Implementing Public Health Modules as an Approach to Improve Knowledge and Attitudes of Medical Students: A Student-Led, Multiyear Study.

PURPOSE: Public health is a necessary focus of modern medical education. However, while numerous studies demonstrate benefits of public health education during medical school among self-selected students (i.e., those interested in public health), there are few educational models shown to be effective across the general medical student population. This study examined the effect of a multiyear, case-based, longitudinal online public health curriculum required for all medical students at an urban, research-focused U.S. medical school. METHOD: The authors created 11 short public health modules to supplement a year-long, organ-based preclerkship course at Columbia University Vagelos College of Physicians and Surgeons. Beginning in 2020, all students were required to complete these modules, with repeated surveys to assess changes in attitudes and knowledge of public health over time. The authors compared responses for these domains before and after each module, across multiple time points throughout the year, and cross-sectionally to a 2019 cohort of students who were not provided the modules. RESULTS: Across 3 cohorts, 405 of 420 (96.4%) students provided responses and were included in subsequent analyses. After completing the modules, students reported perceiving a greater importance of public health to nearly every medical specialty ( P < .001), more positive attitudes toward public health broadly ( P < .001), and increased knowledge of public health content ( P < .001). These findings were consistent across longitudinal analysis of students throughout the year-long course and when compared to the cohort who did not complete the modules. CONCLUSIONS: Case-based, interactive, and longitudinal public health content can be effectively integrated into the required undergraduate medical education curriculum to improve all medical students' knowledge and perceptions of public health. Incorporating evidence-based public health education into medical training may help future physicians to better address the needs of the communities and populations in which they practice.

Rapid Diagnosis of Meningococcal Meningitis in a Patient With Familial Mediterranean Fever by the FilmArray Meningitis/Encephalitis Panel: A Case Report.

Familial Mediterranean fever (FMF) is a rare autoinflammatory disorder of the innate immune system. Patients with innate immune system defects are at a high risk of meningococcal disease, although it is unclear if patients with FMF also have increased susceptibility to invasive infection. Herein, we present a diagnostically challenging case of a male adolescent with a past medical history of FMF stabilized on colchicine who presented with some of the early clinical features of community-acquired bacterial meningitis. To our knowledge, this is the first case of meningococcal meningitis in a patient with FMF diagnosed with the FilmArray Meningitis/Encephalitis (ME) Panel. This case report demonstrates that rapid detection of Neisseria meningitidis by the ME Panel can aid in the early diagnosis and prompt treatment of patients with suspected meningitis and may be the only positive test in patients with early presentation and/or prior antimicrobial therapy.

Impact of the Arg 16 allele of the B2AR gene on the effect of withdrawal of LABA in patients with moderate to severe asthma.

INTRODUCTION: Long-acting beta agonists (LABAs) are effective for controlling asthma, however questions about their safety have led to concerns over use. Genetic polymorphisms at the 16 amino acid position of the beta-2 adrenergic receptor gene (B2AR) may be associated with increased risk. METHODS: A randomized, double blind study was conducted in patients with moderate to severe asthma being treated with combined inhaled corticosteroids/LABA (ICS/LABA), comparing the effect of LABA continuation versus withdrawal on asthma outcomes among patients stratified by B2AR genotype (Arg/Arg vs. Gly/Gly at the 16th amino acid position). RESULTS: 67 participants (31 Arg/Arg, 36 Gly/Gly) were randomized to receive fluticasone alone (F) or continue combined fluticasone/salmeterol (F/S) after a run-in period on F/S. Among Gly/Gly subjects, those in the F/S treatment group showed improvement in AM PEFR (+ 8.4 L/s) whereas those receiving F alone experienced a reduction in AM PEFR over the study period (-14.4 L/s), (p = 0.06). There was no significant difference in morning peak expiratory flow rate (AM PEFR) in Arg/Arg participants randomized to receive F/S (-15.7L) vs F alone (-5.6 L/s) (p = 0.61). There was no significant difference in exacerbations in the Arg/Arg subjects treated with F/S compared with those treated with F (p = 0.65). CONCLUSIONS: Withdrawal of LABA therapy in asthmatics with the Arg/Arg genotype at the 16th amino acid position of B2AR did not lead to significant improvement in AM PEFR. LABA withdrawal in the Gly/Gly genotype however led to a borderline significant decline in AM PEFR.

Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children.

