Direct and indirect effects of and preferences for feedback during the Good Behavior Game in elementary classes.

The Good Behavior Game (GBG) is an effective procedure for reducing disruptive classroom behavior. Students in three fifth-grade classes selected the rules of the GBG and then experienced the GBG with different forms of feedback for rule violations (vocal and visual, vocal only, visual only, no feedback). Following an initial baseline, the four feedback versions of the GBG and a baseline condition were alternated across sessions in a multielement design. All versions of the GBG substantially reduced disruptive behavior below baseline levels. Additionally, in one of the three classes losing the GBG produced an increase in negative peer interactions immediately following the GBG. Following the multielement comparison, we implemented a group-arrangement concurrent-chains preference assessment in which students selected one of the conditions to experience each day. The most selected condition across all classes was the GBG condition, which included both vocal and visual feedback.

Family planning needs of young adults with sickle cell disease.

Sexual and reproductive healthcare standards for adolescents and young adults with sickle cell disease (SCD) are not established. A total of 50 young adults entering adult SCD care completed a Family Planning Survey assessing sexual and reproductive health needs from March 2019 to July 2020. Clinical data were abstracted from respondents' electronic medical records. Linear and logistic regression was applied to explore associations between clinical characteristics and survey results. Few respondents (8%) wished to be pregnant in the coming year, and 46% answered yes to at least one of four needs assessment questions. Those who were not employed full time were more likely to endorse needing help with getting sickle cell trait testing for a partner (ORadj = 9.59, p-value = 0.05). Contraceptive use was associated with having an obstetrician-gynecologist (OR = 6.8, p-value = 0.01). Young adults with SCD entering adult care have diverse reproductive health needs, highlighting opportunities to provide multidisciplinary, SCD-specific reproductive healthcare.

Effects of and preference for student- and teacher-implemented good behavior game in early elementary classes.

Disruptive behavior during instruction is a common problem in elementary classrooms. One intervention to reduce disruptive behavior is the Good Behavior Game (GBG). In this study, the students of 2 early elementary classrooms experienced 3 versions of the GBG: experimenter-implemented, teacher-implemented, and student-implemented. The effects of the GBG on disruptive behavior and peer interactions were evaluated using a combined reversal and multielement design. Student preference for conditions was assessed via a group arrangement of a concurrent-chains preference assessment. All versions of the game reduced disruptive behavior compared to baseline, but the rate of disruptive behavior was slightly higher during the teacher-implemented sessions in Class 1. Few peer interactions occurred during the game; however, negative interactions increased slightly in both classes during the GBG. Students overwhelmingly preferred the student-implemented version of the game. This study provides support for student implementation of the GBG and offers an approach to student shared governance in the classroom.

The Montreal cognitive assessment as a cognitive screening tool in sickle cell disease: Associations with clinically significant cognitive domains.

Adults with sickle cell disease (SCD) are at risk for cognitive impairment, which causes significant morbidity. Guidelines support routine cognitive screening, but no screening test is validated in this population. We explored the Montreal Cognitive Assessment (MoCA) as a possible screening test in SCD. We administered the MoCA; a literacy test, the Wide Range Achievement Test, fourth edition (WRAT-4); and a health literacy test, the Shortened Test of Functional Health Literacy in Adults (S-TOFHLA) to adults with SCD and gathered clinical variables through chart review. Spearman's rho, Mann-Whitney, and Kruskal-Wallis tests and quantile regression models were used. Among our sample of 49 adults with SCD, the median MoCA score was 25.0 [interquartile range (IQR) 22.0-28.0]. Higher educational attainment was associated with MoCA scores (p = 0.001). In multivariable models, MoCA scores were associated with S-TOFHLA (p = 0.001) and WRAT-4 Reading (p = 0.002) scores, and overt stroke (p = 0.03) at the median. This pilot study adds to the limited literature of cognitive screening tests in adults with SCD and demonstrates a relationship between MoCA scores and measures of literacy and health literacy. The MoCA is a promising option for briefly screening for cognitive impairment in adults with SCD, though further study is needed to confirm its validity.

