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DNA i-motif structures are formed in the nuclei of human cells and are believed to provide critical genomic regulation. While the existence, abundance, and distribution of i-motif structures in human cells has been demonstrated and studied by immunofluorescent staining, and more recently NMR and CUT&Tag, the abundance and distribution of such structures in human genomic DNA have remained unclear. Here we utilise high-affinity i-motif immunoprecipitation followed by sequencing to map i-motifs in the purified genomic DNA of human MCF7, U2OS and HEK293T cells. Validated by biolayer interferometry and circular dichroism spectroscopy, our approach aimed to identify DNA sequences capable of i-motif formation on a genome-wide scale, revealing that such sequences are widely distributed throughout the human genome and are common in genes upregulated in G0/G1 cell cycle phases. Our findings provide experimental evidence for the widespread formation of i-motif structures in human genomic DNA and a foundational resource for future studies of their genomic, structural, and molecular roles. Synopsis: i-motifs (iMs) are knot-like DNA structures structures formed in the nuclei of human cells and believed to provide critical genomic regulation. This study uses immunoprecipitation and next-generation sequencing to identify i-motif structures in human DNA on a genome-wide scale. DNA i-motif structures are common in human genomic DNA. ~53,000 iMs are observed among three human cells lines (MCF7, U2OS, HEK293T). iMs are widely distributed throughout the human genome and frequent in genes upregulated in G0/G1 phase. Genome-wide i-motif immunoprecipitation and next-generation sequencing shows that sequences capable of forming these knot-like DNA structures are widely distributed and common in G0/G1-expressed genes. [ABSTRACT FROM AUTHOR]

Simulation, an educational, assessment, and research technique used to mimic real‐world situations, is increasingly used in pharmacy education. The most‐used simulation methods include high‐fidelity simulation (HFS), low‐fidelity simulation (LFS), standardized patients, and game‐based simulation. A common element of simulation is its ability to offer learners the chance to practice a skill or acquire knowledge in a safe and accessible space. Simulation methods differ in key aspects, including cost and other resource investment as well as ideal venue for use in education. HFS provides a more realistic simulation environment than LFS but is typically more expensive. Standardized patients offer learners the opportunity to engage with a live person but may elicit greater variability in responses to learners' input than HFS. Computer‐based simulation uses technology to supply a wide variety of learning opportunities; however, it may require the use of proprietary software and devices. Despite widespread use, literature describing learning outcomes of simulation in pharmacy education is limited. Some existing reports with positive findings have focused on learner satisfaction with or perceived benefit of simulation activities. The few existing publications summarizing changes in skills or knowledge demonstrate a positive impact. Simulation is a promising modality for educating pharmacy students and residents; however, more data summarizing the benefit of learning outcomes are needed. [ABSTRACT FROM AUTHOR]

Postgraduate residency training provides an opportunity to acquire and apply skills and behaviors learned through interprofessional education (IPE) sessions. Little data exists regarding the perceptions of resident trainees on benefits and barriers of IPE. In this paper, we describe the development and implementation of a case‐based IPE activity focused on chronic obstructive pulmonary disease management and inhaler technique in order to explore pharmacy and medicine resident perceptions of IPE. Perceptions of IPE were logged via survey and interviews in parallel with participation in the IPE activity and were analyzed with a constructivist grounded theory approach to identify common themes. Four themes supporting IPE models were found including better understanding of another profession's skills, integration of another profession's skill and perspective to improve patient care, recognition of gaps in expertise, and perception of time and coordination as barriers to learning with other professions. In conclusion, IPE activities improve and advance the perceptions and knowledge that medicine and pharmacy residents have about each other's professions. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Clinical trials addressing treatments for Duchenne muscular dystrophy (DMD) require reliable and valid measurement of muscle contractile function across all disease severity levels. In this work we aimed to evaluate a protocol combining voluntary and evoked contractions to measure strength and excitability of wrist extensor muscles for safety, feasibility, reliability, and discriminant validity between males with DMD and controls. Methods: Wrist extensor muscle strength and excitability were assessed in males with DMD (N = 10; mean ± standard deviation: 15.4 ± 5.9 years of age), using the Brooke Upper Extremity Rating Scale (scored 1‐6), and age‐matched healthy male controls (N = 15; 15.5 ± 5.0 years of age). Torque and electromyographic (EMG) measurements were analyzed under maximum voluntary and stimulated conditions at two visits. Results: A protocol of multiple maximal voluntary contractions (MVCs) and evoked twitch contractions was feasible and safe, with 96% of the participants completing the protocol and having a less than 7% strength decrement on either measure for both DMD patients and controls (P ≥.074). Reliability was excellent for voluntary and evoked measurements of torque and EMG (intraclass correlation coefficient [ICC] over 0.90 and over 0.85 within and between visits, respectively). Torque, EMG, and timing of twitch‐onset measurements discriminated between DMD and controls (P <.001). Twitch contraction time did not differ significantly between groups (P =.10). Discussion: Findings from this study show that the protocol is a safe, feasible, reliable, and a valid method to measure strength and excitability of wrist extensors in males with DMD. [ABSTRACT FROM AUTHOR]

