Dendritic cell migration from the airway to lymph nodes is a key event in the development of airway immunity during infection, allergy, and vaccination. To identify the best approaches to investigate DC migration to lung-draining lymph nodes, we directly compared three methods previously used to track DC migration: airway administration of fluorescent OVA, latex beads, or carboxyfluorescein succinimidyl ester (CFSE). We show that two of the methods employed in optimal conditions-administration of fluorescent OVA or latex particles-have broadly relevant utility in studies of pulmonary DC migration, both in the presence and absence of inflammatory mediators. However, CFSE was of limited value because it induced a robust airway inflammatory response upon instillation. Unexpectedly, antigen-loaded tracers with distinct physical properties differently affected the populations that acquired the tracers and the overall T cell response. Specifically, soluble OVA and OVA formulated as a particulate after conjugation to latex beads were acquired in different proportions in vivo by the two characterized subsets of pulmonary DCs: CD11b(hi)CD103(-) and CD11b(lo)CD103(+)langerin(+) DC populations. Consequently, and in line with recent studies that these two subsets of DCs respectively activate CD4(+) and CD8(+) lymphocyte populations, the physical nature of the antigen delivery vehicle strongly influenced the degree of CD4(+) versus CD8(+) OVA-specific T cell activation. This finding suggests that changes in the physical presentation of the same antigen delivered to the airway during natural immune responses or vaccinations may markedly affect the character of the T cell response that ensues.

Dietary fat and meat as potential risk factors for prostate cancer have been the focus of many epidemiologic investigations, and findings from recent studies in particular have been inconsistent. Therefore, we examined the association between these exposures and prostate cancer risk in the Multiethnic Cohort Study. The analyses included 82,483 men in Hawaii and Los Angeles aged>>or=45, who completed a detailed quantitative food frequency questionnaire in 1993-1996. During the follow-up period of 8 years, a total of 4,404 incident cases, including 1,278 nonlocalized or high-grade cancer cases, were identified. Cox proportional hazard models were used to estimate relative risks of prostate cancer after adjustment for time on study, ethnicity, family history of prostate cancer, education, body mass index, smoking status and energy intake. Intake of different types of fat (total, saturated, monounsaturated or polyunsaturated), n-6 fatty acid, cholesterol, various meats, and fats from meat showed no association with overall prostate cancer risk or with nonlocalized or high-grade prostate cancer. Furthermore, we found little evidence of any relation of fat and meat intake with prostate cancer risk within any of the 4 racial/ethnic groups (African Americans, Japanese Americans, Latinos and Whites). There was a suggestion of a protective effect of n-3 fatty acid intake that was limited to Latinos and Whites. However, overall, our findings from a large cohort study of ethnically diverse population give no indication that intake of fat and meat substantially affects prostate cancer risk.

BACKGROUND

Adiponectin is a hormone secreted by adipocytes that acts as an antidiabetic adipokine. Adiponectin exists as multimers in plasma, and high molecular weight (HMW) adiponectin is particularly thought to be the active form of the protein.

OBJECTIVE

The aim of the study was to assess whether decreased total and HMW adiponectin are independent risk factors for the development of type 2 diabetes.

METHODS

Study subjects were Japanese-Americans enrolled in the Hawaii-Los Angeles-Hiroshima study between 1992 and 2002. Duration of follow-up was an average of 5.4 yr.

METHODS

We investigated 321 men and 445 women who were nondiabetic Japanese-Americans. Glucose tolerance was evaluated according to 1997 American Diabetes Association criteria, and 112 subjects developed type 2 diabetes during the follow-up period.

METHODS

The influence of baseline total and HMW adiponectin on the development of type 2 diabetes was the main outcome measure.

RESULTS

Subjects who developed type 2 diabetes had significantly decreased plasma total and HMW adiponectin compared with those who did not develop the disease (P < 0.001, respectively). In a Cox proportional hazards model, both decreased total and HMW adiponectin levels were independent risk factors for the progression to type 2 diabetes after adjusting for sex, age, body mass index, waist-to-hip ratio, homeostasis model assessment, and classification of 75-g glucose tolerance test (hazards ratio: total, 0.600, P = 0.018; HMW, 0.614, P = 0.001, respectively). Dividing tertiles of adiponectin, hazards ratios in the lowest vs. highest tertile were total, 1.787 (95% confidence interval, 1.006-3.173); and HMW, 2.493 (95% confidence interval, 1.342-4.632), after similar adjustments.

CONCLUSIONS

Decreased total adiponectin is an independent risk factor for the progression to type 2 diabetes in Japanese-Americans. Moreover, HMW adiponectin more closely associates with the progression to type 2 diabetes when compared with total adiponectin.

BACKGROUND

Substantial subgroups of American women, specifically those of ethnic minorities, have not been screened for cervical cancer or are not screened at regular intervals. The rates for receipt of female-related cancer screening tests remain far below the goals set forth in Healthy People 2010.

