Uncovering diffusive states of the yeast membrane protein, Pma1, and how labeling method can change diffusive behavior.

We present and analyze video-microscopy-based single-particle-tracking measurements of the budding yeast (Saccharomyces cerevisiae) membrane protein, Pma1, fluorescently labeled either by direct fusion to the switchable fluorescent protein, mEos3.2, or by a novel, light-touch, labeling scheme, in which a 5 amino acid tag is directly fused to the C-terminus of Pma1, which then binds mEos3.2. The track diffusivity distributions of these two populations of single-particle tracks differ significantly, demonstrating that labeling method can be an important determinant of diffusive behavior. We also applied perturbation expectation maximization (pEMv2) (Koo and Mochrie in Phys Rev E 94(5):052412, 2016), which sorts trajectories into the statistically optimum number of diffusive states. For both TRAP-labeled Pma1 and Pma1-mEos3.2, pEMv2 sorts the tracks into two diffusive states: an essentially immobile state and a more mobile state. However, the mobile fraction of Pma1-mEos3.2 tracks is much smaller ([Formula: see text]) than the mobile fraction of TRAP-labeled Pma1 tracks ([Formula: see text]). In addition, the diffusivity of Pma1-mEos3.2's mobile state is several times smaller than the diffusivity of TRAP-labeled Pma1's mobile state. Thus, the two different labeling methods give rise to very different overall diffusive behaviors. To critically assess pEMv2's performance, we compare the diffusivity and covariance distributions of the experimental pEMv2-sorted populations to corresponding theoretical distributions, assuming that Pma1 displacements realize a Gaussian random process. The experiment-theory comparisons for both the TRAP-labeled Pma1 and Pma1-mEos3.2 reveal good agreement, bolstering the pEMv2 approach.

Evaluating the Implementation of Evidence-based Kidney Nutrition Practice Guidelines: The AUGmeNt Study Protocol.

Evidence-based nutrition practice guidelines (EBNPGs) inform registered dietitian nutritionist (RDN) care for patients with chronic kidney disease grade 5 treated by dialysis; however, there has been little evaluation of best practices for implementing EBNPGs. In this effectiveness-implementation hybrid study with a quasi-experimental design, United States RDNs in hemodialysis clinics will document initial and follow-up nutrition care for patients with chronic kidney disease grade 5 treated by dialysis using the Academy of Nutrition and Dietetics Health Informatics Infrastructure before and after being randomly assigned to a training model: (1) EBNPG knowledge training or (2) EBNPG knowledge training plus an implementation toolkit. The aims of the study include examining congruence of RDN documentation of nutrition care with the EBNPG; describing common RDN-reported EBNPG acceptability, adoption, and adaptation issues; and determining the feasibility of estimating the impact of RDN care on nutrition-related patient outcomes. The AUGmeNt study can inform effective development and implementation of future EBNPGs. Keywords: Chronic kidney diseases; medical nutrition therapy; implementation science; clinical practice guideline; nutrition care process terminology; dietitian.

In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing-remitting multiple sclerosis.

The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease-modifying therapies. Proton MRS (1 H-MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ-aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated 1 H-MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N-acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing-remitting (N = 26) or progressive (N = 21) multiple sclerosis or healthy control adults (N = 25) in a cross-sectional analysis. Only individuals with progressive multiple sclerosis demonstrated reduced glutamate (F2,65 = 3.424, p = 0.04; 12.40 ± 0.62 mM versus control 13.17 ± 0.95 mM, p = 0.03) but not glutamine (F2,65 = 0.352, p = 0.7; 4.71 ± 0.35 mM versus control 4.84 ± 0.42 mM), reduced GABA (F2,65 = 3.89, p = 0.03; 1.29 ± 0.23 mM versus control 1.47 ± 0.25 mM, p = 0.05), and possibly reduced glutathione (F2,65 = 0.352, p = 0.056; 2.23 ± 0.46 mM versus control 2.51 ± 0.48 mM, p < 0.1). As a group, multiple sclerosis patients demonstrated significant negative correlations between disease duration and glutamate or GABA (ρ = -0.4, p = 0.02) but not glutamine or glutathione. Alone, only relapsing-remitting multiple sclerosis patients exhibited a significant negative correlation between disease duration and GABA (ρ = -0.5, p = 0.03). Taken together, these results indicate that frontal cortex metabolism is differentially disturbed in progressive and relapsing-remitting multiple sclerosis.

Food insecurity and depression among low-income adults in the USA: does diet diversity play a role? Findings from the 2013-2014 National Health and Nutrition Examination Survey.

