Several functional areas are proposed to reside in human lateral occipitotemporal cortex, including the motion-selective human homolog of macaque area MT (hMT), object-form-selective lateral occipital complex (LO), and body-selective extrastriate body area (EBA). Indeed, several functional magnetic resonance imaging (fMRI) studies have reported significant activation overlap among these regions. The standard interpretation of this overlap would be that the common areas of activation reflect engagement of common neural systems. Alternatively, motion, object form, and body form may be processed independently within this general region. To distinguish these possibilities, we first analyzed the lateral occipitotemporal responses to motion, objects, bodies, and body parts with whole-brain group-average analyses and within-subjects functional region of interest (ROI) analyses. The activations elicited by these stimuli, each relative to a matched control, overlapped substantially in the group analysis. When hMT, LO, and EBA were defined functionally within subjects, each ROI in each hemisphere (except right-hemisphere hMT) showed significant selectivity for motion, intact objects, bodies, and body parts, although only the peak voxel of each region was tested. In contrast, multi-voxel analyses of variations in selectivity patterns revealed that visual motion, object form, and the form of the human body elicited three relatively independent patterns of fMRI activity in lateral occipitotemporal cortex. Multi-voxel approaches, in contrast to other methods, can reveal the functional significance of overlapping fMRI activity in extrastriate cortex and, by extension, elsewhere in the brain.

BACKGROUND

Since the recognition that human immunodeficiency virus is transmissible by blood transfusion there has been increasing public and professional support for autologous blood donations before elective surgery. Autologous blood donation is, however, a more expensive process than the donation of allogeneic blood by community volunteers. Furthermore, there have been recent improvements in the safety of the volunteer blood supply.

METHODS

We used a decision-analysis model to assess the cost effectiveness of donating autologous blood for four surgical procedures. Cost data were collected from the observation of transfusion practice at the University of California, Los Angeles, in 1992. Estimates of the risks of transfusion-associated diseases and the costs of treating them came from the medical literature. Cost effectiveness was expressed in dollars per quality-adjusted year of life saved. We performed sensitivity analyses of the variables in our model and examined the effect of strategies suggested to reduce costs.

RESULTS

Substituting autologous for allogeneic blood resulted in little expected health benefit (0.0002 to 0.00044 quality-adjusted year of life saved) at considerable additional cost ($68 to $4,783 per unit of blood). The additional cost of autologous blood was primarily a function of the discarding of units that were donated but not transfused and of a more labor-intensive donation process. The cost-effectiveness ratios ranged from $235,000 to over $23 million per quality-adjusted year of life saved.

CONCLUSIONS

Given the improved safety of allogeneic transfusions today, the increased protection afforded by donating autologous blood is limited and may not justify the increased cost.

Many tumor cells are fueled by altered metabolism and increased glutamine (Gln) dependence. We identify regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2) by the ubiquitin ligase RNF5. Paclitaxel-induced ER stress to breast cancer (BCa) cells promotes RNF5 association, ubiquitination, and degradation of SLC1A5/38A2. This decreases Gln uptake, levels of TCA cycle components, mTOR signaling, and proliferation while increasing autophagy and cell death. Rnf5-deficient MMTV-PyMT mammary tumors were less differentiated and showed elevated SLC1A5 expression. Whereas RNF5 depletion in MDA-MB-231 cells promoted tumorigenesis and abolished paclitaxel responsiveness, SLC1A5/38A2 knockdown elicited opposing effects. Inverse RNF5(hi)/SLC1A5/38A2(lo) expression was associated with positive prognosis in BCa. Thus, RNF5 control of Gln uptake underlies BCa response to chemotherapies.

OBJECTIVE

Cervical intraepithelial neoplasia (CIN), a common condition among HIV-infected women, has been linked to HIV load and immune status. Highly active antiretroviral therapy (HAART) improves immunologic and virologic status. This study was undertaken to determine the relationship between HAART use and CIN.

METHODS

Cohort study. The Women's Interagency HIV Study (WIHS) in five cities in the USA (Bronx/Manhattan, New York; Brooklyn, New York; Chicago, Illinois; Los Angeles, California; San Francisco Bay area, California; Washington, District of Columbia).

