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Unlocking Instructors’ Assessment Insights: General Chemistry Instructors’ Perspectives on Types of Questions and their Classroom Application
No full textAssessment communicates to students the takeaways from a course. Unfortunately, studies have demonstrated that assessment in general chemistry courses typically includes lower-cognitive demand questioning, such as recalling information and calculation-based questions. To support chemistry instructors' inclusion of higher-cognitive demand questions, chemistry education researchers have developed research-based assessment tools (e.g., Three-Dimensional Learning -3DL - and concept inventory). However, previous reports have highlighted a low uptake of these tools. To explore the reasons behind this slow adoption, instructors' thinking about these types of assessment tools should be probed. In this study, semi-structured interviews were conducted with 19 general chemistry instructors to explore whether and how instructors would use four different types of multiple-choice questions, including a standard conceptual question, a calculation-based question, a 3DL question, and a concept inventory-type question in their courses' exam/midterm, homework, and/or in-class activity. Instructors in this study were interested in using the research-based assessment tools in at least one assessment context (i.e., home, in-class, or exam). The most common modification described by the instructors across the four types of questions was shifting the format from close to open-ended as it allows instructors to better understand student thinking and can promote better conversations among students in class settings. Finally, the analysis of interviews shows variations in instructors' expectations for the cognitive demand of questions on exams. Taken together, these findings suggest a need to further probe instructors' assessment literacy to inform the development of professional development programs and policies that would support higher-quality assessment in general chemistry courses
Dimorphic regulation of time-restricted feeding effects by hepatocyte Period 1
No full textObjectives: Obesity is linked to metabolic disorders including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease. Lifestyle interventions, such as time-restricted feeding (TRF), have proven to be effective for long-term weight management. The metabolic effects of TRF are closely associated with circadian clock function in the liver. We previously demonstrated that the circadian gene Period 1 (Per1) mediates responses to acute fasting in both sexes. We therefore hypothesized that hepatocyte Per1 contributes to the long-term adaptations to repeated fasting exposure in the form of TRF, and investigated its role in diet-induced obesity in both sexes.
Methods: Male and female mice with or without hepatocyte Per1 (Per1fl/fl and Per1LKO) were subjected to either ad libitum feeding (ALF) or TRF restricted to the active phase (8 h/day).
Results: TRF attenuated Western diet-induced weight gain and peripheral and hepatic lipid accumulation, and improved heat production, metabolic substrate flexibility, and glucose homeostasis in Per1fl/fl and Per1LKO males. In contrast, hepatocyte Per1 was required for TRF-induced improvements in energy expenditure and peripheral and hepatic lipid accumulation in females. Surprisingly, TRF failed to significantly attenuate diet-induced weight gain or glucose and insulin tolerance in females independent of genotype. Transcriptomic data revealed sex-specific transcriptional responses to TRF and to hepatocyte-specific Per1 deletion. Specifically, genes involved in lipid metabolism were differentially regulated when comparing TRF-treated Per1fl/fl and Per1LKO female mice.
Conclusions: Hepatocyte Per1 mediates the energy, lipid, and glucose homeostatic effects of TRF, and this regulation is almost completely sex-dependent
Perioperative Management of a Patient with Hypertrophic Obstructive Cardiomyopathy.
No full textA 69 year old female with medical history of HOCM, GERD, HTN, A-fib with RVR, NSTEMI, and CVA, presented for an EGD. She had undergone a cardiac myomectomy for HOCM one year prior, with transthoracic echocardiogram showing immediately prior to myomectomy demonstrating an LVOT gradient of 80 mmHg at rest and 178 mmHg with the Valsalva maneuver. She developed an acute gastrointestinal bleed secondary to ulcers, resulting in a hemoglobin drop from 12.3 to 7.8 g/dL and persistent tachycardia in the 120s despite transfusion with one unit of packed red blood cells. Her home metoprolol had been held due to concerns about hypotension. Prior to the procedure, metoprolol was administered along with a second unit of PRBCs. Intraoperatively, a phenylephrine infusion was utilized alongside a small dose of fentanyl, oral lidocaine, and a propofol infusion. The patient was successfully weaned off phenylephrine in the PACU and tolerated the endoscopic procedure without complications.
