Search

Esa Rayyan,1 Sarah Polito,1 Lana Leung,1 Ashesh Bhakta,1 Jonathan Kang,1 Justin Willey,1 Wasim Mansour,1 Mitchell L Drumm,2 Layla Al-Nakkash11Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA; 2Pediatric Pulmonology Division, Case Western Reserve University, Cleveland, OH, USAAbstract: Cystic fibrosis (CF) results from the loss or reduction in function of the CFTR (cystic fibrosis transmembrane conductance regulatory protein) chloride channel. The third most common CFTR mutation seen clinically is R117H. Genistein, a naturally occurring phytoestrogen, is known to stimulate CFTR function in vitro. We aimed to determine whether route of administration of genistein could mediate differential effects in R117H male and female CF mice. Mice were fed (4 weeks) or injected subcutaneously (1 week) with the following: genistein 600 mg/kg diet (600Gd); genistein-free diet (0Gd); genistein injection 600 mg/kg body weight (600Gi); dimethyl sulfoxide control (0Gi). In male R117H mice fed 600Gd, basal short circuit current (Isc) was unchanged. In 600Gd-fed female mice, there was a subgroup that demonstrated a significant increase in basal Isc (53.14±7.92 µA/cm2, n=6, P

Lana Leung, Jonathan Kang, Esa Rayyan, Ashesh Bhakta, Brennan Barrett, David Larsen, Ryan Jelinek, Justin Willey, Scott Cochran, Tom L Broderick, Layla Al-NakkashDepartment of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USAAbstract: Patients with diabetes and obesity are at increased risk of developing disturbances in intestinal function. In this study, we characterized jejunal function in the clinically relevant leptin-deficient ob/ob mouse, a model of diabetes and obesity. We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from 12-week-old ob/ob and lean C57BL/6J (female and male) mice. The basal Isc was significantly decreased (~30%) in the ob/ob mice (66.5±5.7 µA/cm2 [n=20]) (P< 0.05) compared with their lean counterparts (95.1±9.1 µA/cm2 [n=19]). Inhibition with clotrimazole (100 µM, applied bilaterally) was significantly reduced in the ob/ob mice (−7.92%±3.67% [n=15]) (P

Jeffrey B Bird,1 Doreen M Olvet,1 Joanne M Willey,1 Judith M Brenner1,2 1Department of Science Education, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, 11549, USA; 2Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, 11549, USACorrespondence: Judith M Brenner, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra University, Hempstead, NY, 11549-1000, USA, Tel +1 516 463-7590, Email Judith.M.Brenner@hofstra.eduIntroduction: The elimination of the USMLE Step 1 three-digit score has created a deficit in standardized performance metrics for undergraduate medical educators and residency program directors. It is likely that there will be greater emphasis on USMLE Step 2 CK, an exam found to be associated with later clinical performance in residents and physicians. Because many previous models relied on Step 1 scores to predict student performance on Step 2 CK, we developed a model using other metrics.Materials and Methods: Assessment data for 228 students in three cohorts (classes of 2018, 2019, and 2020) were collected, including the Medical College Admission Test (MCAT), NBME Customized Assessment Service (CAS) exams and NBME Subject exams. A linear regression model was conducted to predict Step 2 CK scores at five time-points: at the end of years one and two and at three trimester intervals in year three. An additional cohort (class of 2021) was used to validate the model.Results: Significant models were found at 5 time-points in the curriculum and increased in predictability as students progressed: end of year 1 (adj R2 = 0.29), end of year 2 (adj R2 = 0.34), clerkship trimester 1 (adj R2 = 0.52), clerkship trimester 2 (adj R2 = 0.58), clerkship trimester 3 (adj R2 = 0.62). Including Step 1 scores did not significantly improve the final model. Using metrics from the class of 2021, the model predicted Step 2 CK performance within a mean square error (MSE) of 8.3 points (SD = 6.8) at the end of year 1 increasing predictability incrementally to within a mean of 5.4 points (SD = 4.1) by the end of year 3.Conclusion: This model is highly generalizable and enables medical educators to predict student performance on Step 2 CK in the absence of Step 1 quantitative data as early as the end of the first year of medical education with increasingly stronger predictions as students progressed through the clerkship year.Keywords: assessment, prediction model, career advising, match, NBME