METHODS

HIV-infected women were followed every 6 months with Papanicolaou smears and cervicovaginal lavage for human papillomavirus (HPV) DNA testing. To characterize exposures that changed over time and to capture the dynamic nature of cytologic changes, Papanicolaou smear findings from each participant's consecutive visits were defined as a pair. We determined the proportion of all pairs that exhibited either regression or progression, according to HAART exposure, HPV results and Papanicolaou smear status. As participants could contribute multiple pairs, inferences were based on robust methods to adjust for correlated observations.

RESULTS

Women with persistent HPV infection were more likely to have progression of their lesions. After adjustment for CD4 cell count and Papanicolaou smear status, women on HAART were 40% (95% confidence interval, 4-81%) more likely to demonstrate regression and less likely (odds ratio, 0.68; 95% confidence interval, 0.52-0.88) to demonstrate progression

CONCLUSIONS

HAART altered the course of HPV disease in HIV-infected women, reducing progression and increasing regression. As HPV disease is a common sex-specific manifestation of HIV disease this effect of HAART would be a major additional benefit from this modality of therapy.

BACKGROUND

Low fat-free mass may be an independent risk factor for malnutrition that results in an increased length of hospital stay (LOS).

OBJECTIVE

The objectives were to compare differences in fat-free mass and fat mass at hospital admission between patients and healthy control subjects and to determine the association between these differences and the LOS.

METHODS

Patients (525 men, 470 women) were prospectively recruited at hospital admission. Height-corrected fat-free mass and fat mass (fat-free-mass index or fat-mass index; in kg/m2) were determined in patients at admission by bioelectrical impedance analysis and were compared with values for sex-, age-, and height-matched control subjects. Patients were classified as well-nourished, moderately depleted, or severely depleted on the basis of a Subjective Global Assessment questionnaire and a body mass index (in kg/m2) < or>> 20.

RESULTS

Low fat-free mass was noted in 37% and 55.6% of patients hospitalized 1-2 d and>> 12 d, respectively. The odds ratios were significant for fat-free-mass index and were higher in patients with a LOS of>> 12 d [men (odds ratio: 5.6; 95% CI: 3.1, 10.4), women (4.4; 2.3, 8.7)] than in those with a LOS of 1-2 d [men (3.3; 2.2, 5.0), women (2.2; 1.6, 3.1)]. Severe nutritional depletion was significantly associated only with a LOS>> 12 d.

CONCLUSIONS

Fat-free mass and fat-free-mass index were significantly lower in patients than in control subjects. Because the fat-free-mass index is significantly associated with an increased LOS, provides nutritional assessment information that complements that from a Subjective Global Assessment questionnaire, and is a more sensitive determinant of the association of fat-free mass with LOS than is a weight loss>> 10% or a body mass index < 20, it should be used to evaluate nutritional status.

BACKGROUND

Walk Score® and Transit Score® are open-source measures of the neighborhood built environment to support walking ("walkability") and access to transportation.

OBJECTIVE

To investigate associations of Street Smart Walk Score and Transit Score with self-reported transport and leisure walking using data from a large multicity and diverse population-based sample of adults.

METHODS

Data from a sample of 4552 residents of Baltimore MD, Chicago IL, Forsyth County NC, Los Angeles CA, New York NY, and St. Paul MN from the Multi-Ethnic Study of Atherosclerosis (2010-2012) were linked to Walk Score and Transit Score (collected in 2012). Logistic and linear regression models estimated ORs of not walking and mean differences in minutes walked, respectively, associated with continuous and categoric Walk Score and Transit Score. All analyses were conducted in 2012.

RESULTS

After adjustment for site, key sociodemographic, and health variables, a higher Walk Score was associated with lower odds of not walking for transport and more minutes/week of transport walking. Compared to those in a "walker's paradise," lower categories of Walk Score were associated with a linear increase in odds of not transport walking and a decline in minutes of leisure walking. An increase in Transit Score was associated with lower odds of not transport walking or leisure walking, and additional minutes/week of leisure walking.

CONCLUSIONS

Walk Score and Transit Score appear to be useful as measures of walkability in analyses of neighborhood effects.

OBJECTIVE

Problem-based learning (PBL) is now used at many medical schools to promote lifelong learning, open inquiry, teamwork, and critical thinking. PBL has not been compared with other forms of discussion-based small-group learning. Case-based learning (CBL) uses a guided inquiry method and provides more structure during small-group sessions. In this study, we compared faculty and medical students' perceptions of traditional PBL with CBL after a curricular shift at two institutions.

