The Design And Synthesis Of Allosteric Effectors Of Carbon Monoxide Binding To Hemoglobin

The development of small molecule allosteric inhibitors of carbon monoxide (CO) binding to hemoglobin (Hb) is important for the treatment of CO poisoning. We have found that the synthetic peptide IRL 2500 leads to inhibition of CO binding, but with concomitant hemolytic activity. We describe herein the design, synthesis and biological evaluation of analogs of IRL 2500 that inhibit CO binding without hemolysis. The most potent compounds that we have prepared to date contain heteroaromatic biaryls in place of the biphenyl moiety of IRL 2500. These compounds show improved solubility and reduced hemolytic activity. We also describe the synthesis of conformationally constrained analogs of IRL 2500 based on a piperazine-derived scaffold

Quality Improvement for the JeffMD Clinical Experience Program

Introduction: The JeffMD curriculum at Sidney Kimmel Medical College, which completed its inaugural year in the spring of 2018, aims to prepare future physicians to “thrive in the landscape of modern healthcare.” The curriculum is based upon the knowledge that human health exists interdependently with all aspects of life, including but not limited to social, health care system, behavioral, and biological factors. The JeffMD Clinical Experience Program (CE) is a mandatory, experiential, value-added component of the curriculum. Through the CE course, which spans the 21-month preclinical period, students work with a Community Health Worker to screen patients for social needs and connect them to community resources. Objective: The purpose of this Quality Improvement study was twofold. First, we sought to evaluate the extent to which the first year of the CE program (1) contributed to student learning, and (2) added value to the clinical sites. Second, we sought to implement site-specific improvements based upon our results. Methods: We followed the Plan-Do-Study-Act (PDSA) model. We measured the current performance of the CE program through electronic surveys administered to the 260 first-year medical students who participated. The surveys included free response and Likert scale questions. We also conducted small group interviews with key stakeholders from four of the clinical sites using a questionnaire adapted from Penn State. Results: Students valued the opportunity to interact with patients and learn about social determinants of health; however, they did not find the CE program to be an effective learning experience. Key themes from the clinical site interviews included lack of student initiative, physical space constraints, communication barriers, and the positive contribution of Community Health Workers. Conclusion: We performed cause analyses and implemented clinical site-specific changes based upon our results. We believe that the student experience will improve from year-to-year so long as we continue to incorporate feedback from students and other stakeholders

Are We Prepared? Increased Drought Vulnerability Due to Climate Change and State Drought Plan Preparedness

Climate change is one of the largest uncertainties surrounding water resources throughout the end of the century. Warming temperatures have a cascading effect with regard to water, driving up natural and human demand. Changing climatic patterns will also increase the risk of extreme events. One of the costliest and misunderstood natural disasters is drought. In recent years drought planning has moved from a mode of crisis/reactionary management to one of risk/preparedness management. While this shift in planning has occurred in some states, others have not moved beyond reactionary planning. Climate change has the potential of increasing the frequency and severity of drought through the end of century. This research quantifies the increased risk of drought due to climate change and analyzes the state drought policy of a region with amplified drought risk. The research finds that many states lack the inclusion of climate induced drought risk when planning. Finally, recommendations for addressing increased drought risk due to climate change at a state level are provided

Assessing caregiving experience in COPD: content validity of the Zarit Burden Interview

Caring for a relative with COPD influences multiple dimensions of carers' lives. Several instruments have been used to assess the caregiving experience in COPD,1 e.g. the Zarit Burden Interview (ZBI). This instrument was originally developed for use in carers of people with dementia, however, its applicability in COPD has not been tested. This study explored the content validity of the ZBI in carers of patients with COPD. Ten carers (68.2±6.9yrs, all female) of patients with COPD (74.7±5.3yrs, all male, FEV1=49.2±19.0%pred) participated in cognitive debriefing interviews. They were asked to complete the ZBI and verbalise their thinking process to assess the adequacy of its content and instructions. Interviews were recorded and transcribed for further analysis using the qualitative data analysis software (WebQDA). Responses to the ZBI were also analysed to explore floor/ceiling effects. From the 22 items of the ZBI, 6 items were relevant for all carers and 11 items were not relevant for at least one participant. Five of these 11 items were not relevant for ≥40% of the sample and were related to stress for providing care, embarrassment about patient’s behaviour and impacts on social/leisure time. The remaining 5 items were not consensual. Overall, the ZBI was well-understood although 8 items were less clear for some carers. They suggested: improving questions (n=1) and scoring (n=5); eliminating item 4 (n=2); including 2 questions about the caregiving context (n=1). Responses were mostly distributed in the option ‘Never/Not at all’. The ZBI in its current form should not be used to assess carer experience among those caring for patients with COPD.publishe

