Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) After Infection During Pregnancy.

OBJECTIVE: To estimate the prevalence of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) after infection with SARS-CoV-2 during pregnancy and to characterize associated risk factors. METHODS: In a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]-Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC, defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least 6 months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC. RESULTS: Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9-10.9%) measured at a median of 10.3 months (interquartile range 6.1-21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12-2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79-3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05-2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00-3.44) were associated with increased prevalence of PASC. CONCLUSION: The prevalence of PASC at a median time of 10.3 months after SARS-CoV-2 infection during pregnancy was 9.3% in the NIH RECOVER-Pregnancy Cohort. The predominant symptoms were postexertional malaise, fatigue, and gastrointestinal symptoms. Several socioeconomic and clinical characteristics were associated with PASC after infection during pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05172024.

Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers.

Butyrophilin (BTN) molecules are emerging as key regulators of T cell immunity; however, how they trigger cell-mediated responses is poorly understood. Here, the crystal structure of a gamma-delta T cell antigen receptor (γδTCR) in complex with BTN2A1 revealed that BTN2A1 engages the side of the γδTCR, leaving the apical TCR surface bioavailable. We reveal that a second γδTCR ligand co-engages γδTCR via binding to this accessible apical surface in a BTN3A1-dependent manner. BTN2A1 and BTN3A1 also directly interact with each other in cis, and structural analysis revealed formation of W-shaped heteromeric multimers. This BTN2A1-BTN3A1 interaction involved the same epitopes that BTN2A1 and BTN3A1 each use to mediate the γδTCR interaction; indeed, locking BTN2A1 and BTN3A1 together abrogated their interaction with γδTCR, supporting a model wherein the two γδTCR ligand-binding sites depend on accessibility to cryptic BTN epitopes. Our findings reveal a new paradigm in immune activation, whereby γδTCRs sense dual epitopes on BTN complexes.

ONeSAMP 3.0: Estimation of Effective Population Size via SNP Data from One Population.

The genetic effective size (Ne) is arguably one of the most important characteristics of a population as it impacts the rate of loss of genetic diversity. Methods that estimate Ne are important in population and conservation genetic studies as they quantify the risk of a population being inbred or lacking genetic diversity. Yet there are very few methods that can estimate the Ne from data from a single population and without extensive information about the genetics of the population, such as a linkage map, or a reference genome of the species of interest. We present ONeSAMP 3.0, an algorithm for estimating Ne from single nucleotide polymorphism (SNP) data collected from a single population sample using Approximate Bayesian Computation and local linear regression. We demonstrate the utility of this approach using simulated Wright-Fisher populations, and empirical data from five endangered Channel Island fox (Urocyon littoralis) populations to evaluate the performance of ONeSAMP 3.0 compared to a commonly used Ne estimator. Our results show that ONeSAMP 3.0 is is broadly applicable to natural populations and is flexible enough that future versions could easily include summary statistics appropriate for a suite of biological and sampling conditions. ONeSAMP 3.0 is publicly available under the GNU license at https://github.com/AaronHong1024/ONeSAMP_3.

Biliary atresia.

Biliary atresia (BA) is a progressive inflammatory fibrosclerosing disease of the biliary system and a major cause of neonatal cholestasis. It affects 1:5,000-20,000 live births, with the highest incidence in Asia. The pathogenesis is still unknown, but emerging research suggests a role for ciliary dysfunction, redox stress and hypoxia. The study of the underlying mechanisms can be conceptualized along the likely prenatal timing of an initial insult and the distinction between the injury and prenatal and postnatal responses to injury. Although still speculative, these emerging concepts, new diagnostic tools and early diagnosis might enable neoadjuvant therapy (possibly aimed at oxidative stress) before a Kasai portoenterostomy (KPE). This is particularly important, as timely KPE restores bile flow in only 50-75% of patients of whom many subsequently develop cholangitis, portal hypertension and progressive fibrosis; 60-75% of patients require liver transplantation by the age of 18 years. Early diagnosis, multidisciplinary management, centralization of surgery and optimized interventions for complications after KPE lead to better survival. Postoperative corticosteroid use has shown benefits, whereas the role of other adjuvant therapies remains to be evaluated. Continued research to better understand disease mechanisms is necessary to develop innovative treatments, including adjuvant therapies targeting the immune response, regenerative medicine approaches and new clinical tests to improve patient outcomes.

Remote dried blood spot collection for inflammatory markers in older adults is feasible, reliable, and valid.

