Preferential formation of Z-RNA over intercalated motifs in long noncoding RNA.

Secondary structure is a principal determinant of lncRNA function, predominantly regarding scaffold formation and interfaces with target molecules. Noncanonical secondary structures that form in nucleic acids have known roles in regulating gene expression and include G-quadruplexes (G4s), intercalated motifs (iMs), and R-loops (RLs). In this paper, we used the computational tools G4-iM Grinder and QmRLFS-finder to predict the formation of each of these structures throughout the lncRNA transcriptome in comparison to protein-coding transcripts. The importance of the predicted structures in lncRNAs in biological contexts was assessed by combining our results with publicly available lncRNA tissue expression data followed by pathway analysis. The formation of predicted G4 (pG4) and iM (piM) structures in select lncRNA sequences was confirmed in vitro using biophysical experiments under near-physiological conditions. We find that the majority of the tested pG4s form highly stable G4 structures, and identify many previously unreported G4s in biologically important lncRNAs. In contrast, none of the piM sequences are able to form iM structures, consistent with the idea that RNA is unable to form stable iMs. Unexpectedly, these C-rich sequences instead form Z-RNA structures, which have not been previously observed in regions containing cytosine repeats and represent an interesting and underexplored target for protein-RNA interactions. Our results highlight the prevalence and potential structure-associated functions of noncanonical secondary structures in lncRNAs, and show G4 and Z-RNA structure formation in many lncRNA sequences for the first time, furthering the understanding of the structure-function relationship in lncRNAs.

Nonsteroidal anti-inflammatory drug "allergy" labeling is associated with increased postpartum opioid utilization.

BACKGROUND: Current guidelines recommend a stepwise approach to postpartum pain management, beginning with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids added only if needed. Report of a prior NSAID-induced adverse drug reaction (ADR) may preclude use of first-line analgesics, despite evidence that many patients with this allergy label may safely tolerate NSAIDs. OBJECTIVE: We assessed the association between reported NSAID ADRs and postpartum opioid utilization. METHODS: We performed a retrospective cohort study of birthing people who delivered within an integrated health system (January 1, 2017, to December 31, 2020). Study outcomes were postpartum inpatient opioid administrations and opioid prescriptions at discharge. Statistical analysis was performed on a propensity score-matched sample, which was generated with the goal of matching to the covariate distributions from individuals with NSAID ADRs. RESULTS: Of 38,927 eligible participants, there were 883 (2.3%) with an NSAID ADR. Among individuals with reported NSAID ADRs, 49.5% received inpatient opioids in the postpartum period, compared to 34.5% of those with no NSAID ADRs (difference = 15.0%, 95% confidence interval 11.4-18.6%). For patients who received postpartum inpatient opioids, those with NSAID ADRs received a higher total cumulative dose between delivery and hospital discharge (median 30.0 vs 22.5 morphine milligram equivalents [MME] for vaginal deliveries; median 104.4 vs 75.0 MME for cesarean deliveries). The overall proportion of patients receiving an opioid prescription at the time of hospital discharge was higher for patients with NSAID ADRs compared to patients with no NSAID ADRs (39.3% vs 27.2%; difference = 12.1%, 95% confidence interval 8.6-15.6%). CONCLUSION: Patients with reported NSAID ADRs had higher postpartum inpatient opioid utilization and more frequently received opioid prescriptions at hospital discharge compared to those without NSAID ADRs, regardless of mode of delivery.

Differential expression of genes in the RhoA/ROCK pathway in the hippocampus and cortex following intermittent hypoxia and high intensity interval training.

