An HIV-1 CRISPR-Cas9 membrane trafficking screen reveals a role for PICALM intersecting endolysosomes and immunity.

HIV-1 hijacks host proteins involved in membrane trafficking, endocytosis, and autophagy that are critical for virus replication. Molecular details are lacking but are essential to inform on the development of alternative antiviral strategies. Despite their potential as clinical targets, only a few membrane trafficking proteins have been functionally characterized in HIV-1 replication. To further elucidate roles in HIV-1 replication, we performed a CRISPR-Cas9 screen on 140 membrane trafficking proteins. We identified phosphatidylinositol-binding clathrin assembly protein (PICALM) that influences not only infection dynamics but also CD4+ SupT1 biology. The knockout (KO) of PICALM inhibited viral entry. In CD4+ SupT1 T cells, KO cells exhibited defects in intracellular trafficking and increased abundance of intracellular Gag and significant alterations in autophagy, immune checkpoint PD-1 levels, and differentiation markers. Thus, PICALM modulates a variety of pathways that ultimately affect HIV-1 replication, underscoring the potential of PICALM as a future target to control HIV-1.

Effect of Incorporating 1 Avocado per Day Versus Habitual Diet on Vascular Function in Adults With Abdominal Obesity: An Ancillary Study of HAT, a Randomized Controlled Trial.

BACKGROUND: Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. METHODS AND RESULTS: HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. CONCLUSIONS: Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.

Speech markers to predict and prevent recurrent episodes of psychosis: A narrative overview and emerging opportunities.

Preventing relapse in schizophrenia improves long-term health outcomes. Repeated episodes of psychotic symptoms shape the trajectory of this illness and can be a detriment to functional recovery. Despite early intervention programs, high relapse rates persist, calling for alternative approaches in relapse prevention. Predicting imminent relapse at an individual level is critical for effective intervention. While clinical profiles are often used to foresee relapse, they lack the specificity and sensitivity needed for timely prediction. Here, we review the use of speech through Natural Language Processing (NLP) to predict a recurrent psychotic episode. Recent advancements in NLP of speech have shown the ability to detect linguistic markers related to thought disorder and other language disruptions within 2-4 weeks preceding a relapse. This approach has shown to be able to capture individual speech patterns, showing promise in its use as a prediction tool. We outline current developments in remote monitoring for psychotic relapses, discuss the challenges and limitations and present the speech-NLP based approach as an alternative to detect relapses with sufficient accuracy, construct validity and lead time to generate clinical actions towards prevention.

Clinician Prompts for Human Papillomavirus Vaccination: A Cluster Randomized Trial.

OBJECTIVE: We assessed the impact of an online intervention using clinician prompts for human papillomavirus (HPV) vaccination with a cluster randomized controlled trial. METHODS: The randomized trial occurred July 2021-January 2022 in 48 primary care pediatric practices (24 intervention, 24 control) across the US. We trained clinicians via two online learning modules, plus weekly ''quick tips'' delivered via text or email. The training taught practices to implement a staff prompt to the clinician (e.g., printed reminders placed on the keyboard) plus electronic health record (EHR) prompts (if not already done) at well and acute/chronic visits for initial and subsequent HPV vaccination. We assessed missed opportunities for HPV vaccination using logistic regression models accounting for clustering by practice on an intent to treat basis. Surveys assessed facilitators and barriers to using prompts. RESULTS: During the 6-month intervention, missed opportunities for HPV vaccination increased (worsened) in both intervention and control groups. However, at well child care visits, missed opportunities for the initial HPV vaccine increased by 4.5 (95% CI: -9.0%, -0.1%) percentage points less in intervention versus control practices. Change in missed opportunities for subsequent doses at well child care and non-well child care visits did not differ between trial groups. An end-of trial survey found understaffing as a common challenge. CONCLUSIONS: Clinician prompts reduced missed opportunities for HPV vaccination at well child care visits. Understaffing related to the COVID-19 pandemic may have led to worsening missed opportunities for both groups and likely impeded practices in fully implementing changes.