This work reports the first detailed analysis of methanol concentrations in rainwater. Methanol concentrations measured in 49 rain events collected between 28 August 2007 to 10 July 2008 in Wilmington, NC, USA, ranged from below the detection limit of 6 nM to 9.3 µM with a volume weighted average concentration of 1.2 ± 0.2 µM. Methanol concentrations in rainwater were up to ~200x greater than concentrations observed in marine waters indicating wet deposition as a potential significant source to marine waters. Assuming these methanol concentrations are an appropriate proxy for global methanol rainwater concentrations the global methanol wet deposition sink is estimated as 20Tgyr-1 which implies previous methanol budgets underestimate removal by precipitation. Methanol concentrations did not correlate with H+, NO3-, and NSS, which suggest that the dominant source of the alcohol to rainwater is not anthropogenic. However, methanol concentrations were strongly correlated with acetaldehyde which has a primarily biogenic input. Methanol volume weighted concentration during the growing season (1.5 + 0.3 µM) was more than double that of the non-growing season (0.7 + 0.1 µM), further promoting biogenic emissions as the primary cause of fluctuating methanol concentrations. Methanol concentrations peaked in rainwater collected between the time period 12:00-06:00 p.m. Peaking during this period of optimal sunlight implies a direct relationship to photochemical methanol production but there are also increases in biogenic activity during this time period. Rain events with terrestrial origins had higher concentrations than those of marine origin demonstrating the significance of the continental source of methanol in rainwater. [ABSTRACT FROM AUTHOR]

Joanne M Willey, Youn Seon Lim, Thomas Kwiatkowski Department of Science Education, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA Purpose: Calls for revision in undergraduate medical education frequently cite the importance of integrating basic and clinical sciences and the use of active pedagogies. One under-appreciated approach to accomplishing both is interactive co-teaching, defined as two instructors with complementary expertise engaging students and each other instead of lecturing. This study sought to determine if interactive co-teaching helped students integrate and learn basic and clinical sciences, as well as to explore potential advantages and barriers to co-teaching.Methods: The comparative success of solo- and co-teaching in a microbiology/infectious disease course was determined by surveying student perceptions at the end of the course and examination scores for questions based on either solo- or co-taught content. The advantages and barriers to co-teaching were explored by thematic analysis of student responses to open-ended survey questions.Results: Results suggest that co-teaching supported content integration as a significant majority of students (92%, n=112) reported they understood the connection between basic and clinical sciences better when content was co-taught. In addition, a plurality of students indicated that co-teaching provided a better overall learning experience (81%, n=99), was more engaging (74%, n=90), and made it easier to apply content (74%, n=90). These positive perceptions were reflected in better exam outcomes for materials covered in co-taught over solo-taught sessions.Conclusion: Results suggest students value co-teaching as a means to integrate basic and clinical sciences. However, interactive co-teaching pedagogies require careful planning and collaboration among faculty. Co-teaching requires the commitment of both faculty members to this pedagogy. Keywords: team teaching, microbiology, infectious disease, shared teaching, content integration, session integration

A series of seven rainwater samples were collected in Wilmington, North Carolina (USA), originating from both continental and coastal storms and analyzed by ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). This data set is unique in that it represents a detailed comparison of the molecular level composition of DOM in rainwater collected from distinctly different air mass back trajectories by FTICR-MS. Approximately 25 % of the roughly 2000 assigned CHO molecular formulas are unique to each storm classification indicating the importance of air mass back trajectory on the composition of rainwater dissolved organic matter (DOM). Analysis of the unique molecular formula assignments highlighted distinct groupings of various bio- and geo-molecule classes with coastal storms containing unique formulas representative of lignin and cellulose-like formulas, while continental storms had lipid-like formulas. A series of 18 distinct methylene oligomers were identified in coastal storms with 13 unique methylene oligomers in continental storms suggesting oligomer formation is ubiquitous in rainwater albeit different for each storm classification. Oligomers of small acids and C3H4O2 were detected in both storm types indicating their processing may be similar in both back trajectories. Black carbon (BC) was detected in continental storms with phenol moieties that are not as oxidized as aquatic DOM black carbon. The discovery of BC in continental rainwater has significant ramifications towards climate change, because atmospheric BC is such a potent chromophore that reemits absorbed sunlight at longer wavelengths thereby warming the lower atmosphere. [ABSTRACT FROM AUTHOR]