OBJECTIVE: Food insecurity is associated with a greater risk of depression among low-income adults in the USA. Members of food-insecure households have lower diet diversity than their food-secure counterparts. This study examined whether diet diversity moderates the association between food insecurity and depression. DESIGN: Multiple logistic regression was conducted to examine independent associations between food insecurity and depression, between diet diversity and depression, and the moderating effect of diet diversity in the food insecurity-depression link. SETTING: Cross-sectional data from the National Health and Nutrition Examination Survey (2013-2014). PARTICIPANTS: 2636 low-income adults aged 18 years and older. RESULTS: There was a positive association between food insecurity and depression among low-income adults. Diet diversity was not associated with depression. Diet diversity had a moderating effect on the association between food insecurity and depression among low-income adults. CONCLUSIONS: Food insecurity is independently associated with depression among low-income adults in the USA. However, this association differs across levels of diet diversity. Longitudinal studies are needed to confirm the role diet diversity may play in the pathway between food insecurity and depression.

Safety of sildenafil in premature infants with severe bronchopulmonary dysplasia (SILDI-SAFE): a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study.

BACKGROUND: Pulmonary hypertension is a deadly complication of bronchopulmonary dysplasia, the most common pulmonary morbidity of prematurity. Despite these catastrophic consequences, no evidence-based therapies are available for the prevention of pulmonary hypertension in this population. Sildenafil is a potent pulmonary vasodilator approved by the US Food and Drug Administration for the treatment of pulmonary hypertension in adults. Preclinical models suggest a beneficial effect of sildenafil on premature lungs through improved alveolarization and preserved vascular development. Sildenafil may therefore prevent the development of pulmonary hypertension associated with lung disease of prematurity by reducing pulmonary vascular remodeling and lowering pulmonary vascular resistance; however, clinical trial evidence is needed. The present study, supported by the National Institutes of Health's National Heart Lung and Blood Institute, will generate safety, pharmacokinetics, and preliminary effectiveness data on sildenafil in a population of premature infants with severe bronchopulmonary dysplasia at risk for pulmonary hypertension. METHODS: We have designed a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety trial of sildenafil in premature infants with severe bronchopulmonary dysplasia. We will randomize 120 premature infants < 29 weeks gestational age with severe bronchopulmonary dysplasia at 32-40 weeks postmenstrual age in a dose-escalating approach 3:1 (sildenafil: placebo) sequentially into each of 3 cohorts at ~ 30 clinical sites. Participants will receive up to 34 days of study drug, followed by 28 days of safety monitoring. The primary outcome will be safety as determined by incidence of hypotension. Secondary outcomes will include pharmacokinetics and preliminary effectiveness of sildenafil based on presence or absence of pulmonary hypertension diagnosed by echocardiography at the end of treatment period. DISCUSSION: Sildenafil is a promising intervention to prevent the development of pulmonary hypertension in premature infants with bronchopulmonary dysplasia. Clinical trials of sildenafil specifically designed for premature infants are urgently needed. The current study will make substantial contributions to scientific knowledge of the safety of sildenafil in premature infants at risk for pulmonary hypertension. Results from the study will be used by investigators to inform the design of a pivotal efficacy trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04447989 . Registered 25 June 2020.

Effect of loops on the mean-square displacement of Rouse-model chromatin.

Chromatin polymer dynamics are commonly described using the classical Rouse model. The subsequent discovery, however, of intermediate-scale chromatin organization known as topologically associating domains (TADs) in experimental Hi-C contact maps for chromosomes across the tree of life, together with the success of loop extrusion factor (LEF) model in explaining TAD formation, motivates efforts to understand the effect of loops and loop extrusion on chromatin dynamics. This paper seeks to fulfill this need by combining LEF-model simulations with extended Rouse-model polymer simulations to investigate the dynamics of chromatin with loops and dynamic loop extrusion. We show that loops significantly suppress the averaged mean-square displacement (MSD) of a gene locus, consistent with recent experiments that track fluorescently labeled chromatin loci. We also find that loops reduce the MSD's stretching exponent from the classical Rouse-model value of 1/2 to a loop-density-dependent value in the 0.45-0.40 range. Remarkably, stretching exponent values in this range have also been observed in recent experiments [Weber et al., Phys. Rev. Lett. 104, 238102 (2010)0031-900710.1103/PhysRevLett.104.238102; Bailey et al., Mol. Biol. Cell 34, ar78 (2023)1059-152410.1091/mbc.E23-04-0119]. We also show that the dynamics of loop extrusion itself negligibly affects chromatin mobility. By studying static "rosette" loop configurations, we also demonstrate that chromatin MSDs and stretching exponents depend on the location of the locus in question relative to the position of the loops and on the local friction environment.

