Comparisons of intellectual performance among children with psychiatric disorders

The intellectual performances of children with a variety of psychiatric disorders were examined and compared with the findings from a similar study by Hodges and Plow (1990). Mean IQ scores were in the average range for both study samples, and no significant differences were found in WISC-R summary scores. Nevertheless, the Hodges and Plow findings were only partially corroborated. They observed, for instance, a relative deficit in verbal abilities for conduct-disordered children and lower IQ scores for children with anxiety disorders vs. children with all other disorders. Our replication study found no significant differences among the disorder groups for any of the scores examined. Possible explanations for the divergence in findings are discussed.     

Validation of LittlEARS® Early Speech Production Questionnaire in Arabic-speaking children with normal hearing

Objectives:To validate an Arabic version of the LittlEARS^® Early Speech Production Questionnaire (LEESPQ), which assesses the early development of speech and language in infants between 0 and 18 months, in Arabic-speaking children with normal hearing in Saudi Arabia.Methods:This is a cross-sectional study conducted in the city of Riyadh, Saudi Arabia between September and December 2020. Parents completed the LEESPQ regarding their child’s speech production development. To assess the ability of normal hearing children aged 0-18 months in developing speech and language production, a norm curve has been generated based on the standardized values that were calculated from the Arabic normal-hearing data set.Results:A total of 198 questionnaires were analyzed. The total score on the LEESPQ correlated with age, gender, and bilingualism. A norm curve for early speech production in children with normal hearing was created.Conclusion:The Arabic version of LEESPQ appears to be a valid questionnaire that can be used in the assessment of early language and speech development of Arabic-speaking children with normal hearing in the age range of 0-18 months. The Arabic version of the LEESPQ might also be a useful tool to detect developmental delays and hearing disorders in young children.     

Factors Associated with Physician Tolerance of Uncertainty: an Observational Study

BackgroundPhysicians need to learn and work amidst a plethora of uncertainties, which may drive burnout. Understanding differences in tolerance of uncertainty is an important research area.ObjectiveTo examine factors associated with tolerance of uncertainty, including well-being metrics such as burnout.DesignOnline confidential survey.SettingThe Massachusetts General Physicians Organization (MGPO).ParticipantsAll 2172 clinically active faculty in the MGPO.Main MeasuresWe examined associations for tolerance of uncertainty with demographic information, personal and professional characteristics, and physician well-being metrics.Key ResultsTwo thousand twenty (93%) physicians responded. Multivariable analyses identified significant associations of lower tolerance of uncertainty with female gender (OR, 1.23; 95% CI, 1.03–1.48); primary care practice (OR, 1.56; 95% CI, 1.22–2.00); years since training (OR, 0.99; 95% CI, 0.98–0.995); and lacking a trusted advisor (OR, 1.25; 95% CI, 1.03–1.53). Adjusting for demographic and professional characteristics, physicians with low tolerance of uncertainty had higher likelihood of being burned-out (OR, 3.06; 95% CI, 2.41–3.88), were less likely to be satisfied with career (OR, 0.37; 95% CI, 0.26–0.52), and less likely to be engaged at work (RR, 0.87; 95% CI, 0.84–0.90).ConclusionAt a time when concern about physician well-being is high, with much speculation about causes of burnout, we found a strong relationship between tolerance of uncertainty and physician well-being, across specialties. Particular attention likely needs to be paid to those with less experience, those in specialties with high rates of undifferentiated illness and uncertainty, such as primary care, and ensuring all physicians have access to a trusted advisor. These results generate the potential hypothesis that efforts focused in understanding and embracing uncertainty could be potentially effective for reducing burnout. This concept should be tested in prospective trials.KEY WORDS: uncertainty, burnout, well-being, faculty development, continuing medical education     

Copper oxide integrated perylene diimide self-assembled graphitic pencil for robust non-enzymatic dopamine detection

