Patient Preferences for Lifestyle Management in a Multi-site Randomized Lifestyle Trial for Remission of the Metabolic Syndrome.

BACKGROUND: Randomized behavioral clinical trials are the gold standard for evaluating efficacy of a behavioral treatment. However, because participants are generally unblinded to treatment, preference for a specific treatment option can lead to biased results and/or reduced treatment efficacy. The purpose was to describe the relative frequency and correlates of existence of a preference and patient preference for either an in-person group-based or a remote self-directed, lifestyle treatment prior to randomization to one of these treatments. METHODS: The Enhanced Lifestyles for Metabolic Syndrome (ELM) trial is a multi-site behavioral clinical trial that compares efficacy of a group-based vs. a self-directed approach to lifestyle change on 2-year remission of the metabolic syndrome. Prior to randomization, participants were asked whether they had a preference for a particular treatment and, if so, which approach they preferred. Baseline data were used for a series of logistic regression models to determine behavioral correlates of treatment preference, independent of socioeconomic factors. RESULTS: Of the 331 participants, 131 (39.6%) had no preference for either treatment. Among the 200 with a preference, 56 (28.0%) preferred the self-directed program. Strength of a pre-existing habit of eating vegetables on most days was an independent correlate of no preference (adjusted OR, 1.27; 95% CI, 1.01-1.61; p = 0.03) and preference for a self-directed program (adjusted OR, 1.55; 95% CI, 1.09-2.22; p = 0.01). CONCLUSION: A pre-existing habit of eating vegetables was associated with no preference and preference for a less intensive lifestyle treatment. Post-treatment follow-up of the trial results will determine if concordance between preference and treatment assignment influences outcomes.

Host antibacterial defense of 6-10 Gy γ-irradiated mice subjected to lentiviral vector-based Gas5 gene therapy.

Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, all mice exposed to 8 Gy of whole body γ-irradiation (8 Gy GIARS-mice) died by sepsis stemming from bacterial translocation. M1Mϕ located in the bacterial translocation site (i.e., the mesenteric lymph nodes, MLNs) have been characterized as major antibacterial effector cells. However, M2bMϕ, inhibitor cells for M1Mϕ polarization, predominated in the MLNs of these mice. The reduced expression of long noncoding RNA Gas5 was associated with M2bMϕ polarization. In this study, we tried to reduce the mortality rate of 8 Gy GIARS-mice through Gas5 gene transduction using lentivirus (Gas5 lentivirus). After Gas5 lentivirus injection, Gas5 RNA was overexpressed in MLN-F4/80+ cells of 8 Gy GIARS-mice, and these cells were identified as non-M2bMϕ. All of the 8 Gy GIARS-mice injected with Gas5 lentivirus survived 30 days or more after irradiation, and bacterial translocation and subsequent sepsis were shown to be minimal in these mice. These results indicate that the antibacterial resistance of 8 Gy GIASR-mice can be restored through the modulation of M2bMϕ located in the bacterial translocation site by Gas5 transduction.

Racial and Ethnic Differences in Hospital Admissions of Emergency Department COVID-19 Patients.

BACKGROUND: Several studies have found that among patients testing positive for COVID-19 within a health care system, non-Hispanic Black and Hispanic patients are more likely than non-Hispanic White patients to be hospitalized. However, previous studies have looked at odds of being admitted using all positive tests in the system and not only those seeking care in the emergency department (ED). OBJECTIVE: This study examined racial/ethnic differences in COVID-19 hospitalizations and intensive care unit (ICU) admissions among patients seeking care for COVID-19 in the ED. RESEARCH DESIGN: Electronic health records (n=7549) were collected from COVID-19 confirmed patients that visited an ED of an urban health care system in the Chicago area between March 2020 and February 2021. RESULTS: After adjusting for possible confounders, White patients had 2.2 times the odds of being admitted to the hospital and 1.5 times the odds of being admitted to the ICU than Black patients. There were no observed differences between White and Hispanic patients. CONCLUSIONS: White patients were more likely than Black patients to be hospitalized after presenting to the ED with COVID-19 and more likely to be admitted directly to the ICU. This finding may be due to racial/ethnic differences in severity of disease upon ED presentation, racial and ethnic differences in access to COVID-19 primary care and/or implicit bias impacting clinical decision-making.