Post-sequelae symptoms and comorbidities after COVID-19.

The frequency, severity, and forms of symptoms months after coronavirus 2019 (COVID-19) are poorly understood, especially in community settings. To better understand and characterize symptoms months after community-based COVID-19, a retrospective cohort analysis was conducted. Three hundred and twenty-eight consecutive persons with a positive test for SARS-CoV-2 in the Johns Hopkins Health System, Maryland, March-May 2020, were selected for the study. Symptom occurrence and severity were measured through questionnaires. Of 328 persons evaluated, a median of 242 days (109-478 days) from the initial positive SARS-CoV-2 test, 33.2% reported not being fully recovered and 4.9% reported symptoms that constrained daily activities. Compared to those who reported being fully recovered, those with post-acute sequelae were more likely to report a prior history of heart attack (p < 0.01). Among those reporting long-term symptoms, men and women were equally represented (men = 34.8%, women = 34.6%), but only women reported symptoms that constrained daily activities, and 56% of them were caregivers. The types of new or persistent symptoms varied, and for many, included a deviation from prior COVID-19 health, such as being less able to exercise, walk, concentrate, or breathe. A limitation is that self-report of symptoms might be biased and/or caused by factors other than COVID-19. Overall, even in a community setting, symptoms may persist months after COVID-19 reducing daily activities including caring for dependents.

System Level Informatics to Improve Triage Practices for Sickle Cell Disease Vaso-Occlusive Crisis: A Cluster Randomized Controlled Trial.

BACKGROUND: National Heart Lung and Blood Institute guidelines for the treatment of vaso-occlusive crisis among people with sickle cell disease in the emergency department recommend assigning an emergency severity index of 2 at triage. However, patients with sickle cell disease often do not receive guideline-concordant care at triage. To address this gap, a decision support tool was developed, in the form of a text banner on the triage page in the electronic health record system, visible to triage nurses. METHODS: A prospective quality improvement initiative was designed where the emergency severity index clinical decision support tool was deployed to a stratified random sample of emergency department triage nurses to receive the banner (n = 24) or not to receive the banner (n = 27), reminding them to assign the patient to emergency severity index category 2. The acceptability of the emergency severity index clinical decision support tool was evaluated with the Ottawa Acceptability of Decision Rules Instrument. Descriptive and bivariate (chi-square test) statistics were used to characterize the study's primary outcome, proportion of visits assigned an emergency severity index of 2 or higher. A generalized linear mixed model with clustering at the level of the triage nurse was performed to test the association between the banner intervention and triage practices. RESULTS: A total of 384 ED visits were included for analysis. Before study initiation, the percentage of sickle cell disease patients' visits with the proper emergency severity index assignment at triage was 37.04%. After initiation, the proportion of sickle cell disease patients' visits with an emergency severity index of 2 or higher triaged by nurses in the intervention group was markedly higher in the intervention group than in the control group (64.95% vs 35.05%; χ2 = 8.79, P ≤ .003). Accounting for clustering by nurse, the odds ratio for proper triage emergency severity index assignment was 3.22 (95% confidence interval 1.17-8.85; P ≤ .02) for the intervention versus control. Surveyed triage nurses reported the emergency severity index clinical decision support tool to be moderately acceptable (nurses' mean Ottawa Acceptability of Decision Rules Instrument scores ranged from 4.13 to 4.90 on the 6-point scale; n = 11). There were no differences in ED experience outcomes including time to first analgesic or length of stay between the control and intervention groups. CONCLUSION: Substantial improvements in triage guideline concordance were achieved and sustained without direct nursing education.

Delirium Prevention, Detection, and Treatment in Emergency Medicine Settings: A Geriatric Emergency Care Applied Research (GEAR) Network Scoping Review and Consensus Statement.

