Effects of night-float shifts on cognitive function among radiology residents.

BACKGROUND: Many radiology programs utilize a night-float system to mitigate the effects of fatigue, improve patient care, and provide faster report turnaround times. Prior studies have demonstrated an increase in discrepancy rates during night-float shifts. OBJECTIVES: This study was performed to examine the effects of night-float shift work on radiology resident cognition. We hypothesized that there would be diminished cognitive function on testing following night-float shifts when compared to testing following day shifts. METHODS: Diagnostic radiology residents in their second to fifth years of residency at a single institution were recruited to participate in this pilot study. Cognitive function was evaluated using the Lumosity Neurocognitive Performance Tests (NCPT), standardized performance tests that provide real-time, objective measurements of cognitive function. Study participants completed the NCPT in 5 sessions following 5 consecutive day shifts to evaluate their baseline cognitive function. The tests were re-administered at the end of consecutive night-float shifts to assess for any changes. Sleep was objectively monitored using actigraphy devices worn around the wrist during all study weeks. Descriptive and summary statistics were performed. RESULTS: 23 prospectively recruited diagnostic radiology residents working night-float shifts took a mean 13.6 (± 5.1) neurocognitive performance tests during the study period. There was a statistically significant decline in 2 of the 6 cognitive tests administered, signifying a decrease in attention, speed, and complex reasoning ability. Night-float shifts were significantly longer than the day shifts and associated with a significantly higher study volume and cross-sectional study volume. Fitbit data demonstrated that there were no significant differences in level of activity while awake. However, participants slept significantly longer during day shifts. CONCLUSIONS: A sample of 23 radiology residents working night-float shifts demonstrated declines in attention, speed, and complex reasoning ability following sequential administration of standardized neurocognitive performance tests. While the sample size is small, these findings demonstrate the potential deleterious effects of night-float shift work and provide evidence to support further inquiry into this phenomenon.

Multi-omics analysis of green lineage osmotic stress pathways unveils crucial roles of different cellular compartments.

Maintenance of water homeostasis is a fundamental cellular process required by all living organisms. Here, we use the single-celled green alga Chlamydomonas reinhardtii to establish a foundational understanding of osmotic-stress signaling pathways through transcriptomics, phosphoproteomics, and functional genomics approaches. Comparison of pathways identified through these analyses with yeast and Arabidopsis allows us to infer their evolutionary conservation and divergence across these lineages. 76 genes, acting across diverse cellular compartments, were found to be important for osmotic-stress tolerance in Chlamydomonas through their functions in cytoskeletal organization, potassium transport, vesicle trafficking, mitogen-activated protein kinase and chloroplast signaling. We show that homologs for five of these genes have conserved functions in stress tolerance in Arabidopsis and reveal a novel PROFILIN-dependent stage of acclimation affecting the actin cytoskeleton that ensures tissue integrity upon osmotic stress. This study highlights the conservation of the stress response in algae and land plants, and establishes Chlamydomonas as a unicellular plant model system to dissect the osmotic stress signaling pathway.

Accuracy of Instrumented Mouthguards During Direct Jaw Impacts Seen in Boxing.

PURPOSE: Measuring head kinematics data is important to understand and develop methods and standards to mitigate head injuries in contact sports. Instrumented mouthguards (iMGs) have been developed to address coupling issues with previous sensors. Although validated with anthropomorphic test devices (ATDs), there is limited post-mortem human subjects (PMHS) data which provides more accurate soft tissue responses. This study evaluated two iMGs (Prevent Biometrics (PRE) and Diversified Technical Systems (DTS) in response to direct jaw impacts. METHODS: Three unembalmed male cadaver heads were properly fitted with two different boil-and-bite iMGs and impacted with hook (4 m/s) and uppercut (3 m/s) punches. A reference sensor (REF) was rigidly attached to the base of the skull, impact kinematics were transformed to the head center of gravity and linear and angular kinematic data were compared to the iMGs including Peak Linear Acceleration, Peak Angular Acceleration, Peak Angular Velocity, Head Injury Criterion (HIC), HIC duration, and Brain Injury Criterion. RESULTS: Compared to the REF sensor, the PRE iMG underpredicted most of the kinematic data with slopes of the validation regression line between 0.72 and 1.04 and the DTS overpredicted all the kinematic data with slopes of the regression line between 1.4 and 8.7. CONCLUSION: While the PRE iMG was closer to the REF sensor compared to the DTS iMG, the results did not support the previous findings reported with use of ATDs. Hence, our study highlights the benefits of using PMHS for validating the accuracy of iMGs since they closely mimic the human body compared to any ATD's mandible.

Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution.

During each cell cycle, the process of DNA replication timing is tightly regulated to ensure the accurate duplication of the genome. The extent and significance of alterations in this process during malignant transformation have not been extensively explored. Here, we assess the impact of altered replication timing (ART) on cancer evolution by analysing replication-timing sequencing of cancer and normal cell lines and 952 whole-genome sequenced lung and breast tumours. We find that 6%-18% of the cancer genome exhibits ART, with regions with a change from early to late replication displaying an increased mutation rate and distinct mutational signatures. Whereas regions changing from late to early replication contain genes with increased expression and present a preponderance of APOBEC3-mediated mutation clusters and associated driver mutations. We demonstrate that ART occurs relatively early during cancer evolution and that ART may have a stronger correlation with mutation acquisition than alterations in chromatin structure.

An injectable subunit vaccine containing Elongation Factor Tu and Heat Shock Protein 70 partially protects American bison from Mycoplasma bovis infection.

Mycoplasma bovis (M. bovis) is the etiologic agent of high mortality epizootics of chronic respiratory disease in American bison (Bison bison). Despite the severity of the disease, no efficacious commercial vaccines have been licensed for the prevention of M. bovis infection in bison. Elongation factor thermal unstable (EFTu) and Heat Shock Protein 70 (Hsp70, DnaK) are highly conserved, constitutively expressed proteins that have previously been shown to provide protection against M. bovis infection in cattle. To assess the suitability of EFTu and Hsp70 as vaccine antigens in bison, the immune response to and protection conferred by an injectable, adjuvanted subunit vaccine comprised of recombinantly expressed EFTu and Hsp70 was evaluated. Vaccinates developed robust antibody and cellular immune responses against both EFTu and Hsp70 antigens. To assess vaccine efficacy, unvaccinated control and vaccinated bison were experimentally challenged with bovine herpes virus-1 (BHV-1) 4 days prior to intranasal infection with M. bovis. Vaccinated bison displayed reductions in joint infection, lung bacterial loads, and lung lesions compared to unvaccinated controls. Together, these results showed that this subunit vaccine reduced clinical disease and bacterial dissemination from the lungs in M. bovis challenged bison and support the further development of protein subunit vaccines against M. bovis for use in bison.

Mohs Micrographic Surgery for Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The first-line treatment of the localized form of cutaneous squamous cell carcinoma (cSCC) remains surgical excision. Either conventional excision (CE) with margins or Mohs micrographic surgery (MMS) may be preferred, depending on the risk factors of cSCC, the characteristics of the tumor, and the available technical facilities. METHODS: This article presents a systematic review of the current literature spanning from 1974 to 2023, comparing outcomes of cSCC treated with MMS versus cSCC treated with conventional excision. RESULTS: Out of the 6821 records identified through the database search, a total of 156 studies were screened, of which 10 were included in the review. The majority of the included studies showed that treatment of cSCC with MMS consistently exhibits a significantly lower risk of recurrence compared to treatment with CE. In addition, MMS is emerging as the preferred technique for the resection of cSCC located in aesthetically or functionally challenging anatomical areas. CONCLUSION: The studies generally demonstrate that MMS is a safer and more effective treatment of cSCC than CE. Nevertheless, outcomes such as recurrence rates and cost-effectiveness should be assessed more precisely, in order to allow for a more tailored approach in determining the appropriate indication for the use of MMS.