BACKGROUND: Bisphenol A (BPA) is used widely to manufacture food container linings. Mouse models suggest exposure to BPA might increase allergic inflammation. OBJECTIVES: We hypothesized that BPA exposure, as assessed based on urinary BPA concentrations, would be associated with increased odds of wheeze and asthma and increased fraction of exhaled nitric oxide (Feno) values in children. METHODS: The Columbia Center for Children's Environmental Health recruited pregnant women for a prospective birth cohort study (n = 568). Mothers during the third trimester and children at ages 3, 5, and 7 years provided spot urine samples. Total urinary BPA concentrations were measured by using online solid-phase extraction, high-performance liquid chromatography, isotope-dilution tandem mass spectrometry. Wheeze in the last 12 months was measured by using questionnaires at ages 5, 6, and 7 years. Asthma was determined by a physician once between ages 5 and 12 years. Feno values were measured at ages 7 to 11 years. RESULTS: Prenatal urinary BPA concentrations were associated inversely with wheeze at age 5 years (odds ratio [OR], 0.7; 95% CI, 0.5-0.9; P = .02). Urinary BPA concentrations at age 3 years were associated positively with wheeze at ages 5 years (OR, 1.4; 95% CI, 1.1-1.8; P = .02) and 6 years (OR, 1.4; 95% CI, 1.0-1.9; P = .03). BPA concentrations at age 7 years were associated with wheeze at age 7 years (OR, 1.4; 95% CI, 1.0-1.9; P = .04) and Feno values (ß = 0.1; 95% CI, 0.02-0.2; P = .02). BPA concentrations at ages 3, 5, and 7 years were associated with asthma (OR, 1.5 [95% CI, 1.1-2.0], P = .005; OR, 1.4 [95% CI, 1.0-1.9], P = .03; and OR, 1.5 [95% CI, 1.0-2.1], P = .04, respectively). CONCLUSIONS: This is the first report of an association between postnatal urinary BPA concentrations and asthma in children.

Taxonomic revision of true morels (Morchella) in Canada and the United States.

Recent molecular phylogenetic studies have revealed the existence of at least 50 species of Morchella worldwide and demonstrated a high degree of continental endemism within the genus. Here we describe 19 phylogenetic species of Morchella from North America, 14 of which are new (M. diminutiva, M. virginiana, M. esculentoides, M. prava, M. cryptica, M. frustrata, M. populiphila, M. sextelata, M. septimelata, M. capitata, M. importuna, M. snyderi, M. brunnea and M. septentrionalis). Existing species names (M. rufobrunnea, M. tomentosa, M. punctipes and M. angusticeps) are applied to four phylogenetic species, and formal description of one species (M. sp. "Mel-8") is deferred pending study of additional material. Methods for assessing morphological features in Morchella are delineated, and a key to the known phylogenetic species of Morchella in North America is provided. Type studies of M. crassistipa, M. hotsonii, M. angusticeps and M. punctipes are provided. Morchella crassistipa is designated nomen dubium.

Obesity-associated asthma in children: a distinct entity.

BACKGROUND: Obesity-associated asthma has been proposed to be a distinct entity, differing in immune pathogenesis from atopic asthma. Both obesity-mediated inflammation and increase in adiposity are potential mechanistic factors that are poorly defined among children. We hypothesized that pediatric obesity-associated asthma would be characterized by T helper (Th) 1, rather than the Th2 polarization associated with atopic asthma. Moreover, we speculated that Th1 biomarkers and anthropometric measures would correlate with pulmonary function tests (PFTs) in obese asthmatic children. METHODS: We recruited 120 children, with 30 in each of the four study groups: obese asthmatic children, nonobese asthmatic children, obese nonasthmatic children, and nonobese nonasthmatic children. All children underwent pulmonary function testing. Blood was collected for measurement of serum cytokines. T-cell responses to mitogen, phorbol 12-myristate 13-acetate (PMA), or antigens tetanus toxoid or Dermatophagoides farinae were obtained by flow cytometric analysis of intracellular cytokine staining for interferon-γ (IFN-γ) (Th1) or IL-4 (Th2) within the CD4 population. RESULTS: Obese asthmatic children had significantly higher Th1 responses to PMA (P < .01) and tetanus toxoid (P < .05) and lower Th2 responses to PMA (P < .05) and D farinae (P < .01) compared with nonobese asthmatic children. Th-cell patterns did not differ between obese asthmatic children and obese nonasthmatic children. Obese asthmatic children had lower FEV(1)/FVC (P < .01) and residual volume/total lung capacity ratios (P < .005) compared with the other study groups, which negatively correlated with serum interferon-inducible protein 10 and IFN-γ levels, respectively. PFTs, however, did not correlate with BMI z score or waist to hip ratio. CONCLUSIONS: We found that pediatric obesity-associated asthma differed from atopic asthma and was characterized by Th1 polarization. The altered immune environment inversely correlated with PFTs in obese asthmatic children.