Purpose: With decreasing access to rural obstetrical care, this study aimed to identify factors that contribute to the ability of Minnesota's rural communities to continue to offer obstetrical services locally. The study also sought to characterize attributes that differentiate rural communities that continue to offer obstetrical care from those that do not. Methods: Family medicine physicians practicing in communities of fewer than 20,000 people were interviewed through a phone survey that included multiple choice and open‐ended questions. Quantitative and qualitative analyses were performed on data collected from the responses. Findings: Within the Minnesota communities represented (N = 25), prenatal care was provided broadly, regardless of whether labor and delivery services were available. For the communities providing local labor and delivery (N = 17), several factors seemed to be key to sustaining these services: having a sufficient cohort of delivering providers, having surgical backup, having accessible confident nurses and nurse anesthetists, sustaining a sufficient annual birth volume at the hospital, and having organizational and administrative support. In addition, supporting anesthesia and analgesic services, access to specialist consultation, having resources for managing and referring both newborn and maternal complications, and sustaining proper equipment were also requisite. Conclusions: Rural Minnesota family medicine physicians practicing in communities providing local labor and delivery care emphasized several essential components for sustainable provision of these services. With awareness of these essential components, rural health care providers, administrators, and policy makers can focus resources and initiatives on efforts that are most likely to support a sustainable and coordinated rural labor and delivery program. [ABSTRACT FROM AUTHOR]

The introduction of the coronavirus disease 2019 (COVID‐19) pandemic in the Spring semester of 2020 sent many educational units, elementary to higher education, scrambling to move content to remote learning. Within a professional program, this push highlighted gaps or potential pitfalls in preparing students to enter the health care field. This article highlights lessons learned in remote teaching during the pandemic from six unique colleges and schools of pharmacy: Auburn University, Drake University, Purdue University, University of Health Sciences and Pharmacy in St. Louis, Texas Tech University Health Science Center, and University of Utah. These lessons learned pertain to remote content delivery, student engagement, skill development, and assessments within the classroom and experiential settings. Within the classroom setting, the challenges, literature, personal experiences, and key recommendations for lecture‐based learning, group‐based learning, lab‐based learning, and assessments are described. Similarly, for the experiential setting, the challenges, literature, personal experiences, and key recommendations are also described, including training learners for remote patient care as well as examples for remote experiential activities and assessment. Forging ahead, there will be a continued need for future research for remote learning within pharmacy education. [ABSTRACT FROM AUTHOR]

Naphthalene diimide (NDI) dyads exhibiting a different substitution pattern and linker length have been synthesised and evaluated as G‐quadruplex (G4) ligands, by investigating their cytotoxicity in selected cell lines. The dyads with the long C7 linker exhibit extremely low IC50 values, below 10 nm, on different cancer cell lines. Contrary, the dyads with the shorter C4 linker were much less effective, with IC values increasing up to 1 μm. Among the three dyads with the longest linker, small differences in the IC50 values emerge, suggesting that the linker length plays a more important role than the substitution pattern. We have further shown that the dyads are able to induce cellular DNA damage response, which is not limited to the telomeric regions and is likely the origin of their cytotoxicity. Both absorption titration and dynamic light scattering of the most cytotoxic dyads in the presence of hTel22 highlight their ability to induce effective G4 aggregation, acting as non‐covalent cross‐linking agents. [ABSTRACT FROM AUTHOR]

Background: In the parent study of this analysis, patients with type 2 diabetes received lixisenatide before breakfast or the main meal of the day. This substudy was designed to examine the effect of lixisenatide administered before breakfast or the main meal of the day on continuously assessed 24-hour patient glucose profiles.Methods: A subset of patients from the parent study underwent 2 14-day periods of continuous glucose monitoring (CGM) at the start and end of the 24-week study. Ambulatory glucose profile analysis was used to measure changes over time in detailed aspects of the glucose profiles. The breakfast group consumed a standardized meal during both CGM periods to determine change in 4-hour glycemic response.Results: Data were available for 69 patients in the substudy, 40 from the original breakfast group and 29 from the main meal group. Between baseline and end of study, mean (standard deviation) total glucose exposure decreased from 4198.1 (652.3) to 3681.2 (699.6) mg/dL*24 h in the breakfast group (P < .0001) and from 4127.9 (876.8) to 3880.9 (1165.0) mg/dL*24 h in the main meal group (P = .0224). For patients included in the substudy, HbA1c decreased by approximately 0.6% in both groups. Mean (standard deviation) 4-hour total glucose exposure fell by 168.9 (158.4) mg/dL*4 h (P < .0001) from baseline.Conclusions: This analysis demonstrates that lixisenatide has beneficial effects on components of the 24-hour glucose profile, which endure beyond the meal at which it is administered. Continuous glucose monitoring analysis detects changes not captured using HbA1c alone. [ABSTRACT FROM AUTHOR]

Naphthalene diimides with one or two centrosymmetric arylethynyl moieties capable of synergic donor and acceptor hydrogen bonding exhibit promising binding properties and selectivity towards parallel G-quadruplex (G4) nucleic acids (c-myc, bcl-2 and parallel hTel22). The hydrogen-bonding network involving the phosphate backbone and outside rim of the G-quartet represents an opportunity to exploit G4 selectivity for extended aromatics. [ABSTRACT FROM AUTHOR]