OBJECTIVE

This study applied a well-known, recently revised theoretical model of health care access and utilization, the Behavioral Model for Vulnerable Populations, to examine the correlates of the adherence to cervical cancer screening guidelines among publicly housed Hispanic and African-American women, two of the most vulnerable segments of our population.

METHODS

This study conducted a cross-sectional survey of a community-based random sample of 230 African-American and Latino female heads of household, from a geographically defined area, the three urban public housing communities in Los Angeles County, CA.

RESULTS

Only 62% of our sample had received a screening for cervical cancer within the past year. Yet, 29% of the sample claimed that no health care provider had ever told them that they needed a screening test for cervical cancer. Hispanic and older women are by far less likely to adhere to screening guidelines; in this study, 51% of Hispanics and 22% of African-Americans reported no screening within the last year. Multivariate analysis shows that affordability, continuity of care, and receiving advice from health care providers regarding a Papanicolaou (Pap) smear were significant predictors of up-to-date to cervical cancer screening.

CONCLUSIONS

This study documents a significant disparity in screening for cervical cancer among underserved minorities, particularly Hispanic, uninsured, and older women. The continuity of obtaining medical services and receiving recommendations from physicians remain the core factors that are significantly associated with obtaining cervical cancer screening. These results underscore the need for continued efforts to ensure that medically underserved minority women have access to cancer screening services.

OBJECTIVE

To assess the production mechanism of anti-GQ1b autoantibody in Fisher syndrome (FS).

METHODS

The authors conducted a prospective case-control serologic study of five antecedent infections (Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and Haemophilus influenzae) in 73 patients with FS and 73 sex- and age-matched hospital controls (HCs). Serologic evidence in FS patients of C. jejuni (21%) and H. influenzae (8%) infections was present significantly more often than in the HCs. None of the five pathogens examined was found in the 49 (67%) patients with FS. Anti-GQ1b IgG antibody was detected in most FS patients infected with C. jejuni or H. influenzae. Mass spectrometry analysis identified a C. jejuni strain (CF93-6) carrying a GT1a-like lipo-oligosaccharide (LOS) that had been isolated from an FS patient. Immunization of complex ganglioside-lacking knockout mice with the GT1a-like LOS generated IgG class monoclonal antibodies (mAbs) that reacted with GQ1b and GT1a. Thin-layer chromatography with immunostaining showed that anti-GQ1b mAb bound to the C. jejuni LOS (50% of the 20 FS-related strains) more commonly than in the Guillain-Barré syndrome (GBS)-related (7% of 70) or enteritis-related (20% of 65) strains. Anti-GM1 and anti-GD1a mAbs also reacted with the LOS from some FS-related strains (both 20%), but binding frequencies were higher in the GBS-related strains (74 and 57%). The GQ1b epitope was detected in 4 (40%) of the 10 FS-related H. influenzae strains but was absent in strains from patients with GBS (n = 4) and uncomplicated respiratory infections (n = 10).

CONCLUSIONS

C. jejuni and H. influenzae are related to Fisher syndrome (FS) development, and production of anti-GQ1b autoantibody is mediated by the GQ1b-mimicking lipo-oligosaccharides on those bacteria. The causative agents remain unclear in the majority of patients with FS.

OBJECTIVE

To examine the relationship between acculturation and five health practices, including cigarette smoking, alcohol consumption, exercise, obesity, and sleeping habits.

METHODS

The study sample consisted of 573 Latinas, aged 46 to 92 years. Participants were recruited from 17 publicly subsidized housing projects in Los Angeles, Calif. Health practices information was obtained through an interview.

RESULTS

Regression analyses showed an interaction between age and acculturation: the effects of acculturation on health practices were stronger among Latinas aged 64 years and under than among their 65 to 74 year-old counterparts. Level of acculturation did not affect the likelihood of engaging in healthy practices for elderly women (aged 75 and over).

CONCLUSIONS

The data indicate that acculturation negatively affects the health practices of middle-aged Latinas, who are at a particularly critical age during which chronic diseases emerge. Intervention programs are needed to encourage adoption of healthy practices, particularly exercise and weight control, at an earlier stage in life.