Advanced topics in evidence-based urologic oncology: surrogate endpoints.

Clinical trials often report surrogate endpoint data. A surrogate endpoint is a biological marker or clinical sign that can be substituted for a patient-important outcome. Using surrogate endpoints correctly may facilitate and expedite clinical trials and may improve medical decisions. However, rigorous criteria must be met for an endpoint to be considered a valid surrogate. The purpose of this article is to review the topic of surrogate endpoints in the context of a urologic encounter.

Exhaled NO among inner-city children in New York City.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has been proposed as a biomarker of airway inflammation for cohort studies of asthma. OBJECTIVES: To assess the association between FeNO and asthma symptoms among 7-year-old children living in an inner-city community. To test the association between environmental tobacco smoke (ETS) exposure (previous and current) and FeNO among these children. METHODS: As part of a longitudinal study of asthma, children recruited in Head Start centers at age 4 had offline FeNO and lung function testing at age 7. Children with allergen-specific immunoglobulin E (IgE) (≥0.35 IU/mL) at age 7 were considered seroatopic. ETS exposure at ages 4 and 7 was assessed by questionnaire. RESULTS: Of 144 participating children, 89 had complete questionnaire data and achieved valid FeNO and lung function tests. Children with reported wheeze in the previous 12 months (n = 19) had higher FeNO than those without wheeze (n = 70) (geometric means 17.0 vs. 11.0 ppb, p = .005). FeNO remained significantly associated with wheeze (p = .031), after adjusting for seroatopy and forced expiratory volume in 1 second (FEV1) in multivariable regression. FeNO at age 7 was positively associated with domestic ETS exposure at age 4 (29%) (ß = 0.36, p = .015) but inversely associated with ETS exposure at age 7 (16%) (ß = -0.74, p < .001). CONCLUSIONS: Given its association with current wheeze, independent of seroatopy and lung function, FeNO provides a relevant outcome measure for studies in inner-city communities. While compelling, the positive association between ETS exposure at age 4 and a marker of airway inflammation at age 7 should be confirmed in a larger study.

IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching.

IL-4 signaling promotes IgE class switching through STAT6 activation and the induction of Ig germ-line epsilon (GLepsilon) transcription. Previously, we and others identified a transcription factor, Nfil3, as a gene induced by IL-4 stimulation in B cells. However, the precise roles of nuclear factor, IL-3-regulated (NFIL3) in IL-4 signaling are unknown. Here, we report that NFIL3 is important for IgE class switching. NFIL3-deficient mice show impaired IgE class switching, and this defect is B-cell intrinsic. The induction of GLepsilon transcripts after LPS and IL-4 stimulation is significantly reduced in NFIL3-deficient B cells. Expression of NFIL3 in NFIL3-deficient B cells restores the impairment of IgE production, and overexpression of NFIL3 in the presence of cycloheximide induces GLepsilon transcripts. Moreover, NFIL3 binds to Iepsilon promoter in vivo. Together, these results identify NFIL3 as a key regulator of IL-4-induced GLepsilon transcription in response to IL-4 and subsequent IgE class switching.

Asthma, allergy, and IgE levels in NYC head start children.