Dried blood spots (DBS) provide a minimally invasive method to assess inflammatory markers and can be collected remotely at-home or in-person in the lab. However, there is a lack of methodological information comparing these different collection methods and in older adults. We investigated the feasibility (including adherence, yield, quality, and participant preferences) and measurement properties (reliability, validity) of remotely collected DBS inflammatory markers in older adults. Participants (N = 167, mean age = 72, range: 60-96 years) collected their own DBS (finger prick on filter paper) during three remote interviews over âˆ¼ 6 months. Within 4-5 days on average of their last remote interview, a subset of 41 participants also attended an in-person lab visit that included a researcher-collected DBS sample, venous blood draw, and survey to assess participant preferences of DBS collection. DBS and venous blood were assayed for CRP, IL-6, and TNF-α. Adherence: 98% of expected DBS samples (493 out of 501) were completed and mailed back to the lab. Yield: 97% of DBS samples were sufficient for all assays. Quality: On average, 0.80 fewer optimal spots (60uL of blood that filled the entire circle) were obtained remotely vs. in-person (p = 0.013), but the number of useable or better spots (at least 30-40uL of blood) did not differ (p = 0.89). Preference: A slight majority of participants (54%) preferred in-person DBS collection. Reliability: DBS test-retest reliabilities were good: CRP (ICC = 0.74), IL-6 (ICC = 0.76), and TNF-α (ICC = 0.70). Validity: Inflammatory levels from DBS correlated strongly with levels from venous blood (r = 0.60-0.99) and correlated as expected with sociodemographic and physical health and function variables. Older adults can remotely collect their own DBS to acquire reliable and valid inflammatory data. Remote DBS collection is highly feasible and may allow for inflammatory markers to be assessed in larger, more representative samples than are possible with lab- or clinic-based research designs.

Urinary microbiome community types associated with urinary incontinence severity in women.

BACKGROUND: Urinary microbiome (urobiome) studies have previously reported on specific taxa and community differences in women with mixed urinary incontinence compared with controls. Therefore, a hypothesis was made that higher urinary and vaginal microbiome diversity would be associated with increased urinary incontinence severity. OBJECTIVE: This study aimed to test whether specific urinary or vaginal microbiome community types are associated with urinary incontinence severity in a population of women with mixed urinary incontinence. STUDY DESIGN: This planned secondary, cross-sectional analysis evaluated associations between the urinary and vaginal microbiomes and urinary incontinence severity in a subset of Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial participants with urinary incontinence. Incontinence severity was measured using bladder diaries and Urinary Distress Inventory questionnaires collected at baseline. Catheterized urine samples and vaginal swabs were concurrently collected before treatment at baseline to assess the urinary and vaginal microbiomes. Of note, 16S rRNA V4 to V6 variable regions were sequenced, characterizing bacterial taxa to the genus level using the DADA2 pipeline and SILVA database. Using Dirichlet multinomial mixtures methods, samples were clustered into community types based on core taxa. Associations between community types and severity measures (Urinary Distress Inventory total scores, Urinary Distress Inventory subscale scores, and the number of urinary incontinence episodes [total, urgency, and stress] from the bladder diary) were evaluated using linear regression models adjusted for age and body mass index. In addition, alpha diversity measures for richness (total taxa numbers) and evenness (proportional distribution of taxa abundance) were analyzed for associations with urinary incontinence episodes and community type. RESULTS: Overall, 6 urinary microbiome community types were identified, characterized by varying levels of common genera (Lactobacillus, Gardnerella, Prevotella, Tepidimonas, Acidovorax, Escherichia, and others). The analysis of urinary incontinence severity in 126 participants with mixed urinary incontinence identified a Lactobacillus-dominated reference group with the highest abundance of Lactobacillus (mean relative abundance of 76%). A community characterized by fewer Lactobacilli (mean relative abundance of 19%) and greater alpha diversity was associated with higher total urinary incontinence episodes (2.67 daily leaks; 95% confidence interval, 0.76-4.59; P=.007) and urgency urinary incontinence episodes (1.75 daily leaks; 95% confidence interval, 0.24-3.27; P=.02) than the reference group. No significant association was observed between community type and stress urinary incontinence episodes or Urogenital Distress Inventory total or subscores. The composition of vaginal community types and urinary community types were similar but composed of slightly different bacterial taxa. Vaginal community types were not associated with urinary incontinence severity, as measured by bladder diary or Urogenital Distress Inventory total and subscale scores. Alpha diversity indicated that greater sample richness was associated with more incontinence episodes (observed genera P=.01) in urine. Measures of evenness (Shannon and Pielou) were not associated with incontinence severity in the urinary or vaginal microbiomes. CONCLUSION: In the urobiome of women with mixed urinary incontinence, a community type with fewer Lactobacilli and more diverse bacteria was associated with more severe urinary incontinence episodes (total and urgency) compared with a community type with high predominance of a single genus, Lactobacillus. Whether mixed urinary incontinence severity is due to lesser predominance of Lactobacillus, greater presence of other non-Lactobacillus genera, or the complement of bacteria consisting of urobiome community types remains to be determined.

Electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD): A modified study protocol.

OBJECTIVE: This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented. METHODS: Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants. RESULTS: Study is ongoing and open to enrollment. CONCLUSION: The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.

Simultaneous cortical, subcortical, and brainstem mapping of sensory activation.

Nonpainful tactile sensory stimuli are processed in the cortex, subcortex, and brainstem. Recent functional magnetic resonance imaging studies have highlighted the value of whole-brain, systems-level investigation for examining sensory processing. However, whole-brain functional magnetic resonance imaging studies are uncommon, in part due to challenges with signal to noise when studying the brainstem. Furthermore, differentiation of small sensory brainstem structures such as the cuneate and gracile nuclei necessitates high-resolution imaging. To address this gap in systems-level sensory investigation, we employed a whole-brain, multi-echo functional magnetic resonance imaging acquisition at 3T with multi-echo independent component analysis denoising and brainstem-specific modeling to enable detection of activation across the entire sensory system. In healthy participants, we examined patterns of activity in response to nonpainful brushing of the right hand, left hand, and right foot (n = 10 per location), and found the expected lateralization, with distinct cortical and subcortical responses for upper and lower limb stimulation. At the brainstem level, we differentiated the adjacent cuneate and gracile nuclei, corresponding to hand and foot stimulation respectively. Our findings demonstrate that simultaneous cortical, subcortical, and brainstem mapping at 3T could be a key tool to understand the sensory system in both healthy individuals and clinical cohorts with sensory deficits.

Biliary atresia: insights into mechanisms using a toxic model of the disease including Wnt and Hippo signaling pathways and microtubules.

BACKGROUND: Mechanisms underlying bile duct injury in biliary atresia (BA) remain unclear and mechanisms of bile duct repair are unknown. This study aimed to explore the roles of microtubule instability and Wnt and Hippo signaling pathways in a biliatresone-induced BA model. METHODS: Using primary murine neonatal cholangiocytes in both 2D and 3D cultures, and ex-vivo extra hepatic bile ducts (EHBD) which also has peri-cholangiocyte area, we analyzed injury and recovery processes. Injury was induced by the toxin biliatresone and recovery was induced by toxin wash-out. RESULTS: Microtubule stabilizer paclitaxel prevented biliatresone-induced injury, both to cholangiocytes as well as reduced periductal αSMA stain, this process is mediated by decreased glutathione levels. RhoU and Wnt11 (Wnt signaling) and Pard6g and Amotl1 (Hippo signaling) are involved in both injury and recovery processes, with the latter acting upstream to Wnt signaling. CONCLUSIONS: Early stages of biliatresone-induced EHBD injury in cholangiocytes and periductal structures are reversible. Wnt and Hippo signaling pathways play crucial roles in injury and recovery, providing insights into BA injury mechanisms and potential recovery avenues. IMPACT: Microtubule stabilization prevents cholangiocyte injury and lumen obstruction in a toxic model of biliary atresia (biliatresone induced). Early stages of biliatresone-induced injury, affecting both cholangiocytes and periductal structures, are reversible. Both Wnt and Hippo signaling pathways play a crucial role in bile duct injury and recovery, with a noted interplay between the two. Understanding mechanisms of cholangiocyte recovery is imperative to unveil potential therapeutic avenues.

Heterogeneity in suicide risk: Evidence from personalized dynamic models.