Low- vs high-glycemic index Mediterranean-style eating patterns improved some domains of health-related quality of life but not sleep in adults at risk for type 2 diabetes: The MEDGICarb randomized controlled trial.

BACKGROUND: A healthy eating pattern such as the Mediterranean-style (MED-HEP) is associated with favorable effects on both cardiometabolic risk markers and self-reported health outcomes. Limited evidence exists regarding the influence of glycemic index (GI) of carbohydrate foods consumed within a healthy eating pattern on self-reported health-status and sleep. OBJECTIVE: To investigate the effects of a low- vs high-GI MED-HEP on changes in health-related quality of life (HRQoL) and sleep. METHODS: The MedGICarb-intervention trial is a 12-week randomized, controlled, parallel multi-center-trial in adults with at least two features of the metabolic syndrome. Participants consumed an eu-energetic diet profiled as a MED-HEP with either low GI (experimental) or high GI (control). HRQoL and sleep were measured with Medical Outcomes Study 36-Item Short Form Health Survey Version 2 (SF-36v2), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) at baseline and post-intervention. RESULTS: 160 adults with ≥ 2 features of the metabolic syndrome completed the intervention (53 % females, age 56 ± 10 y, BMI 31.0 ± 3.1 kg/m2). Low- vs high-GI MED-HEP resulted in differential changes between the groups in the HRQoL domains role physical (5.6 ± 2.2 AU vs -2.5 ± 2.5 AU) and vitality (6.9 ± 1.7 AU vs 0.0 ± 1.8 AU) (p < 0.05), which were driven mostly by improvements in the low-GI group. There were no significant differences between the MED-HEPs for changes in aggregated physical or mental components or for the other individual domains of HRQoL (physical functioning, bodily pain, general health, social functioning, role emotional and mental health) or for sleep quality or daytime sleepiness. CONCLUSIONS: Low compared to high GI in the context of a MED-HEP resulted in modest improvements in some, but not all, health domains of HRQoL. No major differences were seen between the groups for measures of sleep. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: The trial is registered in the public trial database Clinicaltrials.gov as NCT03410719, https://clinicaltrials.gov/study/NCT03410719?term=NCT03410719&rank=1.

Molecular dynamics study of the sonic horizon of microscopic Laval nozzles.

A Laval nozzle can accelerate expanding gas above supersonic velocities, while cooling the gas in the process. This work investigates this process for microscopic Laval nozzles by means of nonequilibrium molecular dynamics simulations of stationary flow, using grand-canonical Monte Carlo particle reservoirs. We study the steady-state expansion of a simple fluid, a monoatomic gas interacting via a Lennard-Jones potential, through an idealized nozzle with atomically smooth walls. We obtain the thermodynamic state variables pressure, density, and temperature but also the Knudsen number, speed of sound, velocity, and the corresponding Mach number of the expanding gas for nozzles of different sizes. We find that the temperature is well defined in the sense that the each velocity components of the particles obey the Maxwell-Boltzmann distribution, but it is anisotropic, especially for small nozzles. The velocity autocorrelation function reveals a tendency towards condensation of the cooled supersonic gas, although the nozzles are too small for the formation of clusters. Overall we find that microscopic nozzles act qualitatively like macroscopic nozzles in that the particles are accelerated to supersonic speeds while their thermal motion relative to the stationary flow is cooled. We find that, like macroscopic Laval nozzles, microscopic nozzles also exhibit a sonic horizon, which is well defined on a microscopic scale. The sonic horizon is positioned only slightly further downstream compared to isentropic expansion through macroscopic nozzles, where it is situated in the most narrow part. We analyze the sonic horizon by studying space-time density correlations, i.e., how thermal fluctuations at two positions of the gas density are correlated in time and find that after the sonic horizon there are indeed no upstream correlations on a microscopic scale.

