Pervasive environmental chemicals impair oligodendrocyte development.

Exposure to environmental chemicals can impair neurodevelopment, and oligodendrocytes may be particularly vulnerable, as their development extends from gestation into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocytes. Here, using a high-throughput developmental screen in cultured cells, we identified environmental chemicals in two classes that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, ubiquitous in disinfecting agents and personal care products, were potently and selectively cytotoxic to developing oligodendrocytes, whereas organophosphate flame retardants, commonly found in household items such as furniture and electronics, prematurely arrested oligodendrocyte maturation. Chemicals from each class impaired oligodendrocyte development postnatally in mice and in a human 3D organoid model of prenatal cortical development. Analysis of epidemiological data showed that adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified by our screen. This work identifies toxicological vulnerabilities for oligodendrocyte development and highlights the need for deeper scrutiny of these compounds' impacts on human health.

Predictors of Intraoperative Difficulty and Postoperative Examination Abnormalities in 164 Orbital Operations.

BACKGROUND: Although orbital fractures are common, prediction of outcomes in orbital surgery can be quite challenging. PURPOSE: We aim to identify predictors of intraoperative difficulty, operating time, and postoperative examination abnormalities in subjects undergoing post-traumatic orbital reconstructions. STUDY DESIGN, SETTING, AND SAMPLE: This is a retrospective cohort study of all consecutive orbital operations performed at a private, Level 1 trauma center in Portland, Oregon, USA over an 82-month period. All subjects that underwent exploration of the internal orbit for traumatic indications during the study period were included in the cohort. PREDICTOR VARIABLES: Four plating styles, surgical approach (transorbital vs transantral), days from injury to first surgery, fracture size (approximated as a rectangle using linear measurements from computed tomography scans), anteroposterior fracture position, and medial wall involvement were examined. OUTCOME VARIABLES: The primary outcome variable was intraoperative difficulty (defined as requiring revision after intraoperative imaging or return to the operating room). Secondary outcome variables included operating time and postoperative examination abnormalities. COVARIATES: Age and sex were included. ANALYSES: χ2 and Regression analyses were performed using a significance level of P < .05. RESULTS: One hundred and sixty four orbital operations were performed (90 isolated injuries and 74 combined orbital/midface injuries) on 155 subjects (73% male, mean age 39.8 years, standard deviation 16.7). In subjects with isolated orbital fractures, medial wall involvement was associated with intraoperative difficulty (P = .01). When using a transantral approach, intraoperative difficulty was more likely in more anterior fractures (P = .02). Plating style was associated with operating time (P = .03), with median times from 81 to 105 minutes (range 21 to 248 minutes). Postoperative examination abnormalities were more likely in the transorbital approach group (P = .01). Neither days to first surgery nor intraoperative difficulty were associated with postoperative examination abnormalities. Postoperative eyelid changes were seen in 13.6% of transorbital approaches and 0% of transantral approaches. Correction of gaze restriction and enophthalmos were more likely than correction of diplopia (P < .01). CONCLUSIONS AND RELEVANCE: Medial wall involvement is associated with intraoperative difficulty in orbital surgery. Anteriorly positioned fractures are better treated transorbitally, while posterior fractures may be amenable to transantral repair, thus avoiding risk of lower eyelid changes.

Therapy plans for therapeutic apheresis in Epic HealthLink.

BACKGROUND: A common required duty of pathology resident physicians while rotating on transfusion medicine is the medical oversight of the therapeutic apheresis service. A task often performed on this clinical medicine service is formulating and writing orders for therapeutic apheresis procedures. The EpicCare tool called the therapy plan provides unique advantages over a standard electronic order set for therapeutic apheresis. MATERIALS AND METHODS: Transfusion medicine physicians, apheresis nurses, pharmacists, and information technology professionals collaborated to create therapy plans for three therapeutic apheresis procedures: plasmapheresis, red cell exchange, and photopheresis. RESULTS: Therapy plans were implemented and have been well-received for several years. Over a six-year time period, a total of 613 therapy plans were created and signed. We speculate that this implementation may have increased both physician efficiency and patient safety. CONCLUSION: This article reports our experience using therapy plans in EpicCare in order to raise awareness of this tool and to serve as an encouragement for wider adoption.