The heart of Detroit study: a window into urban middle-aged and older African Americans' daily lives to understand psychosocial determinants of cardiovascular disease risk.

BACKGROUND: Cardiovascular disease disproportionately affects African Americans. Psychosocial factors, including the experience of and emotional reactivity to racism and interpersonal stressors, contribute to the etiology and progression of cardiovascular disease through effects on health behaviors, stress-responsive neuroendocrine axes, and immune processes. The full pathway and complexities of these associations remain underexamined in African Americans. The Heart of Detroit Study aims to identify and model the biopsychosocial pathways that influence cardiovascular disease risk in a sample of urban middle-aged and older African American adults. METHODS: The proposed sample will be composed of 500 African American adults between the ages of 55 and 75 from the Detroit urban area. This longitudinal study will consist of two waves of data collection, two years apart. Biomarkers of stress, inflammation, and cardiovascular surrogate endpoints (i.e., heart rate variability and blood pressure) will be collected at each wave. Ecological momentary assessments will characterize momentary and daily experiences of stress, affect, and health behaviors during the first wave. A proposed subsample of 60 individuals will also complete an in-depth qualitative interview to contextualize quantitative results. The central hypothesis of this project is that interpersonal stressors predict poor cardiovascular outcomes, cumulative physiological stress, poor sleep, and inflammation by altering daily affect, daily health behaviors, and daily physiological stress. DISCUSSION: This study will provide insight into the biopsychosocial pathways through which experiences of stress and discrimination increase cardiovascular disease risk over micro and macro time scales among urban African American adults. Its discoveries will guide the design of future contextualized, time-sensitive, and culturally tailored behavioral interventions to reduce racial disparities in cardiovascular disease risk.

A Mediterranean Dietary Pattern Is Associated with Greater Participation in Physical Activity and Better Health-Related Quality of Life among Students and Professors at the Melilla Campus (University of Granada).

The objective of this study was to assess Mediterranean diet (MD) scores (i.e., alignment with a MD pattern) among students and professors, in addition to assessing how adherence to the MD was associated with other lifestyle behaviors. A cross-sectional observational study was conducted with a sample of 127 university professors and 272 students of the Melilla Campus at the University of Granada (Spain). Students were more physically active than professors (mean difference = 1058 METs, p < 0.001) and reported lower negative affect (NA; mean difference = -1.70, p < 0.001) whereas professors reported nominally better perceived mental health. For the total sample, the physical health component (ß = 0.03, p = 0.03) and physical activity (ß = 0.0001, p = 0.01) were significantly associated with higher MD scores. Health behaviors, including MD scores and physical activity, were suboptimal among both students and professors. The results suggest that a dietary pattern reflective of the MD is positively associated with both physical and mental health outcomes among students and professors, though the direction of the associations remains to be clarified.

Missed Opportunities for Adolescent Immunizations at Well-Care Visits During the COVID-19 Pandemic.

PURPOSE: The Coronavirus Disease 2019 pandemic disrupted healthcare, but the impact on vaccination missed opportunities (MOs, vaccine-eligible visits without vaccination) is unknown. We evaluated pandemic-related trends in MOs at adolescent well-care visits for three vaccines: human papillomavirus; quadrivalent meningococcal conjugate; and tetanus, diphtheria, and acellular pertussis (Tdap). METHODS: We analyzed electronic health record data from 24 pediatric primary care practices in 13 states from 1/1/2018 to 12/31/2021. Segmented logistic regression estimated risk differences for MOs during the pandemic relative to prepandemic trends. RESULTS: Among 106,605 well-care visits, we observed decreases in MOs prepandemic followed by an increase in MOs during the pandemic for all three vaccines. Relative to prepandemic, MOs increased for human papillomavirus (+15.9%, 95% confidence interval [CI]: 11.7%, 20.1%), meningococcal conjugate (+9.4%, 95% CI: 5.2%, 13.7%), and tetanus, diphtheria, and acellular pertussis (Tdap) (+ 8.2%, 95% CI: 4.3%, 12.1%). DISCUSSION: Increases in vaccine MOs during the pandemic equaled or exceeded pre-pandemic decreases. Reducing MOs in adolescent well-care could raise vaccine coverage.