HOCM is a genetic cardiac disorder recognized as the leading cause of sudden cardiac death in young people. At least 1400 genetic markers have been associated with this condition, making it incredibly heterogeneous. With this heterogeneity, many cases go unrecognized and are asymptomatic for their entire lives. This means that patients may present at any age without a prior diagnosis of this condition. When symptomatic, its pathophysiology is characterized by hyperdynamic left ventricular function, which can generate a Venturi effect that draws the anterior mitral valve leaflet into the LVOT, sealing against the hypertrophied septum and causing dynamic obstruction at the base of the aorta. Effective anesthetic management, therefore, relies on five key principles: increasing preload, increasing afterload, reducing heart rate, decreasing contractility, and maintaining sinus rhythm. Optimizing preload and afterload prevents LVOT collapse and is achieved through fluid resuscitation and the use of peripherally selective vasopressors like phenylephrine. Heart rate and contractility are controlled with negative inotropes, typically β1-selective β-blockers. Antiarrhythmics such as amiodarone should be considered if necessary for arrhythmia management. With meticulous preoperative planning and hemodynamic optimization, anesthesia providers can significantly improve outcomes for patients with HOCM
Systematic comparison of methods for offline breath sampling
No full textHarnessing the potential of exhaled breath analysis is an emerging frontier in medical diagnostics, given breath is a rich source of volatile organic compound (VOC) biomarkers for different medical conditions. A current downfall in this field, however, is the lack of standardized and widely available methods for offline sampling of exhaled VOCs. Herein, strides are taken toward the standardization of breath sampling in Tedlar bags by exploring several factors that can impact VOC heterogeneity, including tubing material, chemical composition of collection bags, breath fractionation, exhalation volume, and transfer flow rate. After bag-based sampling standardization, performance was benchmarked using two offline breath sampling methods, Tedlar bags and the Respiration Collector for In Vitro Analysis (ReCIVA). Three volunteers from the laboratory with no known respiratory diseases donated ≥ n = 5 samples collected onto adsorption tubes via each method, which were analyzed through thermal desorption (TD) coupled with gas chromatography-mass spectrometry (GC-MS). Data processing revealed a set of 15 highly reliable on-breath VOCs detected across volunteers, and most analytes (except indole) demonstrated higher sensitivity using Tedlar bags. Calculating relative standard deviation (RSD) values showed Tedlar bags were also significantly more reproducible compared to the ReCIVA (p < 0.03). Agreement between the two methods was demonstrated through correlating VOC signals with high statistical significance (R2 = 0.70), indicating both devices are well situated for biomarker discovery applications
Machine learning-based prognostic subgrouping of glioblastoma: A multicenter study
No full textBackground: Glioblastoma (GBM) is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification.
Methods: We developed a highly reproducible, personalized prognostication, and clinical subgrouping system using machine learning (ML) on routine clinical data, magnetic resonance imaging (MRI), and molecular measures from 2838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, and III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]).
Results: The ML model stratified patients into distinct prognostic subgroups with HRs between subgroups I-II and I-III of 1.62 (95% CI: 1.43-1.84, P < .001) and 3.48 (95% CI: 2.94-4.11, P < .001), respectively. Analysis of imaging features revealed several tumor properties contributing unique prognostic value, supporting the feasibility of a generalizable prognostic classification system in a diverse cohort.
Conclusions: Our ML model demonstrates extensive reproducibility and online accessibility, utilizing routine imaging data rather than complex imaging protocols. This platform offers a unique approach to personalized patient management and clinical trial stratification in GBM
High-resolution proteomics unveils salivary gland disruption and saliva-hemolymph protein exchange in Plasmodium-infected mosquitoes
No full textPlasmodium sporozoites, the infective stage of malaria, must invade the mosquito salivary glands (SGs) before being transmitted to a vertebrate host. However, the physiological and biochemical effects of this invasion remain largely unexplored. We examined the impact of Plasmodium infection on Anopheles gambiae salivary glands using high-resolution proteomics, gene expression, and morphological analysis. The data reveal differential expression of various proteins, including the enrichment of hemolymph-derived humoral proteins in infected salivary glands. These proteins diffuse into the SGs due to structural damage caused by the sporozoites during invasion, while saliva proteins diffuse out into the circulation. Moreover, proteomic analysis of saliva from P. berghei- or P. falciparum-infected mosquitoes revealed changes in composition, with a pronounced reduction of immune proteins relative to uninfected mosquitoes. This reduction is likely due to the association of these proteins with the surface of sporozoites and/or changes in the saliva's physical properties within the invaded salivary secretory cavities. The saliva protein profiles from mosquitoes infected with both Plasmodium species are remarkably similar, suggesting a conserved interaction between sporozoites and salivary glands. Our results provide a foundation for understanding the molecular interactions between Plasmodium sporozoites and mosquito salivary glands
Rates of adherence, adherence measurement, and support services for children and adolescents living with HIV followed in global sites of the International Epidemiology Databases to Evaluate AIDS (IeDEA)
No full textIntroduction: Supporting and improving antiretroviral therapy (ART) adherence and preventing the evolution of HIV drug resistance remain major challenges for children and adolescents living with HIV globally. In a large global HIV clinical data consortium, we sought to describe how global HIV care programs measure and support pediatric ART adherence, as well as patient-level measures of adherence.
Methods: We prospectively collected site-level data between June 2014-March 2015 using a site assessment survey and retrospectively examined patient-level data collected during routine clinical care, to provide a comprehensive assessment of pediatric ART adherence across the International Epidemiology Databases to Evaluate AIDS (IeDEA) cohort, in six global regions. All regions capturing patient-level data on adherence by any measure for children living with HIV aged less than 14 years between 2000-2015 were asked to contribute data. ART adherence was conceptualized as a binomial variable of "good" (greater than 90%) or "poor" (90% or less) adherence per visit.
