Pulmonary Nocardiosisin an ImmunocompetentHost

Introduction: • Nocardia is known to cause severe pulmonary or disseminated infection in immunocompromised patients, but can cause infection in immunocompetent patients. Providers should consider Nocardiosis in immunocompetent patients with prolonged and unexplained respiratory failure. • The preferred therapy for pulmonary Nocardiosis is a sulfa antibiotic for 3-6 months. Toxicity from prolonged use of alternative agents presents a therapeutic challenge in those with sulfa allergy. Case Report: • An 85 year-old woman with a history of paroxysmal atrial fibrillation and heart failure with preserved EF presented to her primary care provider with 1 week of cough and progressive dyspnea. Chest x-ray (CXR) was normal, and echocardiogram demonstrated known HFpEFwithout new abnormalities. • Two months later, she presented to the hospital with progressive dyspnea, chest tightness, and was found to be hypoxic. CXR on admission showed bilateral consolidations as well as mediastinal and hilar adenopathy. She was treated with ceftriaxone & azithromycin for presumed community-acquired pneumonia (CAP). • Due to treatment failure, a CT Chest was obtained and showed a mass-like consolidation in the right middle lobe; she was discharged with a several-week prednisone taper for treatment of presumed cryptogenic organizing pneumonia. • Two weeks later, she returned for worsening dyspnea, chest pressure, malaise, and hypoxia. She was again treated for CAP and discharged. • One month later, she was admitted for similar symptoms, and a CT-guided lung biopsy showed several small clusters of long Gram-positive bacteria consistent with Nocardia spp. Tissue culture was positive for Nocardia cyriacigeorgicacomplex. • The patient was offered a challenge of her sulfa allergy (reported as a rash), but refused. She was started on linezolid in anticipation of a 6 month course of therapy. • Her hospitalization was complicated by cardiac & renal dysfunction. Due to severely impaired quality of life, the patient elected for hospice care and died approximately 2 weeks after discharge. Discussion: • Nocardiosis most commonly presents as a pulmonary infection as inhalation is the primary route of exposure. • More than half of all reported Nocardiosis cases are associated with preexisting immunocompromise such as organ transplantation, AIDS, diabetes, chronic granulomatous disease and alcoholism. More recently published case reports depict Nocardia infections in immunocompetent patients with a prior history of lung disease, such as chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, and bronchiectasis. • Our patient was neither immunocompromised, nor had a prior history of lung disease, though was an elderly person. Immunosenescenceis associated with decline in innate as well as T-cell immunity, which may have imparted risk to our patient. • The mainstay for treatment of Nocardia infections is trimethoprim-sulfamethoxazole (TMP-SMX). Alternative oral agents include minocycline, amoxicillin-clavulanate, and linezolid. • Had our patient not chosen the route of hospice care, close monitoring for linezolid toxicity would have been necessary with possible TMP-SMX re-challenge for long term therapy.https://digitalcommons.psjhealth.org/psv_internal/1007/thumbnail.jp

Curricular Innovations to Promote Systems Thinking in a General Chemistry Laboratory Course

Systems thinking is a perspective and set of skills used to examine the dynamic complexities of an entire system and to make predictions about system behavior. Systems thinking is of interest to educators because of its unique potential to enhance students’ critical thinking and problem-solving skills, therefore developing scientists who are capable of addressing many of the complex problems facing our world today. Utilizing previously published pedagogical tools, revisions and additions that promote systems thinking were made to a general chemistry laboratory unit. Through these curricular innovations, students defined systems thinking and employed many systems thinking skills throughout the laboratory unit. Students were surveyed after completing the laboratory unit, and their responses were analyzed to assess the utility of the curriculum revisions and inform subsequent revisions

Development and Use of a Construct Map Framework to Support Teaching and Assessment of Noncovalent Interactions in a Biochemical Context

Most chemistry educators agree that deep understanding of the nature of noncovalent interactions is essential for learning in chemistry. Yet decades of research have shown that students have persistent incorrect ideas about these interactions. We have worked in collaboration with a community of chemistry, biology, and biochemistry educators to develop a construct map to guide development of instructional and assessment resources related to the physical basis of noncovalent interactions in a biochemical context. This map was devised using data about student learning and expert perspectives on noncovalent interactions, resulting in a framework that provides a detailed roadmap for teaching and learning related to this essential concept. Here we describe the development of the construct map and our use of it to reform our biochemistry teaching practice. Because biochemistry relies on application of concepts learned in prerequisite courses, this construct map could be useful for wide range of courses including general chemistry, introductory biology, organic chemistry, and biochemistry

