Integrating the melanoma 31-gene expression profile test with clinical and pathologic features can provide personalized precision estimates for sentinel lymph node positivity: an independent performance cohort.

INTRODUCTION: Up to 88% of sentinel lymph node biopsies (SLNBs) are negative. The 31-gene expression profile (31-GEP) test can help identify patients with a low risk of SLN metastasis who can safely forego SLNB. The 31-GEP classifies patients as low (Class 1 A), intermediate (Class 1B/2A), or high risk (Class 2B) for recurrence, metastasis, and SLN positivity. The integrated 31-GEP (i31-GEP) combines the 31-GEP risk score with clinicopathologic features using a neural network algorithm to personalize SLN risk prediction. METHODS: Patients from a single surgical center with 31-GEP results were included (n = 156). An i31-GEP risk prediction < 5% was considered low risk of SLN positivity. Chi-square was used to compare SLN positivity rates between groups. RESULTS: Patients considered low risk by the i31-GEP had a 0% (0/30) SLN positivity rate compared to a 31.9% (30/94, p < 0.001) positivity rate in those with > 10% risk. Using the i31-GEP to guide SLNB decisions could have significantly reduced the number of unnecessary SLNBs by 19.2% (30/156, p < 0.001) for all patients and 33.0% (30/91, p < 0.001) for T1-T2 tumors. Patients with T1-T2 tumors and an i31-GEP-predicted SLN positivity risk > 10% had a similar SLN positivity rate (33.3%) as patients with T3-T4 tumors (31.3%). CONCLUSION: The i31-GEP identified patients with < 5% risk of SLN positivity who could safely forego SLNB. Combining the 31-GEP with clinicopathologic features for a precise risk estimate can help guide risk-aligned patient care decisions for SLNB to reduce the number of unnecessary SLNBs and increase the SLNB positivity yield if the procedure is performed.

Micronutrient Status During Military Training and Associations With Musculoskeletal Health, Injury, and Readiness Outcomes.

OBJECTIVE: Micronutrient status, specifically vitamin D and iron, represent modifiable factors for optimizing military readiness. The primary purpose of this investigation was to determine associations between micronutrient deficiency (i.e., iron status and 25-hydroxy-vitamin D [25(OH)D]) and operationally relevant outcomes (i.e., skeletal health, musculoskeletal injury) at baseline and post-10 weeks of arduous military training. METHODS: A total of 227 (177 men, 50 women) Marine Officer Candidates School (OCS) candidates who completed OCS training with complete data sets were included in this analysis. Vitamin D and iron status indicators were collected at two timepoints, pre (baseline) and post OCS. Musculoskeletal outcomes at the mid- and proximal tibial diaphysis were assessed via peripheral quantitative computed tomography. RESULTS: Micronutrient status declined following OCS training in men and women and was associated with musculoskeletal outcomes including greater bone strength (strength strain index) at the mid-diaphysis site in those with optimal status (M = 38.26 mm3, SE = 15.59) versus those without (M = -8.03 mm3, SE = 17.27). In women (p = .037), endosteal circumference was greater in the deficient group (M = 53.26 mm, SE = 1.19) compared with the optimal group (M = 49.47 mm, SE = 1.31) at the proximal diaphysis. In men, greater baseline hepcidin concentrations were associated with an increased likelihood of suffering musculoskeletal injury during training. CONCLUSIONS: Vitamin D and iron status declined over the course of training, suggesting impaired micronutrient status. Differences in musculoskeletal outcomes by micronutrient group suggests optimal vitamin D and ferritin concentrations may exert beneficial effects on bone fatigability and fracture reduction during military training.

Utility of Gene Expression Profiling in Skin Cancer: A Comprehensive Review.

Understanding the metastatic potential of a skin cancer is essential to effective management. Gene expression profiling (GEP) is an innovative technology that has allowed for a better understanding of tumor biology in various skin cancers. Current methods focus on identifying and quantifying ribonucleic acid (RNA) transcripts in tissue samples. Using reverse transcriptase-polymerase chain reaction, specific RNA transcripts are reverted into deoxyribonucleic acid (DNA) for quantification. The addition of RNA-seq has further enhanced our knowledge of genomes not only by measuring known sequences, but also by identifying novel genes in various skin cancers. GEP requires only a small amount of RNA and has a high level of reproducibility. Using this technology, several GEPs for skin cancers have been developed to augment diagnosis and prognosis of skin cancer. This article reviews the process of gene expression profiling and the current GEPs that are available or under investigation for skin cancer. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7017.