Results: Clinical staff from 180 pediatric sites in 45 countries completed the adherence survey. Clinician adherence assessment (used at 87% of sites) and pharmacy refills (86% of sites) were the most common adherence measurement methods used globally. Counseling focused on adherence was the most commonly available support service, (94% of sites). 28,664 pediatric patients had at least one adherence measurement, to be included for adherence analyses. In East Africa and Southern Africa, higher baseline CD4 counts were associated with a greater likelihood of viral suppression; however, in Central and South America and the Caribbean (CCASAnet) and Asia-Pacific, we did not find a consistent relationship between baseline CD4 count and the likelihood of viral suppression. We found evidence that very young children ( 10 years of age), and males were less likely to experience viral suppression in East Africa and Southern Africa.
Conclusion: These findings indicate that the majority of global pediatric HIV care services routinely measure ART adherence for children living with HIV; however, few sites use objective or validated measures. Identifying subgroups of children and youth at highest risk for non-adherence allows care programs to target those most in need of adherence support or resistance monitoring
CryoEM structures of evolved Family B DNA polymerase bound to template-primer substrates
No full textThe cryoEM revolution has made it possible to determine structures of many macromolecules of interest that have remained intractable to crystallographic analysis. But, despite the many advances in instrumentation and software, complexes with molecular weights that are less than 100 kDa remain on the small side for cryoEM. Particularly challenging are dynamic proteins that are undersized such as bacterial and archeal replicative DNA polymerases. A long-standing interest in my laboratory has been to provide a structural basis for understanding how laboratory evolved polymerases adapt to enable replication of unnatural nucleic acid. It has been necessary to create polymerase variants to replicate unnatural nucleic acid because the process of natural evolution has conferred very narrow selectivity of DNA polymerases for natural nucleic acid substrates. In our inaugural study, we found that a small change in a hydrophobic core of an evolved Klentaq polymerase capable of replicating Z:P pairs allowed the polymerase to attain a larger range of motion than possible in the parent polymerase. With the goal of structurally characterizing enzymes that are capable of replicating additional unnatural base pairs, we have pursued cryoEM analysis of a family B polymerase that replicates both S:B and Z:P pairs, which were created by Benner laboratory (FfAME). To date, we have established that cryoEM can be used successfully to obtain 2.8- 3 Å structures of nucleic acid complexes with a family B DNA polymerase (∼90 kDa) and that the conformations observed in our cryoEM structures differ from those observed in crystal structures of related enzymes. Future studies will include comparative structural and molecular dynamics analyses of both natural and unnatural DNA substrates bound to this enzyme
Experiences in Healthcare Predicts Pre-Exposure Prophylaxis Awareness and Attitudes: A Brief Report on Adolescent Sexual Minority Males
No full textThis study examines the association between healthcare experiences and LGBTQ + connectedness with beliefs about pre-exposure prophylaxis (PrEP) among adolescent sexual minority males in romantic relationships. Results revealed that connection to the LGBTQ + community and comfort discussing sexual health with a healthcare provider was positively associated with perceived confidence in taking PrEP daily, while experiences of discrimination by a healthcare provider was negatively associated with the perceived PrEP effectiveness to prevent HIV. Findings highlight the importance of fostering an affirming environment for learning about HIV prevention and for increasing confidence in taking care of one's sexual health
Mechanical Quantification in Lipid Membrane and Live Cells using Fluorescence-based Molecular Sensors
No full textIUPUIFluorescence is a well-studied physical phenomenon and has been the basis for many research tools. Yet the recent advancements in ultrafast lasers and fluorescent molecules have opened the door to new ways to study the dynamical forces acting inside living cells. Fluorescence lifetime imaging microscopy, or FLIM, can move the fluorescence microscopy beyond being a tool of simple tracking and identification of cellular features and enables live monitoring of cellular activities and dynamics. New fluorophores and their arrangements have helped to take advantage of FRET, fluorescence resonance energy transfer process which enables measurement of qualities previously difficult to measure. The thesis focuses on demonstration of these newly developed tools and their applications as molecular sensors in biomedical research. Flipper-TR, a recently arrived molecular probe, shows how it can report via FLIM on lipid packing orders in different lipid membranes and how they change with the varying cholesterol contents. The measurements from FLIM-Flipper-TR are compared to those by deuterium NMR, a well-established method to study the structures and phase transitions within lipid membranes, to test an implicit hypothetical relationship between the intermolecular spacing reported by the fluorescence probe and order parameters derived from NMR spectra. The result yields a strong linear correlation between the two techniques and measurements obtained from them; additional experiment reveals a still incomplete picture but a definite potential of interchangeability for the two methods. Additionally, the work lists demonstrations of diverse molecular sensors based on FRET and how their utilization can aid in characterization of tumor cells and development of novel cancer treatments, not to mention study of general cellular dynamics. In summary, the thesis work offers a glimpse into the world of new fluorescence-based molecular sensors and their promising applications in biomedical research