Higher rates of daily assignment completion were related to higher sleep efficiency at night (R 2 = 0.035, p = 0.03). TST was not related to any behavioral outcomes. Conclusion: Sleep efficiency may be more relevant than TST to behavioral performance the next day. Additionally, a bidirectional relationship exists between sleep efficiency and parent ratings of ADHD. Findings highlight the importance of assessing for manifestations of poor sleep efficiency, waking minutes, and wakings after sleep onset when diagnosing and treating ADHD.

Post-infection treatment with the E protein inhibitor BIT225 reduces disease severity and increases survival of K18-hACE2 transgenic mice infected with a lethal dose of SARS-CoV-2.

The Coronavirus envelope (E) protein is a small structural protein with ion channel activity that plays an important role in virus assembly, budding, immunopathogenesis and disease severity. The viroporin E is also located in Golgi and ER membranes of infected cells and is associated with inflammasome activation and immune dysregulation. Here we evaluated in vitro antiviral activity, mechanism of action and in vivo efficacy of BIT225 for the treatment of SARS-CoV-2 infection. BIT225 showed broad-spectrum direct-acting antiviral activity against SARS-CoV-2 in Calu3 and Vero cells with similar potency across 6 different virus strains. BIT225 inhibited ion channel activity of E protein but did not inhibit endogenous currents or calcium-induced ion channel activity of TMEM16A in Xenopus oocytes. BIT225 administered by oral gavage for 12 days starting 12 hours before infection completely prevented body weight loss and mortality in SARS-CoV-2 infected K18 mice (100% survival, n = 12), while all vehicle-dosed animals reached a mortality endpoint by Day 9 across two studies (n = 12). When treatment started at 24 hours after infection, body weight loss, and mortality were also prevented (100% survival, n = 5), while 4 of 5 mice maintained and increased body weight and survived when treatment started 48 hours after infection. Treatment efficacy was dependent on BIT225 dose and was associated with significant reductions in lung viral load (3.5 log10), virus titer (4000 pfu/ml) and lung and serum cytokine levels. These results validate viroporin E as a viable antiviral target and support the clinical study of BIT225 for treatment and prophylaxis of SARS-CoV-2 infection.

Validation of the Farsi Version of the Adult Concentration Inventory for Assessing Cognitive Disengagement Syndrome.

The internal and external validity of cognitive disengagement syndrome (CDS) relative to attention-deficit/hyperactivity disorder-inattention (ADHD-IN) was evaluated herein with Farsi-speaking adults. A total of 837 Iranian adults assessed throughout the whole country (54.72% women, Mage = 23.85; SD = 7.05; age range = 18 to 58 years; 75% between 18 and 24 years old; reporting higher educational training) completed self-report measures of CDS, ADHD-IN, ADHD-hyperactivity/impulsivity (HI), depression, anxiety, and stress. Seven of the fifteen CDS symptoms showed a good convergent (high loadings on the CDS factor) and discriminant (higher loadings on the CDS factor than the ADHD-IN factor) validity. CDS also showed stronger first-order and unique associations with depression than ADHD-IN, whereas ADHD-IN showed stronger first-order and unique associations with ADHD-HI and anxiety than CDS. The first-order and unique associations of CDS and ADHD-IN did not differ in relation to stress. This study is the first to support the validity of the self-report of assessing CDS symptoms with the Adult Concentration Inventory with Farsi-speaking individuals residing in Iran, thus further strengthening the transcultural validity of the CDS, and paving the way for further transcultural research in the field of CDS among adults.