Neuroplasticity is regulated by a balance of neurotrophic factors and inhibitory molecules that are permissive and restrictive to central nervous system (CNS) adaptation, respectively. Intermittent hypoxia (IH) and high intensity interval training (HIIT) are known to upregulate neurotrophic factors which are associated with improvements in learning and memory and greater functional recovery following CNS insults. We investigated whether the RhoA/ROCK signaling pathway (known to restrict neuroplasticity) is also modulated by IH and HIIT in the hippocampus, cortex, and lumbar spinal cord of male Wistar rats. The gene expression of 25 RhoA/ROCK signaling pathway components was determined following IH or IH combined with HIIT (30 minutes/day, five days/week, for six weeks). IH included ten three-minute bouts which alternated between hypoxia (15% O2) and normoxia. IH+HIIT synchronized the hypoxia protocol with treadmill training at speeds of 50 cm.s-1 during hypoxia, and 15 cm.s-1 during normoxia. In the hippocampus, IH and IH+HIIT significantly downregulated aggrecan and Nogo-receptor 2 mRNA which are involved in the inhibition of neuroplasticity. However, IH and IH+HIIT significantly upregulated genes including Lingo-1, Ncan, NgR3, and Sema4d in the cortex. This is the first time IH and HIIT have been linked to the modulation of plasticity inhibiting pathways. These results provide a fundamental step towards elucidating the interplay between the neurotrophic and inhibitory mechanisms involved in experience-driven neural plasticity which will aid in optimizing physiological interventions for the treatment of cognitive decline or neurorehabilitation.

Usual Source of Care and Contraceptive Use.

BACKGROUND: A high proportion of people in the United States at risk of unintended pregnancy also have limited primary care access. STUDY DESIGN: We pooled data for analyses from separate 2015-2017 and 2017-2019 waves of the National Survey of Family Growth. Multivariable logistic regression was used to estimate associations between the usual source of health care and self-reported use of a comprehensive range of contraceptive options, as well as alignment between patient preference and the current method. RESULTS: Compared with having a private doctor or Health Maintenance Organization, not having a usual source of care was associated with lower odds of using short-term hormonal methods (OR=0.54, 95% CI: 0.40-0.73, for an 11 percentage point lower rate); higher odds of using time-based methods (OR=1.47, 95% CI: 1.10-1.97, for a 6 percentage point higher rate); and higher odds of preferring a contraceptive method other than the one most recently used (OR=1.39, 95% CI: 1.01-1.90, for a 6 percentage point higher probability). Reliance on an emergency department as a usual source of care was not associated with contraceptive use or satisfaction with the method used. Reliance on urgent care was associated only with higher odds of using time-based methods (OR=1.60, 95% CI: 1.03-2.50, for a 7 percentage point higher rate). Clinic-based usual care was not associated with any differences in contraceptive use but was associated with preferring a contraceptive method other than the one most recently used (OR=1.65, 95% CI: 1.21-2.25, for an 8 percentage point higher probability). CONCLUSIONS: All sources of usual care can improve contraceptive access.

Docetaxel Inhibits Epithelial-Mesenchymal Transition in Human Mammary Cells.

Epithelial-mesenchymal transition (EMT) is a reversible and dynamic biological process in which epithelial cells acquire mesenchymal characteristics including enhanced stemness and migratory ability. EMT can facilitate cancer metastasis and is a known driver of cellular resistance to common chemotherapeutic drugs, such as docetaxel. Current chemotherapeutic practices such as docetaxel treatment can promote EMT and increase the chance of tumor recurrence and resistance, calling for new approaches in cancer treatment. Here we show that prolonged docetaxel treatment at a sub-IC50 concentration inhibits EMT in immortalized human mammary epithelial (HMLE) cells. Using immunofluorescence, flow cytometry, and bulk transcriptomic sequencing to assess EMT progression, we analyzed a range of cellular markers of EMT in docetaxel-treated cells and observed an upregulation of epithelial markers and downregulation of mesenchymal markers in the presence of docetaxel. This finding suggests that docetaxel may have clinical applications not only as a cytotoxic drug but also as an inhibitor of EMT-driven metastasis and multidrug resistance depending on the concentration of its use.

A Novel Experimental Approach for the Measurement of Vibration-Induced Changes in the Rheological Properties of Ex Vivo Ovine Brain Tissue.