Land cover differentially affects abundance of common and rare birds.

While rare species are vulnerable to global change, large declines in common species (i.e., those with large population sizes, large geographic distributions, and/or that are habitat generalists) also are of conservation concern. Understanding if and how commonness mediates species' responses to global change, including land cover change, can help guide conservation strategies. We explored avian population responses to land cover change along a gradient from common to rare species using avian data from the North American Breeding Bird Survey (BBS) and land cover data from the National Land Cover Database for the conterminous United States. Specifically, we used generalized linear mixed effects models to ask if species' commonness affected the relationship between land cover and counts, using the initial amount of and change in land cover surrounding each North American BBS route from 2001 to 2016. We quantified species' commonness as a continuous metric at the national scale using the logarithm (base 10) of each species' total count across all routes in the conterminous United States in 2001. For our focal 15-year period, we found that higher proportions of initial natural land cover favored (i.e., were correlated with higher) counts of rare but not common species. We also found that commonness mediated how change in human land cover, but not natural land cover, was associated with species' counts at the end of the study period. Increases in developed lands did not favor counts of any species. Increases in agriculture and declines in pasture favored counts of common but not rare species. Our findings show a signal of commonness in how species respond to a major dimension of global change. Evaluating how and why commonness mediates species' responses to land cover change can help managers design conservation portfolios that sustain the spectrum of common to rare species.

WITHDRAWN: Mitochondrial oxygen respiration is associated with loneliness in a sample of community-dwelling adults.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Ex vivo LPS-stimulated cytokine production is associated with hydration status in community-dwelling middle-to-older-aged adults.

PURPOSE: Suboptimal hydration has been linked to a variety of adverse health outcomes. Few studies have examined the impact of hydration status on immune function, a plausible physiological mechanism underlying these associations. Therefore, we tested how variation in hydration status was associated with circulating pro-inflammatory cytokine levels and ex vivo lipopolysaccharide (LPS)-stimulated pro-inflammatory cytokine production. METHODS: Blood samples were obtained from a community sample of healthy middle-to-older-aged adults (N = 72). These samples were used to assess serum osmolality, a biomarker of hydration status, and markers of immune function including circulating pro-inflammatory cytokines and stimulated pro-inflammatory cytokine production after 4 and 24 h of incubation with LPS. Multiple linear regressions were used to test the association between serum osmolality (as a continuous variable) and markers of immune function at baseline and after 4 and 24 h adjusting for age, sex, and BMI. These models were re-estimated with serum osmolality dichotomized at the cut-off for dehydration (> 300 mOsm/kg). RESULTS: While not significantly associated with circulating cytokines (B = - 0.03, p = 0.09), serum osmolality was negatively associated with both 4 h (B = - 0.05, p = 0.048) and 24 h (B = - 0.05, p = 0.03) stimulated cytokine production when controlling for age, sex, and BMI. Similarly, dehydration was associated with significantly lower cytokine production at both 4 h (B = - 0.54, p = 0.02) and 24 h (B = - 0.51, p = 0.02) compared to adequate hydration. CONCLUSION: These findings suggest that dehydration may be associated with suppressed immune function in generally healthy middle-to-older aged community-dwelling adults. Further longitudinal research is needed to more clearly define the role of hydration in immune function.

The Dynamic Interplay of Healthy Lifestyle Behaviors for Cardiovascular Health.