Most theories of suicide propose within-person changes in psychological states cause suicidal thoughts/behaviors; however, most studies use between-person analyses. Thus, there are little empirical data exploring current theories in the way they are hypothesized to occur. We used a form of statistical modeling called group iterative multiple model estimation (GIMME) to explore one theory of suicide: The Interpersonal Theory of Suicide (IPTS). GIMME estimates personalized statistical models for each individual and associations shared across individuals. Data were from a real-time monitoring study of individuals with a history of suicidal thoughts/behavior (adult sample: participants = 111, observations = 25,242; adolescent sample: participants = 145, observations = 26,182). Across both samples, none of theorized IPTS effects (i.e., contemporaneous effect from hopeless to suicidal thinking) were shared at the group level. There was significant heterogeneity in the personalized models, suggesting there are different pathways through which different people come to experience suicidal thoughts/behaviors. These findings highlight the complexity of suicide risk and the need for more personalized approaches to assessment and prediction.

Toward Alleviating Clinician Documentation Burden: A Scoping Review of Burden Reduction Efforts.

BACKGROUND: Studies have shown that documentation burden experienced by clinicians may lead to less direct patient care, increased errors, and job dissatisfaction. Implementing effective strategies within health care systems to mitigate documentation burden can result in improved clinician satisfaction and more time spent with patients. However, there is a gap in the literature regarding evidence-based interventions to reduce documentation burden. OBJECTIVES: The objective of this review was to identify and comprehensively summarize the state of the science related to documentation burden reduction efforts. METHODS: Following Joanna Briggs Institute Manual for Evidence Synthesis and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, we conducted a comprehensive search of multiple databases, including PubMed, Medline, Embase, CINAHL Complete, Scopus, and Web of Science. Additionally, we searched gray literature and used Google Scholar to ensure a thorough review. Two reviewers independently screened titles and abstracts, followed by full-text review, with a third reviewer resolving any discrepancies. Data extraction was performed and a table of evidence was created. RESULTS: A total of 34 articles were included in the review, published between 2016 and 2022, with a majority focusing on the United States. The efforts described can be categorized into medical scribes, workflow improvements, educational interventions, user-driven approaches, technology-based solutions, combination approaches, and other strategies. The outcomes of these efforts often resulted in improvements in documentation time, workflow efficiency, provider satisfaction, and patient interactions. CONCLUSION: This scoping review provides a comprehensive summary of health system documentation burden reduction efforts. The positive outcomes reported in the literature emphasize the potential effectiveness of these efforts. However, more research is needed to identify universally applicable best practices, and considerations should be given to the transfer of burden among members of the health care team, quality of education, clinician involvement, and evaluation methods.

Optimizing Opioid Prescription Quantity After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To test whether an individualized opioid-prescription protocol (IOPP) with a shared decision-making component can be used without compromising postcesarean pain management. METHODS: In this multicenter randomized controlled noninferiority trial, we compared IOPP with shared decision making with a fixed quantity of opioid tablets at hospital discharge. We recruited at 31 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Study participants had uncomplicated cesarean births. Follow-up occurred through 12 weeks postdischarge. Individuals with complicated cesarean births or history of opioid use in the pregnancy were excluded. Participants were randomized 1:1 to IOPP with shared decision making or fixed quantity (20 tablets of 5 mg oxycodone). In the IOPP group, we calculated recommended tablet quantity based on opioid use in the 24 hours before discharge. After an educational module and shared decision making, participants selected a quantity of discharge tablets (up to 20). The primary outcome was moderate to severe pain (score 4 or higher [possible range 0-10]) on the BPI (Brief Pain Inventory) at 1 week after discharge. A total sample size of 5,500 participants was planned to assess whether IOPP with shared decision making was not inferior to the fixed quantity of 20 tablets. RESULTS: From September 2020 to March 2022, 18,990 individuals were screened and 5,521 were enrolled (n=2,748 IOPP group, n=2,773 fixed-quantity group). For the primary outcome, IOPP with shared decision making was not inferior to fixed quantity (59.5% vs 60.1%, risk difference 0.67%; 95% CI, -2.03% to 3.37%, noninferiority margin -5.0) and resulted in significantly fewer tablets received (median 14 [interquartile range 4-20] vs 20, P <.001) through 90 days postpartum. CONCLUSION: Compared with fixed quantity, IOPP with shared decision making was noninferior for outpatient postcesarean analgesia at 1 week postdischarge and resulted in fewer prescribed opioid tablets at discharge. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04296396.

Assessing Contraceptive Switching and Discontinuation Over 3 Years in the HER Salt Lake Study.

