Metabolomic Endotype of Asthma.

Metabolomics, the quantification of small biochemicals in plasma and tissues, can provide insight into complex biochemical processes and enable the identification of biomarkers that may serve as therapeutic targets. We hypothesized that the plasma metabolome of asthma would reveal metabolic consequences of the specific immune and inflammatory responses unique to endotypes of asthma. The plasma metabolomic profiles of 20 asthmatic subjects and 10 healthy controls were examined using an untargeted global and focused metabolomic analysis. Individuals were classified based on clinical definitions of asthma severity or by levels of fraction of exhaled NO (FENO), a biomarker of airway inflammation. Of the 293 biochemicals identified in the plasma, 25 were significantly different among asthma and healthy controls (p < 0.05). Plasma levels of taurine, lathosterol, bile acids (taurocholate and glycodeoxycholate), nicotinamide, and adenosine-5-phosphate were significantly higher in asthmatics compared with healthy controls. Severe asthmatics had biochemical changes related to steroid and amino acid/protein metabolism. Asthmatics with high FENO, compared with those with low FENO, had higher levels of plasma branched-chain amino acids and bile acids. Asthmatics have a unique plasma metabolome that distinguishes them from healthy controls and points to activation of inflammatory and immune pathways. The severe asthmatic and high FENO asthmatic have unique endotypes that suggest changes in NO-associated taurine transport and bile acid metabolism.

Global epidemiology of HIV.

The number of persons living with HIV worldwide reached approximately 35.3 million in 2012. Meanwhile, AIDS-related deaths and new HIV infections have declined. Much of the increase in HIV prevalence is from rapidly increasing numbers of people on antiretroviral treatment who are now living longer. There is regional variation in epidemiologic patterns, major modes of HIV transmission, and HIV program response. It is important to focus on HIV incidence, rather than prevalence, to provide information about HIV transmission patterns and populations at risk. Expanding HIV treatment will function as a preventive measure through decreasing horizontal and vertical transmission of HIV.

Analysis of HIV testing acceptance and risk factors of an adolescent cohort using emergency department-based multimedia HIV testing and counseling.

BACKGROUND: The social environment in the Bronx, NY, has led to HIV infection rates among young people that are much higher than the national average. METHODS: A prospective observational study on a convenience sample of medically stable emergency department (ED) patients was conducted from October 1, 2005, to August 31, 2012. Acceptability of the tested model was determined by assessing the number of patients tested and identified HIV infections. Data were compared with data from the rest of the ED that tested for HIV. RESULTS: A total of 10,149 adolescents were approached during this period, of which 9.5% refused or were ineligible to test. Of those approached, 38.9% of patients were male, 59.7% were Hispanic, and 33.6% were black. The mean age was 19.4 ± 1.4 years, and 8.2% of patients were men who have sex with men. For risk behavior profiles, 24.3% never used condoms in the past 3 months. Incidence of HIV was less than 1%, and 92.6% of HIV-positive patients were linked to care. Of the patients who completed a postsatisfaction survey, 82.4% felt influenced to change their sexual practices. A smaller percentage of adolescent had tested previously for HIV compared with nonadolescents (67.7% vs. 80.6%). There was a slightly larger percentage of adolescents that accepted HIV testing compared with nonadolescents (95.4% vs. 90.8%). Adolescents who were positive for HIV were tested earlier in the progression of the disease, with higher median CD4 cell counts and lower viral loads compared with nonadolescents. CONCLUSIONS: Adolescents were highly receptive to a multimedia-integrated ED-based HIV testing program, as indicated by their high uptake of testing.

Adipocyte hypertrophy is associated with lysosomal permeability both in vivo and in vitro: role in adipose tissue inflammation.

Obesity in both humans and rodents is characterized by adipocyte hypertrophy and the presence of death adipocytes surrounded by macrophages forming "crown-like structures." However, the biochemical pathways involved in triggering adipocyte death as well as the role of death adipocytes in adipose tissue remodeling and macrophage infiltration remain poorly understood. We now show that induction of adipocyte hypertrophy by incubation of mature adipocytes with saturated fatty acids results in lysosomal destabilization and cathepsin B (ctsb), a key lysosomal cysteine protease, activation and redistribution into the cytosol. ctsb activation was required for the lysosomal permeabilization, and its inhibition protected cells against mitochondrial dysfunction. With the use of a dietary murine model of obesity, ctsb activation was detected in adipose tissue of these mice. This is an early event during weight gain that correlates with the presence of death adipocytes, and precedes macrophage infiltration of adipose tissue. Moreover, ctsb-deficient mice showed decreased lysosomal permeabilization in adipocytes and were protected against adipocyte cell death and macrophage infiltration to adipose tissue independent of body weight. These data strongly suggest that ctsb activation and lysosomal permeabilization in adipocytes are key initial events that contribute to the adipocyte cell death and macrophage infiltration into adipose tissue associated with obesity. Inhibition of ctsb activation may be a new therapeutic strategy for the treatment of obesity-associated metabolic complications.