Neuroendocrine, inflammatory, and extracellular vesicle responses during the Navy Special Warfare Screener Selection Course.

Military operational stress is known to increase adrenal hormones and inflammatory cytokines, while decreasing hormones associated with the anabolic milieu and neuroendocrine system. Less is known about the role of extracellular vesicles (EVs), a form of cell-to-cell communication, in military operational stress and their relationship to circulating hormones. The purpose of this study was to characterize the neuroendocrine, cytokine, and EV response to an intense. 24-h selection course known as the Naval Special Warfare (NSW) Screener and identify associations between EVs and cytokines. Blood samples were collected the morning of and following the NSW Screener in 29 men (18-26 yr). Samples were analyzed for concentrations of cortisol, insulin-like growth factor I (IGF-I), neuropeptide-Y (NPY), brain-derived neurotrophic factor (BDNF), α-klotho, tumor necrosis factor-α (TNFα), and interleukins (IL) -1ß, -6, and -10. EVs stained with markers associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1) were characterized using imaging flow cytometry and vesicle flow cytometry. The selection event induced significant changes in circulating BDNF (-43.2%), IGF-I (-24.6%), TNFα (+17.7%), and IL-6 (+13.6%) accompanied by increases in intensities of THSD1+ and VAMP3+ EVs (all P < 0.05). Higher concentrations of IL-1ß and IL-10 were positively associated with THSD1+ EVs (P < 0.05). Military operational stress altered the EV profile. Surface markers associated with apoptotic bodies were positively correlated with an inflammatory response. Future studies should consider a multiomics assessment of EV cargo to discern canonical pathways that may be mediated by EVs during military stress.

Resistance exercise differentially alters extracellular vesicle size and subpopulation characteristics in healthy men and women: an observational cohort study.

Extracellular vesicles (EVs) are established mediators of adaptation to exercise. Currently, there are no published data comparing changes in EVs between men and women after resistance exercise. We tested the hypothesis that EV profiles would demonstrate a sex-specific signature following resistance exercise. Ten men and 10 women completed an acute heavy resistance exercise test for back squats using 75% of their one-repetition maximum. Blood was drawn before and immediately after exercise. EVs were isolated from plasma using size exclusion chromatography and stained with antibodies associated with exosomes (CD63), microvesicles (VAMP3), apoptotic bodies (THSD1), and a marker for skeletal muscle EVs (SGCA). CD63+ EV concentration and proportion of total EVs increased 23% (P = 0.006) and 113% (P = 0.005) in both sexes. EV mean size declined in men (P = 0.020), but not in women, suggesting a relative increase in small EVs in men. VAMP3+ EV concentration and proportion of total EVs increased by 93% (P = 0.025) and 61% (P = 0.030) in men and women, respectively. SGCA+ EV concentration was 69% higher in women compared with men independent of time (P = 0.007). Differences were also observed for CD63, VAMP3, and SGCA median fluorescence intensity, suggesting altered surface protein density according to sex and time. There were no significant effects of time or sex on THSD1+ EVs or fluorescence intensity. EV profiles, particularly among exosome-associated and muscle-derived EVs, exhibit sex-specific differences in response to resistance exercise which should be further studied to understand their relationship to training adaptations.

Optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test.

BACKGROUND: Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not. OBJECTIVE: To develop an algorithm by integrating the 31-gene expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence [i31-ROR]) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions. METHODS: Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma. Using National Comprehensive Cancer Network cut points, i31-ROR performance was evaluated using the midpoint survival rates between patients with stage IIA and stage IIB disease as a risk threshold. RESULTS: Patients with a low-risk i31-ROR result had significantly higher 5-year recurrence-free survival (91% vs 45%, P < .001), distant metastasis-free survival (95% vs 53%, P < .001), and melanoma-specific survival (98% vs 73%, P < .001) than patients with a high-risk i31-ROR result. A combined i31-SLNB/ROR analysis identified 44% of patients who could forego sentinel lymph node biopsy while maintaining high survival rates (>98%) or were restratified as being at a higher or lower risk of recurrence or death. LIMITATIONS: Multicenter, retrospective study. CONCLUSION: Integrating clinicopathologic features with the 31-GEP optimizes patient risk stratification compared to clinicopathologic features alone.

Participatory mapping to address neighborhood level data deficiencies for food security assessment in Southeastern Virginia, USA.