Glycyrrhizin Protects γ-Irradiated Mice from Gut Bacteria-Associated Infectious Complications by Improving miR-222-Associated Gas5 RNA Reduction in Macrophages of the Bacterial Translocation Site.

Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, gut bacteria-associated sepsis caused high mortality rates in mice exposed to 6-9 Gy of γ-rays. IL-12+CD38+ iNOS+ Mϕ (M1Mϕ) located in the bacterial translocation site (mesenteric lymph nodes [MLNs]) of unirradiated mice were characterized as host defense antibacterial effector cells. However, cells isolated from the MLNs of GIARS mice were mostly CCL1+IL-10+LIGHT+miR-27a+ Mϕ (M2bMϕ, inhibitor cells for the M1Mϕ polarization). Reduced long noncoding RNA Gas5 and increased miR-222 expression in MLN-Mϕ influenced by the irradiation were shown to be associated with M2bMϕ polarization. In this study, the mortality of mice exposed to 7 Gy of γ-rays (7 Gy GIARS mice) was completely controlled after the administration of glycyrrhizin (GL), a major active ingredient in licorice root (Glycyrrhiza glabra). Bacterial translocation and subsequent sepsis were minimal in 7 Gy GIARS mice treated with GL. Increased Gas5 RNA level and decreased miR-222 expression were shown in MLN-Mϕ isolated from 7 Gy GIARS mice treated with GL, and these macrophages did not display any properties of M2bMϕ. These results indicate that gut bacteria-associated sepsis in 7 Gy GIARS mice was controlled by the GL through the inhibition of M2bMϕ polarization at the bacteria translocation site. Expression of Ccl1, a gene required for M2bMϕ survival, is silenced in the MLNs of 7 Gy GIARS mice because of Gas5 RNA, which is increased in these cells after the suppression of miR-222 (a Gas5 RNA expression inhibitor) by the GL.

An assessment of physician assistant student diversity in the United States: a snapshot for the healthcare workforce.

BACKGROUND: The Physician Assistant (PA) workforce falls short of mirroring national demographics mainly due to a lack of diversity in student enrollment. Few studies have systematically examined diversity across PA programs at the national level, and little is known about best practices for consistently graduating a diverse group of students. We descriptively characterized the extent to which PA programs are graduating a diverse group of students and identified top performing PA programs. METHODS: Data from the Integrated Postsecondary Education Data System (IPEDS) were used to calculate the number and proportion of racial or ethnically diverse graduates. The study sample included 139 accredited PA programs that had graduated a minimum of five cohorts from 2014-2018. Within each of the United States Census Divisions, programs were ranked according to the number and proportion of graduates who were underrepresented minority (URM) race, Hispanic ethnicity, and of non-white (URM race, Hispanic, and Asian). RESULTS: Amongst PA programs in the United States, a large disparity in the number and proportion of racial and ethnic graduates was observed. Of 34,625 PA graduates, only 2,207 (6.4%) were Hispanic ethnicity and 1,220 (3.5%) were URM race. Furthermore, a large number of diverse graduates came from a small number of top performing programs. CONCLUSION: Despite the abundance of evidence for the need to diversify the healthcare workforce, PA programs have had difficulty recruiting and graduating a diverse group of students. This study provides empirical evidence that PA programs have not been able to attain the level of diversity necessary to shift the lack of diversity in the PA workforce. Based upon this study's findings, the top performing PA programs can be used as role models to establish benchmarks for other programs. The results of this descriptive study are currently being used to guide a qualitative study to identify the top performers' strategies for success.

Assessing and benchmarking equity, diversity, and inclusion in healthcare professions.