A photoreactive molecular dye targeting the G-quadruplex nucleic acid (G4) of the human telomeric sequence Tel22, and several mutated analogues, was activated by green light ( λ=532 nm). Highly selective covalent modification of G4 versus single-stranded and double-stranded DNA was achieved with efficiency up to 64 %. The phenoxyl radical was generated and detected by laser-flash photolysis as a reactive intermediate that targeted loop thymine residues. These insights may suggest a non-invasive tool for selective nucleic acid tagging and 'pull-down' cellular applications. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Eating disorders (EDs) present across a broad age range, yet little is known about the characteristics and outcome of midlife patients compared to younger patients. Among patients seeking ED treatment who were stratified by age at initial assessment (IA), this study aimed to (1) discern sociodemographic and clinical differences, (2) determine outcome rates, and (3) identify predictors of poor outcome including death. Method Participants [219 females (12 years or older, 94.1% Caucasian) who completed outcome assessment and 31 known decedents] were stratified by age at IA (<18 as youth, 18-39 as young adult, and ≥40 years as midlife adult). Analyses of variance and chi-square tests identified group differences; ordered logistic regression with stepwise selection identified factors predicting outcome. Results Midlife adults were more significantly compromised at follow-up compared to youths and young adults, including psychological and physical quality of life, ineffectiveness, interpersonal concerns, and general psychological maladjustment. Midlife adults had the highest rates of poor outcome or death; good outcome was achieved by only 5.9% of midlife adult compared to 14.0% of young adult and 27.5% of youth patients. Older age at IA, alcohol and/or drug misuse, endocrine concerns, and absence of family ED history predicted poor outcome or death. Discussion Midlife adults seeking ED treatment have more complex medical and psychological concerns and poorer outcomes than youths and young adults; further exploration is needed to improve treatment outcome. Specialized treatment focusing on quality of life, comorbid medical concerns, interpersonal connection, and emotion regulation is encouraged. © 2014 Wiley Periodicals, Inc. Int J Eat Disord 2014; 47:825-835 [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Compare general and disease-specific health-related quality of life (HRQoL) among female patients with an eating disorder (ED). Method Female patients ( n = 221; 95.3% Caucasian; 94.0% never married) completed the Medical Outcome Short Form Health Survey (SF-36) and Eating Disorders Quality of Life (EDQoL) as part of a study of treatment outcomes. Multivariate regression models were used to compare HRQoL differences across initial ED diagnosis (85 AN-R, 19 AN-B/P, 27 BN, 90 EDNOS) and ED diagnostic classification at time of outcome assessment (140 no ED, 38 subthreshold ED, 43 full threshold ED). Results There were no significant differences across ED diagnosis at initial assessment on either of the SF-36 Component Summary scores. However, patients with AN-B/P scored poorer on the work/school EDQoL subscales than other ED diagnoses, and on the psychological EDQoL subscale compared to AN-R and EDNOS. At outcome assessment, comparisons across full threshold, subthreshold and no ED classification indicated that those with no ED reported better HRQoL than those with full threshold ED on the SF-36 Mental Components Summary and three of four EDQoL subscales. Furthermore, those with no ED reported better psychological HRQoL than those with subthreshold ED. Discussion Disease-specific HRQOL measures are important to use when comparing HRQoL in ED patients across treatment and outcome, and may have the sensitivity to detect meaningful differences by diagnosis more so than generic instruments. EDQoL scores from patients remitted from symptoms approach but do not reach scores for unaffected college females; thus, treatment should continue until quality of life is restored. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:259-267) [ABSTRACT FROM AUTHOR]

Caught in the oxirane: Naphthalene diimides conjugated to a quinone methide and an oxirane have been synthesized and investigated as selective DNA G‐quadruplex alkylating agents. The oxirane derivative generates a stable adduct with a G‐quadruplex and shows selective alkylation of the loop adenines, as illustrated. [ABSTRACT FROM AUTHOR]

Objectives: Describe characteristics of patients who have both an eating disorder and type 1 diabetes and compare their responses on psychological tests with those with an eating disorder and no diabetes at time of initial assessment to an eating disorder facility. Method: A chart audit conducted on all 48 patients with ED-DMT1 who were seen collaboratively by the diabetes and eating disorder treatment teams between 2005 and 2008 at Park Nicollet Health Services and 96 (1:2) matched eating disordered controls. Results: Diabetes was diagnosed an average of 10.2 years (SD = 9.4) before the diagnosis of an eating disorder; HbA1c at initial assessment was 11% (±3.2%). Those without diabetes reported greater depression ( p = .048) and greater state and trait anxiety ( p = .015 and p = .039, respectively) at initial assessment. Discussion: Persons with both an eating disorder and type 1 diabetes were less psychologically compromised than their matched cohorts with an eating disorder only. These findings may not remain constant during the course of treatment. © 2011 by Wiley Periodicals, Inc. (Int J Eat Disord 2012) [ABSTRACT FROM AUTHOR]