This study concerns the metabolism of inorganic arsenic (As) in children in three villages in northern Argentina: San Antonio de los Cobres and Taco Pozo, each with about 200 microg As/l in the drinking water, and Rosario de Lerma, with 0.65 microg As/l. Findings show that the concentrations of As in the blood and urine of the children in the two As-rich villages were on average 9 and 380 microg/l, respectively, the highest ever recorded for children. The concentrations were about 10 and 30 times higher for blood and urine, respectively, than in Rosario de Lerma. Total As in urine was only slightly higher than the sum of metabolites of inorganic As (U-Asmet), i.e., inorganic As, methylarsonic acid (MMA), and dimethylarsinic acid (DMA); this shows that inorganic As was the main form of As ingested. In contrast to previous studies on urinary metabolites of inorganic As in various population groups, the children and women in the present study excreted very little MMA. Thus, there seems to be a polymorphism for the enzymes (methyltransferases) involved in the methylation of As. Interestingly, the children had a significantly higher percentage of inorganic As in urine than the women, about 50% versus 32%. Also, the percentage of inorganic As in the children is considerably higher than in previous studies on children (about 13% in the two studies available) and adults (about 15-25%) in other population groups. This may indicate that children are more sensitive to As-induced toxicity than adults, as the methylated metabolites bind less to tissue constituents than inorganic As. In the children, the percentage inorganic arsenic in urine decreased, and the percentage of DMA increased with increasing U-Asmet, indicating an induction of As methylation with increasing exposure.

Information on 23,567 Non-Hispanic White, 2,539 Black, and 2,380 Hispanic breast cancer cases diagnosed between 1977 and 1985 was used to evaluate the risk of late stage diagnosis and long duration of symptoms prior to diagnosis in relation to ethnicity, socioeconomic status, age and year of diagnosis. All data were collected by the University of Southern California Cancer Surveillance Program, the comprehensive population-based incidence registry of Los Angeles County. The results indicate that lower socioeconomic status, Black or Hispanic ethnicity, younger age, and earlier year of diagnosis are risk factors for late stage diagnosis and long duration of symptoms. The effect of ethnicity was not explained by lower SES levels among Black or Hispanic women. After controlling for duration of symptoms, race and SES remained significantly predictive of more advanced stage. More recent diagnosis across the 9 year time frame was not associated with improved stage for those of low SES. These results suggest that increased efforts are needed to reach low SES and Black and Hispanic women with campaigns to improve the stage at which breast cancer is detected.

BACKGROUND

Clostridium difficile colitis is the predominant hospital-acquired gastrointestinal infection in the United States and has emerged as an important nosocomial cause of morbidity and death. Although several institutional studies have examined the effects of C. difficile on hospitalized patients, its nationwide impact on surgical patients has yet to be defined.

METHODS

To provide a national estimate of the burden of C. difficile, we performed a five-year retrospective analysis of the Agency for Healthcare Research and Quality's National Inpatient Sample Database, which represents a stratified 20% sample of hospitals in the United States, from 1999 to 2003. All surgical inpatient discharge data from 997 hospitals in 37 states were analyzed to determine the association of C. difficile infections with patient demographics, hospital characteristics, surgical procedure, length of stay (LOS), total charges, and in-hospital mortality rate. Univariate analysis was performed to identify any association between the presence of C. difficile infection and the outcome variables using chi-square contingency table analysis or the Student t-test following the exclusion of patients with other medical complications. Multivariate regression analysis was used to determine whether the presence of C. difficile infection was an independent predictor of increased LOS, total charges, and in-hospital mortality rate when controlling for surgery type, age, sex, payor, and hospital characteristics.

RESULTS

Clostridium difficile infection was reported as a discharge diagnosis for 8,113 (0.52%) of all 1,553,597 inpatients who had undergone a general surgical procedure. The incidence increased significantly in 2002 (34% higher than in 2001; p < 0.0001). The following patient and hospital characteristics were associated with the highest incidence of C. difficile infection (all p < 0.0001): Age>> 64 years (0.95%); Medicare beneficiary status (0.94%); north-eastern hospital location (0.73%); and large (0.55%), urban (0.56%), or teaching hospital (0.61%). Patients undergoing an emergency operation were at higher risk than those having operations performed electively (0.8% vs. 0.3%; p < 0.0001). Colectomy, small-bowel resection, and gastric resection were associated with the highest risk of C. difficile infection (incidence after colectomy 1.11%; odds ratio [OR] 2.77, 95% confidence interval [CI] 2.65, 2.89, p < 0.0001; small-bowel resection 1.17%, OR 2.40, 95% CI 2.26, 2.54, p < 0.0001; gastric resection 1.02%, OR 2.26, 95% CI 2.03, 2.52, p < 0.0001). Patients undergoing cholecystectomy and appendectomy had the lowest risk of C. difficile infection (cholecystectomy 0.41%, OR 0.37, 95% CI 0.35, 0.39, p < 0.0001; appendectomy 0.20%, OR 0.45, 95% CI 0.42, 0.49, p < 0.0001). Multivariable analysis demonstrated that C. difficile was an independent predictor of LOS, which increased by 16.0 days (95% CI 15.6, 16.4 days; p < 0.0001) in the presence of infection. Total charges increased by $77,483 (95% CI $75,174, $79,793; p < 0.0001), and there was a 3.4-fold increase in the mortality rate (95% CI 3.02, 3.77; p < 0.0001) compared with patients who did not acquire C. difficile.