A fluorogenic complementation tool kit for interrogating lipid droplet-organelle interaction.

Contact sites between lipid droplets and other organelles are essential for cellular lipid and energy homeostasis upon metabolic demands. Detection of these contact sites at the nanometer scale over time in living cells is challenging. We developed a tool kit for detecting contact sites based on fluorogen-activated bimolecular complementation at CONtact sites, FABCON, using a reversible, low-affinity split fluorescent protein, splitFAST. FABCON labels contact sites with minimal perturbation to organelle interaction. Via FABCON, we quantitatively demonstrated that endoplasmic reticulum (ER)- and mitochondria (mito)-lipid droplet contact sites are dynamic foci in distinct metabolic conditions, such as during lipid droplet biogenesis and consumption. An automated analysis pipeline further classified individual contact sites into distinct subgroups based on size, likely reflecting differential regulation and function. Moreover, FABCON is generalizable to visualize a repertoire of organelle contact sites including ER-mito. Altogether, FABCON reveals insights into the dynamic regulation of lipid droplet-organelle contact sites and generates new hypotheses for further mechanistical interrogation during metabolic regulation.

An Open-Label Phase II Study Assessing the Safety of Bilateral, Sequential Administration of Retinal Gene Therapy in Participants with Choroideremia: The GEMINI Study.

Choroideremia, an incurable, progressive retinal degeneration primarily affecting young men, leads to sight loss. GEMINI was a multicenter, open-label, prospective, two-period, interventional Phase II study assessing the safety of bilateral sequential administration of timrepigene emparvovec, a gene therapy, in adult males with genetically confirmed choroideremia (NCT03507686, ClinicalTrials.gov). Timrepigene emparvovec is an adeno-associated virus 2 (AAV2) vector encoding the cDNA of Rab escort protein 1 (REP1), augmented by a downstream woodchuck hepatitis virus post-transcriptional regulatory element (WPRE). Up to 0.1 mL of timrepigene emparvovec, containing 1×1011 vector genomes, was administered by subretinal injection following vitrectomy and retinal detachment. The second eye was treated after an intra-surgery window of <6, 6-12, or >12 months. Each eye was followed at up to nine visits over 12 months. Overall, 66 participants received timrepigene emparvovec and 53 completed the study. Visual acuity was generally maintained in both eyes, independent of intra-surgery window duration, even after bilateral retinal detachment and subretinal injection. Bilateral treatment was well tolerated, with predominantly mild or moderate treatment-emergent adverse events (TEAEs) and a low rate of serious surgical complications (7.6%). Retinal inflammation TEAEs were reported in 45.5% of participants, with similar rates in both eyes; post-hoc analyses found these were not associated with clinically significant vision loss at Month 12 versus baseline. Two participants (3.0%) reported serious noninfective retinitis. Prior timrepigene emparvovec exposure did not increase the risk of serious TEAEs or serious ocular TEAEs upon injection of the second eye; furthermore, no systemic immune reaction or inoculation effect was observed. Presence of anti-vector neutralizing antibodies at baseline was potentially associated with a higher percentage of TEAEs related to ocular inflammation or reduced visual acuity after injection of the first eye. The GEMINI study results may inform decisions regarding bilateral sequential administration of other gene therapies for retinal diseases.

Squamoid eccrine ductal carcinoma: clinical, histological and immunohistochemical features.