PURPOSE OF REVIEW: The recent rise in cardiovascular disease (CVD) deaths in the USA has sparked interest in identifying and implementing effective strategies to reverse this trend. Healthy lifestyle behaviors (i.e., healthy diet, regular physical activity, achieve and maintain a healthy weight, avoid tobacco exposure, good quality sleep, avoiding and managing stress) are the cornerstone for CVD prevention. RECENT FINDINGS: Achieving all of these behaviors significantly benefits heart health; however, even small changes lower CVD risk. Moreover, there is interplay among healthy lifestyle behaviors where changing one may result in concomitant changes in another behavior. In contrast, the presence of one or more unhealthy lifestyle behaviors may attenuate changing another lifestyle behavior(s) (poor diet, inadequate physical activity, overweight/obesity, poor sleep quality, tobacco exposure, and poor stress management). It is important to assess all of these lifestyle behaviors with patients to plan an intervention program that is best positioned for adherence.

Effects of Diets Enriched with Conventional or High-Oleic Canola Oils on Vascular Endothelial Function: A Sub-Study of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a Randomized Crossover Controlled Feeding Study.

Partial replacement of saturated fatty acids (SFA) with unsaturated fatty acids is recommended to reduce cardiovascular disease (CVD) risk. Monounsaturated fatty acids (MUFA), including oleic acid, are associated with lower CVD risk. Measurement of flow-mediated dilation of the brachial artery (FMD) is the gold standard for measuring endothelial function and predicts CVD risk. This study examined the effect of partially replacing SFA with MUFA from conventional canola oil and high-oleic acid canola oil on FMD. Participants (n = 31) with an elevated waist circumference plus ≥1 additional metabolic syndrome criterion completed FMD measures as part of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a multi-center, double-blind, three-period crossover, controlled feeding randomized trial. Diet periods were 6 weeks, separated by ≥4-week washouts. Experimental diets were provided during all feeding periods. Diets only differed by the fatty acid profile of the oils: canola oil (CO; 17.5% energy from MUFA, 9.2% polyunsaturated fatty acids (PUFA), 6.6% SFA), high-oleic acid canola oil (HOCO; 19.1% MUFA, 7.0% PUFA, 6.4% SFA), and a control oil blend (CON; 11% MUFA, 10% PUFA, 12% SFA). Multilevel models were used to examine the effect of the diets on FMD. No significant between-diet differences were observed for average brachial artery diameter (CO: 6.70 ± 0.15 mm, HOCO: 6.57 ± 0.15 mm, CON: 6.73 ± 0.14 mm; p = 0.72), peak brachial artery diameter (CO: 7.11 ± 0.15 mm, HOCO: 7.02 ± 0.15 mm, CON: 6.41 ± 0.48 mm; p = 0.80), or FMD (CO: 6.32 ± 0.51%, HOCO: 6.96 ± 0.49%, CON: 6.41 ± 0.48%; p = 0.81). Partial replacement of SFA with MUFA from CO and HOCO had no effect on FMD in participants with or at risk of metabolic syndrome.

Effect of Incorporating 1 Avocado Per Day Versus Habitual Diet on Visceral Adiposity: A Randomized Trial.

Background Excess visceral adiposity is associated with increased risk of cardiometabolic disorders. Short-term well-controlled clinical trials suggest that regular avocado consumption favorably affects body weight, visceral adiposity, and satiety. Methods and Results The HAT Trial (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled parallel-arm trial designed to test whether consuming 1 large avocado per day for 6 months in a diverse group of free-living individuals (N=1008) with an elevated waist circumference compared with a habitual diet would decrease visceral adiposity as measured by magnetic resonance imaging. Secondary and additional end points related to risk factors associated with cardiometabolic disorders were assessed. The primary outcome, change in visceral adipose tissue volume during the intervention period, was not significantly different between the Avocado Supplemented and Habitual Diet Groups (estimated mean difference (0.017 L [-0.024 L, 0.058 L], P=0.405). No significant group differences were observed for the secondary outcomes of hepatic fat fraction, hsCRP (high-sensitivity C-reactive protein), and components of the metabolic syndrome. Of the additional outcome measures, modest but nominally significant reductions in total and low-density lipoprotein cholesterol were observed in the Avocado Supplemented compared with the Habitual Diet Group. Changes in the other additional and post hoc measures (body weight, body mass index, insulin, very low-density lipoprotein concentrations, and total cholesterol:high-density lipoprotein cholesterol ratio) were similar between the 2 groups. Conclusions Addition of 1 avocado per day to the habitual diet for 6 months in free-living individuals with elevated waist circumference did not reduce visceral adipose tissue volume and had minimal effect on risk factors associated with cardiometabolic disorders. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03528031.