ABSTRACT: Healthcare professions are among the fastest growing careers in the United States, but the issues of equity, diversity, and inclusion remain a challenge. The percentage of underrepresented minority groups is disproportionately small despite many efforts to increase workforce diversity over the past several decades. As the demographics in our nation are rapidly changing, increasing racial, ethnic, and cognitive diversity is crucial to achieving a workforce with the capacity to provide accessible and equitable healthcare. Given the growing evidence that a diverse workforce improves healthcare outcomes, fosters unique perspectives (cognitive diversity), and helps to reduce health disparities, there is an urgent need to address perennial barriers such as structural racism, biases, and stereotypes. Educational institutions should be held accountable to integrate equity, diversity, and inclusion in all aspects of healthcare professions education and practice. This article discusses potential areas for innovation and opportunities that can be leveraged in assessing and benchmarking equity, diversity, and inclusion in healthcare professions. The ability to thoroughly assess the PA profession's culture in relationship to diversity, equity, and inclusion provides an opportunity to determine how well the profession is performing, and to strategically plan for what else need to be done.

Adherence and Viral Suppression Among Participants of the Patient-centered Human Immunodeficiency Virus (HIV) Care Model Project: A Collaboration Between Community-based Pharmacists and HIV Clinical Providers.

BACKGROUND: Human immunodeficiency virus (HIV) viral suppression (VS) decreases morbidity, mortality, and transmission risk. METHODS: The Patient-centered HIV Care Model integrated community-based pharmacists with HIV medical providers and required them to share patient clinical information, identify therapy-related problems, and develop therapy-related action plans.Proportions adherent to antiretroviral therapy (proportion of days covered [PDC] ≥90%) and virally suppressed (HIV RNA <200 copies/mL), before and after model implementation, were compared. Factors associated with postimplementation VS were determined using multivariable logistic regression; participant demographics, baseline viral load, and PDC were explanatory variables. PDC was modified to account for time to last viral load in the year postimplementation, and stratified as <50%, 50% to <80%, 80% to <90%, and ≥90%. RESULTS: The 765 enrolled participants were 43% non-Hispanic black, 73% male, with a median age of 48 years; 421 and 649 were included in the adherence and VS analyses, respectively. Overall, proportions adherent to therapy remained unchanged. However, VS improved a relative 15% (75% to 86%, P < .001). Higher PDC (adjusted odds ratio [AOR], 1.74 per 1-level increase in PDC category [95% confidence interval {CI}, 1.30-2.34]) and baseline VS (AOR, 7.69 [95% CI, 3.96-15.7]) were associated with postimplementation VS. Although non-Hispanic black persons (AOR, 0.29 [95% CI, .12-.62]) had lower odds of suppression, VS improved a relative 23% (63% to 78%, P < .001). CONCLUSIONS: Integrated care models between community-based pharmacists and primary medical providers may identify and address HIV therapy-related problems and improve VS among persons with HIV.

Correction to: Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis.

After publication of the original article [1], we were notified that the wrong version of Fig. 2b has been published.

Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis.