Educational effectiveness of an HIV pretest video for adolescents: a randomized controlled trial.

OBJECTIVE: The goal of this study was to compare the effectiveness of a youth-friendly HIV video with in-person counseling in conveying HIV knowledge and obtaining consent for HIV testing among adolescent patients of an urban emergency department. METHODS: A 2-armed, randomized controlled trial was conducted on a convenience sample of 200 stable, sexually active people aged 15 to 21 years in an urban emergency department. Participants in both the in-person counseling group and the video intervention group completed preintervention and postintervention HIV knowledge measures. HIV knowledge was the primary outcome measure, and consent for HIV testing was the secondary outcome. Characteristics associated with voluntary HIV testing were identified. RESULTS: Of 333 eligible people, 200 agreed to participate. There was no difference in preintervention HIV knowledge scores between groups. Mean postintervention knowledge scores differed significantly between the video (78.5% correct) and the counselor (66.3% correct) (P < 0.01) groups. Overall, 51% of the video group accepted HIV testing compared with 22% in the control group (P < .01). Watching the video (OR: 3.6 [95% CI: 1.8-7.2]), being female (OR: 2.1 [95% CI: 1.0-4.2]), engaging in oral sex (OR: 2.8 [95% CI: 1.4-5.9]), and being older than 18 years (OR: 3.8 [95% CI: 1.8-7.8]) were all positively associated with testing. CONCLUSIONS: A youth-friendly HIV educational video improved adolescents' HIV knowledge and increased their participation in HIV testing more than in-person counseling. video-based HIV counseling can perform as well or better than in-person counseling for adolescents in the ED.

Engaging HIV-positive individuals in specialized care from an urban emergency department.

Linking patients who test positive for HIV in an emergency department (ED) setting to HIV care can be challenging. The aim of this study was to assess whether a multimedia HIV testing model utilized in an inner-city ED can effectively link HIV-positive individuals into specialized medical care. A prospective cohort study was performed from October 2005 to January 2009 at an urban academic hospital with a Level 1 trauma center and in-house specialized HIV clinic. Patients were HIV tested in the ED using a multimedia video counseling program which included computer-assisted data collection. Patients who tested positive were linked to care by the same counselor who gave the test result. Linkage was immediate for discharged patients during clinic hours and patients tested during off-hours were scheduled a visit on the next business day. All follow-up was conducted through chart review. The public health advocates (PHAs) tested 24,495 patients over the course of the study, of whom 116 (0.47%) were HIV positive and 93 were newly diagnosed. A total of 83.6% (97/116) of HIV-positive individuals were linked into specialized care, defined here as an outpatient clinic visit within 30 days of diagnosis in the ED. The findings suggest that a multimedia testing model that includes a counselor who acts as tester and navigator can successfully link a high percentage of patients into specialized care.

High-volume rapid HIV testing in an urban emergency department.

New Centers for Disease Control and Prevention (CDC) guidelines recommend routine HIV screening in locations including emergency departments. This study evaluates a novel approach to HIV counseling and testing (C&T) in a high-volume inner-city emergency department in terms of the number of patients who can be recruited, tested, test positive, and are linked to care. This prospective evaluation was conducted for 26 months. Noncritically ill or injured patients presenting to an inner-city emergency department were recruited. Patients used a multimedia program that facilitated data entry and viewed previously evaluated HIV counseling videos. Demographic characteristics, risk factors, and sexual history were collected. Data were collected on the number of patients tested, number of HIV-positive patients identified, and number linked to care. Demographic characteristics of the participants were as follows: 48.7% males, mean age 32.6 +/- 11.3, 34.6% Hispanic, and 37.9 % African American. Of the 7109 eligible patients approached, 6214 (87.4%) agreed to be HIV tested. There were 57 newly diagnosed or confirmed HIV-positive patients, representing a seroprevalence of 0.92%. Of those testing positive, 49 (84.2%) were linked to care and had a mean initial CD4 count of 238 cells/mm(3). In conclusion, a video-assisted rapid HIV program in a busy inner-city hospital emergency department can effectively test a high volume of patients and successfully link HIV-positive individuals to care, while providing high-quality education and prevention messages for all those who test.