Psychometric Properties of Attention Measures in Young Children with Neurofibromatosis Type 1: Preliminary Findings.

Children with neurofibromatosis type 1 (NF1) often demonstrate difficulties with attention and executive functioning that can be evident starting at a young age. There has been little research about which measures of attention are most suitable for use with young children with NF1. This pilot study explored several computerized measures of attention, a digits forward task, and parent report measures of attention to compare their reliability, validity, and the degree to which they capture attention difficulty in this population. Participants with NF1 ages 4 to 6 years were seen for one (n=2) or two (n=18) time points. Statistical analyses for evaluating evidence for test-retest reliability, convergent and discriminant validity, practice effects, and identification of difficulties were conducted. Each measure demonstrated relative strengths and weaknesses, and there may not be a "one size fits all" measure for use with young children with NF1. However, the Behavior Rating Inventory of Executive Function Preschool/Second Edition, Conners Early Childhood Inattention/Hyperactivity Scale, and the Conners Kiddie Continuous Performance Test Second Edition generally had the highest reliability and most evidence of validity. More specific recommendations are provided for the appropriate measure to use in clinical and research batteries.

Assessing individual patients' knowledge of benign versus malignant skin lesions in the dermatology clinic population.

Skin cancer education targeted to patients' needs is a goal of practicing dermatologists. Data regarding dermatology patients' baseline knowledge regarding skin cancer could aid clinicians in tailoring education efforts. Objective: To help quantify existing patients' existing visual recognition of skin cancer and common benign lesions, with the goal of helping to provide more targeted and meaningful education to patients. Methods: Two hundred forty-four adult patients from the dermatology clinics at University of Oklahoma and Loyola University Chicago were surveyed using digital images and questions regarding personal and family history of skin cancer, sun protection practices and sun protection knowledge. Results: Of the 244 subjects, 43% percent had a positive personal history of skin cancer, 40% had a positive family history. Scores differed minimally by personal history of skin cancer (p = .37) but differed more markedly by family history of skin cancer (p = .02). Limitations: Lack of generalizability to the general public, age range of subjects. Conclusions: There are knowledge gaps within the dermatology patient population regarding common benign and malignant skin lesions.

Patterns of performance of children with neurofibromatosis type 1 on the K-CPT and K-CPT 2.

Children with neurofibromatosis type 1 (NF1) often have attention difficulties with emerging evidence that these difficulties can be seen even in early childhood. This study aimed to explore the relative utility of two versions of a commonly used computerized attention measure for young children with NF1 and to explore relations with parent-reported attention in young children with NF1. Two independent samples of young children with NF1 participated. One sample (Study 1; N = 22; Mage = 4.95 (SD = 0.66)) completed the Conner's Kiddie Continuous Performance Test (K-CPT). A second and separate sample (Study 2; N = 19; Mage = 5.46 (SD = 0.74)) completed the K-CPT second edition (K-CPT 2). Relations of the K-CPT and K-CPT 2 with concurrent parent-reported attention (Kiddie Disruptive Behavior Disorder Schedule; Conners parent report questionnaires) were explored. The K-CPT sample's scores significantly differed from the normative median on Commissions, Hit Rate Standard Error, Variability, Detectability, Perseverations, and Hit Rate Inter Stimulus Interval. No relations with parent-report were identified. The K-CPT 2 sample's scores were significantly worse than normative data on every score except Hit Rate Block Change. Multiple scores on the K-CPT 2 were significantly related to parent-report of inattention and hyperactivity with some evidence of construct validity for the distinction between inattention and hyperactivity. The K-CPT 2 may be more useful for the assessment of attention problems in young children with NF1 as more challenges were observed and performance was more closely related to parent-reported attention difficulties than its predecessor the K-CPT.

A pilot study on predictors of length of stay in a geriatric psychiatric hospital.