Sequential sampling of rainwater from Hurricane Irene was carried out in Wilmington, NC, USA on 26 and 27 August 2011. Eleven samples were analyzed for pH, major ions (Cl-, NO3-, SO42-, Na+, K+, Mg2+, Ca2+, NH4+), dissolved organic carbon (DOC) and hydrogen peroxide (H2O2). Hurricane Irene contributed 16% of the total rainwater and 18% of the total chloride wet deposition received in Wilmington NC during all of 2011. This work highlights the main physical factors influencing the chemical composition of tropical storm rainwater: wind speed, wind direction, air mass back trajectory and vertical mixing, time of day and total rain volume. Samples collected early in the storm, when winds blew out of the east, contained dissolved components indicative of marine sources (salts from sea spray and low DOC). The seasalt components in the samples had two maxima in concentration during the storm the first of which occurred before the volume of rain had sufficiently washed out seasalt from the atmosphere and the second when the air mass dipped to low elevations over the Atlantic Ocean followed by rapid vertical mixing. As the storm progressed and winds shifted to a westerly direction, the chemical composition of the rainwater became characteristic of terrestrial storms (high DOC and NH4+ and low seasalt). This work demonstrates that tropical storms are not only responsible for significant wet deposition of marine components to land, but terrestrial components can also become entrained in rainwater, which can then be delivered to coastal waters via wet deposition. This study also underscores why analysis of one composite sample can lead to an incomplete interpretation of the factors that influence the chemically divergent analytes in rainwater during extreme weather events. [ABSTRACT FROM AUTHOR]

Samara B Ginzburg,1 Judith Brenner,1 Michael Cassara,2 Thomas Kwiatkowski,1 Joanne M Willey,1 1Department of Science Education, Hofstra Northwell School of Medicine, Hempstead, 2Department of Emergency Medicine, Northwell Health, Great Neck, NY, USA Aim: There has been a call for increased integration of basic and clinical sciences during ­preclinical years of undergraduate medical education. Despite the recognition that clinical simulation is an effective pedagogical tool, little has been reported on its use to demonstrate the relevance of basic science principles to the practice of clinical medicine. We hypothesized that simulation with an integrated science and clinical debrief used with early learners would illustrate the importance of basic science principles in clinical diagnosis and management of patients. Methods: Small groups of first -and second-year medical students were engaged in a high-fidelity simulation followed by a comprehensive debrief facilitated by a basic scientist and clinician. Surveys including anchored and open-ended questions were distributed at the conclusion of each experience. Results: The majority of the students agreed that simulation followed by an integrated debrief illustrated the clinical relevance of basic sciences (mean ± standard deviation: 93.8% ± 2.9% of first-year medical students; 96.7% ± 3.5% of second-year medical students) and its importance in patient care (92.8% of first-year medical students; 90.4% of second-year medical students). In a thematic analysis of open-ended responses, students felt that these experiences provided opportunities for direct application of scientific knowledge to diagnosis and treatment, improving student knowledge, simulating real-world experience, and developing clinical reasoning, all of which specifically helped them understand the clinical relevance of basic sciences. Conclusion: Small-group simulation followed by a debrief that integrates basic and clinical sciences is an effective means of demonstrating the relationship between scientific fundamentals and patient care for early learners. As more medical schools embrace integrated curricula and seek opportunities for integration, our model is a novel approach that can be utilized. Keywords: basic and clinical science integration, preclinical simulation, clinical reasoning simulation

To establish a cell culture model for lung carcinogenesis, independent populations of the human papillomavirus 18-immortalized human bronchial epithelial cell line BEP2D were treated with high linear energy transfer radon-simulated alpha-particles, expanded and xenotransplanted into Nu/Nu mice. Six independent cell lines were established from tumors that developed from three separate radiation treatments as follows: treatment (Tx) 1 (30 cGy--two doses), H2BT, Tx 2 (30 cGy--single dose), R30T1L, R30T2 and R30T3L, Tx 3 (30 cGy--single dose), H1ATN and H1ATBA1. Cytogenetic analysis revealed common changes in all tumor lines: loss of the Y chromosome (ch), one of three copies of ch8, one of three copies of ch14, and one of two copies of ch4p16-pter and ch11p15-pter. Analysis of polymerase chain reaction-amplified short tandem repeats of informative loci confirmed the loss of chY in all lines and loss of heterozygosity (LOH) at eight loci spanning the length of ch8 in all lines from Tx's 1 and 2. Our data support previous studies indicating the presence of tumor suppressor genes on ch8. LOH also was confirmed on ch14 at locus D14S306 in all cell lines from Tx 2 and in one of two lines from Tx 3. This region, 14q12-q13, may contain changes in one of the five known somatostatin receptor genes (SSTR1). No LOH was detected at any of the informative loci tested for on ch4 or ch11. [ABSTRACT FROM PUBLISHER]