OBJECTIVE: To assess contraceptive switching and discontinuation among participants enrolled in a contraceptive access project over 3 years and to identify variables associated with contraceptive change. METHODS: The HER Salt Lake study enrolled individuals between 2015 and 2017 from four clinics in Salt Lake County into a prospective, longitudinal cohort. All participants were able to switch or discontinue at no cost (between March 2016 and March 2020). We collected eight follow-up surveys over 3 years after enrollment. Each survey wave included questions about method use in the previous 4 weeks. We categorized participants in three ways, allowing for time-varying outcomes by wave: 1) those who reported using the same method as previous wave (continuers), 2) those who reported using a different method from previous wave (switchers), and 3) those who reported using no contraceptive method at that wave (discontinuers). We report the frequency of outcomes and conducted multinomial regression models assessing predictors of switching and discontinuation. RESULTS: Among 4,289 participants included in this analysis, 2,179 (50.8%) reported at least one instance of switching or discontinuation, and 2,110 (49.1%) reported continuing with their baseline method at the end of the study. Those reporting method change (switching or discontinuing) reported an average of 1.93 change events over the study follow-up period (range 1-8). Among those reporting any method change, 522 participants (23.9%) reporting at least one instance of both switching and discontinuation. Among those reporting any instance of discontinuation (n=966), 498 (51.6%) never reported uptake of a subsequent method. Among those who did report a subsequent method (n=468), 210 (44.8%) reported restarting a previously used method, and 258 (55.1%) reported starting a new method. Although we identified overlap among variables associated with switching and discontinuation, other predictors were discordant between switching and discontinuation. CONCLUSION: New contraceptive users commonly switch and discontinue methods. User behavior is associated with certain demographic characteristics and pregnancy planning. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02734199.

Validation of an ICD-Code-Based Case Definition for Psychotic Illness Across Three Health Systems.

BACKGROUND AND HYPOTHESIS: Psychosis-associated diagnostic codes are increasingly being utilized as case definitions for electronic health record (EHR)-based algorithms to predict and detect psychosis. However, data on the validity of psychosis-related diagnostic codes is limited. We evaluated the positive predictive value (PPV) of International Classification of Diseases (ICD) codes for psychosis. STUDY DESIGN: Using EHRs at 3 health systems, ICD codes comprising primary psychotic disorders and mood disorders with psychosis were grouped into 5 higher-order groups. 1133 records were sampled for chart review using the full EHR. PPVs (the probability of chart-confirmed psychosis given ICD psychosis codes) were calculated across multiple treatment settings. STUDY RESULTS: PPVs across all diagnostic groups and hospital systems exceeded 70%: Mass General Brigham 0.72 [95% CI 0.68-0.77], Boston Children's Hospital 0.80 [0.75-0.84], and Boston Medical Center 0.83 [0.79-0.86]. Schizoaffective disorder PPVs were consistently the highest across sites (0.80-0.92) and major depressive disorder with psychosis were the most variable (0.57-0.79). To determine if the first documented code captured first-episode psychosis (FEP), we excluded cases with prior chart evidence of a diagnosis of or treatment for a psychotic illness, yielding substantially lower PPVs (0.08-0.62). CONCLUSIONS: We found that the first documented psychosis diagnostic code accurately captured true episodes of psychosis but was a poor index of FEP. These data have important implications for the case definitions used in the development of risk prediction models designed to predict or detect undiagnosed psychosis.

On the relationship between viscoelasticity and water diffusion in soft biological tissues.

Magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) are complementary imaging techniques that detect disease based on viscoelasticity and water mobility, respectively. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering the clinical translation of combined DWI-MRE markers. We used DWI-MRE to study 129 biomaterial samples including native and cross-linked collagen, glycosaminoglycans (GAGs) with different sulfation levels, and decellularized specimens of pancreas and liver, all with different proportions of solid tissue, or solid fractions. We developed a theoretical framework of the relationship between mechanical loss and tissue-water mobility based on two parameters, solid and fluid viscosity. These parameters revealed distinct DWI-MRE property clusters characterizing weak, moderate, and strong water-network interactions. Sparse networks interacting weakly with water, such as collagen or diluted decellularized tissue, resulted in marginal changes in water diffusion over increasing solid viscosity. In contrast, dense networks with larger solid fractions exhibited both free and hindered water diffusion depending on the polarity of the solid components. For example, polar and highly sulfated GAGs as well as native soft tissues hindered water diffusion despite relatively low solid viscosity. Our results suggest that two fundamental properties of tissue networks, solid fraction and network polarity, critically influence solid and fluid viscosity in biological tissues. Since clinical DWI and MRE are sensitive to these viscosity parameters, the framework we present here can be used to detect tissue remodeling and architectural changes in the setting of diagnostic imaging. STATEMENT OF SIGNIFICANCE: The viscoelastic properties of biological tissues provide a wealth of information on the vital state of cells and host matrix. Combined measurement of viscoelasticity and water diffusion by medical imaging is sensitive to tissue microarchitecture. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering full exploitation of these properties as a combined clinical biomarker. Therefore, we analyzed the parameter space accessible by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) and developed a theoretical framework for the relationship between water mobility and mechanical parameters in biomaterials. Our theory of solid material properties related to particle motion can be translated to clinical radiology using clinically established MRE and DWI.