Identification of Threshold Concepts for Biochemistry

Threshold concepts (TCs) are concepts that, when mastered, represent a transformed understanding of a discipline without which the learner cannot progress. We have undertaken a process involving more than 75 faculty members and 50 undergraduate students to identify a working list of TCs for biochemistry. The process of identifying TCs for biochemistry was modeled on extensive work related to TCs across a range of disciplines and included faculty workshops and student interviews. Using an iterative process, we prioritized five concepts on which to focus future development of instructional materials. Broadly defined, the concepts are steady state, biochemical pathway dynamics and regulation, the physical basis of interactions, thermodynamics of macromolecular structure formation, and free energy. The working list presented here is not intended to be exhaustive, but rather is meant to identify a subset of TCs for biochemistry for which instructional and assessment tools for undergraduate biochemistry will be developed

Identification of Threshold Concepts for Biochemistry

Threshold concepts (TCs) are concepts that, when mastered, represent a transformed understanding of a discipline without which the learner cannot progress. We have undertaken a process involving more than 75 faculty members and 50 undergraduate students to identify a working list of TCs for biochemistry. The process of identifying TCs for biochemistry was modeled on extensive work related to TCs across a range of disciplines and included faculty workshops and student interviews. Using an iterative process, we prioritized five concepts on which to focus future development of instructional materials. Broadly defined, the concepts are steady state, biochemical pathway dynamics and regulation, the physical basis of interactions, thermodynamics of macromolecular structure formation, and free energy. The working list presented here is not intended to be exhaustive, but rather is meant to identify a subset of TCs for biochemistry for which instructional and assessment tools for undergraduate biochemistry will be developed

Development of a Certification Exam to Assess Undergraduate Students\u27 Proficiency in Biochemistry and Molecular Biology Core Concepts

With support from the American Society for Biochemistry and Molecular Biology (ASBMB), a community of biochemistry and molecular biology (BMB) scientist-educators has developed and administered an assessment instrument designed to evaluate student competence across four core concept and skill areas fundamental to BMB. The four areas encompass energy and metabolism; information storage and transfer; macromolecular structure, function, and assembly; and skills including analytical and quantitative reasoning. First offered in 2014, the exam has now been administered to nearly 4000 students in ASBMB-accredited programs at more than 70 colleges and universities. Here, we describe the development and continued maturation of the exam program, including the organic role of faculty volunteers as drivers and stewards of all facets: content and format selection, question development, and scoring

Darbepoetin Administration to Neonates Undergoing Cooling for Encephalopathy: A Safety and Pharmacokinetic Trial

Background: Despite therapeutic hypothermia, neonates with encephalopathy (NE) have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable biological activity to erythropoietin, but has extended circulating half-life (t1/2). Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia. Study design: Thirty infants (n = 10/arm) ≥36 wk gestation undergoing therapeutic hypothermia for NE were randomized to receive placebo, Darbe low dose (2 μg/kg), or high dose (10 μg/kg) given intravenously within 12 h of birth (first dose/hypothermia condition) and at 7 d (second dose/normothermia condition). Adverse events were documented for 1 mo. Serum samples were obtained to characterize Darbe pharmacokinetics. Results: Adverse events (hypotension, altered liver and renal function, seizures, and death) were similar to placebo and historical controls. Following the first Darbe dose at 2 and 10 μg/kg, t1/2 was 24 and 32 h, and the area under the curve (AUCinf) was 26,555 and 180,886 h*mU/ml*, respectively. In addition, clearance was not significantly different between the doses (0.05 and 0.04 l/h). At 7 d, t1/2 was 26 and 35 h, and AUCinf was 10,790 and 56,233 h*mU/ml*, respectively (*P \u3c 0.01). Conclusion: Darbe combined with hypothermia has similar safety profile to placebo with pharmacokinetics sufficient for weekly administration

Darbepoetin Administration to Neonates Undergoing Cooling for Encephalopathy: A Safety and Pharmacokinetic Trial

Background: Despite therapeutic hypothermia, neonates with encephalopathy (NE) have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable biological activity to erythropoietin, but has extended circulating half-life (t1/2). Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia. Study design: Thirty infants (n = 10/arm) ≥36 wk gestation undergoing therapeutic hypothermia for NE were randomized to receive placebo, Darbe low dose (2 μg/kg), or high dose (10 μg/kg) given intravenously within 12 h of birth (first dose/hypothermia condition) and at 7 d (second dose/normothermia condition). Adverse events were documented for 1 mo. Serum samples were obtained to characterize Darbe pharmacokinetics. Results: Adverse events (hypotension, altered liver and renal function, seizures, and death) were similar to placebo and historical controls. Following the first Darbe dose at 2 and 10 μg/kg, t1/2 was 24 and 32 h, and the area under the curve (AUCinf) was 26,555 and 180,886 h*mU/ml*, respectively. In addition, clearance was not significantly different between the doses (0.05 and 0.04 l/h). At 7 d, t1/2 was 26 and 35 h, and AUCinf was 10,790 and 56,233 h*mU/ml*, respectively (*P \u3c 0.01). Conclusion: Darbe combined with hypothermia has similar safety profile to placebo with pharmacokinetics sufficient for weekly administration