Increased incidence of traumatic brain injury (TBI) imposes a growing need to understand the pathology of brain trauma. A correlation between the incidence of multiple brain traumas and rates of behavioural and cognitive deficiencies has been identified amongst people that experienced multiple TBI events. Mechanically, repetitive TBIs may affect brain tissue in a similar way to cyclic loading. Hence, the potential susceptibility of brain tissue to mechanical fatigue is of interest. Although temporal changes in ovine brain tissue viscoelasticity and biological fatigue of other tissues such as tendons and arteries have been investigated, no methodology currently exists to cyclically load ex vivo brain tissue. A novel rheology-based approach found a consistent, initial stiffening response of the brain tissue before a notable softening when subjected to a subsequential cyclic rotational shear. History dependence of the mechanical properties of brain tissue indicates susceptibility to mechanical fatigue. Results from this investigation increase understanding of the fatigue properties of brain tissue and could be used to strengthen therapy and prevention of TBI, or computational models of repetitive head injuries.

Long-term complications in classic galactosemia are not progressive.

Classic galactosemia (CG) is a potentially lethal genetic disorder that results from profound deficiency of galactose-1-P uridylyltransferase. Despite early detection and life-long dietary restriction of galactose, which is the current standard of care, many patients with CG grow to experience a range of long-term developmental complications that can include difficulties with speech/voice/language, cognitive, motor, and psychosocial outcomes, among other problems. That these complications are common in CG is well-documented, but whether they are also progressive has been a point of controversy for decades. Here, we addressed the question of whether long-term outcomes in CG are progressive by analyzing a robust data set in each of 4 ways. First, we compared cross-sectional Vineland-3 Adaptive Behavior Scales scores for 101 cases and 65 unaffected sibling controls and found no evidence of consistently declining scores with age. Second, we analyzed longitudinal Vineland-3 subdomain scores for 45 cases and 34 controls to see if individual participants demonstrated developmental gains (positive slope) or losses (negative slope) over time. The changes in most growth scale value (GSV) scores, which are not normed, were positive for both cases and controls <10y, and either positive or near zero for participants ≥10y. In contrast, the slopes of most v-Scale scores, which are normed, were negative for many cases <10y, indicating that these children, while gaining milestones, were gaining them at a slower pace than their counterparts in the reference population. Third, we analyzed medical records from 76 cases, assigning ordinal scores for complications and gathering the quantitative results of relevant formal assessments where available. Both cross-sectional and longitudinal analyses of both ordinal and formal assessment scores confirmed that outcomes were mostly stable, albeit with some ups and downs in isolated cases. Finally, we analyzed data collected via custom family-response surveys from 124 cases and 67 controls regarding each participant's perceived symptom severity over time. Among cases, the percentages of respondents reporting worsening symptoms over time for speech, cognitive, motor, and psychosocial outcomes were 0.8%, 6.6%, 5.2%, and 9.8%, respectively. Among controls, the corresponding percentages were 0.0%, 1.5%, 1.5%, and 6.5%, respectively. These results provide compelling evidence that long-term developmental complications are not progressive for a majority of patients with CG.

Clinical correlation but no elevation of striatal dopamine synthesis capacity in two independent cohorts of medication-free individuals with schizophrenia.

Dysregulation of dopamine systems has been considered a foundational driver of pathophysiological processes in schizophrenia, an illness characterized by diverse domains of symptomatology. Prior work observing elevated presynaptic dopamine synthesis capacity in some patient groups has not always identified consistent symptom correlates, and studies of affected individuals in medication-free states have been challenging to obtain. Here we report on two separate cohorts of individuals with schizophrenia spectrum illness who underwent blinded medication withdrawal and medication-free neuroimaging with [18F]-FDOPA PET to assess striatal dopamine synthesis capacity. Consistently in both cohorts, we found no significant differences between patient and matched, healthy comparison groups; however, we did identify and replicate robust inverse relationships between negative symptom severity and tracer-specific uptake widely throughout the striatum: [18F]-FDOPA specific uptake was lower in patients with a greater preponderance of negative symptoms. Complementary voxel-wise and region of interest analyses, both with and without partial volume correction, yielded consistent results. These data suggest that for some individuals, striatal hyperdopaminergia may not be a defining or enduring feature of primary psychotic illness. However, clinical differences across individuals may be significantly linked to variability in striatal dopaminergic tone. These findings call for further experimentation aimed at parsing the heterogeneity of dopaminergic systems function in schizophrenia.

Harnessing Electronic Medical Record Tools to Provide Proceduralist Feedback on Pediatric Endoscopy Quality Metrics.

