How the presentation of patient information and decision-support advisories influences opioid prescribing behavior: A simulation study

ObjectiveThe United States faces an opioid crisis. Integrating prescription drug monitoring programs into electronic health records offers promise to improve opioid prescribing practices. This study aimed to evaluate 2 different user interface designs for prescription drug monitoring program and electronic health record integration.Materials and MethodsTwenty-four resident physicians participated in a randomized controlled experiment using 4 simulated patient cases. In the conventional condition, prescription opioid histories were presented in tabular format, and computerized clinical decision support (CDS) was provided via interruptive modal dialogs (ie, pop-ups). The alternative condition featured a graphical opioid history, a cue to visit that history, and noninterruptive CDS. Two attending pain specialists judged prescription appropriateness.ResultsParticipants in the alternative condition wrote more appropriate prescriptions. When asked after the experiment, most participants stated that they preferred the alternative design to the conventional design.ConclusionsHow patient information and CDS are presented appears to have a significant influence on opioid prescribing behavior

FGF2-Dependent Mesenchyme and Laminin-111 are Niche Factors in Salivary Gland Organoids

Epithelial progenitor cells are dependent upon a complex 3D niche to promote their proliferation and differentiation during development, which can be recapitulated in organoids. The specific requirements of the niche remain unclear for many cell types, including the proacinar cells that give rise to secretory acinar epithelial cells that produce saliva. Here, using ex vivo cultures of E16 primary mouse submandibular salivary gland epithelial cell clusters, we investigated the requirement for mesenchymal cells and other factors in producing salivary organoids in culture. Native E16 salivary mesenchyme, but not NIH3T3 cells or mesenchymal cell conditioned medium, supported robust protein expression of the progenitor marker Kit and the acinar/proacinar marker AQP5, with a requirement for FGF2 expression by the mesenchyme. Enriched salivary epithelial clusters that were grown in laminin-enriched basement membrane extract or laminin-111 together with exogenous FGF2, but not with EGF, underwent morphogenesis to form organoids that displayed robust expression of AQP5 in terminal buds. Knockdown of FGF2 in the mesenchyme or depletion of mesenchyme cells from the organoids significantly reduced AQP5 levels even in the presence of FGF2, suggesting a requirement for autocrine FGF2 signaling in the mesenchyme cells for AQP5 expression. We conclude that basement membrane proteins and mesenchyme cells function as niche factors in salivary organoids

Joyful by nature : approaches to investigate the evolution and function of joy in non-human animals

This work was supported by Grant #0333 from the Templeton World Charity Foundation (TWCF) and a Brian Mason Technical Trust Fund grant to X. J. N. and A. H. T.The nature and evolution of positive emotion is a major question remaining unanswered in science and philosophy. The study of feelings and emotions in humans and animals is dominated by discussion of affective states that have negative valence. Given the clinical and social significance of negative affect, such as depression, it is unsurprising that these emotions have received more attention from scientists. Compared to negative emotions, such as fear that leads to fleeing or avoidance, positive emotions are less likely to result in specific, identifiable, behaviours being expressed by an animal. This makes it particularly challenging to quantify and study positive affect. However, bursts of intense positive emotion (joy) are more likely to be accompanied by externally visible markers, like vocalisations or movement patterns, which make it more amenable to scientific study and more resilient to concerns about anthropomorphism. We define joy as intense, brief, and event-driven (i.e. a response to something), which permits investigation into how animals react to a variety of situations that would provoke joy in humans. This means that behavioural correlates of joy are measurable, either through newly discovered 'laughter' vocalisations, increases in play behaviour, or reactions to cognitive bias tests that can be used across species. There are a range of potential situations that cause joy in humans that have not been studied in other animals, such as whether animals feel joy on sunny days, when they accomplish a difficult feat, or when they are reunited with a familiar companion after a prolonged absence. Observations of species-specific calls and play behaviour can be combined with biometric markers and reactions to ambiguous stimuli in order to enable comparisons of affect between phylogenetically distant taxonomic groups. Identifying positive affect is also important for animal welfare because knowledge of positive emotional states would allow us to monitor animal well-being better. Additionally, measuring if phylogenetically and ecologically distant animals play more, laugh more, or act more optimistically after certain kinds of experiences will also provide insight into the mechanisms underlying the evolution of joy and other positive emotions, and potentially even into the evolution of consciousness.Publisher PDFPeer reviewe

Photoperiod Manipulation Reveals a Light-Driven Component to Daily Patterns of Ventilation in Male C57Bl/6J Mice