BACKGROUND: Among preschool-age children in New York City neighborhoods with high asthma hospitalization rates, we analyzed the associations of total immunoglobulin E (IgE), specific IgE to common indoor allergens, and allergy symptoms with asthma. METHODS: Parents of children in New York City Head Start programs were asked to complete a questionnaire covering demographic factors, health history (including respiratory conditions), lifestyle, and home environment. Children's serum samples were analyzed for total IgE and specific IgE antibodies to cockroach, dust mite, mouse, and cat allergens by immunoassay. Logistic regression was used to model the association between asthma and IgE, controlling for age, gender, ethnicity/national origin, BMI, parental asthma, smokers in the household, and allergy symptoms (e.g., runny nose, rash). RESULTS: Among 453 participating children (mean age 4.0+/-0.5 years), 150 (33%) met our criteria for asthma. In our multivariable logistic regression models, children with asthma were more likely than other children to be sensitized to each allergen, to be sensitized to any of the four allergens (OR=1.6, 95% CI 1.0-2.6), or to be in the highest quartile of total IgE (OR=3.1, 95% CI 1.5-6.4). Allergy symptoms based on questionnaire responses were independently associated with asthma (OR=3.7, 95% CI 2.3-5.9). CONCLUSIONS: Among preschool-aged urban children, asthma was associated with total IgE and sensitization to cat, mouse, cockroach, and dust mite allergens. However, allergy symptoms were more prevalent and more strongly associated with asthma than was any allergen-specific IgE; such symptoms may precede elevated specific IgE or represent a different pathway to asthma.

Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma.

Matrix metalloproteinase-9 (MMP-9) is hypothesized to facilitate leukocyte extravasation and extracellular remodeling in asthmatic airways. Careful descriptive studies have shown that MMP-9 levels are higher in the sputum of asthmatics; however, the consequence of increased MMP-9 activity has not been determined in this disease. We induced asthma in transgenic mice that express human MMP-9 in the murine lung tissue macrophage to determine the direct effect of human MMP-9 expression on airway inflammation. Transgenic (TG) and wild-type (WT) mice were immunized and challenged with ovalbumin. Forty-eight hours after the ovalbumin challenge, airway hyperresponsiveness (AHR) was measured, and inflammatory cell infiltration was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue. Baseline levels of inflammation were similar in the TG and WT groups of mice, and pulmonary eosinophilia was established in both groups by sensitization and challenge with ovalbumin. There was a significant reduction in AHR in sensitized and challenged trangenics compared with WT controls. Although total BALF cell counts were similar in both groups, the lymphocyte number in the lavage of the TG group was significantly diminished compared with the WT group (0.25 +/- 0.08 vs. 0.89 +/- 0.53; P = 0.0032). In addition, the draining lymphocytes were found to be larger in the TG animals compared with the WT mice. Equal numbers of macrophages, eosinophils, and neutrophils were seen in both groups. IL-13 levels were found to be lower in the sensitized TG compared with the WT mice. These results demonstrate an inverse relationship between human MMP-9 and AHR and suggest that MMP-9 expression alters leukocyte extravasation by reducing lymphocyte accumulation in the walls of asthmatic airways.

Early respiratory infections and asthma among New York City Head Start children.

BACKGROUND: Respiratory infections in neonates have been found to predict wheeze among young children. We hypothesized that among preschool children from low-income minority communities in New York City, current asthma would be associated with a history of respiratory infection in the first few months after their birth. METHODS: We asked parents of children in New York City Head Start centers (preschool programs for children of low-income families) to respond to a questionnaire covering demographic factors, lifestyle, home environment, and health history, including a detailed history of respiratory conditions. We used logistic regression to model the association of asthma and asthma severity with history of respiratory infections, controlling for gender, ethnicity, family history of asthma, and other factors. RESULTS: Among 1,022 children (mean age 4+/- 0.6 years) whose parents provided information about their health history, 359 (35%) met our criteria for asthma. Overall, 22% had had a cold by 6 months and 17% an ear infection by 8 months of age. In multivariable models, children with asthma had had more colds (OR = 2.8, 95% confidence interval [CI] 1.4-6.0) and ear infections (OR = 3.4, 95% CI 1.7-6.9) in the past year than other children. Associations of respiratory infections with emergency department use for asthma (as a measure of severity) were similar. In models that did not control for infections in the past year, ages at first cold and first ear infection were associated with asthma and emergency department visits in the past year. CONCLUSIONS: In this sample of preschool children, respiratory infections were common and were associated with asthma and health care utilization for asthma exacerbations. If these findings are confirmed, preventive measures among children who develop such infections at a very early age should be explored to help reduce the burden of asthma in this age group.

Total and specific IgE associations between New York City Head Start children and their parents.