BACKGROUND: We wanted to determine the factors that influence geriatric psychiatric hospitalization length of stay (LOS). METHODS: We conducted a retrospective cohort study of a sample of hospital admission records from 2012 to 2018. The hospital records were the geriatric inpatient records of St. John's Hospital, Springfield, Illinois. The data collection was based on the inclusion criteria as approved by the Southern Illinois University School of Medicine Institutional Review Board. To be eligible, participants had to have at least 1 inpatient hospitalization between 2012 and 2017. For the purposes of this study, psychiatric diagnosis was based on DSM-IV criteria. RESULTS: The 141 participants' average age was 71.7 years, and approximately 57% were female; average length of stay was 16 days (range: 1 to 116 days). Indications for current admission included depression and suicidal ideation (45%), psychosis (30%), psychosis and agitation (22%), and mania (3%). Results indicate that having a major depressive disorder (MDD) diagnosis (vs bipolar disorder and schizophrenia) was significantly associated with shorter LOS (P < .001). Other significant predictors were psychosis (P = .03), using mood stabilizers (P = .02), using antidepressants (P = .05), and use of ≥2 (vs 1 or 0) psychotropic medications (P = .02). CONCLUSIONS: Geriatric psychiatric hospitalization was longer in patients with psychosis, but shorter for patients with MDD. Patients receiving mood stabilizers, as well as those receiving ≥2 psychotropics, had longer LOS, while those receiving antidepressants had shorter LOS. This highlights the idea that patients with serious mental illnesses may have longer LOS.

Clinical Reasoning, Judgment, and Safe Medication Administration Practices in Senior Nursing Students.

BACKGROUND AND PURPOSE: Medication errors occur at alarming rates. Safe medication administration practices require more than observing patient safety rights and psychomotor skills. The purpose of this study was to explore the relationships between clinical judgment skills and reasoning processes and safe medication practices in senior nursing students. METHODS: Using a cross-sectional design, 29 students from 3 schools of nursing watched a video simulation of a nurse administering medications in a clinical setting. At predetermined times, reflections on the medication administration practices were journaled. Journals were scored for clinical reasoning processes and clinical judgment using the Clinical Judgment Rubric-Reflective Journal (CJR-RJ) and for medication administration best practices. RESULTS: Students scored low on the CJR-RJ (mean [SD], 5.2 [1.7]). We found a positive relationship between clinical judgment skills and safe medication practices (r = 0.39, t27 = 2.94, P = .018). The clinical reasoning process of Interpreting was a significant indicator of best practices (b = 1.4, t28 = 2.81, P = .010). CONCLUSION: Our findings suggest that students struggle to connect theory to practice, emphasizing the need to plan experiential learning opportunities for students to develop clinical reasoning, particularly in Interpreting, and judgment skills to prevent medication errors upon entry to practice.

Skin cancer discovery during total body skin examinations.

BACKGROUND: Patients presenting with a site-specific skin complaint may receive a total body skin examination (TBSE) or a more focused examination. A TBSE may be time-consuming but can potentially detect unsuspected or early stage skin cancers. The purpose of this study was to assess the detection of skin cancers associated with dermatologist-initiated TBSE performed immediately after a focused skin examination on the same patients. METHODS: The dermatology records of patients with biopsy-proven melanoma, basal cell carcinoma (BCC), or squamous cell carcinoma (SCC) during a 2-year period were reviewed. Generalized linear mixed-effects models were used to estimate the odds of a lesion being identified by a dermatologist (rather than the patient or the patient's primary health care provider). RESULTS: A total 1563 biopsy-proven cutaneous malignancies were found on 1010 patients. Of these, 797 cancers (51%) were first identified by a dermatologist on TBSE and 764 (48.9%) by the patient or the referring provider. Among tumors first identified by dermatologists (n = 797), 553 (69%) were BCCs, 220 (28%) were SCCs, and 24 (3%) were melanomas. The mean Breslow depth was 0.53 mm (standard deviation: 0.31 mm) for melanomas found on TBSE versus 1.04 mm (standard deviation: 1.68 mm) if identified by patients or referring providers. BCCs were more likely to be identified by a dermatologist during a TBSE (n = 553 [56%] vs. n = 434 [44%]; odds ratio: 1.79; p < .001). Tumors ultimately diagnosed as SCCs were more often identified by patients or patients' primary care providers (n = 302 [58%]; odds ratio: 0.56; p < .001). However, 220 otherwise undetected SCCs were found during dermatologist-performed TBSE. CONCLUSION: Dermatologist-performed TBSEs identified numerous cutaneous malignancies that might otherwise have remained undiagnosed. Early detection of melanoma or nonmelanoma skin cancer by TBSEs may spare patients significant morbidity and mortality.