Selecting trial centers using a standardized, automated site assessment survey instrument (SASI).

BACKGROUND: To improve the site selection process for clinical trials, we expanded a site survey to include standardized assessments of site commitment time, team experience, feasibility of tight timelines, and local medical community equipoise as factors that might better predict performance. We also collected contact information about institutional research services ahead of site onboarding. AIM: As a first step, we wanted to confirm that an expanded survey could be feasible and generalizable-that asking site teams for more details upfront was acceptable and that the survey could be completed in a reasonable amount of time, despite the assessment length. METHODS: A standardized, two-part Site Assessment Survey Instrument (SASI), examining qualitative components and with multiple contact list sections, was developed using a publicly accessible dashboard and later transferred to a REDCap platform. After multiple rounds of internal testing, the SASI was deployed 11 times for multicenter trials. Follow-up questionnaires were sent to site teams to confirm that an expanded survey instrument is acceptable to the research community and could be completed during a brief work shift. RESULTS: Respondents thought the SASI collected useful and relevant information about their sites (100%). Sites were "comfortable" (90%) supplying detailed information early in the site selection process and 57% completed the SASI in one to two hours. CONCLUSIONS: Coordinating centers and sites found the SASI tool to be acceptable and helpful when collecting data in consideration of multicenter trial site selection.

Loops and the activity of loop extrusion factors constrain chromatin dynamics.

The chromosomes-DNA polymers and their binding proteins-are compacted into a spatially organized, yet dynamic, three-dimensional structure. Recent genome-wide chromatin conformation capture experiments reveal a hierarchical organization of the DNA structure that is imposed, at least in part, by looping interactions arising from the activity of loop extrusion factors. The dynamics of chromatin reflects the response of the polymer to a combination of thermal fluctuations and active processes. However, how chromosome structure and enzymes acting on chromatin together define its dynamics remains poorly understood. To gain insight into the structure-dynamics relationship of chromatin, we combine high-precision microscopy in living Schizosaccharomyces pombe cells with systematic genetic perturbations and Rouse model polymer simulations. We first investigated how the activity of two loop extrusion factors, the cohesin and condensin complexes, influences chromatin dynamics. We observed that deactivating cohesin, or to a lesser extent condensin, increased chromatin mobility, suggesting that loop extrusion constrains rather than agitates chromatin motion. Our corresponding simulations reveal that the introduction of loops is sufficient to explain the constraining activity of loop extrusion factors, highlighting that the conformation adopted by the polymer plays a key role in defining its dynamics. Moreover, we find that the number of loops or residence times of loop extrusion factors influence the dynamic behavior of the chromatin polymer. Last, we observe that the activity of the INO80 chromatin remodeler, but not the SWI/SNF or RSC complexes, is critical for ATP-dependent chromatin mobility in fission yeast. Taking the data together, we suggest that thermal and INO80-dependent activities exert forces that drive chromatin fluctuations, which are constrained by the organization of the chromosome into loops.

Food Pantry Clients' Needs, Preferences, and Recommendations for Food Pantries: A Qualitative Study.

A qualitative formative approach was used to explore food pantry clients' needs, preferences, and recommendations regarding food received from food pantries. Fifty adult clients of six Arkansas food pantries were interviewed in English, Spanish, or Marshallese. Data analysis used the constant comparative qualitative methodology. In choice and minimal choice pantries, three themes emerged: clients need increased quantities of food, particularly more proteins and dairy; clients desire higher quality food, including healthy food and food not close to expiration; and clients desire familiar foods and food appropriate for their health needs. System level policy changes are needed to address clients' recommendations.

Interim guidelines for the assessment and treatment of pain in children with multiple sclerosis.

Introduction: Pain in multiple sclerosis (MS) is common, but literature on pain in children with MS remains scarce. Pain has physical, psychological, and social implications in MS, and both comprehensive assessment and interdisciplinary management approaches are needed. We sought to develop an interdisciplinary interim guideline for the assessment and management of pain in children with MS. Methods and materials: We convened a modified Delphi panel composed of 13 experts in pediatric and adult MS neurology, physiotherapy, pain, patient lived-experience, advanced practice nursing, psychology, physiatry, and MS research. A survey was sent to panelists for anonymous completion. The panel discussed survey themes extracted by the panel chair. The process was repeated twice. Results: Thirteen assessment and treatment recommendations were produced regarding pain in children with MS. Discussion: Future studies will assess implementation of these pain assessment and treatment guidelines in the clinical setting.

Food insecurity and chronic diseases among Native Hawaiians and Pacific Islanders in the US: results of a population-based survey.

