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To describe approaches that public health and social entrepreneurs take to address health equity, and identify strategies for equitable collaborations with these entrepreneurs.

The Joint Commission’s hospital antimicrobial stewardship (AS) standards became effective in January 2017. Surveyors’ experience to date suggests that almost all hospitals have established AS leadership commitment and organized structures. Thus, The Joint Commission sought to examine advances in AS interventions and measures that hospitals could implement to strengthen their existing AS programs.

Using a chimera in which the Sec7d of GBF1 was replaced with the Sec7d from ARNO, we show that 1) targeting of GEFs is independent of Sec7d, but Sec7d influences GEF substrate specificity to affect downstream effector events; 2) all ARFs have access to all membranes; and 3) effector recruitment is restricted by activated ARFs and specific membrane identifiers.

Stridor, a common presenting sign of respiratory distress in a newborn, has many systemic causes. It may arise from the larynx or the tracheobronchial airway. This article presents the most common pathologic conditions in this anatomic region, with highlights on management.

For millions of Americans living in vulnerable rural and urban communities, their hospital is an important, and often their only, source of health care. As transformation in the hospital and health care field continues, some communities may be at risk of losing access to health care services and the opportunities and resources they need to improve and maintain their health. Integrated, comprehensive strategies to reform health care delivery and payment, within which vulnerable communities can make individual choices based on their needs, support structures, and preferences, are needed.In this Invited Commentary, the authors outline characteristics and parameters of vulnerable communities as well as the essential health care services that hospitals should strive to maintain locally identified by the American Hospital Association Task Force on Ensuring Access in Vulnerable Communities. They also describe four of nine emerging strategies—recommended by the task force—to reform health care delivery and payment and allow hospitals to provide the essential health care services, along with implementation barriers and how to address them. While this Invited Commentary focuses on vulnerable communities, the four highlighted strategies (addressing the social determinants of health, adopting new and innovative virtual care strategies, designing global budgets, and using inpatient/outpatient transformation strategy), as well as the other five strategies, may have broader applicability for all communities.

ABSTRACTThe human mitochondrial chaperonin is a macromolecular machine that catalyzes the proper folding of mitochondrial proteins and is of vital importance to all cells. This chaperonin is composed of 2 distinct proteins, Hsp60 and Hsp10, that assemble into large oligomeric complexes that mediate the folding of non-native polypeptides in an ATP dependent manner. Here, we report the bacterial expression and purification of fully assembled human Hsp60 and Hsp10 recombinant proteins and that Hsp60 forms a stable tetradecameric double-ring conformation in the absence of co-chaperonin and nucleotide. Evidence of the stable double-ring conformation is illustrated by the 15 Å resolution electron microscopy reconstruction presented here. Furthermore, our biochemical analyses reveal that the presence of a non-native substrate initiates ATP-hydrolysis within the Hsp60/10 chaperonin to commence protein folding. Collectively, these data provide insight into the architecture of the intermediates used by the human mitochondrial chaperonin along its protein folding pathway and lay a foundation for subsequent high resolution structural investigations into the conformational changes of the mitochondrial chaperonin.

Mobile health (mHealth) is being recognized as an innovative approach to deliver health care in an accessible, portable and cost effective manner. Despite the numerous benefits associated with the use of mobile devices, there are major concerns with mhealth in the area of privacy and security. These aspects need to be considered at every stage of design and development of mHealth devices and applications which need to be developed by security-trained, trusted manufacturers who should be accountable to minimize damages in the healthcare industry. It is also crucial for users and/or organizations to be more cautious and responsible to use mobile devices. Major stakeholders, including those in the user׳s community (patients and providers), vendors and developers, and policy makers need to come together to survey the landscape, identify the issues, and develop policies, regulations, safeguards and industry standards.

Descending necrotizing mediastinitis (DNM) can be a deadly medical emergency that is not well described in pediatric patients. Usually stemming from an oropharyngeal infection, it can spread rapidly to the mediastinum through the alar fascia known as the “danger space.”