In 2022, the Pediatric Endoscopy Quality Improvement Network published quality metrics related to pediatric endoscopy. We utilized electronic medical record (EMR) tools to collect pediatric endoscopy quality metrics (PEQM) and to standardize proceduralist feedback. EMR tools were created to capture and display PEQM: (1) an endoscopy documentation template, (2) nursing documentation of events during endoscopy for timed calculations, and (3) a data dashboard. Dashboard metrics provided individualized PEQM feedback relative to group performance and ideals where available. Utilization of the endoscopy documentation tools and data dashboard was measured. Utility was assessed using a survey based on the Technology Adoption Model. Adoption of documentation tools has been nearly universal with positive survey outcomes. Robust dashboard visualization has been demonstrated. Use of EMR documentation tools standardized PEQM collection. Future capture and sharing of common PEQM data across institutions could help determine PEQM benchmarks.

Maternal and perinatal outcomes of prolonged second stage of labour: a historical cohort study of over 51,000 women.

BACKGROUND: Prolonged second stage of labour has been associated with adverse maternal and perinatal outcomes. The maximum length of the second stage from full dilatation to birth of the baby remains controversial. Our aim was to determine whether extending second stage of labour was associated with adverse maternal and perinatal outcomes. METHODS: A retrospective cohort study was conducted using routinely collected hospital data from 51592 births in Aberdeen Maternity Hospital between 2000 and 2016. The hospital followed the local guidance of allowing second stage of labour to extend by an hour compared to national guidelines since 2008 (nulliparous and parous). The increasing duration of second stage of labour was the exposure. Baseline characteristics, maternal and perinatal outcomes were compared between women who had a second stage labour of (a) ≤ 3 h and (b) > 3 h duration for nulliparous women; and (a) ≤ 2 h or (b) > 2 h for parous women. An additional model was run that treated the duration of second stage of labour as a continuous variable (measured in hours). All the adjusted models accounted for: age, BMI, smoking status, deprivation category, induced birth, epidural, oxytocin, gestational age, baby birthweight, mode of birth and parity (only for the final model). RESULTS: Each hourly increase in the second stage of labour was associated with an increased risk of obstetric anal sphincter injury (aOR 1.21 95% CI 1.16,1.25), having an episiotomy (aOR 1.48 95% CI 1.45, 1.52) and postpartum haemorrhage (aOR 1.27 95% CI 1.25, 1.30). The rates of caesarean and forceps delivery also increased when second stage duration increased (aOR 2.60 95% CI 2.50, 2.70, and aOR 2.44 95% CI 2.38, 2.51, respectively.) Overall adverse perinatal outcomes were not found to change significantly with duration of second stage on multivariate analysis. CONCLUSIONS: As the duration of second stage of labour increased each hour, the risk of obstetric anal sphincter injuries, episiotomies and PPH increases significantly. Women were over 2 times more likely to have a forceps or caesarean birth. The association between adverse perinatal outcomes and the duration of second stage of labour was less convincing in this study.

The Burden of Cardiac Implantable Electronic Device Checks in the Peri-MRI Setting: The CHECK-MRI Study.

BACKGROUND: Most modern cardiac implantable electronic device (CIED) systems are now compatible with magnetic resonance imaging (MRI) scans. The requirement for both pre- and post-MRI CIED checks imposes significant workload to the cardiac electrophysiology service. Here, we sought to determine the burden of CIED checks associated with MRI scans. METHODS: We identified all CIED checks performed peri-MRI scans at our institution over a 3-year period between 1 July 2017 to 30 June 2020, comprising three separate financial years (FY). Device check reports, MRI scan reports and clinical summaries were collated. The workload burden was determined by assessing the occasions and duration of service. Analysis was performed to determine cost burden/projections for this service and identify factors contributing to the workload. RESULTS: A total of 739 CIED checks were performed in the peri-MRI scan setting (370 pre- and 369 post-MRI scan), including 5% (n=39) that were performed outside of routine hours (weekday <8 am or >5 pm, and weekends). MRIs were performed for 295 patients (75±13 years old, 64% male) with a CIED (88% permanent pacemaker, and 12% high voltage device), including 49 who had more than one MRI scan. The proportion of total MRI scans for patients with a CIED in-situ increased each FY (from 0.5% of all MRIs in FY1, to 0.9% in FY2, to 1.0% in FY3). The weekly workload increased (R2=0.2, p<0.001), but with week-to-week variability due to ad hoc scheduling (209 days with only one MRI vs 78 days with ≥2 MRIs for CIED patients). The projected annual cost of this service will increase to AUD$161,695 in 10 years for an estimated annual 546 MRI scans for CIED patients. CONCLUSIONS: There is an increasing workload burden and expense associated with CIED checks in the peri-MRI setting. Appropriate budgeting, staff allocation and standardisation of automated CIED pre-programming features among manufacturers are urgently needed.

