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Dissemination and implementation (D&I) researchers serve critical scientific, practical, and personal roles in translating science to public health benefit. However, they face multifaceted barriers that may erode their capacity to plan, lead, and evaluate implementation. Individualized coaching focused on human flourishing is an unexplored approach to fully actualize D&I researchers’ capacity to bridge the research-practice gap. The purpose of this exploratory pilot study was to investigate a tailored coaching program to support human flourishing among D&I researchers. A pragmatic, mixed-methods approach guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) Framework was used to evaluate an individualized, nine session coaching program called FUEL (Focus, Unplug, Exercise, Love). Reach and Implementation were assessed through descriptive statistics and rapid qualitative analysis of surveys and coaching logs. Effectiveness and Maintenance were assessed through descriptive statistics and iterative content analysis of participant surveys, as well as iterative content analysis of proxy (e.g., colleague) semi-structured interviews. Reach results indicated that demand for coaching exceeded study enrollment capacity (n = 16 participants). Implementation results showed that the coach spent 12.96 ± 2.82 hr per participant over 3 months. Effectiveness and Maintenance results indicated that FUEL was well-received and provided participants with myriad psychological and professional benefits. Preliminary evidence suggests that the FUEL coaching program is a promising and feasible approach to enhance flourishing among D&I researchers. Future research is needed to evaluate Adoption and scalability. This pilot study may inform future D&I capacity-building initiatives that address researchers’ holistic situatedness within the implementation process.

Maintaining water balance is essential for organismal health, and lactating females must balance individual needs with milk production and offspring hydration. Primate milk is dilute and presumed to be the primary source for infant hydration for a considerable time period. Few studies have investigated the hydration burden that lactation may place on female primates. In this study, we investigated sources of variation in female and offspring drinking frequency among wild chimpanzees (Pan troglodytes). We hypothesized females would experience seasonal and lactation hydration burdens and adjust their drinking behavior to accommodate these, but this hydration burden would vary between females of different dominance ranks. We also predicted that parity would relate to maternal drinking frequency since primiparous females are still investing in their own growth. Finally, we predicted that offspring would drink more in the dry season and as they aged and lost milk as a water source, but that offspring of high-ranking females would be buffered from these effects. Using 41 years of long-term data on the behavior of mothers and offspring of Gombe National Park, we found that mothers drank more in the dry season, but there was no significant difference between mothers of different ranks during this period. Low-ranking females drank significantly more than mid- and high-ranking females during late lactation. Offspring also drank more in the dry season and as they aged, but there was no evidence of buffering for those with high-ranking mothers. While chimpanzees in our study population drank infrequently, they do demonstrate noticeable shifts in drinking behavior that suggests seasonal and reproductive hydration burdens.

Importance Ten years have passed since the Institute of Medicine (IOM) released its recommendations for gestational weight gain (GWG), based on a woman's prepregnancy body mass index. Despite this, the majority of women do not gain the appropriate gestational weight; most women gain too much weight, and a small but substantial number gain too little. Objective We review the literature concerning GWG, the opinions and practices of clinicians in managing their patients' weight, and how these practices are perceived by patients. We also review several randomized control trials that investigate the efficacy of clinical intervention in managing GWG. Evidence Acquisition A literature review search was conducted with no limitations on the number of years searched. Results The number of clinicians who are aware of and use the IOM recommendations has increased, but the prevalence of inappropriate GWG has not decreased. Clinicians report feeling less than confident in their ability to have an impact on their patients' weight gain, and there are discrepancies between what clinicians and patients report regarding counseling. Many randomized control trials demonstrate a beneficial impact of clinical intervention, highlighting the importance of collaboration and technology to provide educational information and support throughout a pregnancy. Conclusions Pregnancy provides an opportunity for clinicians to have open and direct conversations with their patients about their weight. Providing clinicians with the tools, skillset, and confidence to assist in the management of GWG is essential to the health of women and their children, and warrants further investigation.