CONCLUSIONS

Epidemiologic data suggest that the incidence of C. difficile infection is increasing in U.S. surgical patients and that the infection is most prevalent after emergency operations and among patients having intestinal tract resections. Infection with C. difficile is an independent predictor of increased LOS, total charges, and mortality rate after surgery and represents a considerable burden to both patients and hospitals. Preventing C. difficile infection offers a potentially significant improvement in patient outcomes, as well as a reduction in hospital costs and resource expenditures.

Obesity has been associated with an increased risk of postmenopausal breast cancer. Adipokines and systemic inflammation have been hypothesized to underlie this association. In a case-control study nested within the Multiethnic Cohort, conditional logistic regression was used to calculate the ORs and 95% confidence intervals (CI) for postmenopausal breast cancer associated with prediagnostic levels of serum leptin, adiponectin, the leptin:adiponectin ratio, and C-reactive protein (CRP). The 706 cases and 706 controls were matched on ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, hours fasting before blood draw, and hormone replacement therapy use at blood draw. Higher circulating levels of leptin [ORQ4 vs. Q1, 1.94 (1.37-2.75); Ptrend ≤ 0.001), the leptin:adiponectin ratio [OR, 1.91 (1.36-2.68); Ptrend = 0.005], and CRP [OR, 1.41 (1.01-1.96); Ptrend = 0.014] were associated with an increased risk of postmenopausal breast cancer. The positive associations for these markers remained after adjustment for body mass index (BMI). No associations were detected for adiponectin. These data suggest that adipokines and systemic inflammation may be associated with the risk of postmenopausal breast cancer independently of BMI. Further prospective studies examining the role of adipokines and inflammatory processes in the etiology of postmenopausal breast cancer are warranted. Cancer Prev Res; 6(3); 188-95. ©2013 AACR.

The BODE index, which integrates body mass index, airflow limitation (forced expiratory volume in one second), dyspnoea and 6-min walk distance, predicts mortality in chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves some components of BODE. It was hypothesised that changes in BODE may reflect the effects of PR. To test this, participation in PR was offered to 246 patients (BODE quartiles 2-4). The patients were divided as follows: no PR (130 who declined rehabilitation or who dropped out from PR), and PR (116 who completed PR). BODE was determined at entry, after PR, and at 1 and 2 yrs. Other outcomes were: length of stay (LOS) for respiratory-related hospitalisations and mortality. At entry, the two groups had similar age and comorbidity but different BODE. After PR, the BODE improved by 19% and returned to baseline after 2 yrs. The BODE worsened in the no PR group by 4% at 12 months and 18% at 2 yrs. Respiratory mortality at 2 yrs for PR was 7%, compared with 39% for no PR. LOS at 1 yr for COPD decreased 20% in PR, while it increased 25% in no PR. In conclusion, pulmonary rehabilitation participation improves BODE and is associated with better outcomes. The BODE index change after pulmonary rehabilitation provides valuable prognostic information.

We used functional magnetic resonance imaging (fMRI) to demonstrate the existence of a mechanism in the human lateral occipital (LO) cortex that supports recognition of real-world visual scenes through parallel analysis of within-scene objects. Neural activity was recorded while subjects viewed four categories of scenes and eight categories of 'signature' objects strongly associated with the scenes in three experiments. Multivoxel patterns evoked by scenes in the LO cortex were well predicted by the average of the patterns elicited by their signature objects. By contrast, there was no relationship between scene and object patterns in the parahippocampal place area (PPA), even though this region responds strongly to scenes and is believed to be crucial for scene identification. By combining information about multiple objects within a scene, the LO cortex may support an object-based channel for scene recognition that complements the processing of global scene properties in the PPA.

BACKGROUND

Major teaching hospitals are perceived as being more expensive than other hospitals and, thus, unattractive to managed care. However, little empirical data exist about their relative quality and efficiency. The current study compared severity-adjusted mortality and length of stay (LOS) in teaching and nonteaching hospitals.

METHODS

Retrospective cohort study.

METHODS

Thirty hospitals in northeast Ohio.

METHODS

A total of 89851 consecutive eligible patients discharged in 1991 through 1993 with myocardial infarction, congestive heart failure, obstructive airway disease, gastrointestinal hemorrhage, pneumonia, or stroke.

METHODS

In-hospital mortality and LOS of patients in major teaching (n=5), minor teaching (n=6), and nonteaching (n=19) hospitals were adjusted for admission severity of illness using multivariable models based on demographic and clinical data abstracted from patients' medical records.