Data from the 2014 Native Hawaiian and Pacific Islander (NHPI) National Health Interview Survey were used to examine associations between food security and individual chronic diseases, total number of chronic diseases, and general health status among 637 NHPI adults with income below 200 percent federal poverty level. Very low food security was associated with hypertension, diabetes, and asthma. Very low food security and marginal food security were associated with having any chronic disease and with having a higher number of chronic diseases. Risk for food insecurity increased as health status decreased. These associations had not previously been documented for NHPI.

Food Pantry Usage Patterns are Associated with Client Sociodemographics and Health.

Characterizing food pantry (FP) clients' FP usage patterns may provide opportunities to tailor health-related interventions. Respondents (n=245) at seven FPs reported their frequency and reliance on FPs and their sociodemographics, health status, and health-related trade-offs. Clients were categorized via latent class analysis. Higher FP usage was associated with being older, having a household member with heart disease, and putting off buying medicine to buy food. Lower FP usage was associated with higher levels of education and having a household member with cancer. Findings highlight the potential importance of measuring FP clients' degree of FP use.

Covariance distributions in single particle tracking.

Several recent experiments, including our own experiments in the fission yeast, Schizosaccharomyces pombe, have characterized the motions of gene loci within living nuclei by measuring the locus position over time, then proceeding to obtain the statistical properties of this motion. To address the question of whether a population of such single-particle tracks, obtained from many different cells, corresponds to a single mode of diffusion, we derive theoretical equations describing the probability distribution of the displacement covariance, assuming the displacement itself is a zero-mean multivariate Gaussian random variable. We also determine the corresponding theoretical means, variances, and third central moments. Bolstering the theory is good agreement between its predictions and the results obtained for various simulated and measured data sets, including simulated particle trajectories undergoing simple and anomalous diffusion, and the measured trajectories of an optically trapped bead in water, and in a viscoelastic polymer solution. We also show that, for sufficiently long tracks, each covariance distribution in all of these examples is well-described by a skew-normal distribution with mean, variance, and skewness given by the theory. However, for the experimentally measured motion of a gene locus in S. pombe, we find that the first two covariance distributions are wider than predicted, although the third and subsequent covariance distributions are well-described by theory. This observation suggests that the origin of the theory-experiment discrepancy in this case is associated with localization noise, which influences only the first two covariances. Thus, we hypothesized that the discrepancy is caused by locus-to-locus heterogeneity in the localization noise, of independent measurements of the same tagged site. Indeed, simulations implementing heterogeneous localization noise revealed that the excess covariance widths can be largely recreated on the basis of heterogeneous noise. Thus, we conclude that the motion of gene loci in fission yeast is consistent with a single mode of diffusion.

Extrusion of chromatin loops by a composite loop extrusion factor.

Chromatin loop extrusion by structural maintenance of chromosome (SMC) complexes is thought to underlie intermediate-scale chromatin organization inside cells. Motivated by a number of experiments suggesting that nucleosomes may block loop extrusion by SMCs, such as cohesin and condensin complexes, we introduce and characterize theoretically a composite loop extrusion factor (composite LEF) model. In addition to an SMC complex that creates a chromatin loop by encircling two threads of DNA, this model includes a remodeling complex that relocates or removes nucleosomes as it progresses along the chromatin, and nucleosomes that block SMC translocation along the DNA. Loop extrusion is enabled by SMC motion along nucleosome-free DNA, created in the wake of the remodeling complex, while nucleosome rebinding behind the SMC acts as a ratchet, holding the SMC close to the remodeling complex. We show that, for a wide range of parameter values, this collection of factors constitutes a composite LEF that extrudes loops with a velocity, comparable to the velocity of remodeling complex translocation on chromatin in the absence of SMC, and much faster than loop extrusion by an isolated SMC that is blocked by nucleosomes.

A New England COVID-19 Registry of Patients With CNS Demyelinating Disease: A Pilot Analysis.