Squamoid eccrine ductal carcinoma (SEDC) is a cutaneous adnexal malignancy that is histologically challenging to distinguish from squamous cell carcinoma. We report three cases of this rare entity and review the present literature regarding clinical, histological, and immunohistochemical features. Patients presented with a single nodule or plaque lesion on their back and temple. The shave biopsies for Patient A and C were interpreted as SEDC. Patient B's initial shave biopsy was interpreted as probable surface of squamous cell carcinoma, and subsequent excision revealed SEDC. Ductal differentiation was confirmed by positive expression of epithelial membrane antigen and carcinoembryonic antigen immunostains in all three patients. Review of the 67 previously reported cases emphasizes the importance of diagnosing SEDC accurately and promptly given its potential for distant metastasis and mortality. Perineural or lymphatic invasion is associated with higher rate of recurrence or metastasis. There should be high pathologic suspicion for SEDC in an elderly patient presenting with a palpable lesion, even if located outside of the head and neck area, particularly when there is suggestion of ductal differentiation in a sample of a squamous neoplasm.

A pH-sensitive closed-loop nanomachine to control hyperexcitability at the single neuron level.

Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed. Here, we develop pH-sensitive inhibitory luminopsin (pHIL), a closed-loop chemo-optogenetic nanomachine composed of a luciferase-based light generator, a fluorescent sensor of intracellular pH (E2GFP), and an optogenetic actuator (halorhodopsin) for silencing neuronal activity. Stimulated by coelenterazine, pHIL experiences bioluminescence resonance energy transfer between luciferase and E2GFP which, under conditions of acidic pH, activates halorhodopsin. In primary neurons, pHIL senses the intracellular pH drop associated with hyperactivity and optogenetically aborts paroxysmal activity elicited by the administration of convulsants. The expression of pHIL in hippocampal pyramidal neurons is effective in decreasing duration and increasing latency of pilocarpine-induced tonic-clonic seizures upon in vivo coelenterazine administration, without affecting higher brain functions. The same treatment is effective in markedly decreasing seizure manifestations in a murine model of genetic epilepsy. The results indicate that pHIL represents a potentially promising closed-loop chemo-optogenetic strategy to treat drug-refractory epilepsy.

Liver-specific Mettl14 deletion induces nuclear heterotypia and dysregulates RNA export machinery.

Modification of RNA with N6-methyladenosine (m6A) has gained attention in recent years as a general mechanism of gene regulation. In the liver, m6A, along with its associated machinery, has been studied as a potential biomarker of disease and cancer, with impacts on metabolism, cell cycle regulation, and pro-cancer state signaling. However these observational data have yet to be causally examined in vivo. For example, neither perturbation of the key m6A writers Mettl3 and Mettl14, nor the m6A readers Ythdf1 and Ythdf2 have been thoroughly mechanistically characterized in vivo as they have been in vitro. To understand the functions of these machineries, we developed mouse models and found that deleting Mettl14 led to progressive liver injury characterized by nuclear heterotypia, with changes in mRNA splicing, processing and export leading to increases in mRNA surveillance and recycling.

Cellular and transcriptional profiles of peripheral blood mononuclear cells pre-vaccination predict immune response to preventative MUC1 vaccine.

A single arm trial (NCT007773097) and a double-blind, placebo controlled randomized trial ( NCT02134925 ) were conducted in individuals with a history of advanced colonic adenoma to test the safety and immunogenicity of the MUC1 tumor antigen vaccine and its potential to prevent new adenomas. These were the first two trials of a non-viral cancer vaccine administered in the absence of cancer. The vaccine was safe and strongly immunogenic in 43% (NCT007773097) and 25% ( NCT02134925 ) of participants. The lack of response in a significant number of participants suggested, for the first time, that even in a premalignant setting, the immune system may have already been exposed to some level of suppression previously reported only in cancer. Single-cell RNA-sequencing (scRNA-seq) on banked pre-vaccination peripheral blood mononuclear cells (PBMCs) from 16 immune responders and 16 non-responders identified specific cell types, genes, and pathways of a productive vaccine response. Responders had a significantly higher percentage of CD4+ naive T cells pre-vaccination, but a significantly lower percentage of CD8+ T effector memory (TEM) cells and CD16+ monocytes. Differential gene expression (DGE) and transcription factor inference analysis showed a higher level of expression of T cell activation genes, such as Fos and Jun, in CD4+ naive T cells, and pathway analysis showed enriched signaling activity in responders. Furthermore, Bayesian network analysis suggested that these genes were mechanistically connected to response. Our analyses identified several immune mechanisms and candidate biomarkers to be further validated as predictors of immune responses to a preventative cancer vaccine that could facilitate selection of individuals likely to benefit from a vaccine or be used to improve vaccine responses.