BACKGROUND: Older adult delirium is often unrecognized in the emergency department (ED), yet the most compelling research questions to overcome knowledge-to-practice deficits remain undefined. The Geriatric Emergency care Applied Research (GEAR) Network was organized to identify and prioritize delirium clinical questions. METHODS: GEAR identified and engaged 49 transdisciplinary stakeholders including emergency physicians, geriatricians, nurses, social workers, pharmacists, and patient advocates. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews, clinical questions were derived, medical librarian electronic searches were conducted, and applicable research evidence was synthesized for ED delirium detection, prevention, and management. The scoping review served as the foundation for a consensus conference to identify the highest priority research foci. RESULTS: In the scoping review, 27 delirium detection "instruments" were described in 48 ED studies and used variable criterion standards with the result of delirium prevalence ranging from 6% to 38%. Clinician gestalt was the most common "instrument" evaluated with sensitivity ranging from 0% to 81% and specificity from 65% to 100%. For delirium management, 15 relevant studies were identified, including one randomized controlled trial. Some intervention studies targeted clinicians via education and others used clinical pathways. Three medications were evaluated to reduce or prevent ED delirium. No intervention consistently prevented or treated delirium. After reviewing the scoping review results, the GEAR stakeholders identified ED delirium prevention interventions not reliant on additional nurse or physician effort as the highest priority research. CONCLUSIONS: Transdisciplinary stakeholders prioritize ED delirium prevention studies that are not reliant on health care worker tasks instead of alternative research directions such as defining etiologic delirium phenotypes to target prevention or intervention strategies.

A Survey-Based Needs Assessment of Barriers to Optimal Sickle Cell Disease Care in the Emergency Department.

STUDY OBJECTIVE: Guided by an implementation science framework, this needs assessment identifies institutional-, provider-, and patient-level barriers to care of sickle cell disease (SCD) in the emergency department (ED) to inform future interventions conducted by the multicenter Sickle Cell Disease Implementation Consortium. METHODS: The consortium developed and implemented a validated needs assessment survey administered to a cross-sectional convenience sample of patients with SCD and ED providers caring for them. In total, 516 adolescents and adults with SCD and 243 ED providers from 7 and 5 regions of the United States, respectively, responded to the ED care delivery for SCD survey. RESULTS: Survey results demonstrated that 84.5% of respondents with SCD have an outpatient provider who treats many patients with SCD. In the ED, 54.3% reported not receiving care fast enough and 46.0% believed physicians did not care about them and believed similarly of nurses (34.9%). Consequently, 48.6% of respondents were "never" or "sometimes" satisfied with their ED care. Of surveyed ED providers, 75.1% were unaware of the National Heart, Lung, and Blood Institute recommendations for vaso-occlusive crises, yet 98.1% were confident in their knowledge about caring for patients with SCD. ED providers identified the following factors as barriers to care administration: opioid epidemic (62.1%), patient behavior (60.9%), crowding (58.0%), concern about addiction (47.3%), and implicit bias (37.0%). CONCLUSION: The results underscore that many patients with SCD are dissatisfied with their ED care and highlight challenges to optimal care on the practice, provider, and patient levels. Exploring these differences may facilitate improvements in ED care.

Publication of data collection forms from NHLBI funded sickle cell disease implementation consortium (SCDIC) registry.

BACKGROUND: Sickle cell disease (SCD) is an autosomal recessive blood disorder affecting approximately 100,000 Americans and 3.1 million people globally. The scarcity of relevant knowledge and experience with rare diseases creates a unique need for cooperation and infrastructure to overcome challenges in translating basic research advances into clinical advances. Despite registry initiatives in SCD, the unavailability of descriptions of the selection process and copies of final data collection tools, coupled with incomplete representation of the SCD population hampers further research progress. This manuscript describes the SCDIC (Sickle Cell Disease Implementation Consortium) Registry development and makes the SCDIC Registry baseline and first follow-up data collection forms available for other SCD research efforts. RESULTS: Study data on 2400 enrolled patients across eight sites was stored and managed using Research Electronic Data Capture (REDCap). Standardized data collection instruments, recruitment and enrollment were refined through consensus of consortium sites. Data points included measures taken from a variety of validated sources (PHENX, PROMIS and others). Surveys were directly administered by research staff and longitudinal follow-up was coordinated through the DCC. Appended registry forms track medical records, event-related patient invalidation, pregnancy, lab reporting, cardiopulmonary and renal functions. CONCLUSIONS: The SCDIC Registry strives to provide an accurate, updated characterization of the adult and adolescent SCD population as well as standardized, validated data collecting tools to guide evidence-based research and practice.