Lyme disease diagnostic workups conducted on active and retired U.S. service members and their dependents at U.S. Air Force military treatment facilities (MTFs) in Germany between 2013 and 2017 were assessed to determine the appropriateness of laboratory testing and antibiotic prescriptions. Of the 1,176 first-tier immunoassays, 1,114 (94.7%) were negative, and of the 285 immunoglobulin M (IgM) immunoblots, 242 (84.9%) followed a negative first-tier assay or were performed without an antecedent first-tier assay. Eighty-three positive IgM immunoblot tests were adjudicated using modified published criteria, of which 40 (48.2%) were deemed false positives. Thirtytwo patients with false-positive tests were treated with an antibiotic. Additionally, 30 patients with uncomplicated erythema migrans could have been treated without laboratory confirmation. Understanding the use and limitations of 2-tier diagnostic criteria, as well as the common pitfalls in diagnosing Lyme disease, may help prevent overdiagnosis, reduce unnecessary testing, and promote antibiotic stewardship.

To determine the benefit of the addition of low-fidelity simulation-based training to the standard didactic-based training in teaching radiology residents common CT-guided procedures.This was a prospective study involving 24 radiology residents across all years in a university program. All residents underwent standard didactic lecture followed by low-fidelity simulation-based training on three common CT-guided procedures: random liver biopsy, lung nodule biopsy, and drain placement. Baseline knowledge, confidence, and performance assessments were obtained after the didactic session and before the simulation training session. Approximately 2 months later, all residents participated in a simulation-based training session covering all three of these procedures. Knowledge, confidence, and performance data were obtained afterward. These assessments covered topics related to preprocedure workup, intraprocedure steps, and postprocedure management. Knowledge data were collected based on a 15-question assessment. Confidence data were obtained based on a 5-point Likert-like scale. Performance data were obtained based on successful completion of predefined critical steps.There was significant improvement in knowledge (P = .005), confidence (P.008), and tested performance (P.043) after the addition of simulation-based training to the standard didactic curriculum for all procedures.This study suggests that the addition of low-fidelity simulation-based training to a standard didactic-based curriculum is beneficial in improving resident knowledge, confidence, and tested performance of common CT-guided procedures.

Herein, we examine the synergistic impact of both ion clustering and block copolymer morphology on ion conductivity in two polymerized ionic liquid (PIL) diblock copolymers with similar chemistries but different side alkyl spacer chain lengths (ethyl versus undecyl). When saturated in liquid water, water/ion clusters were observed only in the PIL block copolymer with longer alkyl side chains (undecyl) as evidenced by both small-angle neutron scattering and intermediate-angle X-ray scattering, i.e., water/ion clusters form within the PIL microdomain under these conditions. The resulting bromide ion conductivity in the undecyl sample was higher than the ethyl sample (14.0 mS cm(-1)versus 6.1 mS cm(-1) at 50 °C in liquid water) even though both samples had the same block copolymer morphology (lamellar) and the undecyl sample had a lower ion exchange capacity (0.9 meq g(-1)versus 1.4 meq g(-1)). No water/ion clusters were observed in either sample under high humidity or dry conditions. The resulting ion conductivity in the undecyl sample with lamellar morphology was significantly higher in the liquid water saturated state compared to the high humidity state (14.0 mS cm(-1)versus 4.2 mS cm(-1)), whereas there was no difference in ion conductivity in the ethyl sample when comparing these two states. These results show that small chemical changes to ion-containing block copolymers can induce water/ion clusters within block copolymer microdomains and this can subsequently have a significant effect on ion transport.