RESULTS

The adjusted odds of death was 19% lower (95% confidence interval [CI], 2%-34%; P=.03) for patients in major teaching hospitals compared with non-teaching hospitals but was similar (95% CI, 7% lower to 28% higher; P=.28) for patients in minor teaching hospitals. The findings were generally consistent in analyses stratified according to diagnosis, age, race, predicted risk of death, and other covariates. In addition, risk-adjusted LOS was 9% lower (95% CI, 8%-10%; P<.001) among patients in major teaching hospitals relative to nonteaching hospitals but was similar (95% CI, 2% lower to 11% higher; P=.17) in minor teaching hospitals. Major teaching hospitals also cared for higher proportions of nonwhite and poorly insured patients.

CONCLUSIONS

Risk-adjusted mortality and LOS were lower for patients in major teaching hospitals than for patients in minor teaching and nonteaching hospitals. If generalizable to other regions, the results provide evidence that hospital performance, as assessed by 2 commonly used indicators, may be higher in major teaching hospitals. These findings are noteworthy at a time when the viability of many major teaching hospitals is threatened by powerful health care market forces and by potential changes in federal financing of graduate medical education.

OBJECTIVE

To evaluate Latina breast cancer patient perspectives regarding informed decision making related to surgical treatment decision making for breast cancer.

METHODS

2030 women with non-metastatic breast cancer diagnosed from 8/05 to 5/06 and reported to the Los Angeles metropolitan SEER registries were mailed a survey shortly after surgical treatment. Latina and African-American women were over-sampled. We conducted regression of four decision outcome to evaluate associations between race/ethnicity, demographic and clinical factors, and mechanistic variables (i.e., health literacy) and decision outcomes.

RESULTS

Our analytic sample was 877 women: 24.5% Latina-Spanish speaking (Latina-SP), 20.5% Latina-English speaking, 24% African-American and 26.6% Caucasian. Approximately 28% of women in each ethnic group reported a surgeon-based, 36% a shared, and 36% a patient-based surgery decision. Spanish-preferent Latina women had the greatest odds of high decision dissatisfaction and regret controlling for other factors (OR 5.5, 95% CI: 2.9, 10.5 and OR 4.1, 95% CI: 2.2, 8.0, respectively). Low health literacy was independently associated with dissatisfaction and regret (OR 5.6, 95% CI: 2.9, 11.1 and OR 3.5, 95% CI 1.8, 7.1, respectively) and slightly attenuated associations between Latina-SP ethnicity and decision outcomes.

CONCLUSIONS

Despite similar clinical outcomes, patients report very different experiences with treatment decision making. Latina women, especially those who prefer Spanish, are vulnerable to poor breast cancer treatment decision outcomes.

CONCLUSIONS

Providers need to be aware of the role of ethnicity, acculturation and literacy in breast cancer treatment discussions.

Immunization by intramuscular injection of plasmid DNA expressing mycobacterial 65-kDa heat shock protein (hsp65) protects mice against challenge with virulent Mycobacterium tuberculosis H37Rv. During infection or after immunization, CD4+/CD8- and CD8+/CD4- hsp65-reactive T cells increased equally in spleens. During infection, the majority of these cells were weakly CD44 positive (CD44(lo)) and produced interleukin 4 (IL-4) whereas after immunization the majority were highly CD44 positive (CD44(hi)) and produced gamma interferon (IFN-gamma). In adoptive transfer of protection to naive mice, the total CD8+/CD4- cell population purified from spleens of immunized mice was more protective than that from infected mice. When the cells were separated into CD4+/CD8- and CD8+/CD4- types and then into CD44(hi) and CD44(lo) types, CD44(lo) cells were essentially unable to transfer protection, the most protective CD44(hi) cells were CD8+/CD4-, and those from immunized mice were much more protective than those from infected mice. Thus, whereas the CD44(lo) IL-4-producing phenotype prevailed during infection, protection was associated with the CD8+/CD44(hi) IFN-gamma-producing phenotype that predominated after immunization. This conclusion was confirmed and extended by analysis of 16 hsp65-reactive T-cell clones from infected mice and 16 from immunized mice; the most protective clones, in addition, displayed antigen-specific cytotoxicity.

Leukotrienes (LT) are a group of proinflammatory lipid mediators that are implicated in the pathogenesis and progression of atherosclerosis. Here we report that mRNA levels for the three key proteins in LTB4 biosynthesis, namely 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTA4 hydrolase (LTA4H), are significantly increased in human atherosclerotic plaque (n = 72) as compared with healthy controls (n = 6). Neither LTC4 synthase nor any of the LT receptors exhibits significantly increased mRNA levels. Immunohistochemical staining revealed abundant expression of 5-LO, FLAP, and LTA4H protein, colocalizing in macrophages of intimal lesions. Human lesion tissue converts arachidonic acid into significant amounts of LTB4, and a selective, tight-binding LTA4H inhibitor can block this activity. Furthermore, expression of 5-LO and LTA4H, but not FLAP, is increased in patients with recent or ongoing symptoms of plaque instability, and medication with warfarin correlates with increased levels of FLAP mRNA. In contrast to human plaques, levels of 5-LO mRNA are not significantly increased in plaque tissues from two atherosclerosis-prone mouse strains, and mouse plaques exhibit segregated cellular expression of LTA4H and 5-LO as well as strong increases of CysLT1 and CysLT2 mRNA. These discrepancies indicate that phenotypic changes in the synthesis and action of LT in specific mouse models of atherosclerosis should be cautiously translated into human pathology. The abundant expression of LTA4H and correlation with plaque instability identify LTA4H as a potential target for pharmacological intervention in treatment of human atherosclerosis.