Abstract Background Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists. Results Using the data sets generated by the MicroArray Quality Control (MAQC) project, we investigated the impact on the reproducibility of DEG lists of a few widely used gene selection procedures. We present comprehensive results from inter-site comparisons using the same microarray platform, cross-platform comparisons using multiple microarray platforms, and comparisons between microarray results and those from TaqMan – the widely regarded "standard" gene expression platform. Our results demonstrate that (1) previously reported discordance between DEG lists could simply result from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion with a non-stringent P-value cutoff filtering, the DEG lists become much more reproducible, especially when fewer genes are selected as differentially expressed, as is the case in most microarray studies; and (3) the instability of short DEG lists solely based on P-value ranking is an expected mathematical consequence of the high variability of the t-values; the more stringent the P-value threshold, the less reproducible the DEG list is. These observations are also consistent with results from extensive simulation calculations. Conclusion We recommend the use of FC-ranking plus a non-stringent P cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists. Specifically, the P-value cutoff should not be stringent (too small) and FC should be as large as possible. Our results provide practical guidance to choose the appropriate FC and P-value cutoffs when selecting a given number of DEGs. The FC criterion enhances reproducibility, whereas the P criterion balances sensitivity and specificity.

Background: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. The outcome for patients with IBC is bleak despite multimodality treatment approaches. 10-year disease-free survival rates after combined anthracycline and taxane- containing chemotherapy, surgery, and radiation are only 20%-25%. Our recent study found EGFR overexpression, a predictive factor of poor outcome, in 12 of 40 (30%) patients with IBC. Panitumumab has shown activity against EGFR overexpressing breast cancer xenograft model. Trial design: This is a single center, open-label, phase II study to evaluate the safety and efficacy of panitumumab in combination with preoperative chemotherapy. The treatment regimen consists panitumumab 2.5 mg/Kg given intravenously alone for the first week, followed by weekly panitumumab, nab-paclitaxel (100mg/m²) and carboplatin (2 AUC) (PNC) for 12 weeks. Patients then will receive 5-FU, epirubicin, and cyclophosphamide (FEC) every 3 weeks for 4 cycles prior to surgery. Eligibility criteria: 1) Histological confirmation of breast carcinoma with pathologic evidence of dermal lymphatic invasion and clinical diagnosis of IBC, including diffuse erythema, heat, ridging, and peau d'orange; 2) Normal HER2 expression; 3) No prior therapies for IBC; 4) Adequate hematologic, cardiac, renal and hepatic functions. Specific aims: 1) Primary objective is to determine the pathologic complete response (pCR) rate in patients with primary IBC without HER2 overexpression; 2) Secondary objectives are to determine the disease-free survival (DFS), overall survival (OS), the safety and tolerability of PNC regimens and the correlates of pathologic response rate and EGFR expression level. Statistical methods: 1) Previous studies have shown that this IBC patient population achieved a 13% pCR rate on the standard of care. We assume a beta (0.26, 1.74) prior distribution for the pCR rate. This prior distribution has a mean of 13% and a standard deviation of 19%. 2) We will stop the trial early if P (pCR rate >/= 13%) is < 0.01. If we determine that there is less than a 1% chance that the pCR rate is 13% or more we will consider stopping the trial. 3) Once we have completed the study we will estimate the pCR rate with a 90% credible interval. If we have pCR in 4 of the 40 patients (10%), then our 90% credible interval for the pCR rate will be 4.0-19.6%. If we have pCR in 8 of the 40 patients (20%), then our 90% credible interval for the pCR rate will be 10.6-30.4%. We will also report the posterior probability that the pCR rate is 13% or more. For example, if we have pCR in 8 of the 40 patients (20%), then the probability that the pCR rate is 13% or more is 0.869. Present accrual and target accrual: To date, 13 patients have been enrolled. Target accrual is 40 patients. [ABSTRACT FROM AUTHOR]