Lower-Third Standardized Letters of Evaluation in Emergency Medicine: Does Gender Make a Difference in Match Outcome?

Objective The purpose of this study was to determine whether gender influences the likelihood of receiving a lower-third global assessment (GA) on the standardized letter of evaluation (SLOE) submitted as part of the emergency medicine (EM) application process as well as the impact of gender on ultimate match outcomes for applicants receiving a lower-third GA ranking. Our hypothesis was that female applicants with a lower-third GA ranking have a higher risk of not matching. Methods We conducted a retrospective cohort study evaluating U.S.-based allopathic applicants to a single EM residency program in the Mid-Atlantic region during the 2017-2018 and 2018-2019 match cycles. GA SLOE rankings and gender for all applicants were extracted and compared to the National Resident Matching Program (NRMP) data for each applicant on match outcome. Comparative analyses were conducted between gender and SLOE GA rankings in order to obtain an odds ratio (OR) of gender and match outcomes. Results A total of 2,017 SLOEs were reviewed from 798 applicants in the 2018 and 2019 EM match cycles. Overall, 716 (90%) applicants successfully matched in EM, with 82 (10%) applicants failing to match into EM; 277 students had at least one lower-third GA ranking. For all applicants, having at least one lower-third GA ranking was associated with a significant risk of not matching (OR: 0.20; 95% CI: 0.12-0.34). Of the 277 students with at least one lower-third GA ranking, 85 (31%) were female and 192 (69%) were male. Of the female applicants with a lower-third GA ranking, 15 (18%) failed to match in EM, and 39 (20%) of the males failed to match in EM. For applicants with a lower-third GA ranking, female gender alone was not associated with a significantly increased risk of not matching (OR: 1.18; 95% CI: 0.61-2.21). Conclusions Female applicants receive a lower-third GA ranking less frequently than their male counterparts. One or more lower-third rankings on the GA significantly reduced an applicant's chances of matching into an EM program. For those with a lower-third GA ranking, female gender alone does not significantly increase the risk of not matching into EM.

Herbs and spices at a relatively high culinary dosage improves 24-hour ambulatory blood pressure in adults at risk of cardiometabolic diseases: a randomized, crossover, controlled-feeding study.

BACKGROUND: Intake of a single meal containing herbs and spices attenuates postprandial lipemia, hyperglycemia, and oxidative stress, and improves endothelial function. There has been limited investigation of the effect of longer-term intake of mixed herbs and spices on risk factors for cardiometabolic diseases. OBJECTIVES: The objective was to assess the effect of an average American diet containing herbs and spices at 0.5 (low-spice diet; LSD), 3.3 (moderate-spice diet; MSD), and 6.6 (high-spice diet; HSD) g · d-1 · 2100 kcal-1 on lipids and lipoproteins as well as other risk factors for cardiometabolic diseases in at-risk adults. METHODS: A 3-period, randomized, crossover, controlled-feeding study with 71 participants was conducted at the Pennsylvania State University. Each diet was consumed for 4 wk with a minimum 2-wk washout period. Outcomes were assessed at baseline and the end of each diet period. RESULTS: No between-diet effects were observed for LDL cholesterol, the primary outcome. Between-diet differences were observed for mean 24-h systolic (P = 0.02) and diastolic (P = 0.005) ambulatory blood pressure. The HSD lowered mean 24-h systolic blood pressure compared with the MSD (-1.9 mm Hg; 95% CI: -3.6, -0.2 mm Hg; P = 0.02); the difference between the HSD and LSD was not statistically significant (-1.6 mm Hg; 95% CI: -3.3, 0.04 mm Hg; P = 0.058). The HSD lowered mean 24-h diastolic blood pressure compared with the LSD (-1.5 mm Hg; 95% CI: -2.5, -0.4 mm Hg; P = 0.003). No differences were detected between the LSD and MSD. No between-diet effects were observed for clinic-measured blood pressure, markers of glycemia, or vascular function. CONCLUSIONS: In the context of a suboptimal US-style diet, addition of a relatively high culinary dosage of mixed herbs and spices (6.6 g · d-1 · 2100 kcal-1) tended to improve 24-h blood pressure after 4 wk, compared with lower dosages (0.5 and 3.3 g · d-1 · 2100 kcal-1), in adults at elevated risk of cardiometabolic diseases.This trial was registered at clinicaltrials.gov as NCT03064932.