BACKGROUND: Limited information is available on biomarker(s) for triple-negative breast cancer (TNBC) that can address the higher incidence and aggressiveness of TNBC in African-American (AA) women. Our previous studies have demonstrated annexin A2 (AnxA2) association with exosomes which promotes angiogenesis and metastasis. Therefore, our goal was to examine the expression and function of exosomal-annexin A2 (exo-AnxA2) derived from the serum samples of breast cancer patients. METHODS: The expression of serum exo-AnxA2 and its association with clinicopathological features of the breast cancer patients were determined. The role of serum exo-AnxA2 to promote angiogenesis was determined by an in vivo Matrigel plug assay. RESULTS: Our results show that the expression of serum exo-AnxA2 in breast cancer patients (n = 169; 83.33 ± 2.040 ng/mL, P < 0.0001) is high compared to non-cancer females (n = 68; 34.21 ± 2.238 ng/mL). High expression of exo-AnxA2 levels in breast cancer was significantly associated with tumor grade (P < 0.0001), poor overall survival (hazard ratio (HR) 2.802; 95% confidence intervals (CI) = 1.030-7.620; P = 0.0353), and poor disease-free survival (HR 7.934; 95% CI = 1.778-35.398; P = 0.0301). The expression of serum exo-AnxA2 levels was significantly elevated in TNBC (n = 68; 109.1 ± 2.905 ng/mL; P < 0.0001) in comparison to ER+ (n = 50; 57.35 ± 1.545 ng/mL), HER2+ (n = 59; 78.25 ± 1.146 ng/mL), and non-cancer females (n = 68; 34.21 ± 2.238 ng/mL). Exo-AnxA2 showed diagnostic values with a maximum AUC as 1.000 for TNBC, 0.8304 for ER+, and 0.9958 for HER2+ compared to non-cancer females. The expression of serum exo-AnxA2 was significantly elevated in AA women with TNBC (n = 29; 118.9 ± 4.086 ng/mL, P < 0.0001) in comparison to Caucasian-American TNBC (n = 27; 97.60 ± 3.298 ng/mL) patients. Our in vivo results suggest a role of serum exo-AnxA2 in angiogenesis and its association with aggressiveness of TNBC in AA women. CONCLUSIONS: Our results demonstrated that the expression of serum exo-AnxA2 is high in AA women with TNBC and promotes angiogenesis. These findings suggest that exo-AnxA2 holds promise as a potential prognosticator of TNBC and may lead to an effective therapeutic option.

Improvements in Retention in Care and HIV Viral Suppression Among Persons with HIV and Comorbid Mental Health Conditions: Patient-Centered HIV Care Model.

The Patient-centered HIV Care Model (PCHCM) integrated community-based pharmacists with medical providers and required sharing of patient clinical information and collaborative therapy-related action planning. We determined the proportions of participants with HIV and mental health conditions who were retained in care and the proportion virally suppressed, pre- and post-implementation. Overall, we found a relative 13% improvement in both retention [60% to 68% (p = 0.009)] and viral suppression [79% to 90% (p < 0.001)]. Notable improvements were seen among persons triply diagnosed with HIV, mental illness and substance use [+ 36% (50% to 68%, p = 0.036) and + 32% (66% to 86%, p = 0.001) in retention and viral suppression, respectively]. There were no differences in the proportions of persons adherent to psychiatric medications, pre- to post-implementation, nor were there differences in the proportions of persons retained in care or virally suppressed by psychiatric medication adherence, post-implementation. PCHCM demonstrated that collaborations between community-based pharmacists and medical providers can improve HIV care continuum outcomes among persons with mental health conditions.

Survival of Mice with Gastrointestinal Acute Radiation Syndrome through Control of Bacterial Translocation.

Macrophages (Mϕ) with the M2b phenotype (Pheno2b-Mϕ) in bacterial translocation sites have been described as cells responsible for the increased susceptibility of mice with gastrointestinal acute radiation syndrome to sepsis caused by gut bacteria. In this study, we tried to reduce the mortality of mice exposed to 7-10 Gy of gamma rays by controlling Pheno2b-Mϕ polarization in bacterial translocation sites. MicroRNA-222 was induced in association with gamma irradiation. Pheno2b-Mϕ polarization was promoted and maintained in gamma-irradiated mice through the reduction of a long noncoding RNA growth arrest-specific transcript 5 (a CCL1 gene silencer) influenced by this microRNA. Therefore, the host resistance of 7-9-Gy gamma-irradiated mice to sepsis caused by bacterial translocation was improved after treatment with CCL1 antisense oligodeoxynucleotide. However, the mortality of 10-Gy gamma-irradiated mice was not alleviated by this treatment. The crypts and villi in the ileum of 10-Gy gamma-irradiated mice were severely damaged, but these were markedly improved after transplantation of intestinal lineage cells differentiated from murine embryonic stem cells. All 10-Gy gamma-irradiated mice given both of the oligodeoxynucleotide and intestinal lineage cells survived, whereas all of the same mice given either of them died. These results indicate that high mortality rates of mice irradiated with 7-10 Gy of gamma rays are reducible by depleting CCL1 in combination with the intestinal lineage cell transplantation. These findings support the novel therapeutic possibility of victims who have gastrointestinal acute radiation syndrome for the reduction of their high mortality rates.