Intracellular Communication between Synthetic Macromolecules.

Non-viral delivery is an important strategy for selective and efficient gene therapy, immunization, and RNA interference, which overcomes problems of genotoxicity and inherent immunogenicity associated with viral vectors. Liposomes and polymers are compelling candidates as carriers for intracellular, non-viral delivery, but maximal efficiencies of around 1% have been reported for the most advanced non-viral carriers. Here, we develop a library of dendronized bottlebrush polymers with controlled defects, displaying a level of precision surpassed only by biological molecules like DNA, RNA, and proteins. We test concurrent and competitive delivery of DNA and show for the first time that, while intracellular communication is thought to be an exclusively biomolecular phenomenon, such communication between synthetic macromolecular complexes can also take place. Our findings challenge the assumption that delivery agents behave as bystanders that enable transfection by passive intracellular release of genetic cargo and improve upon coarse strategies in intracellular carrier design lacking control over polymer sequence, architecture, and composition, leading to a hit-or-miss outcome. Understanding the communication that takes place between macromolecules will help improve the design of non-viral delivery agents and facilitate translation of genome engineering, vaccines, and nucleic acid-based therapies.

Perceptions and realities of mercury contamination in a Peruvian artisanal and small-scale gold mining (ASGM) community.

Artisanal and small-scale gold mining (ASGM) is the leading global source of mercury pollution. Efforts to reduce or eliminate mercury use in ASGM have produced limited results, in part because they do not engage the complex socio-technical nature of mercury issues in ASGM. The paper takes a multidisciplinary approach to understand the mercury issue with a socio-technical lens, pairing sampling of mercury in soils with surveys of miners' and residents' perceptions of mercury pollution and its dispersion. The research was conducted in Secocha, an ASGM boomtown in southern Peru. Mercury levels in soils exceeded relevant standards in both industrial zones (average of 72.6 mg/kg, versus the Peruvian standard of 24 mg/kg) and residential/urban zones (average of 9.5 mg/kg, versus the Peruvian standard of 6.6 mg/kg). Mercury levels were highest where processing and gold buying activity were concentrated. Surveys revealed that miners and residents correctly assumed mercury pollution to be highest in those areas. However, respondents seemed to underestimate the extent of mercury pollution in other parts of town, and many believed that only those who handle mercury directly were affected by it. Respondents also placed low priority on reducing mercury pollution. Miners' and residents' partial knowledge about mercury contamination and the low priority accorded to the issue suggest that mercury reduction efforts would likely be met with indifference and potentially resistance.

Epigenetic modification of cytosines fine tunes the stability of i-motif DNA.

i-Motifs are widely used in nanotechnology, play a part in gene regulation and have been detected in human nuclei. As these structures are composed of cytosine, they are potential sites for epigenetic modification. In addition to 5-methyl- and 5-hydroxymethylcytosine modifications, recent evidence has suggested biological roles for 5-formylcytosine and 5-carboxylcytosine. Herein the human telomeric i-motif sequence was used to examine how these four epigenetic modifications alter the thermal and pH stability of i-motifs. Changes in melting temperature and transitional pH depended on both the type of modification and its position within the i-motif forming sequence. The cytosines most sensitive to modification were next to the first and third loops within the structure. Using previously described i-motif forming sequences, we screened the MCF-7 and MCF-10A methylomes to map 5-methylcytosine and found the majority of sequences were differentially methylated in MCF7 (cancerous) and MCF10A (non-cancerous) cell lines. Furthermore, i-motif forming sequences stable at neutral pH were significantly more likely to be epigenetically modified than traditional acidic i-motif forming sequences. This work has implications not only in the epigenetic regulation of DNA, but also allows discreet tunability of i-motif stability for nanotechnological applications.