IMPORTANCE: Tinnitus is a common problem for millions of individuals and can cause substantial negative effects on their quality of life. A large epidemiologic study of tinnitus and its management patterns in the US adult population is lacking. OBJECTIVES: To quantify the epidemiologic features and effect of tinnitus and to analyze the management of tinnitus in the United States relative to the 2014 American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF) clinical practice guidelines. DESIGN, METHODS, AND PARTICIPANTS: This cross-sectional analysis of the representative 2007 National Health Interview Survey (raw data, 75 764 respondents) identified a weighted national sample of adults (age, ≥18 years) who reported tinnitus in the preceding 12 months. Data were collected in November 2014 at the University of California, Irvine, and Harvard Medical School. MAIN OUTCOMES AND MEASURES: In addition to quantifying prevalence, severity, duration, and regularity of tinnitus, specific data regarding noise exposure and tinnitus management patterns during health care visits were analyzed. RESULTS: Among an estimated (SE) 222.1 (3.4) million US adults, 21.4 (3.4) million (9.6% [0.3%]) experienced tinnitus in the past 12 months. Among those who reported tinnitus, 27% had symptoms for longer than 15 years, and 36% had nearly constant symptoms. Higher rates of tinnitus were reported in those with consistent exposure to loud noises at work (odds ratio, 3.3; 95% CI, 2.9-3.7) and during recreational time (odds ratio, 2.6; 95% CI, 2.3-2.9). Years of work-related noise exposure correlated with increasing prevalence of tinnitus (r = 0.13; 95% CI, 0.10-0.16). In terms of subjective severity, 7.2% reported their tinnitus as a big or a very big problem compared with 41.6% who reported it as a small problem. Only 49.4% had discussed their tinnitus with a physician, and medications were the most frequently discussed recommendation (45.4%). Other interventions, such as hearing aids (9.2%), wearable (2.6%) and nonwearable (2.3%) masking devices, and cognitive behavioral therapy (0.2%), were less frequently discussed. CONCLUSIONS AND RELEVANCE: The prevalence of tinnitus in the United States is approximately 1 in 10 adults. Durations of occupational and leisure time noise exposures correlated with rates of tinnitus and are likely targetable risk factors. Management options suggested by the recently published AAO-HNSF guidelines were followed infrequently.

Hearing loss can be attributed to a variety of inherited and environmental noises (medications, infections, etc.). In recent decades, our improved understanding of genetics, molecular biology, and audiologic pathways has led to the discovery of a variety of Hereditary Hearing Impairments (HHI). HHI can be categorized as syndromic HL and non-syndromic HL, in which HL is associated with other pathophysiological manifestations. Currently, greater than 300 syndromic HLs are recognized, while more than 100 chromosomal loci and 40 genes are attributed for non-syndromic HLs. Improved understanding of the genes impaired in HL, including their structure and function, will soon lead to improvements in screening and possibly treatments. The following is a review of genetic HL where we discuss the definition, classifications, etiology, epidemiology, recognized syndromes, genetics, diagnostics, and screening methods of HL.

Ifenprodil is an allosteric inhibitor of GluN1/GluN2B N-methyl-D-aspartate receptors. Despite its widespread use as a prototype for drug development and a subtype-selective tool for physiologic experiments, its precise effect on GluN1/GluN2B gating is yet to be fully understood. Interestingly, recent crystallographic evidence identified that ifenprodil, unlike zinc, binds at the interface of the GluN1/GluN2B amino terminal domain dimer by an induced-fit mechanism. To delineate the effect of this unique binding on GluN1/GluN2B receptor gating, we recorded steady-state currents from cell-attached and outside-out patches. At pH 7.9 in cell-attached patches, ifenprodil increased the occupancy of the long-lived shut conformations, thereby reducing the open probability of the receptor with no change in the mean open time. In addition, ifenprodil selectively affected the area of shut time constants, but not the time constants themselves. Kinetic analyses suggested that ifenprodil prevents the transition of the receptor to an open state and increases its dwell time in an intrinsically occurring closed conformation or desensitized state. We found distinct differences in the action of ifenprodil at GluN1/GluN2B in comparison with previous studies on the effect of zinc on GluN1/GluN2A gating, which may arise due to their unique binding sites. Our data also uncover the potential pH-dependent action of ifenprodil on gating. At a low pH (pH 7.4), but not pH 7.9, ifenprodil reduces the mean open time of GluN1/GluN2B receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic.

Activity of the c-jun N-terminal kinase (JNK) has been shown in hematopoietic cells transformed by p210 BCR-ABL. However, analysis has not been reported for hematopoietic cells on the consequences of this activity for c-jun promoter regulation within its distinctive proximal 8-base consensus CRE-like element, an element linked to JNK-mediated increase in c-jun transcription. In the present study, regulation of the proximal c-jun promoter was studied in murine myeloid cells transformed by p210 BCR-ABL. Promoter regulation in p210 BCR-ABL transformed cells was compared with regulation of the promoter in nontransformed interleukin-3 (IL-3)–dependent parental cells. The composition of nuclear AP-1 proteins contained within cells with p210 BCR-ABL, and their binding to the c-jun promoter proximal CRE-like element, was compared with the composition and binding of AP-1 proteins in IL-3–treated parental cells without p210 BCR-ABL. The present analysis found fivefold increased c-jun transcription occurring in p210 BCR-ABL transformed murine myeloid cells possessing a corresponding magnitude of increased kinase activity of JNK, compared with IL-3–stimulated parental cells. Augmented JNK activity was accompanied by increased nuclear abundance of c-jun and c-fos proteins that bound specifically to the proximal c-jun promoter CRE element. Also, representative human leukemic cell lines expressing p210 BCR-ABL and possessing abundant kinase activity of JNK, when compared with parental cells that were deficient in JNK activity, had increased c-jun and c-fosproteins. Finally, to show the relevance of these observations in model systems, we studied blast cells from patients with Philadelphia chromosome–positive acute leukemic transformation, and observed comparable activities of JNK catalysis and c-jun/AP-1 protein relative to the cell lines that possessed p210 BCR-ABL and JNK activity. These studies provide a basis for investigating the set of downstream genes which augmented c-jun/AP-1 activity enlists in the process of transformation by p210 BCR-ABL.