Environment-wide association study on childhood obesity in the U.S.

BACKGROUND: Childhood obesity is a national public health issue with increasing prevalence. It has been linked to diet, lack of physical activity, and genetic susceptibility, with more recent evidence that it could also result from environmental factors. Studies linking it to environmental factors are limited, unsystematic, incomprehensive, and inconclusive. OBJECTIVE: To conduct an environment-wide association study (EWAS) to comprehensively investigate all the environmental factors available in a nationally representative sample of children to determine factors associated with childhood obesity. METHODS: We utilized the 1999-2016 National Health and Nutrition Examination Survey (NHANES) datasets and included all children/adolescents (6-17 years). Obesity was measured using body mass index and waist to height ratio. A multinomial and binary logistic regression were used adjusting for age, sex, race/ethnicity, creatinine, calorie intake, physical activity, screen time, limitation to physical activities, and socioeconomic status. We then controlled for multiple hypothesis testing and validated our findings on a different cohort of children. RESULTS: We found that metals such as beryllium (OR: 3.305 CI: 1.460-7.479) and platinum (OR: 1.346 CI: 1.107-1.636); vitamins such as gamma-tocopherol (OR: 8.297 CI: 5.683-12.114) and delta-tocopherol (OR: 1.841 CI:1.476-2.297); heterocyclic aromatic amines such as 2-Amino-9H-pyrido (2,3-b) indole (OR: 1.323 CI: 1.083-1.617) and 2-Amino-3-methyl-9H-pyriodo(2,3-b)indole (OR: 2.799 CI: 1.442-5.433); polycyclic aromatic amines such as 9- fluorene (OR: 1.509 CI: 1.230-1.851) and 4-phenanthrene (OR: 2.828 CI: 1.632-4.899); and caffeine metabolites such as 1,3,7-trimethyluric acid (OR: 1.22 CI: 1.029-1.414) and 1,3,7-trimethylxanthine (OR: 1.258 CI: 1.075-1.473) were positively and significantly associated with childhood obesity. CONCLUSION: Following the unique concept of EWAS, certain environmental factors were associated with childhood obesity. Further studies are required to confirm these associations while investigating their mechanisms of action.

The Podiatric Medical Profession: A Gender Comparison.

The number of women in podiatric medicine and surgery has increased steadily over the past 4 decades; however, there appears to be a large and continued gender gap with respect to representation in academic medicine and other positions of power. National and state level organizational data were obtained from multiple podiatry professional societies to evaluate the rate at which women achieved leadership roles within the podiatric profession over time. A secondary questionnaire was also developed and electronically mailed to 8684 doctors of podiatric medicine to help capture additional leadership information and to provide further insight into the trends observed. The response rate was 26% (2276/8684). Female representation in academia, research/publications, most leadership positions, and board certifications has increased over time, but at a slower rate than the number of women entering the profession. We observed a decreasing trend of females completing fellowships, speaking at national meetings, becoming residency directors, and receiving American College of Foot and Ankle Surgeons- and American Podiatric Medical Association-sponsored grants/awards. Based on the survey results, female podiatric physicians were more likely to be single, have fewer children, spend more time in a clinical setting, be less satisfied with work, and experience higher work stress levels than their male colleagues. Of the female respondents, 73% described experiencing gender discrimination at some point in their career, and 42% reported experiencing sexual harassment, compared with only 6% and 5% of men, respectively. There continues to be a gender gap in leadership roles, which may be explained partially by work/life balance issues, gender discrimination, and other issues.

Price of Four Loko in Large U.S. Cities, 2018.