Transcriptional pathways controlling the development of CD44(hi) memory phenotype (MP) T cells with "innate-like" functions are not well understood. Here we show that the BTB (bric-a-brac, tramtrack, broad complex) domain-containing protein promyelocytic leukemia zinc finger (PLZF) is expressed in CD44(hi), but not in CD44(lo), CD4(+) T cells. Transgenic expression of PLZF during T cell development and in CD4(+) and CD8(+) T cells induced a T cell intrinsic program leading to an increase in peripheral CD44(hi) MP CD4(+) and CD8(+) T cells and a corresponding decrease of naïve CD44(lo) T cells. The MP CD4(+) and CD8(+) T cells produced IFNgamma upon PMA/ionomycin stimulation, thus showing innate-like function. Changes in the naïve versus memory-like subset distribution were already evident in single-positive thymocytes, indicating PLZF-induced T cell developmental alterations. In addition, CD1d-restricted natural killer T cells in PLZF transgenic mice showed impaired development and were severely reduced in the periphery. Finally, after anti-CD3/CD28 stimulation, CD4(+) transgenic T cells showed reduced IL-2 and IFNgamma production but increased IL-4 secretion as a result of enhanced IL-4 production of the CD44(hi)CD62L(+) subset. Our data indicate that PLZF is a novel regulator of the development of CD44(hi) MP T cells with a characteristic partial innate-like phenotype.

Intra-neuronal metabolism of dopamine (DA) begins with production of 3,4-dihydroxyphenylacetaldehyde (DOPAL),which is toxic. According to the 'catecholaldehyde hypothesis', DOPAL destroys nigrostriatal DA terminals and contributes to the profound putamen DA deficiency that characterizes Parkinson’s disease (PD). We tested the feasibility of using post-mortem patterns of putamen tissue catechols to examine contributions of altered activities of the type 2 vesicular monoamine transporter (VMAT2) and aldehyde dehydrogenase(ALDH) to the increased DOPAL levels found in PD. Theoretically, the DA : DOPA concentration ratio indicates vesicular uptake, and the 3,4-dihydroxyphenylacetic acid: DOPAL ratio indicates ALDH activity. We validated these indices in transgenic mice with very low vesicular uptake VMAT2-Lo) or with knockouts of the genes encoding ALDH1A1 and ALDH2 (ALDH1A1,2 KO), applied these indices in PD putamen, and estimated the percent decreases in vesicular uptake and ALDH activity in PD. VMAT2-Lo mice had markedly decreased DA:DOPA (50 vs. 1377, p < 0.0001),and ALDH1A1,2 KO mice had decreased 3,4-dihydroxyphenylacetic acid:DOPAL (1.0 vs. 11.2, p < 0.0001). In PD putamen, vesicular uptake was estimated to be decreased by 89% and ALDH activity by 70%. Elevated DOPAL levels in PD putamen reflect a combination of decreased vesicular uptake of cytosolic DA and decreased DOPAL detoxification by ALDH.

This study evaluates associations between online social networking and sexual health behaviors among homeless youth in Los Angeles. We analyzed survey data from 201 homeless youth accessing services at a Los Angeles agency. Multivariate (regression and logistic) models assessed whether use of (and topics discussed on) online social networking technologies affect HIV knowledge, sexual risk behaviors, and testing for sexually transmitted infections (STIs). One set of results suggests that using online social networks for partner seeking (compared to not using the networks for seeking partners) is associated with increased sexual risk behaviors. Supporting data suggest that (1) using online social networks to talk about safe sex is associated with an increased likelihood of having met a recent sex partner online, and (2) having online sex partners and talking to friends on online social networks about drugs and partying is associated with increased exchange sex. However, results also suggest that online social network usage is associated with increased knowledge and HIV/STI prevention among homeless youth: (1) using online social networks to talk about love and safe sex is associated with increased knowledge about HIV, (2) using the networks to talk about love is associated with decreased exchange sex, and (3) merely being a member of an online social network is associated with increased likelihood of having previously tested for STIs. Taken together, this study suggests that online social networking and the topics discussed on these networks can potentially increase and decrease sexual risk behaviors depending on how the networks are used. Developing sexual health services and interventions on online social networks could reduce sexual risk behaviors.