Parent-Reported Social Skills in Children with Neurofibromatosis Type 1: Longitudinal Patterns and Relations with Attention and Cognitive Functioning.

OBJECTIVE: Social skills difficulties are commonly reported by parents and teachers of school age (SA) children with neurofibromatosis type 1 (NF1). Investigations of social skills of young children with NF1 are scarce. This study aimed to characterize the emergence of social skills challenges beginning in early childhood, examine social skills longitudinally into SA, and explore interrelations with attention-deficit hyperactivity disorder (ADHD) symptomatology and cognitive functioning among children with NF1 cross-sectionally and longitudinally. METHOD: Three samples of children with NF1 and their parents participated: (1) early childhood (n = 50; ages 3-6; mean [M] = 3.96, SD = 1.05), (2) SA (n = 40; ages 9-13; [M] = 10.90, SD = 1.59), and (3) both early childhood and SA (n = 25). Parent-reported social skills (Social Skills Rating System and Social Skills Improvement System), ADHD symptomatology (Conners Parent Rating Scales - Revised and Conners - Third Edition), and parent-reported cognitive abilities (Differential Ability Scales - Second Edition) were evaluated. RESULTS: Parental ratings of social skills were relatively stable throughout childhood. Ratings of social skills at the end of early childhood significantly predicted school-age social skills. Parental ratings of ADHD symptomatology showed significant negative relations with social skills. Early childhood inattentive symptoms predicted school-age social skills ratings. Cognitive functioning was not significantly related to social skills. CONCLUSION: Parent-reported social skills difficulties are evident during early childhood. This work adds to the literature by describing the frequency and stability of social skills challenges in early childhood and in the school-age period in NF1. Research about interventions to support social skills when difficulties are present is needed.

Recommendations for Measurement of Attention Outcomes in Preschoolers With Neurofibromatosis.

Children with neurofibromatosis type 1 (NF1) are at increased risk for attention problems. While most research has been conducted with school-aged cohorts, preschool-aged children offer a novel developmental window for clinical studies, with the promise that treatments implemented earlier in the developmental trajectory may most effectively modify risk for later difficulties. Designing research studies around the youngest children with NF1 can result in intervention earlier in the developmental cascade associated with NF1 gene abnormalities. Furthermore, clinical trials for medications targeting physical and psychological aspects of NF1 often include individuals spanning a wide age range, including preschool-aged children. In a prior report, the REiNS Neurocognitive Subcommittee made recommendations regarding performance-based and observer-rated measures of attention for use in clinical trials and highlighted the need for separate consideration of assessment methods for young children. The observer-rated Attention-Deficit/Hyperactivity Disorder Rating Scale-Preschool version is recommended as a primary outcome measure. The NIH Toolbox Flanker, Dimensional Change Card Sort, and List Sort Working Memory tasks and Digits Forward from the Differential Ability Scales-2nd Edition (performance-based measures) are recommended as secondary outcome measures. Specific methodologic recommendations for inclusion of preschoolers in clinical trials research are also offered.

Molecular Parallelism Underlies Convergent Highland Adaptation of Maize Landraces.

Convergent phenotypic evolution provides some of the strongest evidence for adaptation. However, the extent to which recurrent phenotypic adaptation has arisen via parallelism at the molecular level remains unresolved, as does the evolutionary origin of alleles underlying such adaptation. Here, we investigate genetic mechanisms of convergent highland adaptation in maize landrace populations and evaluate the genetic sources of recurrently selected alleles. Population branch excess statistics reveal substantial evidence of parallel adaptation at the level of individual single-nucleotide polymorphism (SNPs), genes, and pathways in four independent highland maize populations. The majority of convergently selected SNPs originated via migration from a single population, most likely in the Mesoamerican highlands, while standing variation introduced by ancient gene flow was also a contributor. Polygenic adaptation analyses of quantitative traits reveal that alleles affecting flowering time are significantly associated with elevation, indicating the flowering time pathway was targeted by highland adaptation. In addition, repeatedly selected genes were significantly enriched in the flowering time pathway, indicating their significance in adapting to highland conditions. Overall, our study system represents a promising model to study convergent evolution in plants with potential applications to crop adaptation across environmental gradients.