Hospital Admissions, Mortality and Comorbidities Among New York State Sickle Cell Patients, 2005-2013.

Analyses of administrative and large data sources in Sickle Cell Disease (SCD) can answer questions not suitable for prospective study but have been hampered by lack of validated methods to adjust for individual comorbidities and lack of baseline utilization data over time. We sought to develop a database to characterize inpatient SCD care across New York State and generate a re-weighted sickle-cell specific Charlson Comorbidity index (S-CCI) for use in future large data SCD research. We identified 18,541 individual SCD patients admitted to New York State hospitals between 2005 and 2013 from the SPARCS database. We present data from both a randomly selected derivation cohort, used to develop the S-CCI and a validation cohort, The S-CCI resulted in small improvements in model fit and discrimination while using fewer covariates, allowing a more parsimonious model. Despite being the most common comorbidity, chronic pulmonary disease was not predictive of mortality. Mortality per hospitalization was 0.61%. Many patients (32%) were admitted only once during the nine year period. However, the majority was admitted more frequently with over 15% of patients being admitted more than once per year.

Copper(II)- and palladium(II)-catalyzed enantioselective Claisen rearrangement of allyloxy- and propargyloxy-indoles to quaternary oxindoles and spirocyclic lactones.

In this Article, a strategy to obtain highly enantioselective catalysts for the Claisen rearrangement of allyloxy- and propargyloxy-indoles is outlined. Ultimately, copper BOX and palladium BINAP or PHOX catalysts were discovered as superior in catalyzing Claisen rearrangements of allyloxy- or proparyloxy-substituted indoles to generate oxindoles bearing allyl- or allenyl-substituted quaternary centers. This method proved to be tolerant of a broad range of functional groups. Tandem reactions of the silyl-allene products provide rapid access to a variety of spirocyclic oxindoles in one operation.

RhoE is regulated by cyclic AMP and promotes fusion of human BeWo choriocarcinoma cells.

Fusion of placental villous cytotrophoblasts with the overlying syncytiotrophoblast is essential for the maintenance of successful pregnancy, and disturbances in this process have been implicated in pathological conditions such as pre-eclampsia and intra-uterine growth retardation. In this study we examined the role of the Rho GTPase family member RhoE in trophoblast differentiation and fusion using the BeWo choriocarcinoma cell line, a model of villous cytotrophoblast fusion. Treatment of BeWo cells with the cell permeable cyclic AMP analogue dibutyryl cyclic AMP (dbcAMP) resulted in a strong upregulation of RhoE at 24 h, coinciding with the onset of fusion. Using the protein kinase A (PKA)-specific cAMP analogue N(6)-phenyl-cAMP, and a specific inhibitor of PKA (14-22 amide, PKI), we found that upregulation of RhoE by cAMP was mediated through activation of PKA signalling. Silencing of RhoE expression by RNA interference resulted in a significant decrease in dbcAMP-induced fusion. However, expression of differentiation markers human chorionic gonadotrophin and placental alkaline phosphatase was unaffected by RhoE silencing. Finally, we found that RhoE upregulation by dbcAMP was significantly reduced under hypoxic conditions in which cell fusion is impaired. These results show that induction of RhoE by cAMP is mediated through PKA and promotes BeWo cell fusion but has no effect on functional differentiation, supporting evidence that these two processes may be controlled by separate or diverging pathways.

Downregulation of caveolin-1 enhances fusion of human BeWo choriocarcinoma cells.