Do people know how suicidal they will be? Understanding suicidal prospection.

INTRODUCTION: Little research has been done on how people mentally simulate future suicidal thoughts and urges, a process we term suicidal prospection. METHODS: Participants were 94 adults with recent suicidal thoughts. Participants completed a 42-day real-time monitoring study and then a follow-up survey 28 days later. Each night, participants provided predictions for the severity of their suicidal thoughts the next day and ratings of the severity of suicidal thoughts over the past day. We measured three aspects of suicidal prospection: predicted levels of desire to kill self, urge to kill self, and intent to kill self. We generated prediction errors by subtracting participants' predictions of the severity of their suicidal thoughts from their experienced severity. RESULTS: Participants tended to overestimate (although the average magnitude was small and the modal error was zero) the severity of their future suicidal thoughts. The best fitting models suggested that participants used both their current suicidal thinking and previous predictions of their suicidal thinking to generate predictions of their future suicidal thinking. Finally, the average severity of predicted future suicidal thoughts predicted the number of days participants thought about suicide during the follow-up period. CONCLUSIONS: This study highlights prospection as a psychological process to better understand suicidal thoughts and behaviors.

In Utero Extrahepatic Bile Duct Damage and Repair: Implications for Biliary Atresia.

Biliary atresia (BA) is a cholangiopathy affecting the extrahepatic bile duct (EHBD) of newborns. The etiology and pathophysiology of BA are not fully understood; however, multiple causes of damage and obstruction of the neonatal EHBD have been identified. Initial damage to the EHBD likely occurs before birth. We discuss how different developmental stages in utero and birth itself could influence the susceptibility of the fetal EHBD to damage and a damaging wound-healing response. We propose that a damage-repair response of the fetal and neonatal EHBD involving redox stress and a program of fetal wound healing could-regardless of the cause of the initial damage-lead to either obstruction and BA or repair of the duct and recovery. This overarching concept should guide future research targeted toward identification of factors that contribute to recovery as opposed to progression of injury and fibrosis. Viewing BA through the lens of an in utero damage-repair response could open up new avenues for research and suggests exciting new therapeutic targets.

Basic science knowledge underlies clinical science knowledge and clinical problem solving: evidence from veterinary medicine.

Medical sciences education emphasizes basic science learning as a prerequisite to clinical learning. Studies exploring relationships between achievement in the basic sciences and subsequent achievement in the clinical sciences generally suggest a significant positive relationship. Basic science knowledge and clinical experience are theorized to combine to form encapsulated knowledge- a dynamic mix of information that is useful for solving clinical problems. This study explores the relationship between basic science knowledge (BSK), clinical science knowledge (CSK), and clinical problem-solving ability, as measured within the context of four veterinary colleges using both college-specific measures and professionally validated, standardized measures of basic and clinical science knowledge and problem-solving ability. Significant correlations existed among all variables. Structural equation modeling and confirmatory factor analysis were used to produce models showing that newly acquired BSK directly and significantly predicted BSK retained over time and newly acquired CSK, as well as indirectly predicted clinical problem-solving ability (mediated by newly acquired CSK and BSK retained over time). These findings likely suggest a gradual development of schema (encapsulated knowledge) and not an isolated development of biomedical versus clinical knowledge over time. A broader implication of these results is that explicitly teaching basic science knowledge positively and durably affects subsequent clinical knowledge and problem-solving ability independent of instructional strategy or curricular approach. Furthermore, for veterinary colleges specifically, student performance as measured by both course-level and standardized tests are likely to prove useful for predicting subsequent academic achievement in classroom and clinical settings, licensing examination performance, and/or for identifying students likely in need of remediation in clinical knowledge.