The timing of human adaptation from Neanderthal introgression.

Admixture has the potential to facilitate adaptation by providing alleles that are immediately adaptive in a new environment or by simply increasing the long-term reservoir of genetic diversity for future adaptation. A growing number of cases of adaptive introgression are being identified in species across the tree of life, however the timing of selection, and therefore the importance of the different evolutionary roles of admixture, is typically unknown. Here, we investigate the spatio-temporal history of selection favoring Neanderthal-introgressed alleles in modern human populations. Using both ancient and present-day samples of modern humans, we integrate the known demographic history of populations, namely population divergence and migration, with tests for selection. We model how a sweep placed along different branches of an admixture graph acts to modify the variance and covariance in neutral allele frequencies among populations at linked loci. Using a method based on this model of allele frequencies, we study previously identified cases of adaptive Neanderthal introgression. From these, we identify cases in which Neanderthal-introgressed alleles were quickly beneficial and other cases in which they persisted at low frequency for some time. For some of the alleles that persisted at low frequency, we show that selection likely independently favored them later on in geographically separated populations. Our work highlights how admixture with ancient hominins has contributed to modern human adaptation and contextualizes observed levels of Neanderthal ancestry in present-day and ancient samples.

The Lasater Clinical Judgment Rubric: Implications for Evaluating Teaching Effectiveness.

BACKGROUND: Concern with patient safety necessitates valid and reliable measures to evaluate clinical judgment. The purpose of this article is to describe how the Lasater Clinical Judgment Rubric (LCJR) has been used to evaluate the effectiveness of educational interventions to promote clinical judgment and its psychometric properties. METHOD: Search terms included nurse, student, clinical judgment, and Lasater Clinical Judgment Rubric in Scopus, ERIC, and CINAHL with EBSCOhost databases. The final review included 20 studies. RESULTS: Researchers reported alphas for total scales as .80 to .97, subscales as .89 to .93, and students' self-scored as .81 to .82. Themes were: Individual Versus Group Evaluations, Clinical Judgment Scenarios, and Adaptation for Nonobservation Activities. CONCLUSION: Results of this review indicate that the LCJR can be used to evaluate clinical judgment, but educators need to consider inter- and intrarater reliability, individual versus group evaluation, clinical judgment scenarios, and adapting the rubric for nondirect observation activities. [J Nurs Educ. 2021;60(2):67-73.].

Surgical training tools for dermatology trainees: porcine vs. synthetic skin for excision and repair.

Since dermatologists routinely perform surgery in an outpatient setting, ensuring that dermatology trainees are provided with opportunities to develop sufficient proficiency in excisional surgery and suture technique is paramount. The objectives of this study are to assess trainee preference for silicone-based synthetic skin compared with porcine skin as a surgical training medium and to assess the ability of trainees to successfully demonstrate basic surgical skills using the simulated skin model. Participants were a convenience sample of dermatology residents from the greater Chicago area, who were asked to perform an elliptical excision and bilayered repair on a silicone-based synthetic skin model. Residents were then surveyed regarding their satisfaction with the model. Four blinded dermatologist raters evaluated digital photographs obtained during the performance of the procedures and graded the execution of each maneuver using a surgical task checklist. Nineteen residents were enrolled. Residents were more likely to prefer pig skin to simulated skin for overall use (p = 0.040) and tissue repair (p = 0.018), but the nominal preference for tissue handling was nonsignificant (p = 0.086). There was no significant difference between satisfaction with pig skin versus synthetic skin with regard to excision experience (p = 0.82). The majority of residents (10/19) performed all surgical checklist tasks correctly. Of those residents who did not perform all steps correctly, many had difficulty obtaining adequate dermal eversion and wound approximation. Synthetic skin may be conveniently and safely utilized for hands-on surgical practice. Further refinement may be necessary to make synthetic skin comparable in feel and use to animal skin.