Obstructive sleep apnea is a common sleep disorder that increases risk for cardiovascular disease and mortality. The severity of sleep-disordered breathing in obstructive sleep apnea patients fluctuates with the seasons, opening the possibility that seasonal changes in light duration, or photoperiod, can influence mechanisms of breathing. Photoperiod can have profound effects on internal timekeeping and can reshape metabolic rhythms in mammals. While the daily rhythm in ventilation is largely shaped by the metabolic rate, less is known about whether ventilatory rhythms are altered in accordance with metabolism under different photoperiods. Here, we investigate the relationship between ventilation and metabolism under different photoperiods using whole-body plethysmography and indirect calorimetry. We find that the daily timing of ventilation is chiefly synchronized to dark onset and that light cues are important for maintaining daily ventilatory rhythms. Moreover, changes in ventilatory patterns are not paralleled by changes in oxygen consumption, energy expenditure, or respiratory exchange rate under different photoperiods. We conclude that ventilatory patterns are not only shaped by the metabolic rate and circadian timing but are also influenced by other light-driven factors. Collectively, these findings have clinical implications for the seasonal variations in sleep-disordered breathing found in individuals with obstructive sleep apnea

Pilot Data on the Nature of Trauma Exposure in Military Couples

Using a sample of 50 couples, this pilot study examined the associations between service member and spouse PTSD symptoms on both self and partner relationship quality across trauma-type (i.e., interpersonal, non-interpersonal, military) and perpetrator-type (i.e., family member, non-family member, military) groups. Four multiple-group actor-partner interdependence models were used to analyze the actor and partner effects of husband and wives’ PTSD symptoms and relationship quality, as couples were classified into distinct groups. Results suggest that under some conditions, husband and wife PTSD symptoms were negatively associated with both their own and their partner’s relationship quality. Findings from these preliminary analyses invite a more dynamic conceptualization of the possible relationship between PTSD, relationship quality, and distinct facets of trauma exposure in veteran couples

Early executive control buffers risk for adolescent psychopathology during the COVID‐19 pandemic

Background: The coronavirus disease 2019 (COVID‐19) pandemic has had a global impact on youth mental health, and there is a critical need for research examining individual factors that contribute to increased psychopathology during the pandemic. The current study explored whether executive control (EC) abilities in early childhood interact with COVID‐related stress to attenuate risk for adolescent psychopathology during the first 6 months of the pandemic. Methods: Participants were 337 youth (49% female) living in a small midwestern city in the United States. Participants completed EC tasks when they were approximately 4.5 years old as part of a longitudinal study investigating cognitive development. At annual laboratory visits during adolescence and before the pandemic, participants (Mage = 14.57) reported on mental health symptoms. In July and August of 2020, participants (Mage = 16.57) reported on COVID‐related stress and depression, anxiety, and trauma symptoms. Results: COVID‐related stress was associated with increased internalizing problems after controlling for prepandemic symptom levels. Further, the impact of COVID-related stress on adolescent internalizing problems was moderated by preschool EC, with higher levels of EC buffering the effects of COVID‐related stress on adolescent internalizing problems. Conclusions: Findings highlight the importance of promoting EC early in development, as well as screening for EC deficits and implementing targeted intervention strategies across the lifespan to help reduce the impact of stress on adolescent internalizing problems

Person-environment fit and retention of racially minoritized college students: Recommendations for faculty, support staff, and administrators

Although colleges in the United States have become increasingly racially and ethnically diverse, degree attainment remains disproportionately low among students from underrepresented and minoritized racial backgrounds. In this paper, we discuss the interactive influence of both person and environment factors in shaping academic persistence and argue that college administrators, faculty, and student support staff can intervene and take specific steps to improve the academic experience of racially minoritized college students. To this end, we offer specific evidence-based recommendations for campus leaders and stakeholders on how to adapt their campus community to facilitate the requisite person-environment fit to maximize academic persistence

Life in Hot Carbon Monoxide: The Complete Genome Sequence of Carboxydothermus hydrogenoformans Z-2901