Special Section Guest Editorial: Molecular Neurophotonics.

The editorial introduces the Special Section on Molecular Neurophotonics.

Parent version of the Eating Disorder Examination: Reliability and validity in a treatment-seeking sample.

BACKGROUND: Assessment of eating disorders (ED) in youth relies heavily on self-report, yet persistent lack of recognition of the presence and/or seriousness of symptoms can be intrinsic to ED. This study examines the psychometric properties of a semi-structured interview, the parent version of the Eating Disorder Examination (PEDE), developed to systematically assess caregiver report of symptoms. METHODS: A multi-site, clinical sample of youth (N = 522; age range: 12 to 18 years) seeking treatment for anorexia nervosa (AN) and subsyndromal AN were assessed using the Eating Disorder Examination (EDE) for youth and the PEDE for collateral caregiver report. RESULTS: Internal consistencies of the four PEDE subscales were on par with established ranges for the EDE. Significant medium-sized correlations and poor to moderate levels of agreement were found between the corresponding subscales on each measure. For the PEDE, confirmatory factor analysis of the EDE four-factor model provided a poor fit; an exploratory factor analysis indicated that a 3-factor model better fits the PEDE. CONCLUSIONS: Findings suggest that the PEDE has psychometric properties on par with the original EDE. The addition of the caregiver perspective may provide incremental information that can aid in the assessment of AN in youth. Future research is warranted to establish psychometric properties of the PEDE in broader transdiagnostic ED samples.

Assessments for eating disorders rely primarily on self-report; yet, the denial of symptoms or symptom severity among adolescents with anorexia nervosa can complicate assessment and delay treatment in this population. The Parent Eating Disorder Examination (PEDE) is the first semi-structured interview formally developed to improve childhood eating disorder assessment by including caregiver perspectives. In this study, a large sample of adolescents with anorexia nervosa completed a self-report interview (the Eating Disorder Examination or EDE) and their parents completed the PEDE. The PEDE appeared to measure parents' report of their child's eating disorder symptoms consistently. Results from both interviews were related to one another but did not completely agree. This suggests that in an eating disorder assessment, the PEDE can provide additional information from caregivers that might reduce diagnostic confusion and lead to earlier intervention for youth with anorexia nervosa.

Deploying a metabolic dysfunction-associated steatohepatitis consensus care pathway: findings from an educational pilot in three health systems.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease, impacts 30% of the global population. This educational pilot focused on the role primary care providers may play in the delivery of guidelines-based metabolic dysfunction-associated steatohepatitis (MASH) care. OBJECTIVE: Accelerate the application of guidelines-based MASH care pathways to clinical workflows. METHODS: A panel of six hepatologists was convened in 2021 to develop the care pathway and the subsequent pilot occurred between 2022 - 2023. The pilot was conducted across three U.S. health systems: Boston Medical Center (Boston), Methodist Health System (Dallas), and Weill Cornell Medicine (New York). Clinicians were educated on the care pathway and completed baseline/follow-up assessments. 19 primary care clinicians participated in the educational pilot baseline assessment, nine primary care clinicians completed the two-month assessment, and 15 primary care clinicians completed the four-month assessment. The primary endpoint was to assess clinician-reported adherence to and satisfaction with the care pathway. The pilot was deemed exempt by the Western Consensus Group Institutional Review Board. RESULTS: At baseline, 38.10% (n = 8) of respondents felt they had received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and 42.86% (n = 9) had not referred any patients suspected of metabolic dysfunction-associated liver disease to hepatology within a month. At four months post-intervention, 79% (n = 15) of respondents agreed or strongly agreed they received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and there was a 25.7% increase in self-reported adherence to the institution's referral guidelines. Barriers to care pathway adherence included burden of manually calculating fibrosis-4 scores and difficulty ordering non-invasive diagnostics. CONCLUSIONS: With therapeutics anticipated to enter the market this year, health systems leadership must consider opportunities to streamline the identification, referral, and management of patients with metabolic dysfunction-associated steatohepatitis. Electronic integration of metabolic dysfunction-associated steatohepatitis care pathways may address implementation challenges.