Transcriptome profiling with focus on potential key genes for wing development and evolution in Megaloprepus caerulatus, the damselfly species with the world's largest wings

The evolution, development and coloration of insect wings remains a puzzling subject in evolutionary research. In basal flying insects such as Odonata, genomic research regarding bauplan evolution is still rare. Here we focus on the world’s largest odonate species—the “forest giant” Megaloprepus caerulatus, to explore its potential for looking deeper into the development and evolution of wings. A recently discovered cryptic species complex in this genus previously considered monotypic is characterized by morphological differences in wing shape and color patterns. As a first step toward understanding wing pattern divergence and pathways involved in adaptation and speciation at the genomic level, we present a transcriptome profiling of M. caerulatus using RNA-Seq and compare these data with two other odonate species. The de novo transcriptome assembly consists of 61,560 high quality transcripts and is approximately 93% complete. For almost 75% of the identified transcripts a possible function could be assigned: 48,104 transcripts had a hit to an InterPro protein family or domain, and 28,653 were mapped to a Gene Ontology term. In particular, we focused on genes related to wing development and coloration. The comparison with two other species revealed larva-specific genes and a conserved ‘core’ set of over 8,000 genes forming orthologous clusters with Ischnura elegans and Ladona fulva. This transcriptome may provide a first point of reference for future research in odonates addressing questions surrounding the evolution of wing development, wing coloration and their role in speciation

Adolescent brain cognitive development (ABCD) study: Overview of substance use assessment methods.

One of the objectives of the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org/) is to establish a national longitudinal cohort of 9 and 10 year olds that will be followed for 10 years in order to prospectively study the risk and protective factors influencing substance use and its consequences, examine the impact of substance use on neurocognitive, health and psychosocial outcomes, and to understand the relationship between substance use and psychopathology. This article provides an overview of the ABCD Study Substance Use Workgroup, provides the goals for the workgroup, rationale for the substance use battery, and includes details on the substance use module methods and measurement tools used during baseline, 6-month and 1-year follow-up assessment time-points. Prospective, longitudinal assessment of these substance use domains over a period of ten years in a nationwide sample of youth presents an unprecedented opportunity to further understand the timing and interactive relationships between substance use and neurocognitive, health, and psychopathology outcomes in youth living in the United States

An Overview of Major Health Information Technology, Public Health, Medicaid, and COBRA Provisions of the American Recovery and Reinvestment Act of 2009

A detailed side-by-side analysis of the individual components of the American Recovery and Reinvestment Act of 2009 (ARRA), signed into law on February 17, 2009. One of the most sweeping pieces of economic legislation ever enacted, ARRA not only provides hundreds of billions of dollars in new health and health care spending but also makes comprehensive reforms in health law and policy, particularly in the area of health information law, including health information technology (HIT) adoption and health information privacy

An Overview of Major Health Provisions Contained in the American Recovery and Reinvestment Act of 2009

On February 17, 2009, President Barack Obama signed the American Recovery and Reinvestment Act of 2009 (ARRA) into law. One of the most sweeping pieces of economic legislation ever enacted, ARRA not only provides hundreds of billions of dollars in new health and health care spending but also makes comprehensive reforms in health law and policy, particularly in the area of health information law, including health information technology (HIT) adoption and health information privacy

Health Information Technology in the United States: On the Cusp of Change, 2009

In this report we use the data collected for ONCHIT to focus on EHR adoption in the inpatient setting. We report on several important policy issues. These include the rate of adoption of EHRs among U.S. hospitals generally and among safety-net hospitals, changes in both state and federal policy, and the potential of EHRs to change the quality measurement enterprise