BACKGROUND AND OBJECTIVES: We sought to define the risk of severe coronavirus disease 2019 (COVID-19) infection requiring hospitalization in patients with CNS demyelinating diseases such as MS and the factors that increase the risk for severe infection to guide decisions regarding patient care during the COVID-19 pandemic. METHODS: A pilot cohort of 91 patients with confirmed or suspected COVID-19 infection from the Northeastern United States was analyzed to characterize patient risk factors and factors associated with an increased severity of COVID-19 infection. Univariate analysis of variance was performed using the Mann-Whitney U test or analysis of variance for continuous variables and the χ2 or Fisher exact test for nominal variables. Univariate and stepwise multivariate logistic regression identified clinical characteristics or symptoms associated with hospitalization. RESULTS: Our cohort demonstrated a 27.5% hospitalization rate and a 4.4% case fatality rate. Performance on Timed 25-Foot Walk before COVID-19 infection, age, number of comorbidities, and presenting symptoms of nausea/vomiting and neurologic symptoms (e.g., paresthesia or weakness) were independent risk factors for hospitalization, whereas headache predicted a milder course without hospitalization. An absolute lymphocyte count was lower in hospitalized patients during COVID-19 infection. Use of disease-modifying therapy did not increase the risk of hospitalization but was associated with an increased need for respiratory support. DISCUSSION: The case fatality and hospitalization rates in our cohort were similar to those found in MS and general population COVID-19 cohorts within the region. Hospitalization was associated with increased disability, age, and comorbidities but not disease-modifying therapy use.

Evaluation of the Impact of 2 Disposable Diapers in the "Natural" Diaper Category on Diapered Skin Condition.

The demand for natural infant care products, including diapers, has increased. However, few disposable diapers have been able to provide the performance caregivers desire while also incorporating ingredients consistent with the "natural" category. In an examiner-blinded clinical study, the performance of a new cotton-enhanced diaper with high-performance materials was compared with an existing natural diaper offering. A total of 131 infants wore 1 of the 2 diapers for a 4-week period. Diaper performance was assessed based on skin marking assessments, scored by a trained grader, and incidence of diaper dermatitis. Skin grading for diaper dermatitis was assessed at 4 sites in the diaper area. The new diaper offering was associated with less skin marking and significantly less diaper rash at the genitals and intertriginous regions versus the comparator. These data suggest that the new diaper provided significant improvement in both skin marking and prevalence of diaper rash.

Registered Nurses' Self-Assessed Knowledge of Evidence-Based Practice and Research: Moving Forward With New Information.

By 2020, most clinical decisions should be supported by best evidence. Therefore, nurses need institutional support and education about evidence-based practice (EBP) and research. The aim of this study was to describe nurses' self-assessed knowledge of EBP and research. Findings revealed nurses' knowledge of EBP and research ranged from no knowledge to high knowledge with opportunities for education. Providing for the use of best evidence is a dynamic process involving clinicians, educators, and administrators.

A food hub to address healthy food access gaps: Residents' preferences.

Interventions aimed at improving access to healthy food in low-income communities should consider the preferences of residents. Household food shoppers in two urban, low-income communities were asked about their preferences for vendors at, and qualities of, a potential nearby food hub. Universally, participants preferred availability of whole foods, primarily fruits and vegetables. They also favored cleanliness, quality, and affordability. The demographics and preferences of potential customers raise central issues that would need to be integrated into the development of a food hub, namely affordability (likely through subsidization), attention to accommodation and cultural accessibility, and programming that builds community.

Testing educational strategies for Shaken Baby Syndrome.

UNLABELLED: Shaken Baby Syndrome (SBS) occurs from the violent shaking of an infant, which may lead to brain damage or death. The goal of this study was to assess educational methods used to teach new mothers about SBS. METHODS: Forty six parents at a community hospital were selected and randomly divided into three groups. Group 1 received a short lesson about SBS. Group 2 received the lesson and watched a locally developed SBS video. Group 3 received the lesson and watched a true dramatization of SBS created by a national organization. Pre and post surveys were administered. RESULTS: Study groups were similar in regard to age, marital status, socioeconomic status and education. Group 1 parents showed no differences in scoring. Group 2 parents showed a significant increase in defining SBS and what to do for persistent infant crying. Group 3 parents scored significantly higher in defining SBS. CONCLUSION: Both video presentations improved scoring on understanding SBS but only the local video presentation increased scores in the management of persistent infant crying.

Patterns of depressive symptoms in children.

PROBLEM: Depressive symptoms in children have been linked to recurrent problems with depression, school problems, and risky health behaviors. Adolescent girls report depressive symptoms three to four times more frequently than adolescent boys. Few studies, however, have examined gender-related depressive symptoms in younger, school-aged children. METHODS: In the present study, gender differences in depressive symptoms in children ages 10-12 years were explored using the Children's Depression Inventory (CDI) with a convenience sample of 122 suburban middle-class public school fifth and sixth graders. FINDINGS: A distinct pattern of depressive symptom expression was found with girls reporting more internalizing and more negative self-esteem, and boys reporting more externalizing and more school problems. CONCLUSION: These findings suggest that despite similarities on a total depressive symptom score, there are distinct gender differences in depressive symptom expression that are identifiable before adolescence and may be associated with normative development.