Exploring a robust, extremely sensitive, cost-effective and reliable assay platform for the precise analysis of dopamine (DA) has become a big challenge predominantly at the clinical level. To participate in this quest, herein, we fabricated a perylene diimide (PDI) self-assembled graphitic surface of the graphitic pencil electrode (GPE) anchored copper oxide (CuO). The self-assembled N-rich PDI led to the fast movement of ions by decreasing the bandgap and improved the electron transport kinetics with more exposed catalytic active sites, thus resulting in the robust electrochemical sensing of DA. The designed sensor exhibited good sensitivity (4 μM⁻¹ cm⁻²), high structural stability, repeatability and excellent reproducibility with an RSD value of 2.9%. Moreover, the developed system showed a wide linear range (5 μM to 500 μM) and reliable selectivity even in the presence of co-existing interferants, such as ascorbic acid and uric acid. The fabricated nanohybrid was eventually employed to analyze DA in spiked physiological fluids and provided satisfactory recoveries. The designed PDI-CuO based interface also showed a very low detection limit of 6 nM (S/N = 3), consequently confirming its suitability for clinical and biological applications.

Exploring a robust, extremely sensitive, cost-effective and reliable assay platform for the precise analysis of dopamine (DA) has become a big challenge predominantly at the clinical level.     

In silico identification of potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations

In the present era, there are many efforts trying to face the emerging and successive waves of the COVID-19 pandemic. This has led to considering new and unusual targets for SARS CoV-2. 2′-O-Methyltransferase (nsp16) is a key and attractive target in the SARS CoV-2 life cycle since it is responsible for the viral RNA protection via a cap formation process. In this study, we propose a new potential inhibitor for SARS COV-2 2′-O-methyltransferase (nsp16). A fragment library was screened against the co-crystal structure of the SARS COV-2 2′-O-methyltransferase complexed with Sinefungin (nsp16 – PDB ID: 6WKQ), and consequently the best proposed fragments were linked via a de novo approach to build molecule AP-20. Molecule AP-20 displayed a superior docking score to Sinefungin and reproduced the key interactions in the binding site of 2′-O-methyltransferase. Three molecular dynamic simulations of the 2′-O-methyltransferase apo structure and its complexed forms with AP-20 and Sinefungin were performed for 150 nano-seconds to provide insights on the dynamic nature of such setups and to assess the stability of the proposed AP-20/enzyme complex. AP-20/enzyme complex demonstrated better stability for the ligand–enzyme complex compared to Sinefungin in a respective setup. Furthermore, MM-PBSA binding free energy calculations showed a better profile for AP-20/enzyme complex compared to Sinefungin/enzyme complex emphasizing the potential inhibitory effect of AP-20 on SARS COV-2 2′-O-methyltransferase. We endorse our designed molecule AP-20 to be further explored via experimental evaluations to confront the spread of the emerging COVID-19. Also, in silico ADME profiling has ascribed to AP-20 an excellent safety and metabolic stability profile.

The identification of AP-20 as a potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations.     

Comparative metabolomics analysis of bronchial epithelium during barrier establishment after allergen exposure

BackgroundSeveral studies have shown a correlation between an altered metabolome and respiratory allergies. The epithelial barrier hypothesis proposes that an epithelial barrier dysfunction can result in allergic diseases development. Der p 1 allergen from house dust mite is a renowned epithelial barrier disruptor and allergy initiator due to its cysteine‐protease activity. Here, we compared the metabolic profile of the bronchial epithelium exposed or not to Der p 1 during barrier establishment to understand its active role in allergy development.MethodsCalu‐3 cells were cultivated in air‐liquid interface cultures and exposed to either Der p 1 or Ole e 1 allergens during barrier establishment. The comparative metabolomics analysis of apical and basolateral media were performed using liquid chromatography and capillary electrophoresis both coupled to mass spectrometry.ResultsWe showed that epithelial barrier disruption by Der p 1 was associated with a specific metabolic profile, which was highly dependent on the state of the epithelium at the time of contact. Moreover, an apical‐basolateral distribution of the metabolites was also observed, indicating a compartmentalization of the response with differential metabolic patterns. A number of metabolites were changed by Der p 1, mainly related to amino acids metabolism, such as L‐arginine, L‐kynurenine and L‐methionine.ConclusionThis work is the first report on the metabolic response in human bronchial epithelial cells associated with cysteine‐protease Der p 1 activity, which could contribute to allergy development. Moreover, it supports a reformulated epithelial barrier hypothesis that might help to explain allergies and their increasing prevalence.     