High resolution crystal structure of a KRAS promoter G-quadruplex reveals a dimer with extensive poly-A π-stacking interactions for small-molecule recognition.

Aberrant KRAS signaling is a driver of many cancers and yet remains an elusive target for drug therapy. The nuclease hypersensitive element of the KRAS promoter has been reported to form secondary DNA structures called G-quadruplexes (G4s) which may play important roles in regulating KRAS expression, and has spurred interest in structural elucidation studies of the KRAS G-quadruplexes. Here, we report the first high-resolution crystal structure (1.6 Å) of a KRAS G-quadruplex as a 5'-head-to-head dimer with extensive poly-A π-stacking interactions observed across the dimer. Molecular dynamics simulations confirmed that the poly-A π-stacking interactions are also maintained in the G4 monomers. Docking and molecular dynamics simulations with two G4 ligands that display high stabilization of the KRAS G4 indicated the poly-A loop was a binding site for these ligands in addition to the 5'-G-tetrad. Given sequence and structural variability in the loop regions provide the opportunity for small-molecule targeting of specific G4s, we envisage this high-resolution crystal structure for the KRAS G-quadruplex will aid in the rational design of ligands to selectively target KRAS.

Mode of Delivery and Unplanned Cesarean: Differences in Rates and Indication by Race, Ethnicity, and Sociodemographic Characteristics.

OBJECTIVE: We aimed to examine the relationship of sociodemographic variables with racial/ethnic disparities in unplanned cesarean births in a large academic hospital system. Secondarily, we investigated the relationship of these variables with differences in cesarean delivery indication, cesarean delivery timing, length of second stage and operative delivery. STUDY DESIGN: We conducted a retrospective cohort study of births >34 weeks between 2017 and 2019. Our primary outcome was unplanned cesarean delivery after a trial of labor. Multiple gestations, vaginal birth after cesarean, elective repeat or primary cesarean delivery, and contraindications for vaginal delivery were excluded. Associations between mode of delivery and patient characteristics were assessed using Chi-square, Fisher exact tests, or t-tests. Odds ratios were estimated by multivariate logistic regression. Goodness of fit was assessed with Hosmer Lemeshow test. RESULTS: Among 18,946 deliveries, the rate of cesarean delivery was 14.8% overall and 21.3% in nulliparous patients. After adjustment for age, body mass index (BMI), and parity, women of Black and Asian races had significantly increased odds of unplanned cesarean delivery; 1.69 (95% CI: 1.45,1.96) and 1.23 (1.08, 1.40), respectively. Single Hispanic women had adjusted odds of 1.65 (1.08, 2.54). Single women had increased adjusted odds of cesarean delivery of 1.18, (1.05, 1.31). Fetal intolerance was the indication for 39% (613) of cesarean deliveries among White women as compared to 63% (231) of Black women and 49% (71) of Hispanic women (p <0.001). CONCLUSION: Rates of unplanned cesarean delivery were significantly higher in Black and Asian compared to White women, even after adjustment for age, BMI, parity, and zip code income strata, and rates of unplanned cesarean delivery were higher for Hispanic women self-identifying as single. Racial and ethnic differences were seen in cesarean delivery indications and operative vaginal deliveries. Future work is urgently needed to better understand differences in provider care or patient attributes, and potential provider bias, that may contribute to these findings. KEY POINTS: · Racial, ethnic, and socioeconomic differences exist in the odds of unplanned cesarean.. · Indications for unplanned cesarean delivery differed significantly among racial and ethnic groups.. · There may be unmeasured provider level factors which contribute to disparities in cesarean rates..

A preliminary assessment of the link between anxiety sensitivity cognitive concerns and suicidal thoughts through dissociative symptoms.