BACKGROUND: Supersized alcopops are flavored alcoholic beverages that contain up to 5.5 standard alcoholic drinks in a single can. Limited research suggests Four Loko-the most commonly consumed supersized alcopop by underage drinkers-is among the least expensive ready-to-drink alcohol products on the U.S. market. This is a public health concern because alcohol prices are inversely associated with consumption and related harms, particularly among youth. This study investigated Four Loko's retail price per volume of alcohol in large U.S. cities. METHODS: This study used multistage random sampling to collect data in the largest city of each state and Washington, DC. A simple random sample of 5 ZIP codes from each city was selected and entered into Four Loko's website product locator. Within ZIP codes, up to 4 stores were randomly selected and contacted by telephone. Retailers were interviewed about Four Loko in regard to: availability, volume, alcohol by volume (abv), price for 1 can, and discounts for purchasing more than 1 can. RESULTS: The sample included 344 retail stores with Four Loko in stock. Average price per standard alcoholic drink (i.e., 14 g of absolute alcohol) was $0.54 for Four Loko products. Taking into account volume, price, and discounts, an average of 17 standard alcoholic drinks could be purchased via Four Loko with $10. Adjusted analysis using linear regression showed that availability of bulk price discounts and higher abv (14% vs. 12%) were associated with lower price per drink. CONCLUSION: This study verifies that Four Loko is among the least expensive ready-to-drink alcohol available for purchase in the United States. Given that consuming a single supersized alcopop constitutes binge drinking and is therefore unsafe, regulatory agencies should consider a variety of steps to reduce the availability and abv of these products and increase their retail price in order to reduce and prevent unsafe alcohol consumption.

Short-Term Alcohol Abstinence Improves Antibacterial Defenses of Chronic Alcohol-Consuming Mice against Gut Bacteria-Associated Sepsis Caused by Enterococcus faecalis Oral Infection.

The effects of short-term alcohol abstinence on host antibacterial resistance against Enterococcus faecalis oral infection was investigated in chronic alcohol-consuming mice [mice with 0.1 g/day of 20% ethanol consumption for 12 or 16 weeks (CAC-mice)]. These mice were highly susceptible to the infection; however, after 7 days of alcohol abstinence (aaCAC-mice), their antibacterial resistances were completely restored to the normal mouse level. Normal mice inoculated with CAC-mouse hepatic macrophages were shown to be susceptible to the infection, whereas the same macrophage preparation from aaCAC-mice did not impair the antibacterial resistance of normal mice. aaCAC-mouse liver macrophages protected nonobese diabetic-severe combined immunodeficiency IL-2Rγnull mice exposed to E. faecalis, whereas those from CAC-mice did not. Monocyte-derived (MD) M2b macrophages were predominantly isolated from CAC-mouse livers, but these cells were not significantly isolated from aaCAC-mouse livers. Hepatic MD macrophages from aaCAC-mice switched to M1 macrophages in response to bacterial antigen, whereas the same macrophage preparation from CAC-mice did not. M1 Kupffer cells, M2a Kupffer cells, and MD M2b macrophages were shown to be not bactericidal, whereas E. faecalis was killed effectively by M1 macrophages derived from aaCAC-mouse hepatic MD macrophages. These results indicate that MD M2b macrophages predominantly distributed in the liver are responsible for the impaired resistance of CAC-mice to E. faecalis oral infection, and aaCAC-mice without MD M2b macrophages in the livers are resistant to the infection.

Alcohol retail sales licenses and sexually transmitted infections in Texas counties, 2008-2015.