TRIM5α is an interferon-inducible retroviral restriction factor that prevents infection by inducing the abortive disassembly of capsid cores recognized by its C-terminal PRY/SPRY domain. The mechanism by which TRIM5α mediates the disassembly of viral cores is poorly understood. Previous studies demonstrated that proteasome inhibitors abrogate the ability of TRIM5α to induce premature core disassembly and prevent reverse transcription; however, viral infection is still inhibited, indicating that the proteasome is partially involved in the restriction process. Alternatively, we and others have observed that TRIM5α associates with proteins involved in autophagic degradation pathways, and one recent study found that autophagic degradation is required for the restriction of retroviruses by TRIM5α. Here, we show that TRIM5α is basally degraded via autophagy in the absence of restriction-sensitive virus. We observe that the autophagy markers LC3b and lysosome-associated membrane protein 2A (LAMP2A) localize to a subset of TRIM5α cytoplasmic bodies, and inhibition of lysosomal degradation with bafilomycin A1 increases this association. To test the requirement for macroautophagy in restriction, we examined the ability of TRIM5α to restrict retroviral infection in cells depleted of the autophagic mediators ATG5, Beclin1, and p62. In all cases, restriction of retroviruses by human TRIM5α, rhesus macaque TRIM5α, and owl monkey TRIM-Cyp remained potent in cells depleted of these autophagic effectors by small interfering RNA (siRNA) knockdown or clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 genome editing. Collectively, these results are consistent with observations that the turnover of TRIM5α proteins is sensitive to autophagy inhibition; however, the data presented here do not support observations that the inhibition of autophagy abrogates retroviral restriction by TRIM5 proteins. IMPORTANCE Restriction factors are a class of proteins that inhibit viral replication. Following fusion of a retrovirus with a host cell membrane, the retroviral capsid is released into the cytoplasm of the target cell. TRIM5α inhibits retroviral infection by promoting the abortive disassembly of incoming retroviral capsid cores; as a result, the retroviral genome is unable to traffic to the nucleus, and the viral life cycle is extinguished. In the process of restriction, TRIM5α itself is degraded by the proteasome. However, in the present study, we have shown that in the absence of a restriction-sensitive virus, TRIM5α is degraded by both proteasomal and autophagic degradation pathways. Notably, we observed that restriction of retroviruses by TRIM5α does not require autophagic machinery. These data indicate that the effector functions of TRIM5α can be separated from its degradation and may have further implications for understanding the mechanisms of other TRIM family members.

Background Assessment of weight and counselling on nutrition and physical activity is infrequently conducted during well child visits, despite recent expert recommendations. Objective We investigated whether automatic calculation of body mass index (BMI) in an electronic health record improved assessment of weight and counselling on nutrition and physical activity. Methods Retrospective review of well child visit records of children between two and 18 years of age (n=550) before and after implementation of an electronic health record system at an academic medical centre's paediatric clinic. Body mass index was automatically calculated and presented within the electronic health record. We measured clinicians' documentation of assessment of weight status, and assessment of and counselling for nutrition and physical activity risk factors. Results Documentation of assessment of BMI and weight status did not increase. There were no consistent increases in assessment for or counselling on specific nutrition and physical activity behaviours, except with respect to high calorie food intake. Although overall assessment of physical activity decreased, physical activity counselling significantly increased. Documentation of the presence of highrisk family history increased significantly; the provision of counselling for high-risk family history did not show any corresponding increase. Patients with higher BMI percentile scores were more completely assessed for weight status. Completeness of weight status assessment was associated with increased counselling for nutrition and physical activity. Conclusions Passive changes, such as automatic calculation of BMI, are insufficient to result in systematic improvements in assessment of weight and counselling for nutrition and physical activity.

Arabidopsis mutants containing gene disruptions in AHA1 and AHA2, the two most highly expressed isoforms of the Arabidopsis plasma membrane H(+)-ATPase family, have been isolated and characterized. Plants containing homozygous loss-of-function mutations in either gene grew normally under laboratory conditions. Transcriptome and mass spectrometric measurements demonstrate that lack of lethality in the single gene mutations is not associated with compensation by increases in RNA or protein levels. Selected reaction monitoring using synthetic heavy isotope-labeled C-terminal tryptic peptides as spiked standards with a triple quadrupole mass spectrometer revealed increased levels of phosphorylation of a regulatory threonine residue in both isoforms in the mutants. Using an extracellular pH assay as a measure of in vivo ATPase activity in roots, less proton secreting activity was found in the aha2 mutant. Among 100 different growth conditions, those that decrease the membrane potential (high external potassium) or pH gradient (high external pH) caused a reduction in growth of the aha2 mutant compared with wild type. Despite the normal appearance of single mutants under ideal laboratory growth conditions, embryos containing homozygous double mutations are lethal, demonstrating that, as expected, this protein is absolutely essential for plant cell function. In conclusion, our results demonstrate that the two genes together perform an essential function and that the effects of their single mutations are mostly masked by overlapping patterns of expression and redundant function as well as by compensation at the post-translational level.

