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

Background: The Lung Cancer Risk Test (LCRT) trial is a prospective cohort study comparing lung cancer incidence among persons with a positive or negative value for the LCRT, a 15 gene test measured in normal bronchial epithelial cells (NBEC). The purpose of this article is to describe the study design, primary endpoint, and safety; baseline characteristics of enrolled individuals; and establishment of a bio-specimen repository.Methods/design: Eligible participants were aged 50-90 years, current or former smokers with 20 pack-years or more cigarette smoking history, free of lung cancer, and willing to undergo bronchoscopic brush biopsy for NBEC sample collection. NBEC, peripheral blood samples, baseline CT, and medical and demographic data were collected from each subject.Discussion: Over a two-year span (2010-2012), 403 subjects were enrolled at 12 sites. At baseline 384 subjects remained in study and mean age and smoking history were 62.9 years and 50.4 pack-years respectively, with 34% current smokers. Obstructive lung disease (FEV1/FVC <0.7) was present in 157 (54%). No severe adverse events were associated with bronchoscopic brushing. An NBEC and matched peripheral blood bio-specimen repository was established. The demographic composition of the enrolled group is representative of the population for which the LCRT is intended. Specifically, based on baseline population characteristics we expect lung cancer incidence in this cohort to be representative of the population eligible for low-dose Computed Tomography (LDCT) lung cancer screening. Collection of NBEC by bronchial brush biopsy/bronchoscopy was safe and well-tolerated in this population. These findings support the feasibility of testing LCRT clinical utility in this prospective study. If validated, the LCRT has the potential to significantly narrow the population of individuals requiring annual low-dose helical CT screening for early detection of lung cancer and delay the onset of screening for individuals with results indicating low lung cancer risk. For these individuals, the small risk incurred by undergoing once in a lifetime bronchoscopic sample collection for LCRT may be offset by a reduction in their CT-related risks. The LCRT biospecimen repository will enable additional studies of genetic basis for COPD and/or lung cancer risk.Trial Registration: The LCRT Study, NCT 01130285, was registered with Clinicaltrials.gov on May 24, 2010. [ABSTRACT FROM AUTHOR]

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 (FT-ICR 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 FT-ICR MS. Approximately 25% of the roughly 2000 assigned CHO molecular formulas are unique to a single 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 and 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. Condensed aromatic hydrocarbons were detected in continental storms with phenol moieties that are not as oxidized as similar compounds detected in aquatic DOM. [ABSTRACT FROM AUTHOR]

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]

Water based electrolyzers offer a promising approach for generating hydrogen gas for renewable energy storage. 3M's nanostructured thin film (NSTF) catalyst technology platform has been shown to significantly reduce many of the performance, cost and durability barriers standing in the way of H2/air PEM fuel cells for vehicles. In this paper we describe results from the first evaluations of low loaded NSTF catalysts in H2/O2 electrolyzers at Proton OnSite and Giner, Inc. Over two dozen membrane electrode assemblies comprising nine different NSTF catalyst types were tested in 11 short stack durability tests at Proton OnSite and 14 performance tests in 50 cm2 single cells at Giner Electrochemical Systems. NSTF catalyst alloys of Pt68Co29Mn3, Pt50Ir50 and Pt50Ir25Ru25, with Pt loadings in the range of 0.1 to 0.2 mg/cm2, were investigated for beginning-of-life performance and durability up to 4000 hours as both electrolyzer cathodes and anodes. Catalyst composition, deposition and process conditions were found to be important for meeting the performance of standard PGM blacks on electrolyzer anodes while using only 10% as much PGM catalyst. Analyses of MEA's after the durability tests by multiple techniques document changes in catalyst alloy composition, loading, crystallite structure and support stability. [ABSTRACT FROM AUTHOR]

Goals Of Work: Determining resuscitation status (RS) for inpatients with advanced cancer is emotionally charged and often conflictual. Available data suggest that clinicians have inconsistent practices when establishing and documenting do-not-resuscitate (DNR) orders. Lack of standardization may contribute to ineffective and unclear discussions regarding RS. To inform revisions of DNR order forms used at one comprehensive cancer center, we surveyed National Cancer Institute-designated cancer centers (NCICCs) to determine if a standardized approach to documenting inpatient DNR orders exists.Materials and Methods: Over a 12-week period in 2002-2003, the 50 NCICCs providing inpatient care were contacted regarding participation in this Institutional Review Board-approved study. Using a 69-item database, inpatient DNR order forms were analyzed for content and elements of process used to establish and document RS. Each form was evaluated by two raters to assess inter-rater reliability. Analysis was descriptive; inter-rater agreement was summarized using the kappa statistic.Main Results: Sixty percent (30 out of 50) of NCICCs participated. Eighty percent of responding sites confined the order process exclusively to cardiopulmonary resuscitation and did not include other interventions for possible limitation. Two thirds of responding sites used preformatted order forms specific for establishing inpatient RS; forms varied widely in content and elements of process used to establish and document DNR orders.Conclusions: NCICCs do not have a standardized approach to establishing and documenting DNR orders. Lack of standardization may reflect the absence of a common understanding of these difficult issues which may contribute to unclear and ineffective communication when addressing RS. [ABSTRACT FROM AUTHOR]