Anxiety sensitivity (AS) and AS subfactors (physical, cognitive, and social) have been found to have robust associations with suicide risk. While the direct association between AS subfactors and suicide risk have been explored, little is known about how specific mechanisms, such as dissociation, might explain this relationship. This study aimed to run three analyses to examine the direct and indirect effects of suicidal thoughts and AS via dissociative symptoms. We predicted that dissociation would be a pathway through which AS physical concerns (ASPC) and AS cognitive concerns (ASCC) predicts suicidal ideation. Participants included 84 undergraduate students from a Southeastern University who were elevated on ASCC. Participants completed measures examining dissociative experiences, anxiety sensitivity, and current suicidal ideation. Results revealed that dissociation had a significant indirect effect with ASPC but not ASCC. The current preliminary study showed that ASCC had direct associations with suicide risk; however, those with lower levels of ASPC and dissociation may also be more likely to develop suicide risk. Future research should explore the possibility that the dissociation/ASPC and ASCC pathways are separate, but related, paths to suicidality.

Application of the cognitive load theory in prelicensure nursing education: a quantitative measurement focusing on instructional design.

The objective of this study was to examine differences in principles from the cognitive load theory (CLT) combined with active learning strategies. To examine these differences, simple to complex activities were imbedded into two active learning instructional strategies: cooperative learning (CPL) and problem-based learning (PBL) and evaluated for its impact on mental effort for learning and intrinsic cognitive load. A two-within repeated-measures design was used in a nursing fundamentals classroom. The simple and complex activities were grounded in recommendations from the CLT and validated by nurse experts. The instructional strategies of CPL and PBL were chosen based on recommendations from the literature. Results revealed no statistically significant differences. A small interaction showed a decrease in mental effort and intrinsic load when problem-based learning was used. Progressing learning activities from simple to complex, informed by the CLT, offers an approach to designing instruction in nursing classrooms when using active learning strategies.

Expanding Fear of Loss of Vigilance: Intolerance of Uncertainty, Responsibility for Harm, and Fear of Sleep for Predicting Nocturnal Panic.

OBJECTIVE/BACKGROUND: Nocturnal panic involves experiencing panic attacks out of a sleeping state without obvious causes. Roughly half of patients with panic disorder will experience nocturnal panic in addition to panic attacks while awake, or daytime panic. Like daytime panic, nocturnal panic also occurs in other disorders such as PTSD. The Fear of Loss of Vigilance theory is currently the only model available to explain nocturnal panic. It suggests nocturnal panickers fear states in which they cannot easily react to or protect themselves from danger. The current study sought to expand upon the existing theory by including constructs from the broader anxiety literature. Nocturnal panickers were expected to report higher scores on these measures when compared to daytime panickers and non-panickers. PARTICIPANTS: A sample of 166 participants were screened for panic history. METHODS: Participants completed self-report measures regarding panic attacks, fear of sleep, intolerance of uncertainty, responsibility for harm, and fear of loss of vigilance. RESULTS: Measures of fear of sleep and responsibility for harm successfully differentiated nocturnal from daytime panickers, whereas measures of intolerance of uncertainty and fear of loss of vigilance did not. CONCLUSIONS: These results provide partial support for the Fear of Loss of Vigilance theory. Modifications to the theory to incorporate additional constructs are suggested.

Enhancing Engineering Ethics: Role Ethics and Corporate Social Responsibility.

Engineering ethics calls the attention of engineers to professional codes of ethical responsibility and personal values, but the practice of ethics in corporate settings can be more complex than either of these. Corporations too have cultures that often include corporate social responsibility (CSR) practices and policies, but few discussions of engineering ethics make any explicit reference to CSR. This article proposes critical attention to CSR and role ethics as an opportunity to help prepare engineers to think through the ethics of their professional practice. After a brief overview of the evolution of social responsibility within engineering ethics in the United States, this article shares empirical research with practicing engineers in the mining and energy industries to explore how their formal ethics training did and did not prepare them to grapple with the ethical dimensions of their professional practice. It then illustrates the ways in which these dilemmas and the strategies employed for navigating them are framed within CSR policies and practices and resonate more strongly with role ethics rather than ethical theory as currently taught in most US engineering programs. The article concludes that engineering ethics teaching and learning would benefit from explicitly incorporating critical discussions of role ethics and CSR.