BACKGROUND: Research suggests that reduced retail alcohol outlet density may be associated with lower prevalence of HIV and other sexually transmitted infections (STIs). On-premise sale of alcohol for immediate consumption is theorized as increasing social interactions that can lead to sexual encounters. OBJECTIVE: We examined associations between on- and off-premise retail alcohol sales licenses and number of newly diagnosed HIV and STI cases in Texas counties. METHODS: Retail alcohol sales license data were obtained from the Texas Alcoholic Beverage Commission. HIV and bacterial STI data were obtained from the Texas Department of State Health Services. Associations between retail alcohol sales licenses and STIs were estimated using spatial linear models and Poisson mixed effects models for over-dispersed count data. RESULTS: Adjusting for county-specific confounders, there was no evidence of residual spatial correlation. In Poisson models, each additional on-premise (e.g., bar and restaurant) alcohol license per 10,000 population in a county was associated with a 1.5% increase (95% CI: 0.4%, 2.6%) in the rate of HIV and a 2.4% increase (95% CI: 1.9%, 3.0%) in the rate of bacterial STIs, adjusting for potential confounders. In contrast, number of off-premise licenses (e.g., take-out stores) was inversely associated with the incidence of STI and HIV, although the association with HIV was not statistically significant. CONCLUSIONS: This study adds to the limited literature on the association between retail alcohol availability and STIs. Additional research is needed on the role of alcohol availability (and policies affecting availability) in the spread of HIV and other STIs.

M2b macrophage polarization accompanied with reduction of long noncoding RNA GAS5.

Macrophages (Mϕ) are highly plastic and change their functional phenotypes depending on microenvironmental signals. Recent studies have shown that microRNAs are involved in the polarization of Mϕ. In this study, we demonstrated that the phenotype of M2bMϕ [CCL1(+) IL-10(+) LIGHT(+)] switches to other phenotypes with interchangeability attained through the increased expression of growth arrest-specific 5 RNA (GAS5 RNA), a long noncoding RNA. GAS5 RNA has been described as a silencer of the CCL1 gene. Various phenotypes of Mϕ were prepared from bone marrow-derived Mϕ (BMDMϕ) after stimulation with IFNγ [M(IFNγ)/M1Mϕ], IL-4 [M(IL-4)/M2aMϕ], LPS and immobilized IgG [M(LPS + IC)/M2bMϕ], and IL-10 [M(IL-10)/M2cMϕ]. BMDMϕ cultured with medium [M(no)/quiescent Mϕ] were used as a control. As compared to Μ(no), M(IFNγ), M(IL-4) and M(IL-10), the reduced level of GAS5 RNA was shown in M(LPS + IC). CCL1 and LIGHT mRNAs (typical biomarkers of M2bMϕ) were not expressed by M(LPS + IC) transduced with a GAS5 gene using lentiviral vector. The reduction of GAS5 RNA in M(LPS + IC) was mediated by the activation of nonsense-mediated RNA decay (NMD) pathway. BMDMϕ overexpressed with GAS5 RNA after GAS5 gene transduction did not polarize to M2bMϕ even though they were stimulated with LPS and IC in combination. These results indicate that the reduction of GAS5 RNA influenced by the NMD pathway activation leads to the Mϕ polarization stimulated with LPS and IC in combination.

Macrophage polarization and MRSA infection in burned mice.

Mortality associated with Staphylococcus aureus infection remains high during the sub-acute phase of burn injury. In this study, we aimed to improve antibacterial resistance of sub-acutely burned mice through macrophage polarization. Sepsis did not develop in mice at the sub-acute phase of 5% total body surface area (TBSA) burn after being infected with methicillin-resistant S. aureus (MRSA), and M1 macrophages (interleukin (IL)-10-IL-12+ inducible nitric oxide synthase+ Mφ) were isolated from these mice. In contrast, predominantly M2b macrophages (C-C motif chemokine ligand 1 (CCL1)+IL-10+IL-12- Mφ) were isolated from mice with >15% TBSA burn, and all of these mice died after the same MRSA infection. Comparing NOD scid gamma mice inoculated with Mφ with 25% TBSA burns, all mice treated with CCL1 antisense oligodeoxynucleotide (ODN) survived after MRSA infection, whereas all untreated mice given the same infection died within 4 days. CCL1 antisense ODN has been characterized as a specific polarizer of M2bMφ. M1Mφ were isolated from MRSA-infected mice with 25% TBSA burn after treatment with CCL1 antisense ODN, and these mice were shown to be resistant against a lethal dose of MRSA infection. M1Mφ were also isolated from 25% TBSA-burned mice infected with MRSA when the ODN was administered therapeutically, and subsequent sepsis was effectively controlled in these mice. These results indicate that the M2bMφ polarizer is beneficial for controlling MRSA infection in mice at the sub-acute phase of severe burn injury.