The metabolic syndrome is a constellation of specific anthropometric, physiological, and biochemical abnormalities predisposing affected individuals to the development of diabetes and cardiovascular disease. The syndrome is well described in the adult literature. However, its description in the pediatric literature is more limited. Due in large part to the normal physiological changes that occur in children and adolescents with respect to growth and puberty, investigators have also struggled to establish a standard definition of the syndrome in the pediatric age group, hindering coordinated research efforts. However, whatever definition of the syndrome is used, the prevalence of the metabolic syndrome in the pediatric age group has increased worldwide. Insulin resistance is the principal metabolic abnormality that is common to the development of the metabolic syndrome in both children and adults. This review summarizes current research regarding the pathophysiology of insulin resistance and how this may contribute to specific abnormalities seen in children and adolescents with the metabolic syndrome. Specifically, insulin resistance in pediatric patients is correlated with cardiovascular risk factors such as elevated blood pressure, dyslipidemia, and type 2 diabetes mellitus, all of which are significant risk factors for adult disease. In addition, current treatment and prevention strategies, including lifestyle modifications, pharmacologic agents, and certain surgical therapies, are highlighted. The need for collaborative changes at the family, school, city, state, and national levels to address the growing prevalence of the metabolic syndrome in the pediatric age group is also reviewed.

The goal of this review is to discuss post-irradiation analysis of low-energy (≤50 eV) electron-induced processes in nanoscale thin films. Because electron-induced surface reactions in monolayer adsorbates have been extensively reviewed, we will instead focus on low-energy electron-induced reactions in multilayer adsorbates. The latter studies, involving nanoscale thin films, serve to elucidate the pivotal role that the low-energy electron-induced reactions play in high-energy radiation-induced chemical reactions in condensed matter. Although electron-stimulated desorption (ESD) experiments conducted during irradiation have yielded vital information relevant to primary or initial electron-induced processes, we wish to demonstrate in this review that analyzing the products following low-energy electron irradiation can provide new insights into radiation chemistry. This review presents studies of electron-induced reactions in nanoscale films of molecular species such as oxygen, nitrogen trifluoride, water, alkanes, alcohols, aldehydes, ketones, carboxylic acids, nitriles, halocarbons, alkane and phenyl thiols, thiophenes, ferrocene, amino acids, nucleotides, and DNA using post-irradiation techniques such as temperature-programmed desorption (TPD), reflection–absorption infrared spectroscopy (RAIRS), X-ray photoelectron spectroscopy (XPS), high-resolution electron energy loss spectroscopy (HREELS), gel electrophoresis, and microarray fluorescence. Post-irradiation temperature-programmed desorption, in particular, has been shown to be useful in identifying labile radiolysis products as demonstrated by the first identification of methoxymethanol as a reaction product of methanol radiolysis. Results of post-irradiation studies have been used not only to identify radiolysis products, but also to determine the dynamics of electron-induced reactions. For example, studies of the radiolysis yield as a function of incident electron energy have shown that dissociative electron attachment plays an important role in the electron-induced single strand breaks in DNA leading to mutagenic damage. Studies such as these not only provide insight into the fundamentals of electron–molecule interactions in the condensed phase but also may provide information valuable to (a) furthering cost-efficient destruction of hazardous chemicals, (b) understanding the electron-induced decomposition of feed gases used in the plasma processing of semiconductor devices, (c) clarifying the role, if any, of low-energy electrons, produced by cosmic rays, contributing to the formation of the ozone hole by interacting with halocarbons and producing Cl atoms, (d) illuminating the dynamics of electron-induced oligomerization and/or polymerization, and (e) explicating the astrochemistry of icy grains.

We report on a 5-year-old male with expressive language delay, developmental delay, short stature, and facial anomalies consistent with Floating–Harbor syndrome (FHS). In addition, he developed an intramedullary ganglioglioma. This is the first reported case of a tumor associated with FHS, and may represent an as yet undefined genetic link between spinal cord tumors and FHS, adding this syndrome to the growing list of disorders with a predisposition for tumor development. © 2009 Wiley-Liss, Inc.