BACKGROUND: Fusion of placental villous cytotrophoblasts with the overlying syncytiotrophoblast is essential for the maintenance of successful pregnancy, and disturbances in this process have been implicated in pathological conditions such as pre-eclampsia and intra-uterine growth retardation. Caveolin-1 has been shown to be expressed in human villous cytotrophoblast and to be downregulated during fusion into syncytiotrophoblast but it is unclear whether it plays a role in this process. METHODOLOGY/PRINCIPAL FINDINGS: We used RNA interference to determine whether caveolin-1 plays a role in differentiation and fusion in the BeWo choriocarcinoma cell line, a model of villous cytotrophoblast fusion. Assessment of cell fusion by desmosomal protein immunostaining revealed that cells transfected with caveolin-1 siRNA showed significantly enhanced fusion in response to treatment with dibutyryl cyclic AMP compared with cells transfected with a non-silencing control. Furthermore, caveolin-1 knockdown alone was sufficient to promote spontaneous fusion. In addition, biochemical differentiation, assessed by expression of placental alkaline phosphatase, was upregulated in caveolin-1 siRNA-transfected cells, with or without dbcAMP treatment. Assessment of Akt phosphorylation showed that caveolin-1 knockdown resulted in a significant reduction in phosphorylation at Thr(308). CONCLUSIONS/SIGNIFICANCE: Taken together, these results suggest that caveolin-1 regulates BeWo cell differentiation and fusion, possibly through a mechanism involving modulation of Akt activity.

Total synthesis of chiral biaryl natural products by asymmetric biaryl coupling.

This tutorial review highlights the use of catalytic asymmetric 2-naphthol couplings in total synthesis. The types of chirality, chiral biaryl natural products, prior approaches to chiral biaryl natural products, and other catalytic asymmetric biaryl couplings are outlined. The three main categories of chiral catalysts for 2-naphthol coupling (Cu, V, Fe) are described with discussion of their limitations and advantages. Applications of the copper catalyzed couplings in biomimetic syntheses are discussed including nigerone, hypocrellin, calphostin D, phleichrome, and cercosporin.

Design of a bisamidinium claisen rearrangement catalyst for monodentate substrates.

A bisamidinium catalyst has been designed for the Claisen rearrangement. The primary design feature is a dual hydrogen bonding array that can coordinate a singular oxygen atom of the substrate. The ability to function as a dual hydrogen donor is key as the bisamidinium accelerates the Claisen rearrangement to a greater extent than Brønsted acids with lower pK(a) values.

Catalytic enantioselective Meerwein-Eschenmoser Claisen rearrangement: asymmetric synthesis of allyl oxindoles.

The first catalytic, enantioselective Meerwein-Eschenmoser Claisen rearrangement has been achieved. Palladium(II) BINAP or phosphinooxazoline catalysts were employed to generate oxindole products with 100% conversion and up to 92% ee.

Prediction of preterm delivery based on maternal plasma urocortin.

CONTEXT: Preterm birth still remains a significant management problem, and a large number of markers of the disease have been investigated. OBJECTIVE: We measured plasma levels of urocortin, a neuropeptide expressed by gestational tissues, in women with threatened preterm labor (TPTL) to evaluate whether the measurement may predict preterm delivery (PTD). DESIGN: We studied patients as part of an open observational study. SETTING: The study was conducted at a tertiary referral center for obstetric care. PATIENTS: Eighty-five women with singleton pregnancies between 28 and 34 completed gestational weeks with TPTL participated in the study. INTERVENTIONS: Interventions included clinical examination and urocortin measurement. MAIN OUTCOME MEASURES: Pregnancy outcome and evaluation of sensitivity, specificity, and predictive values of urocortin as diagnostic test for PTD were measured. RESULTS: Thirty of 85 patients (35.3%) had PTD: 23 of 30 delivered within 7 d from admission (delivery time interval: 2.91 +/- 1.62 d; gestational weeks at delivery: 32.12 +/- 1.7); the remaining delivered later (delivery time interval: 11.71 +/- 4.27 d; gestational weeks at delivery: 33.5 +/- 2.18). Urocortin was significantly higher in women who delivered preterm (median 131.2 pg/ml, interquartile interval 115.1-139.4 pg/ml) than in those who progressed to term delivery [95.4 (69.9-101.3) pg/ml, P < 0.0001] and still higher in those delivering within 7 d from admission [137.7 (124.8-141.2) pg/ml]. Receiver operating characteristic curve analysis revealed that urocortin at the cutoff of 113.9 pg/ml had sensitivity of 80%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 90% as a marker for PTD. CONCLUSIONS: Maternal plasma urocortin concentration is increased in patients with TPTL who have PTD, and its measurement may be a promising new biochemical marker of PTD.