Semiarid grasslands and extreme precipitation events: do experimental results scale to the landscape?

The frequency and magnitude of deluges (extremely large rain events) are increasing globally as the atmosphere warms. Small-scale experiments suggest that semiarid grasslands are particularly sensitive to both the timing and size of deluge events. However, the assumption that plot-scale results can be extrapolated across landscapes with variable soil textures, plant communities, and grazing regimes has seldom been tested, despite being key to forecasting regional consequences of precipitation extremes. We used precipitation data from an extensive rain gauge network to identify natural deluges (mean size = 60 ± 31 mm, 1984-2012) that occurred across a ˜60-km2 heterogeneous native shortgrass steppe landscape in Colorado. We then related spatial variation in deluge precipitation to postdeluge responses in canopy greenness (normalized difference vegetation index, NDVI) via satellite imagery. Consistent with results from experiments, this semiarid grassland was most sensitive to mid-growing-season deluges, and postdeluge canopy greenness usually increased linearly (67% of the time) with increasing deluge size. This suggests that aboveground productivity in these semiarid systems will likely increase, rather than asymptote, with forecasted increases in deluge size. Importantly, differences in grazing regime did not significantly alter deluge responses, indicating that these patterns are robust to this widespread management practice.

Ex vivo LPS-stimulated cytokine production is associated with cortisol curves in response to acute psychosocial stress.

BACKGROUND: Empirical and theoretical evidence suggest that because of the co-evolution of the endocrine and immune response systems, different types of stressors may lead to similar levels of physiological activation. The present analyses examined associations between two physiological stress responses: the cortisol response to an acute laboratory stressor and ex vivo lipopolysaccharide (LPS) stimulated inflammatory cytokine production. METHODS: Healthy middle-aged adults (N = 65) completed testing at two appointments, two weeks apart. Blood was collected at each appointment to measure circulating inflammatory cytokine levels and stimulated inflammatory cytokine production after 4 and 24 hours of incubation with LPS. A cumulative standardized composite measure of inflammation was calculated using the cytokines interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and interferon-γ (IFN-γ). At visit two, after the blood draw, participants completed the Trier Social Stress Test (TSST); saliva samples were collected before and after to generate cortisol response curves (area under the curve with respect to ground [AUCG] and increase/decrease [AUCI]). RESULTS: AUCG was significantly associated with stimulated cytokine production at visit 2 after both 4 hours (B = 6.89; p = 0.007) and 24 hours (B = 7.50; p = 0.005) of incubation, controlling for age, sex, and BMI. AUCI was also significantly associated with stimulated cytokine production at visit 2 after 4 hours (B = 6.28; p = 0.004) and 24 hours (B = 6.16; p = 0.007) of incubation, controlling for age, sex, and BMI. Stimulated inflammatory cytokine production was strongly correlated across the two visits (2 weeks apart) after 4 hours of incubation (r = 0.80, p < 0.001) and after 24 hours (r = 0.80, p < 0.001). Within each visit, stimulated cytokine production after 4 hours was significantly correlated with stimulated inflammation at 24 hours (r = 0.93-0.94, p < 0.05) CONCLUSIONS: These results suggest that LPS-stimulated inflammatory cytokine production and the cortisol response to the TSST contain comparable information about acute human physiological stress responses. Moreover, measurement of stimulated cytokines was highly stable across a two-week time period whether measured after 4 or 24 hours of incubation with LPS.