BACKGROUND: Allergy and asthma risk share strong inherited components; however, the relative importance of maternal and paternal atopy in predicting child atopy remain unclear. OBJECTIVE: We sought to identify relationships between parents' and children's total and specific IgE levels within family units as predictors of allergic risk in children. METHODS: Total and allergen-specific IgE (to dust mite, cockroach, mouse, and cat) were determined by means of ImmunoCap (Phadia, Inc, Portage, Mich) in a sample of families participating in New York City Head Start programs. Regression models were developed to determine the associations of parents' and children's total IgE levels and sensitization patterns. RESULTS: Blood specimens were collected from 161 family triads of mother, father, and child (83 boys and 78 girls). At a mean age of 4 years, boys had significantly higher total IgE levels than girls. Boys' total IgE levels were highly correlated with both mothers' (P < .002) and fathers' (P = .002) total IgE levels; girls' total IgE levels were not. Unlike total IgE levels, specific IgE levels among both boys and girls were associated with their mothers' specific IgE levels. Dust mite sensitization among mothers was predictive of children's sensitization to each of the 4 aeroallergens. CONCLUSION: The strong associations between parents' and children's IgE levels suggest that assessment of parents' total and locally relevant allergen-specific IgE levels might have value in predicting atopy in children of preschool age.

Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea.

BACKGROUND: Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea (OSA). We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA. The effects of continuous positive airway pressure (CPAP) therapy on endothelial function and repair capacity were assessed. METHODS AND RESULTS: Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied. Proteins that regulate basal endothelial nitric oxide (NO) production (endothelial NO synthase [eNOS] and phosphorylated eNOS) and inflammation (cyclooxygenase-2 and inducible NOS) and markers of oxidative stress (nitrotyrosine) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy. Vascular reactivity was measured by flow-mediated dilation. Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity. Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59% and 94%, respectively, in patients with OSA compared with control subjects. Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects, whereas inducible NOS expression was 56% greater. Expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine, cyclooxygenase-2, and inducible NOS significantly decreased in patients who adhered to CPAP > or = 4 hours daily. Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects, and both significantly increased in patients who adhered to CPAP > or = 4 hours daily. CONCLUSIONS: OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity. Effective CPAP therapy is associated with the reversal of these alterations.

Cockroach allergen levels and associations with cockroach-specific IgE.

BACKGROUND: Among inner-city children with asthma, cockroach allergen exposure has been associated with allergic sensitization. OBJECTIVE: We hypothesized that cockroach allergen levels in homes would be associated with sensitization to cockroach allergens in children. METHODS: From a low-income preschool program, 341 four-year-old children selected on the basis of the willingness of their caregivers to participate in the study were enrolled. Dust from their beds and kitchens were analyzed for cockroach (Bla g 2), mouse (mouse urinary proteins), and cat allergens (Fel d 1). Serum samples were analyzed for allergen-specific IgE antibodies by immunoassay. RESULTS: Bla g 2 levels >1 U/g in children's bed and kitchen dust samples were independently associated with cockroach-specific IgE (odds ratio [OR], 2.7; 95% CI, 1.1-6.4; and OR, 3.4; 95% CI, 1.2-9.4, respectively), adjusting for sex, ethnicity, asthma, pet ownership, mother's allergic sensitization, environmental tobacco smoke, and having lived in other homes. Bla g 2 was associated (OR, 3.6; 95% CI, 1.0-13.1) with cockroach-specific IgE among children with asthma. Among children without asthma, the ORs were similar (OR, 3.0; 95% CI, 0.9-10.3), but the association was not statistically significant. CONCLUSION: Concentrations of the major cockroach allergen, Bla g 2, in settled dust were associated with cockroach-specific IgE independent of other factors in a cohort of 4-year-old inner-city children.

Cutting edge: IL-4 induces suppressor of cytokine signaling-3 expression in B cells by a mechanism dependent on activation of p38 MAPK.

The signaling cascade initiated by IL-4 is classically divisible into two major pathways: one mediated by STAT6, and the other by insulin receptor substrates-1 and -2 via activation of PI3K. In murine splenic B cells, the suppressor of cytokine signaling (SOCS)3 is inducible by IL-4 via a mechanism independent of STAT6 and PI3K. SOCS3 expression increases 9-fold within 5 h of IL-4 treatment. This induction occurs normally in B cells deficient in STAT6 and is unaffected by pretreatment with the PI3K inhibitor wortmannin, or with the ERK pathway inhibitor, PD98059. However, the IL-4 induction of SOCS3 is blocked by inhibitors of either the JNK or p38 MAPK pathways (SP600125 and SB203580, respectively). Direct examination of these pathways reveals rapid, IL-4-directed activation of p38 MAPK, uncovering a previously unappreciated pathway mediating IL-4 signal transduction.