Inclusion of phenacetin among 'proven' human carcinogens by the IARC in 1987, raised concerns about the carcinogenic potential of acetaminophen, its major metabolite. Acetaminophen has been implicated as a possible causal agent in the development of cancer of the renal pelvis. The bladder and renal pelvis, which derive from the same embryological structure, share the same transitional type of epithelium. Past studies have been inconclusive on the possible relationship among these analgesics and bladder cancer but no large, highly detailed study of this association has been conducted. A population-based case-control study conducted in Los Angeles, California, involved 1514 incident bladder cancer cases and an equal number of controls who were matched to the index cases by sex, date of birth (within 5 years) and race. Detailed information on medication use and prior medical conditions was collected through in-person interviews. Regular use of analgesics was not associated with an increased risk of bladder cancer in either men or women. In fact, compared with non- or irregular users, regular analgesic users were at a decreased risk of bladder cancer overall (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68-0.96). However, there were clear differences in both the direction and strength of the associations between the different formulation classes of analgesics and bladder cancer risk. Intake of phenacetin was positively related to bladder cancer risk in a dose-dependent manner while intake of its major metabolite in humans, acetaminophen, was unrelated to risk. Intake of all classes of NSAIDs, except pyrazolon derivatives, were negatively associated with bladder cancer risk, with suggestive evidence that the protective effect varies in strength by subcategories of formulation. Acetic acids seemed to exhibit the strongest protective effect, whereas aspirin/other salicylic acids and oxicam showed the weakest protection.

BACKGROUND

Enhanced recovery after surgery (ERAS) is a multimodal approach to perioperative care that combines a range of interventions to enable early mobilization and feeding after surgery. We investigated the feasibility, clinical effectiveness, and cost savings of an ERAS program at a major U. S. teaching hospital.

METHODS

Data were collected from consecutive patients undergoing open or laparoscopic colorectal surgery during 2 time periods, before and after implementation of an ERAS protocol. Data collected included patient demographics, operative, and perioperative surgical and anesthesia data, need for analgesics, complications, inpatient medical costs, and 30-day readmission rates.

RESULTS

There were 99 patients in the traditional care group, and 142 in the ERAS group. The median length of stay (LOS) was 5 days in the ERAS group compared with 7 days in the traditional group (P < 0.001). The reduction in LOS was significant for both open procedures (median 6 vs 7 days, P = 0.01), and laparoscopic procedures (4 vs 6 days, P < 0.0001). ERAS patients had fewer urinary tract infections (13% vs 24%, P = 0.03). Readmission rates were lower in ERAS patients (9.8% vs 20.2%, P = 0.02).

CONCLUSIONS

Implementation of an enhanced recovery protocol for colorectal surgery at a tertiary medical center was associated with a significantly reduced LOS and incidence of urinary tract infection. This is consistent with that of other studies in the literature and suggests that enhanced recovery programs could be implemented successfully and should be considered in U.S. hospitals.

BACKGROUND

Since pulmonary artery balloon flotation catheterization was first introduced in 1970, by HJ Swan and W Ganz, it has been widely disseminated as a diagnostic tool without rigorous evaluation of its clinical utility and effectiveness in critically ill patients. A pulmonary artery catheter (PAC) is inserted through a central venous access into the right side of the heart and floated into the pulmonary artery. PAC is used to measure stroke volume, cardiac output, mixed venous oxygen saturation and intracardiac pressures with a variety of additional calculated variables to guide diagnosis and treatment. Complications of the procedure are mainly related to line insertion. Relatively uncommon complications include cardiac arrhythmias, pulmonary haemorrhage and infarct, and associated mortality from balloon tip rupture.

OBJECTIVE

To provide an up-to-date assessment of the effectiveness of a PAC on mortality, length of stay (LOS) in intensive care unit (ICU) and hospital and cost of care in adult intensive care patients.

METHODS

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 12); MEDLINE (1954 to January 2012); EMBASE (1980 to January 2012); CINAHL (1982 to January 2012), and reference lists of articles. We contacted researchers in the field. We did a grey literature search for articles published until January 2012.

METHODS

We included all randomized controlled trials conducted in adults ICUs, comparing management with and without a PAC.

METHODS

We screened the titles and abstracts and then the full text reports identified from our electronic search. Two authors (SR and MG) independently reviewed the titles, abstracts and then the full text reports for inclusion. We determined the final list of included studies by discussion among the group members (SR, ND, MG, AK and SC) with consensus agreement. We included all the studies that were in the original review. We assessed seven domains of potential risk of bias for the included studies. We examined the clinical, methodological and statistical heterogeneity and used random-effects model for meta-analysis. We calculated risk ratio for mortality across studies and mean days for LOS.