Epiglottopexy with or without aryepiglottic fold division: Comparing outcomes in the treatment of pediatric obstructive sleep apnea.

OBJECTIVE: To determine the success of epiglottopexy with or without aryepiglottic fold division for treatment of patients with obstructive sleep apnea (OSA) with epiglottic obstruction. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care academic hospital. METHODS: Children with sleep study proven OSA who underwent epiglottopexy with or without aryepiglottic fold division from January 2013 to June 2017 were included. The epiglottis contributed to airway obstruction in all patients. Pre- and post-operative apnea-hypopnea index (AHI) were compared. Age, sex, body mass index (BMI) z-score and post-operative complications were also evaluated. Success was defined by post-operative AHI < 5.0 with resolution of OSA symptoms or AHI ≤ 1.0 events per hour. RESULTS: Twenty-eight children (age 2-17 years) underwent either epiglottopexy with division of aryepiglottic folds (N = 18) or epiglottopexy alone (N = 10). There was no difference in preoperative age, AHI, or BMI between the groups. Post-operative AHI was lower in the group undergoing epiglottopexy alone (AHI 1.50) versus with aryepiglottic fold division (AHI 3.17) (P < 0.05). No difference was found in mean AHI improvement between the two groups. For the entire cohort, success criteria were met by 53.6% of patients for AHI < 5.0 without symptoms and 25.0% of patients for AHI ≤ 1.0, with no difference in surgical success between procedures (P > 0.05). CONCLUSIONS: Children undergoing epiglottopexy with division of aryepiglottic folds for laryngeal collapse were as likely to have improved OSA symptoms as children undergoing epiglottopexy alone.

Lower-Third SLOE Rankings Impede, But Do Not Prevent, A Match in Emergency Medicine Residency Training.

OBJECTIVE: Emergency medicine program directors (PD) value the standardized letter of evaluation (SLOE) as the most important aspect of a residency application when making both invitation and ranking decisions. This study aims to determine whether the presence of any lower-third in either SLOE global assessment (GA) question impacted the ability of an applicant to match into EM. We hypothesized that any lower-third ranking would be associated with increased odds of not matching into EM. METHODS: We conducted a retrospective cohort study evaluating allopathic applicants from medical schools in the United States (US allopathic applicants) to a single EM residency program during the 2018/2019 match cycles. GA SLOE rankings from all applications were tabulated and compared to the applicant's National Resident Matching Program (NRMP) match outcome. Comparative analyses were conducted between SLOE groupings and odds ratios (OR) were calculated. RESULTS: A total of 2,017 SLOEs from 781 US allopathic applicants were analyzed during the study period. Of the total, 277 (35%) applicants in our sample had any lower-third GA ranking, which significantly decreased an applicant's odds of matching in EM by 79% (OR 0.21, 95% CI, 0.12-0.34). Having more than one lower-third GA ranking did not further statistically decrease the odds of a successful EM match (OR 0.60, 95% CI 0.31-1.17). As a secondary finding of the study, results demonstrate that those applicants having no lower-third GA rankings had a nearly 5 times increased odds of an EM match (OR 4.84, 95% CI, 2.91-8.03). CONCLUSION: Having any lower-third GA ranking significantly reduced an applicant's chances of matching into an EM program. Faculty advisors should be aware of the increased risk of not matching for any applicant with any lower-third GA ranking and advise students appropriately, while maintaining the integrity of the SLOE and not divulging the confidential information contained within.