Factors Associated with Self-Estimated Breath Alcohol Concentration Among Bar Patrons.

BACKGROUND: Few studies have examined the context in which drinkers underestimate their breath alcohol concentration (BrAC) in natural drinking environments. This study examined factors associated with bar patrons' self-estimated BrAC in high-risk college town settings. METHODS: Guided interview and BrAC data were collected from 510 participants recruited as they exited bars located close to large universities: 1 in Florida and 1 in Texas. RESULTS: Participants with the highest measured BrACs underestimated their BrAC levels the most. Findings from multivariable linear regression analysis indicated that BrAC (std ß = 0.014, p < 0.001), number of alcoholic drinks consumed (std ß = 0.006, p < 0.01), and perceived drunkenness (std ß = 0.024, p < 0.001) had significant positive associations with BrAC self-estimates, where the regression coefficients were scaled by values approximately equal to each variable's interquartile range. Among the 321 participants with BrAC levels ≥ 0.08 g/dl, 21.2% believed their BrAC was below the legal per se driving limit of 0.08 g/dl. Results from a logistic regression analysis indicated that higher levels of perceived drunkenness were associated with better self-recognition that one's BrAC level exceeded the legal driving threshold (OR = 3.312, p < 0.001). Further, participants under 26 years of age had reduced odds of recognizing that their BrAC was greater than 0.079 g/dl (OR = 0.245, p < 0.05). CONCLUSIONS: These findings highlight the inaccuracy of self-estimated BrAC when drinking, particularly among younger drinkers. Adjusting for BrAC, situational factors were strongly associated with self-estimated BrAC. Future research is needed to better understand how altering drinking environments may improve accuracy of BrAC self-estimates and deter driving after drinking.

M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria-Associated Sepsis in Alcoholics.

Chronic alcohol consumption markedly impairs host antibacterial defense against opportunistic infections. γ-irradiated NOD-SCID IL-2Rγ(null) mice inoculated with nonalcoholic PBMCs (control PBMC chimeras) resisted Klebsiella pneumonia and gut bacteria-associated sepsis, whereas the chimeras created with alcoholic PBMCs (alcoholic PBMC chimeras) were very susceptible to these infections. M1 monocytes (IL-12(+)IL-10(-)CD163(-)CD14(+) cells), major effector cells in antibacterial innate immunity, were not induced by a bacterial Ag in alcoholic PBMC cultures, and M2b monocytes (CCL1(+)CD163(+)CD14(+) cells), which predominated in alcoholic PBMCs, were shown to be inhibitor cells on the Ag-stimulated monocyte conversion from quiescent monocytes to M1 monocytes. CCL1, which functions to maintain M2b macrophage properties, was produced by M2b monocytes isolated from alcoholic PBMCs. These M2b monocytes reverted to quiescent monocytes (IL-12(-)IL-10(-)CCL1(-)CD163(-)CD14(+) cells) in cultures supplemented with CCL1 antisense oligodeoxynucleotide, and the subsequent quiescent monocytes easily converted to M1 monocytes under bacterial Ag stimulation. Alcoholic PBMC chimeras treated with CCL1 antisense oligodeoxynucleotide were resistant against pulmonary infection by K. pneumoniae and sepsis stemming from enterococcal translocation. These results indicate that a majority of monocytes polarize to an M2b phenotype in association with alcohol abuse, and this polarization contributes to the increased susceptibility of alcoholics to gut and lung infections. Bacterial pneumonia and gut bacteria-associated sepsis, frequently seen in alcoholics, can be controlled through the polarization of macrophage phenotypes.