Coronavirus Disease Case Definitions,Diagnostic Testing Criteria,and Surveillance in 25 Countries with Highest Reported Case Counts

We compared case definitions for suspected, probable, and confirmed coronavirus disease (COVID-19), as well as diagnostic testing criteria, used in the 25 countries with the highest reported case counts as of October 1, 2020. Of the identified countries, 56% followed World Health Organization (WHO) recommendations for using a combination of clinical and epidemiologic criteria as part of the suspected case definition. A total of 75% of identified countries followed WHO recommendations on using clinical, epidemiologic, and diagnostic criteria for probable cases; 72% followed WHO recommendations to use PCR testing to confirm COVID-19. Finally, 64% of countries used testing eligibility criteria at least as permissive as WHO. We observed marked heterogeneity in testing eligibility requirements and in how countries define a COVID-19 case. This heterogeneity affects the ability to compare case counts, transmission, and vaccine effectiveness, as well as estimates derived from case surveillance data across countries.     

Interventions on Microbiota: Where Do We Stand on a Gut–Brain Link in Autism? A Systematic Review

The alteration of the microbiota–gut–brain axis has been recently recognized as a critical modulator of neuropsychiatric health and a possible factor in the etiopathogenesis of autism spectrum disorders (ASD). This systematic review offers practitioners an overview of the potential therapeutic options to modify dysbiosis, GI symptoms, and ASD severity by modulating the microbiota–gut–brain axis in ASD, taking into consideration limits and benefits from current findings. Comprehensive searches of PubMed, Scopus, the Web of Science Core Collection, and EMBASE were performed from 2000 to 2021, crossing terms referred to ASD and treatments acting on the microbiota–gut–brain axis. A total of 1769 publications were identified, of which 19 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Despite the encouraging findings, considering the variability of the treatments, the samples size, the duration of treatment, and the tools used to evaluate the outcome of the examined trials, these results are still partial. They do not allow to establish a conclusive beneficial effect of probiotics and other interventions on the symptoms of ASD. In particular, the optimal species, subspecies, and dosages have yet to be identified. Considering the heterogeneity of ASD, double-blind, randomized, controlled trials and treatment tailored to ASD characteristics and host-microbiota are recommended.     

Viewpoints among experts and the public in the Netherlands on including a lifestyle criterion in the healthcare priority setting

ContextIt remains unclear whether there would be societal support for a lifestyle criterion for the healthcare priority setting. This study examines the viewpoints of experts in healthcare and the public regarding support for a lifestyle‐related decision criterion, relative to support for the currently applied criteria, in the healthcare priority setting in the Netherlands.MethodsWe conducted a Q methodology study in samples of experts in healthcare (n = 37) and the public (n = 44). Participants (total sample N = 81) ranked 34 statements that reflected currently applied decision criteria as well as a lifestyle criterion for setting priorities in healthcare. The ranking data were subjected to principal component analysis, followed by oblimin rotation, to identify clusters of participants with similar viewpoints.FindingsWe identified four viewpoints. Participants with Viewpoint 1 believe that treatments that have been proven to be effective should be reimbursed. Those with Viewpoint 2 believe that life is precious and every effort should be made to save a life, even when treatment still results in a very poor state of health. Those with Viewpoint 3 accept government intervention in unhealthy lifestyles and believe that individual responsibility should be taken into account in reimbursement decisions. Participants with Viewpoint 4 attribute importance to the cost‐effectiveness of treatments; however, when priorities have to be set, treatment effects are considered most important. All viewpoints were supported by a mix of public and experts, but Viewpoint 1 was mostly supported by experts and the other viewpoints were mostly supported by members of the public.ConclusionsThis study identified four distinct viewpoints on the healthcare priority setting in the Netherlands, each supported by a mix of experts and members of the public. There seems to be some, but limited, support for a lifestyle criterion—in particular, among members of the public. Experts seem to favour the decision criteria that are currently applied. The diversity in views deserves attention when policymakers want to adhere to societal preferences and increase policy acceptance.