BACKGROUND: Food is not equitably available. Deficiencies and generalizations limit national datasets, food security assessments, and interventions. Additional neighborhood level studies are needed to develop a scalable and transferable process to complement national and internationally comparative data sets with timely, granular, nuanced data. Participatory geographic information systems (PGIS) offer a means to address these issues by digitizing local knowledge. METHODS: The objectives of this study were two-fold: (i) identify granular locations missing from food source and risk datasets and (ii) examine the relation between the spatial, socio-economic, and agency contributors to food security. Twenty-nine subject matter experts from three cities in Southeastern Virginia with backgrounds in food distribution, nutrition management, human services, and associated research engaged in a participatory mapping process. RESULTS: Results show that publicly available and other national datasets are not inclusive of non-traditional food sources or updated frequently enough to reflect changes associated with closures, expansion, or new programs. Almost 6 percent of food sources were missing from publicly available and national datasets. Food pantries, community gardens and fridges, farmers markets, child and adult care programs, and meals served in community centers and homeless shelters were not well represented. Over 24 km2 of participant identified need was outside United States Department of Agriculture low income, low access areas. Economic, physical, and social barriers to food security were interconnected with transportation limitations. Recommendations address an international call from development agencies, countries, and world regions for intervention methods that include systemic and generational issues with poverty, incorporate non-traditional spaces into food distribution systems, incentivize or regulate healthy food options in stores, improve educational opportunities, increase data sharing. CONCLUSIONS: Leveraging city and regional agency as appropriate to capitalize upon synergistic activities was seen as critical to achieve these goals, particularly for non-traditional partnership building. To address neighborhood scale food security needs in Southeastern Virginia, data collection and assessment should address both environment and utilization issues from consumer and producer perspectives including availability, proximity, accessibility, awareness, affordability, cooking capacity, and preference. The PGIS process utilized to facilitate information sharing about neighborhood level contributors to food insecurity and translate those contributors to intervention strategies through discussion with local subject matter experts and contextualization within larger scale food systems dynamics is transferable.

Effects of Multi-ingredient Preworkout Supplements on Physical Performance, Cognitive Performance, Mood State, and Hormone Concentrations in Recreationally Active Men and Women.

ABSTRACT: Beckner, ME, Pihoker, AA, Darnell, ME, Beals, K, Lovalekar, M, Proessl, F, Flanagan, SD, Arciero, PJ, Nindl, BC, and Martin, BJ. Effects of multi-ingredient preworkout supplements on physical performance, cognitive performance, mood state, and hormone concentrations in recreationally active men and women. J Strength Cond Res 36(9): 2493-2501, 2022-Performance enhancement supplement research has primarily focused on the effectiveness of individual ingredients, rather than the combination. This study investigated the acute effects of 2 multi-ingredient preworkout supplements (MIPS), with beta-alanine and caffeine (BAC) and without (NBAC), compared with placebo (PLA) on anaerobic performance, endurance capacity, mood state, cognitive function, vascular function, and anabolic hormones. Thirty exercise-trained individuals (24.4 ± 4.9 years, 15 men and 15 women) completed a fatiguing exercise protocol on 3 separate occasions, 30 minutes after ingestion of BAC, NBAC, or PLA. Outcomes were analyzed using one-way or two-way repeated-measures analysis of variance, as appropriate (alpha = 0.05). Anaerobic power was greater when supplementing with NBAC (10.7 ± 1.2 W·kg -1 ) and BAC (10.8 ± 1.4 W·kg -1 ) compared with PLA (10.4 ± 1.2 W·kg -1 ) ( p = 0.014 and p = 0.022, respectively). BAC improved V̇ o2 peak time to exhaustion ( p = 0.006), accompanied by an increase in blood lactate accumulation ( p < 0.001), compared with PLA. Both NBAC and BAC demonstrated improved brachial artery diameter after workout ( p = 0.041 and p = 0.005, respectively), but PLA did not. L-arginine concentrations increased from baseline to postsupplement consumption of BAC ( p = 0.017). Reaction time significantly decreased after exercise for all supplements. There was no effect of supplement on mood states. Exercise-trained individuals looking to achieve modest improvements in power and endurance may benefit from consuming MIPS before exercise.

Loss of SPEG Inhibitory Phosphorylation of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation.