Our primary objective in this study was to determine the preferred strength setting for the sinogram- affirmed iterative reconstruction algorithm (SAFIRE) in abdominal computed tomography (CT) imaging. Sixteen consecutive clinical CT scans of the abdomen were reconstructed by use of traditional filtered back projection (FBP) and 5 SAFIRE strengths: S1-S5. Six readers of differing experience were asked to rank the images on preference for overall diagnostic quality. The contrast-to- noise ratio was not significantly different between SAFIRE S1 and FBP, but increased with increasing SAFIRE strength. For pooled data, S2 and S3 were preferred equally but both were preferred over all other reconstructions. S5 was the least preferred, with FBP the next least preferred. This represents a marked disparity between the image quality based on quantitative parameters and qualitative preference. Care should be taken to factor in qualitative in addition to quantitative aspects of image quality when one is optimizing iterative reconstruction images.

There is an active interest in peptides that readily cross cell membranes without the assistance of cell membrane receptors(1). Many of these are referred to as cell-penetrating peptides, which are frequently noted for their potential as drug delivery vectors(1-3). Moreover, there is increasing interest in antimicrobial peptides that operate via non-membrane lytic mechanisms(4,5), particularly those that cross bacterial membranes without causing cell lysis and kill cells by interfering with intracellular processes(6,7). In fact, authors have increasingly pointed out the relationship between cell-penetrating and antimicrobial peptides(1,8). A firm understanding of the process of membrane translocation and the relationship between peptide structure and its ability to translocate requires effective, reproducible assays for translocation. Several groups have proposed methods to measure translocation into large unilamellar lipid vesicles (LUVs)(9-13). LUVs serve as useful models for bacterial and eukaryotic cell membranes and are frequently used in peptide fluorescent studies(14,15). Here, we describe our application of the method first developed by Matsuzaki and co-workers to consider antimicrobial peptides, such as magainin and buforin II(16,17). In addition to providing our protocol for this method, we also present a straightforward approach to data analysis that quantifies translocation ability using this assay. The advantages of this translocation assay compared to others are that it has the potential to provide information about the rate of membrane translocation and does not require the addition of a fluorescent label, which can alter peptide properties(18), to tryptophan-containing peptides. Briefly, translocation ability into lipid vesicles is measured as a function of the Foster Resonance Energy Transfer (FRET) between native tryptophan residues and dansyl phosphatidylethanolamine when proteins are associated with the external LUV membrane (Figure 1). Cell-penetrating peptides are cleaved as they encounter uninhibited trypsin encapsulated with the LUVs, leading to disassociation from the LUV membrane and a drop in FRET signal. The drop in FRET signal observed for a translocating peptide is significantly greater than that observed for the same peptide when the LUVs contain both trypsin and trypsin inhibitor, or when a peptide that does not spontaneously cross lipid membranes is exposed to trypsin-containing LUVs. This change in fluorescence provides a direct quantification of peptide translocation over time.

Buforin II is a 21-amino acid polycationic antimicrobial peptide derived from a peptide originally isolated from the stomach tissue of the Asian toad Bufo bufo gargarizans. It is hypothesized to target a wide range of bacteria by translocating into cells without membrane permeabilization and binding to nucleic acids. Previous research found that the structure and membrane interactions of buforin II are related to lipid composition. In this study, we used molecular dynamics (MD) simulations along with lipid vesicle experiments to gain insight into how buforin II interacts differently with phosphatidylcholine (PC), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) lipids. Fluorescent spectroscopic measurements agreed with the previous assertion that buforin II does not interact with pure PC vesicles. Nonetheless, the reduced entry of the peptide into anionic PG membranes versus neutral PC membranes during simulations correlates with the experimentally observed reduction in BF2 translocation through pure PG membranes. Simulations showing membrane entry into PC also provide insight into how buforin II may initially penetrate cell membranes. Our MD simulations also allowed us to consider how neutral PE lipids affect the peptide differently than PC. In particular, the peptide had a more helical secondary structure in simulations with PE lipids. A change in structure was also apparent in circular dichroism measurements. PE also reduced membrane entry in simulations, which correlates with decreased translocation in the presence of PE observed in previous studies. Together, these results provide molecular-level insight into how lipid composition can affect buforin II structure and function and will be useful in efforts to design peptides with desired antimicrobial and cell-penetrating properties.

Cathy PhillipsandRachel Muir-Nelson,Trainee and Assistant Co-Chairs for 2005–6, look at the Group’s activities over the past year