We report here the sequencing and analysis of the genome of the thermophilic bacterium Carboxydothermus hydrogenoformans Z-2901. This species is a model for studies of hydrogenogens, which are diverse bacteria and archaea that grow anaerobically utilizing carbon monoxide (CO) as their sole carbon source and water as an electron acceptor, producing carbon dioxide and hydrogen as waste products. Organisms that make use of CO do so through carbon monoxide dehydrogenase complexes. Remarkably, analysis of the genome of C. hydrogenoformans reveals the presence of at least five highly differentiated anaerobic carbon monoxide dehydrogenase complexes, which may in part explain how this species is able to grow so much more rapidly on CO than many other species. Analysis of the genome also has provided many general insights into the metabolism of this organism which should make it easier to use it as a source of biologically produced hydrogen gas. One surprising finding is the presence of many genes previously found only in sporulating species in the Firmicutes Phylum. Although this species is also a Firmicutes, it was not known to sporulate previously. Here we show that it does sporulate and because it is missing many of the genes involved in sporulation in other species, this organism may serve as a “minimal” model for sporulation studies. In addition, using phylogenetic profile analysis, we have identified many uncharacterized gene families found in all known sporulating Firmicutes, but not in any non-sporulating bacteria, including a sigma factor not known to be involved in sporulation previously

Increased Myocardial Extracellular Volume in Active Idiopathic Systemic Capillary Leak Syndrome

BACKGROUND: The Systemic Capillary Leak Syndrome (SCLS) is a rare disorder of unknown etiology presenting as recurrent episodes of shock and peripheral edema due to leakage of fluid into soft tissues. Insights into SCLS pathogenesis are few due to the scarcity of cases, and the etiology of vascular barrier disruption in SCLS is unknown. Recent advances in cardiovascular magnetic resonance (CMR) allow for the quantitative assessment of the myocardial extracellular volume (ECV), which can be increased in conditions causing myocardial edema. We hypothesized that measurement of myocardial ECV may detect myocardial vascular leak in patients with SCLS. METHODS: Fifty-six subjects underwent a standard CMR examination at the NIH Clinical Center from 2009 until 2014: 20 patients with acute intermittent SCLS, six subjects with chronic SCLS, and 30 unaffected controls. Standard volumetric measurements; late gadolinium enhancement imaging and pre- and post-contrast T1 mapping were performed. ECV was calculated by calibration of pre- and post-contrast T1 values with blood hematocrit. RESULTS: Demographics and cardiac parameters were similar in both groups. There was no significant valvular disorder in either group. Subjects with chronic SCLS had higher pre-contrast myocardial T1 compared to healthy controls (T1: 1027 ± 44 v. 971 ± 41, respectively; p = 0.03) and higher myocardial ECV than patients with acute intermittent SCLS or controls: 33.8 ± 4.6, 26.9 ± 2.6, 26 ± 2.4, respectively; p = 0.007 v. acute intermittent; P = 0.0005 v. controls). When patients with chronic disease were analyzed together with five patients with acute intermittent disease who had just experienced an acute SCLS flare, ECV values were significantly higher than in subjects with acute intermittent SCLS in remission or age-matched controls and (31.2 ± 4.6 %, 26.5 ± 2.7 %, 26 ± 2.4 %, respectively; p = 0.01 v. remission, p = 0.001 v. controls). By contrast, T1 values did not distinguish these three subgroups (1008 ± 40, 978 ± 40, 971 ± 41, respectively, p = 0.2, active v. remission; p = 0.06 active v. controls). Abundant myocardial edema without evidence of acute inflammation was detected in cardiac tissue postmortem in one patient. CONCLUSIONS: Patients with active SCLS have significantly higher myocardial ECV than age-matched controls or SCLS patients in remission, which correlated with histopathological findings in one patient

An Integrated Biomechanical Model for Microgravity-Induced Visual Impairment

When gravitational unloading occurs upon entry to space, astronauts experience a major shift in the distribution of their bodily fluids, with a net headward movement. Measurements have shown that intraocular pressure spikes, and there is a strong suspicion that intracranial pressure also rises. Some astronauts in both short- and long-duration spaceflight develop visual acuity changes, which may or may not reverse upon return to earth gravity. To date, of the 36 U.S. astronauts who have participated in long-duration space missions on the International Space Station, 15 crew members have developed minor to severe visual decrements and anatomical changes. These ophthalmic changes include hyperopic shift, optic nerve distension, optic disc edema, globe flattening, choroidal folds, and elevated cerebrospinal fluid pressure. In order to understand the physical mechanisms behind these phenomena, NASA is developing an integrated model that appropriately captures whole-body fluids transport through lumped-parameter models for the cerebrospinal and cardiovascular systems. This data feeds into a finite element model for the ocular globe and retrobulbar subarachnoid space through time-dependent boundary conditions. Although tissue models and finite element representations of the corneo-scleral shell, retina, choroid and optic nerve head have been integrated to study pathological conditions such as glaucoma, the retrobulbar subarachnoid space behind the eye has received much less attention. This presentation will describe the development and scientific foundation of our holistic model