BACKGROUND: Enhanced diastolic calcium (Ca2+) release through ryanodine receptor type-2 (RyR2) has been implicated in atrial fibrillation (AF) promotion. Diastolic sarcoplasmic reticulum Ca2+ leak is caused by increased RyR2 phosphorylation by PKA (protein kinase A) or CaMKII (Ca2+/calmodulin-dependent kinase-II) phosphorylation, or less dephosphorylation by protein phosphatases. However, considerable controversy remains regarding the molecular mechanisms underlying altered RyR2 function in AF. We thus aimed to determine the role of SPEG (striated muscle preferentially expressed protein kinase), a novel regulator of RyR2 phosphorylation, in AF pathogenesis. METHODS: Western blotting was performed with right atrial biopsies from patients with paroxysmal AF. SPEG atrial knockout mice were generated using adeno-associated virus 9. In mice, AF inducibility was determined using intracardiac programmed electric stimulation, and diastolic Ca2+ leak in atrial cardiomyocytes was assessed using confocal Ca2+ imaging. Phosphoproteomics studies and Western blotting were used to measure RyR2 phosphorylation. To test the effects of RyR2-S2367 phosphorylation, knockin mice with an inactivated S2367 phosphorylation site (S2367A) and a constitutively activated S2367 residue (S2367D) were generated by using CRISPR-Cas9. RESULTS: Western blotting revealed decreased SPEG protein levels in atrial biopsies from patients with paroxysmal AF in comparison with patients in sinus rhythm. SPEG atrial-specific knockout mice exhibited increased susceptibility to pacing-induced AF by programmed electric stimulation and enhanced Ca2+ spark frequency in atrial cardiomyocytes with Ca2+ imaging, establishing a causal role for decreased SPEG in AF pathogenesis. Phosphoproteomics in hearts from SPEG cardiomyocyte knockout mice identified RyR2-S2367 as a novel kinase substrate of SPEG. Western blotting demonstrated that RyR2-S2367 phosphorylation was also decreased in patients with paroxysmal AF. RyR2-S2367A mice exhibited an increased susceptibility to pacing-induced AF, and aberrant atrial sarcoplasmic reticulum Ca2+ leak, as well. In contrast, RyR2-S2367D mice were resistant to pacing-induced AF. CONCLUSIONS: Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2-mediated sarcoplasmic reticulum Ca2+ release. Reduced SPEG levels and RyR2-S2367 phosphorylation typified patients with paroxysmal AF. Studies in S2367 knockin mouse models showed a causal relationship between reduced S2367 phosphorylation and AF susceptibility. Thus, modulating SPEG activity and phosphorylation levels of the novel S2367 site on RyR2 may represent a novel target for AF treatment.

The 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma.

Aim: Sentinel node biopsy is a prognostic indicator of melanoma recurrence. We hypothesized that adding the primary melanoma molecular signature from the 31-gene expression profile (31-GEP) test could refine the risk of recurrence prognosis for patients with stage I-III melanoma. Materials & methods: Four hundred thirty-eight patients with stage I-III melanoma consecutively tested with the 31-GEP were retrospectively analyzed. The 31-GEP stratified patients as low-risk (Class 1A), intermediate-risk (Class 1B/2A) or high risk (Class 2B) of recurrence or metastasis. Results: The 31-GEP significantly stratified patient risk for recurrence-free survival (p < 0.001), distant metastasis-free survival (p < 0.001) and melanoma-specific survival (p < 0.001) and was a significant, independent predictor of metastatic recurrence (hazard ratio: 5.38; p = 0.014). Conclusion: The 31-GEP improves prognostic accuracy in stage I-III melanoma.

Lay abstract Cutaneous melanoma is a type of skin tumor affecting 100,000 new patients each year. Even with the best tools available today, knowing which patients will die from their cancer can be challenging. Using individual tumors from over 400 patients, we analyzed the expression of 31 genes from each tumor. Doing this helped us split the patients into groups who are more or less likely to die from their tumor. By combining this technique with current medical practices and guidelines, we hope to help identify which patients may or may not benefit from more intense therapies.

Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding.