Abstract: A laser balloon angioscopic procedure was developed in a canine model for intraluminal mass lesions in the superior vena cava, using an endoscope bearing a very thin balloon through which Nd:YAG laser could penetrate. The balloon was made from artificially modified natural latex rubber and well expanded with saline infused through a biopsy channel. The endoscopic image of the object obtained through direct contact of the balloon expanded with saline was clear enough to observe the internal surface or branches in not only normal, but also pathological conditions of the canine SVC. The Nd:YAG laser was able to be successfully irradiated through the balloon using this procedure which, although still in its preliminary state, may be a useful clinical, diagnostic and therapeutic tool of the future.

The article reviews the web site Synthesis from Morgan & Claypool Publishers, available at www.morganandclaypool.com.

The optical-limiting behavior and two-photon absorption properties of four novel organic compound solutions in tetrahydrofuran have been investigated. An ultrashort laser source with 0.5-ps pulse width and 602-nm wavelength was employed. The transmissivities of the various 1-cm-thick solution samples have been measured as a function of the beam intensity as well as of the solute concentration. The measured results can be fitted on the assumption that two-photon absorption is the only predominant mechanism causing the observed optical-limiting behavior. Based on the intensity-dependent transmissivity measurements, the molecular two-photon absorption coefficients for the four compounds are presented.

Genetic analysis in model systems can provide a rich context for conceptual understanding of gene structure, regulation, and function. With an intent to create a rich learning experience in molecular genetics, we developed a semester-long course-based undergraduate research experience (CURE) using the CRISPR-Cas9 gene editing system to disrupt specific genes in the zebrafish. The course was offered to freshman students; nine students worked in four groups (two to three members per group) to design, synthesize, and test the nuclease activity of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/sgRNAs for targeted disruption of specific genes in the zebrafish. Each group worked with a gene with an already known mutant phenotype that can be visually scored and a gene that had not been studied in zebrafish previously. Embedded in the course were a series of workshop-styled units or tutorials, including tours to core facilities. The focus was on introducing and developing skills that could be accommodated within the span of a semester. Each group successfully cloned at least one plasmid-encoding CRISPR/sgRNA template, visually analyzed injected embryos, and performed genotyping assays to detect CRISPR-Cas9 activity. In-class discussions, a final end-of-semester written test, and group oral presentations were assessed for an understanding of the CRISPR-Cas9 system, application of the CRISPR-Cas9 system as a gene manipulation tool, and experimental methods used to create plasmid vectors and synthesize sgRNA. In addition, poster presentations were evaluated by faculty, graduate students, and senior undergraduate students at a University research exposition. Self-reflections in the form of group conversations were video recorded. All students (9/9) distinctly showed learning gains after completing the activity, but the extent of the gains was variable, as seen from results of a written test and poster presentation assessment. Qualitative analysis of evaluations and self-reporting data indicated several gains, suggesting that all students found many aspects of the CURE valuable and gained project-specific (conceptual) and transferrable skills (science process and science identity).

Course-based undergraduate research experiences (CUREs) have been identified as a promising vehicle to broaden novices’ participation in authentic scientific opportunities. While recent studies in the bioeducation literature have focused on the influence of CUREs on cognitive and non-cognitive student outcomes (e.g., attitudes and motivation, science process skills development), few investigations have examined the extent to which the contextual features inherent in such experiences affect students’ academic and professional growth. Central among these factors is that of ethics and the responsible conduct of research (RCR)—essential cornerstones of the scientific enterprise. In this article, we examine the intersectionality of ethics/RCR instruction within CURE contexts through a critical review of existing literature that details mechanisms for the integration of ethics/RCR education into undergraduate laboratory experiences in the science domains. Building upon this foundation, we propose a novel, evidence-based framework that seeks to illustrate posited interactions between core ethics/RCR principles and unique dimensions of CUREs. It is our intent that this framework will inform and encourage open dialogue around an often-overlooked aspect of CURE instruction—how to best prepare ethically responsible scholars for entrance into the global scientific workforce.

The article reports on the application developed by the students which could help other students in learning through game based learning techniques and discusses approaches to Science,Technology, Engineering, and Mathematics (STEM) teaching and learning and Design of Engineering Academic Challenge.