Implementing evidence-based practices in rural settings: a scoping review of theories, models, and frameworks.

Background: Rural healthcare has unique characteristics that affect the dissemination and implementation of evidence-based interventions. Numerous theories, models, and frameworks have been developed to guide implementation of healthcare interventions, though not specific to rural healthcare. The present scoping review sought to identify the theories, models, and frameworks most frequently applied to rural health and propose an approach to rural health research that harnesses selected constructs from these theories, models, and frameworks. This resulting synthesis can serve as a guide to researchers, policy makers, and clinicians seeking to employ commonly used theories, models, and frameworks to rural health. Methods: We used the Scopus abstract indexing service to identify peer-reviewed literature citing one or more of theories, models, or frameworks used in dissemination and implementation research and including the word "rural" in the Title, Abstract, or Keywords. We screened the remaining titles and abstracts to ensure articles met additional inclusion criteria. We conducted a full review of the resulting 172 articles to ensure they identified one or more discrete theory, model, or framework applied to research or quality improvement projects. We extracted the theories, models, and frameworks and categorized these as process models, determinant frameworks, classic theories, or evaluation frameworks. Results: We retained 61 articles of which 28 used RE-AIM, 11 used Community-Based Participatory Research (CBPR) framework, eight used the Consolidated Framework for Implementation Research (CFIR), and six used the integrated-Promoting Action on Research Implementation in Health Services (iPARIHS). Additional theories, models, and frameworks were cited in three or fewer reports in the literature. The 14 theories, models, and frameworks cited in the literature were categorized as seven process models, four determinant frameworks, one evaluation framework, and one classic theory. Conclusions: The RE-AIM framework was the most frequently cited framework in the rural health literature, followed by CBPR, CFIR, and iPARIHS. A notable advantage of RE-AIM in rural healthcare settings is the focus on reach as a specified outcome, given the challenges of engaging a geographically diffuse and often isolated population. We present a rationale for combining the strengths of these theories, models, and frameworks to guide a research agenda specific to rural healthcare research. Systematic Review Registration: https://osf.io/fn2cd/.

Contrast Media in Pregnant and Lactating Patients, From the AJR Special Series on Contrast Media.

IV contrast media improve the diagnostic power of radiology examinations. These media include gadolinium-based contrast media and iron-oxide nanoparticles for MRI, iodinated contrast material for CT, microbubbles for ultrasound, and radiopharmaceuticals for nuclear medicine. As for all medications, contrast media carry risks, which may be heightened in the conditions of pregnancy and lactation. Radiologists must understand the potential risks from contrast media exposure to the pregnant patient, fetus, and nursing infant, as well as understand these administrations' impact on examinations' clinical utility. This article reviews the available literature on these media, along with key regulatory bodies' and professional societies' current recommendations for their use, in the settings of pregnancy and lactation. This knowledge should help radiologists make well-reasoned risk-benefit analyses regarding contrast media administration and provide informed consent discussions with pregnant and nursing patients in whom contrast media administration is being considered. This information and analysis can also assist facilities in designing policies and standard operating procedures of possible clinical benefit to the pregnant patient, fetus, or nursing infant, balancing contrast media exposure considerations versus augmented diagnostic capabilities.