Plasma urocortin levels in the diagnosis of ovarian endometriosis.

OBJECTIVE: Urocortin is a neuropeptide, member of the corticotropin-releasing hormone family, that is produced by the human endometrium. Ovarian endometrioma is a prevalent gynecologic disorder still lacking specific serum markers. In the present study we measured systemic levels of urocortin to assess the diagnostic performance of its determination in distinguishing endometriomas from other benign ovarian cysts. METHODS: Plasma urocortin was measured by radioimmunoassay in women with ovarian endometrioma (n=40) and in women with benign, nonendometriotic ovarian cysts (n=40). The diagnostic accuracy of urocortin measurement was evaluated by receiver operating characteristic curve and compared with the standard marker, CA 125. To support the local origin of the peptide, we also evaluated its localization in endometriomas by immunohistochemistry and its concentrations in cyst fluid and peritoneal fluid of 12 women with endometrioma. RESULTS: Plasma urocortin levels were twice as high in women with endometrioma (median 49 pg/mL, interquartile range 41-63 pg/mL) than in the control group (19 [15-23] pg/mL, P<.001) and significantly higher in the cystic content of endometriomas than in the peritoneal fluid and plasma (P<.05). The peptide was immunolocalized in endometrioma glands and stromal capillary vessels. Elevated plasma urocortin levels detected 88% of the cases of endometrioma with 90% specificity, whereas CA 125 detected only 65% of the cases with the same specificity. CONCLUSION: Plasma urocortin is increased in women with endometriomas, and its measurement may be useful for the differential diagnosis of endometrioma compared with other benign ovarian cysts. LEVEL OF EVIDENCE: II.

High maternal and fetal plasma urocortin levels in pregnancies complicated by hypertension.

OBJECTIVE: We evaluated maternal and fetal plasma levels and placental mRNA expression of urocortin, a placental vasoactive neuropeptide, in singleton pregnancies (n = 70) complicated by hypertensive disorders classified as gestational hypertension (n = 36), pre-eclampsia (n = 19), and pre-eclampsia complicated by intrauterine growth restriction (PE/IUGR, n = 15), and in 70 healthy normotensive singleton pregnancies. METHODS: Plasma levels were assayed by radioimmunoassay, fetal biometry by ultrasound scans, utero-placental and fetal perfusion by Doppler velocimetry, and placental urocortin mRNA expression by quantitative real time reverse transcriptase-polymerase chain reaction. The main outcome measures were the correlation of urocortin concentrations with patterns of the utero-placental and fetal circulation, and the early prediction of a poor neonatal outcome such as the occurrence of perinatal death and intraventricular hemorrhage. RESULTS: Maternal and fetal urocortin levels were significantly (both P < 0.001) higher in gestational hypertension, pre-eclampsia and PE/IUGR women than in controls, and correlated with Doppler velocimetry patterns. Fetal concentrations were significantly (P < 0.0001) higher than and significantly (P < 0.0001) correlated to maternal levels. Placental mRNA expression did not change. Ten out of 140 newborns had a poor neonatal outcome, with an overall prevalence of 7.14% (pretest probability). Using the receiver operator characteristics curve analysis cut-off values, the probability of a poor neonatal outcome was 66.7% when urocortin was used, and was 0% if levels were unaltered. CONCLUSIONS: Maternal and fetal urocortin levels are increased in hypertensive disorders of pregnancy. Since urocortin has vasoactive properties, the evidence of increased urocortin levels in hypertensive disorders may represent an adaptive fetal response.