Two classes of peptide-producing neurons in the arcuate nucleus (Arc) of the hypothalamus are known to exert opposing actions on feeding: the anorexigenic neurons that express proopiomelanocortin (POMC) and the orexigenic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY). These neurons are thought to arise from a common embryonic progenitor, but our anatomical and functional understanding of the interplay of these two peptidergic systems that contribute to the control of feeding remains incomplete. The present study uses a combination of optogenetic stimulation with viral and transgenic approaches, coupled with neural activity mapping and brain transparency visualization to demonstrate the following: (i) selective activation of Arc POMC neurons inhibits food consumption rapidly in unsated animals; (ii) activation of Arc neurons arising from POMC-expressing progenitors, including POMC and a subset of AgRP neurons, triggers robust feeding behavior, even in the face of satiety signals from POMC neurons; (iii) the opposing effects on food intake are associated with distinct neuronal projection and activation patterns of adult hypothalamic POMC neurons versus Arc neurons derived from POMC-expressing lineages; and (iv) the increased food intake following the activation of orexigenic neurons derived from POMC-expressing progenitors engages an extensive neural network that involves the endogenous opioid system. Together, these findings shed further light on the dynamic balance between two peptidergic systems in the moment-to-moment regulation of feeding behavior.

Dens Invaginatus in Patients With Cleft Lip and Palate: A Case Series.

Dens invaginatus is a rare developmental anomaly characterized by an infolding of the enamel organ within the crown or root of a tooth, and it is an example of a dental anomaly that has a higher incidence in patients with CL/P. If undiagnosed, dens invaginatus can lead to severe, acute pain and pulpal necrosis since it can permit direct entry of bacteria into the dental pulp. Treatment of dens invaginatus includes prophylactic sealant or composite restoration, endodontic therapy if pulpal involvement has already occurred, or extraction if aberrant tooth morphology precludes endodontic therapy. Few studies report on the incidence of dens invaginatus in patients with CL/P. The purpose of this article is to describe 4 cases of dens invaginatus in patients with CL/P which were encountered in a cleft-craniofacial orthodontic clinic. Each case describes dens invaginatus in a maxillary lateral incisor, and treatments ranged from sealant application to endodontic therapy to extraction. These cases highlight the importance of awareness of this dental anomaly among cleft team providers to facilitate early diagnosis in patients with CL/P.

A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.

BACKGROUND: The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD. METHODS: We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed. RESULTS: The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months. CONCLUSIONS: This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSV∆G-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408 .).

The effects of 16-weeks of prebiotic supplementation and aerobic exercise training on inflammatory markers, oxidative stress, uremic toxins, and the microbiota in pre-dialysis kidney patients: a randomized controlled trial-protocol paper.

BACKGROUND: Chronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated. METHODS: The study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3-4 CKD patients (ages of 30-75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55-65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks. DISCUSSION: This study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables. TRIAL REGISTRATION: Clinicaltrials.gov Trial registration# NCT03689569 . 9/28/2018, retrospectively registered.

Utilization of Healthcare Resources by HIV-Positive Children in the United States: A National Perspective.

OBJECTIVE: We characterized and estimated the cost of inpatient hospital utilization by US pediatric patients who tested positive for the human immunodeficiency virus (HIV). METHODS: The 2012 Kids' Inpatient Database was analyzed to provide a descriptive assessment of national inpatient hospital utilization. We analyzed a stratified probability sampling of 3.2 million pediatric hospital discharges weighted to 6.7 million national discharges. Descriptive statistics for hospital and patient characteristics were identified and binary variables were analyzed using the Student t test. The Kids' Inpatient Database is the largest available all-payer pediatric (20 years old and younger) inpatient care database in the United States, yielding national estimates of hospital inpatient stays. Children aged 17 years and younger were included in the study and conditions related to pregnancy and delivery. RESULTS: We estimated that 1344 pediatric discharges were associated with an HIV diagnosis, totaling 10,704 inpatient days at a cost of $91 million. Among pediatric patients with HIV, 55% were African American, 20% were white, 15% were Asian/Pacific Islander, 8% were other races (including Hispanics and Native Americans), and 51% were female. Children who were HIV positive were more likely to have longer mean hospital stays, have higher mean hospital charges, be of a higher median age (8 years and older), have Medicaid insurance, come from lower-income families, be treated in urban teaching hospitals, and be more likely to die during hospitalization (P < 0.01 for all). Among non-HIV-related pediatric discharges, 20% occurred in households with a mean annual income >$63,000 compared with only 12% for children who were HIV positive. During hospitalization, at least one procedure was performed in 56.6% of children with HIV compared with 45.65% of hospitalized children without HIV. The most frequently observed diagnoses associated with children infected with HIV were gastrointestinal disorders, mental disorders, and bacterial infections and sepsis. CONCLUSIONS: The results suggest that pediatric patients who were HIV positive were significantly older, from lower-income areas, and members of minority groups. They underwent more procedures during hospitalization, incurred more than twice the total cost, stayed in the hospital twice as long, and had statistically higher in-hospital mortality than children who were HIV negative. As we continue to explore effective and judicious treatment options for patients who are HIV positive, our national estimates of resource utilization can be used to conduct a more detailed examination of current medical practices and specific patterns of diagnoses associated with HIV infection in the US pediatric population.