RESULTS

We included 13 studies (5686 patients). We judged blinding of participants and personnel and blinding of outcome assessment to be at high risk in about 50% of the included studies and at low risk in 25% to 30% of the studies. Regardless of the high risk of performance bias these studies were included based on the low weight the studies had in the meta-analysis. We rated 75% of the studies as low risk for selection, attrition and reporting bias. All 13 studies reported some type of hospital mortality (28-day, 30-day, 60-day or ICU mortality). We considered studies of high-risk surgery patients (eight studies) and general intensive care patients (five studies) separately as subgroups for meta-analysis. The pooled risk ratio (RR) for mortality for the studies of general intensive care patients was 1.02 (95% confidence interval (CI) 0.96 to 1.09) and for the studies of high-risk surgery patients the RR was 0.98 (95% CI 0.74 to 1.29). Of the eight studies of high-risk surgery patients, five evaluated the effectiveness of pre-operative optimization but there was no difference in mortality when these studies were examined separately. PAC did not affect general ICU LOS (reported by four studies) or hospital LOS (reported by nine studies). Four studies, conducted in the United States (US), reported costs based on hospital charges billed, which on average were higher in the PAC groups. Two of these studies qualified for analysis and did not show a statistically significant hospital cost difference (mean difference USD 900, 95% CI -2620 to 4420, P = 0.62).

CONCLUSIONS

PAC is a diagnostic and haemodynamic monitoring tool but not a therapeutic intervention. Our review concluded that use of a PAC did not alter the mortality, general ICU or hospital LOS, or cost for adult patients in intensive care. The quality of evidence was high for mortality and LOS but low for cost analysis. Efficacy studies are needed to determine if there are optimal PAC-guided management protocols, which when applied to specific patient groups in ICUs could result in benefits such as shock reversal, improved organ function and less vasopressor use. Newer, less-invasive haemodynamic monitoring tools need to be validated against PAC prior to clinical use in critically ill patients.

Processing of binocular disparity is thought to be widespread throughout cortex, highlighting its importance for perception and action. Yet the computations and functional roles underlying this activity across areas remain largely unknown. Here, we trace the neural representations mediating depth perception across human brain areas using multivariate analysis methods and high-resolution imaging. Presenting disparity-defined planes, we determine functional magnetic resonance imaging (fMRI) selectivity to near versus far depth positions. First, we test the perceptual relevance of this selectivity, comparing the pattern-based decoding of fMRI responses evoked by random dot stereograms that support depth perception (correlated RDS) with the decoding of stimuli containing disparities to which the perceptual system is blind (anticorrelated RDS). Preferential disparity selectivity for correlated stimuli in dorsal (visual and parietal) areas and higher ventral area LO (lateral occipital area) suggests encoding of perceptually relevant information, in contrast to early (V1, V2) and intermediate ventral (V3v, V4) visual cortical areas that show similar selectivity for both correlated and anticorrelated stimuli. Second, manipulating disparity parametrically, we show that dorsal areas encode the metric disparity structure of the viewed stimuli (i.e., disparity magnitude), whereas ventral area LO appears to represent depth position in a categorical manner (i.e., disparity sign). Our findings suggest that activity in both visual streams is commensurate with the use of disparity for depth perception but the neural computations may differ. Intriguingly, perceptually relevant responses in the dorsal stream are tuned to disparity content and emerge at a comparatively earlier stage than categorical representations for depth position in the ventral stream.

OBJECTIVE

The rapid increase in obesity over the past two decades suggests that behavioral and environmental influences, including poor nutrition and physical inactivity, are fueling what is now widely recognized as a public health crisis. Yet, limited research has been conducted to examine how environmental factors, such as neighborhood-level characteristics, may be associated with increased risk for obesity.

METHODS

Community-level risk associated with childhood obesity was examined in East Los Angeles, a community with one of the highest rates of childhood obesity in Los Angeles by triangulating: 1) spatial data for the number and location of food establishments relative to the location of schools; 2) observations regarding the availability and quality of fruits and vegetables in local grocery stores; and 3) observations regarding the quality and utilization of local parks.

RESULTS

The findings revealed that there were 190 food outlets in the study community, of which 93 (49%) were fast-food restaurants. Of the fast-food restaurants, 63% were within walking distance of a school. In contrast, there were 62 grocery stores, of which only 18% sold fresh fruits and/or vegetables of good quality. Of the stores that did sell fruits and/or vegetables, only four were within walking distance of a school. Although well maintained, the five parks in this community accounted for only 37.28 acres, or 0.543 acres per 1000 residents.

CONCLUSIONS

These findings suggest that children have easy access to fast food, and limited access to both healthy food options and parks in which to engage in physical fitness activities. This was particularly true in areas around schools. The implications for these findings with regards to policy-related prevention and future research are discussed.