Cancer patients receiving radiation therapy are exposed to photon (gamma/X-ray), electron, and less commonly proton radiation. Similarly, astronauts on exploratory missions will be exposed to extended periods of lower-dose radiation from multiple sources and of multiple types, including heavy ions. Therapeutic doses of radiation have been shown to have deleterious consequences on bone health, occasionally causing osteoradionecrosis and spontaneous fractures. However, no animal model exists to study the cause of radiation-induced osteoporosis. Additionally, the effect of lower doses of ionizing radiation, including heavy ions, on general bone quality has not been investigated. This study presents data developing a murine model for radiation-induced bone loss. Female C57BL/6 mice were exposed to gamma, proton, carbon, or iron radiation at 2-Gray doses, representing both a clinical treatment fraction and spaceflight exposure for an exploratory mission. Mice were euthanized 110 days after irradiation. The proximal tibiae and femur diaphyses were analyzed using microcomputed tomography. Results demonstrate profound changes in trabecular architecture. Significant losses in trabecular bone volume fraction were observed for all radiation species: gamma, (-29%), proton (-35%), carbon (-39%), and iron (-34%). Trabecular connectivity density, thickness, spacing, and number were also affected. These data have clear implications for clinical radiotherapy in that bone loss in an animal model has been demonstrated at low doses. Additionally, these data suggest that space radiation has the potential to exacerbate the bone loss caused by microgravity, although lower doses and dose rates need to be studied. [ABSTRACT FROM AUTHOR]

Background: A plateau in oxygen consumption (...O2 MAX) is the primary means of confirming that maximal oxygen uptake (...O2 MAX) is attained during incremental exercise to fatigue. However, it is still unresolved what causes expression of a plateau in ...O2 at the end of incremental exercise. Objectives: To elucidate incidence and identify determinants of the ...O2 plateau in subjects of varying fitness. Methods: Thirty subjects (mean (SD) age and ...O2 MAX 26.9 (9.8) years and 3.4 (0.8) litre/mm respectively) were separated into three groups: endurance trained (El; n = 9), recreationally active (Rec; n = 11), and strength/sprint trained (SIR; n = 10). During three separate visits, subjects completed incremental treadmill exercise during which breath by breath gas exchange data were obtained. Body composition was measured using a three site skinfolds model. Force production of the knee extensors and flexors was assessed using isokinetic dynamometry. Results: ...O2 MAX was significantly higher (p<0.05) in the El group vs SIR and Rec. The change in ...O2 (Δ...O2 MAX) at ...O2 MAX was not different (p>0.05) in the El group (33.0(27.3) ml/mm) compared with the Rec group (30.3 (24.1) ml/min) and the STR group (44.4 (23.8) ml/mm). No correlations (p>0.05) were evident between Δ...O2 at ...O2 MAX and ...O2 MAX (r = 0.05), fat-free mass (r = 0.12), and muscular strength (r = -0.12). Conclusions: The incidence of a plateau in ...O2 at ...O2 MAX (from correlation data) is not due to factors related to training status or physical fitness of subjects, but is altered by analysis and interpretation of gas exchange data. [ABSTRACT FROM AUTHOR]

Photochemically produced Fe(ll) is oxidized within hours under environmentally realistic conditions in rainwater. The diurnal variation between photochemical production and re- oxidation of Fe(ll) observed in our laboratory accurately mimics the behavior of ferrous iron observed in field studies where the highest concentrations of dissolved Fe(II) occur in afternoon rain during the period of maximum sunlight intensity followed by gradually decreasing concentrations eventually returning to early morning pre- light values. The experimental work presented here, along with the results of kinetics studies done by others, suggests that the primary process responsible for the decline in photochemically produced Fe(ll) concentrations is oxidation by hydrogen peroxide. This reaction is first order with respect to both the concentrations of Fe(ll) and H2O2. The second-order rate constant determined for six different authentic rain samples varied over an order of magnitude and was always less than or equal to the rate constant determined for this reaction in simple acidic solutions. Oxidation of photochemically produced ferrous iron by other oxidants including molecular oxygen, ozone, hydroxyl radical, hydroperoxyl/superoxide radical, and hexavalent chromium were found to be insignificant under the conditions present in rainwater. This study shows that Fe(ll) occurs as at least two different chemical species in rain; photochemically produced Fe(ll) that is oxidized over time periods of hours, and a background Fe(ll) that is protected against oxidation, perhaps by organic complexation, and is stable against oxidation for days. Because the rate of oxidation of photochemically produced Fe(ll) does not increase with increasing rainwater pH, the speciation of this more labile form of Fe(ll) is also not controlled by simple hydrolysis reactions. [ABSTRACT FROM AUTHOR]