Psychological and Physiological Predictors of Resilience in Navy SEAL Training.

This research examines resilience from both cognitive and physiological perspectives and the relative importance of resilience for progression within an extremely physical training environment for 116 individuals. Our study provides a unique contribution as an examination of the combined effects of psychological and physiological resilience in the success of individuals in the first phase of a military special operations training course, the Navy's Basic Underwater Demolition/SEAL (BUD/S) course. Our study used the Connor-Davidson Resilience Scale (CD-RISC) for the psychological assessment and a blood sample to measure the concentrations of cortisol, DHEA and BDNF, each associated with stress adaptation and neuronal integrity. Our contributions include: heeding the call for more extensive research for resilience, examining physiological markers as predictors in training situations, combining psychological and physiological resilience into a single metric to assess resilience, and providing empirical support for the vital role of resilience in both stamina and persistence in training. Our findings indicate that both psychological and physiological resilience can be important predictors of persistence individually, but combining the measures provides a more holistic view to predict the success of an individual in this intensive training program. The present study has implications not only for the military community, but also for those individuals seeking elite performance in a broad array of fields, like professional athletes, CEO's, and emergency response workers.

Relationship of Velopharyngeal Insufficiency With Face Mask Therapy in Patients With Cleft Lip and Palate.

OBJECTIVE: To determine whether orthodontic/dentofacial orthopedic maxillary protraction face mask therapy induces changes in velopharyngeal functioning in a cohort of pediatric patients having cleft palate with or without cleft lip. DESIGN: Retrospective chart review. SETTING: A children's hospital in the United States. PARTICIPANTS: Forty-three pediatric patients with cleft palate, with or without cleft lip, syndromic or with isolated clefts, who received face mask therapy from January 2009 to April 2016. INTERVENTION: Clinical data were extracted for review and analysis from medical records obtained from the Cleft Database/Research Registry (CDB-RR). MAIN OUTCOME MEASURES: Pittsburgh Weighted Speech Scores (PWSS) before and after therapy. RESULTS: There was a significant increase in PWSS after face mask therapy for patients with a PWSS score of 0 prior to treatment. Patients with PWSS >0 before treatment remained largely stable after face mask therapy. Maxillary advancement was not significantly associated with change in PWSS or fistula presence/absence. CONCLUSIONS: There is an increased risk of velopharyngeal insufficiency with maxillary protraction face mask treatment in patients with cleft palate. Patient counseling and obtaining consent regarding speech changes during treatment are recommended.

Comparative evaluation of pathogenicity of three isolates of vesicular stomatitis virus (Indiana serotype) in pigs.

Vesicular stomatitis (VS) is a notifiable disease of livestock affecting cattle, horses, pigs and humans. Vesicular stomatitis virus (VSV) serotypes Indiana and New Jersey are endemic to Central America; however, they also cause sporadic and scattered outbreaks in various countries in South and North America, including the USA. In order to develop an effective experimental challenge model for VSV, we compared the pathogenicity of three VSV serotype Indiana isolates in 36 4-5 week-old pigs. Two bovine isolates of Central American origin and one equine isolate from the USA were used for the experimental infections. Each pig was inoculated with a single isolate by both the intradermal and intranasal routes. Clinical signs of VSV infection were recorded daily for 10 days post-inoculation (days p.i.). Nasal and tonsillar swab samples and blood were collected to monitor immune responses, virus replication and shedding. Post-challenge, characteristic signs of VS were observed, including vesicles on the nasal planum and coronary bands, lameness, loss of hoof walls and pyrexia. Pigs inoculated with the Central American isolates showed consistently more severe clinical signs in comparison to the pigs infected with the USA isolate. Genomic RNA was isolated from the original challenge virus stocks, sequenced and compared to VSV genomes available in GenBank. Comparative genome analysis demonstrated significant differences between the VSV isolate from the USA and the two Central American isolates. Our results indicate that the Central American isolates of VSV serotype Indiana used in this study are more virulent in swine than the USA VSV serotype Indiana isolate and represent good candidate challenge strains for future VSV studies.