METHODS

Over periods of three years, the medical schools at the University of California, Los Angeles (UCLA) and the University of California, Davis (UCD) changed first-, second-, and third-year Doctoring courses from PBL to CBL formats. Ten months after the shift (2001 at UCLA and 2004 at UCD), students and faculty who had participated in both curricula completed a 24-item questionnaire about their PBL and CBL perceptions and the perceived advantages of each format

RESULTS

A total of 286 students (86%-97%) and 31 faculty (92%-100%) completed questionnaires. CBL was preferred by students (255; 89%) and faculty (26; 84%) across schools and learner levels. The few students preferring PBL (11%) felt it encouraged self-directed learning (26%) and valued its greater opportunities for participation (32%). From logistic regression, students preferred CBL because of fewer unfocused tangents (59%, odds ration [OR] 4.10, P = .01), less busy-work (80%, OR 3.97, P = .01), and more opportunities for clinical skills application (52%, OR 25.6, P = .002).

CONCLUSIONS

Learners and faculty at two major academic medical centers overwhelmingly preferred CBL (guided inquiry) over PBL (open inquiry). Given the dense medical curriculum and need for efficient use of student and faculty time, CBL offers an alternative model to traditional PBL small-group teaching. This study could not assess which method produces better practicing physicians.

Guillain-Barré syndrome (GBS) is a post-infectious disease in which the human peripheral nervous system is affected after infection by specific pathogenic bacteria, including Campylobacter jejuni. GBS is suggested to be provoked by molecular mimicry between sialylated lipooligosaccharide (LOS) structures on the cell envelope of these bacteria and ganglioside epitopes on the human peripheral nerves, resulting in autoimmune-driven nerve destruction. Earlier, the C. jejuni sialyltransferase (Cst-II) was found to be linked to GBS and demonstrated to be involved in the biosynthesis of the ganglioside-like LOS structures. Apart from a role in pathogenicity, we report here that Cst-II-generated ganglioside-like LOS structures confer efficient bacteriophage resistance in C. jejuni. By bioinformatic analysis, it is revealed that the presence of sialyltransferases in C. jejuni and other potential GBS-related pathogens correlated significantly with the apparent degeneration of an alternative anti-virus system: type II Clusters of Regularly Interspaced Short Palindromic Repeat and associated genes (CRISPR-Cas). Molecular analysis of the C. jejuni CRISPR-Cas system confirmed the bioinformatic investigation. CRISPR degeneration and mutations in the cas genes cas2, cas1 and csn1 were found to correlate with Cst-II sialyltransferase presence (p < 0.0001). Remarkably, type II CRISPR-Cas systems are mainly found in mammalian pathogens. To study the potential involvement of this system in pathogenicity, we inactivated the type II CRISPR-Cas marker gene csn1, which effectively reduced virulence in primarily cst-II-positive C. jejuni isolates. Our findings indicate a novel link between viral defence, virulence and GBS in a pathogenic bacterium.

Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a well-characterized murine model of the chronic-progressive form of human multiple sclerosis (MS) characterized by the activation of myelin-specific autoreactive CD4 Th1 cells via epitope spreading. To gain an understanding of the potential role of central nervous system (CNS)-resident cells in the presentation of endogenous myelin epitopes, we determined the individual antigen presentation and effector potential of resident microglia vs. infiltrating macrophages in the CNS of mice with ongoing TMEV-IDD by performing functional analysis of these populations separated to high purity by flow cytometric sorting based on their level of CD45 expression. Unlike microglia from nai;ve mice, peptide-pulsed CD45(lo) microglia isolated at the onset of clinical disease were as efficient as CNS-infiltrating CD45(hi) macrophages in activating proliferation and IFN-gamma production by myelin-peptide specific Th1 cells. In contrast, during the chronic stages of TMEV-IDD, CNS-infiltrating macrophages were more highly activated than the resident microglia as reflected both by higher expression of cell surface molecules associated with APC function and enhanced functional ability of spinal cord-infiltrating macrophages to stimulate T cell proliferation in vitro. Interestingly, both microglia and infiltrating macrophages expressed similar profiles of effector molecules such as IL-1, IL-6, IL-12 p40, TNF-alpha, and iNOS. Collectively, this is the first report comparing the antigen-presenting phenotype and function of microglia and infiltrating macrophages in a virus-induced model of CNS demyelination demonstrating that the resident microglia are capable APCs and may play an important role in antigen presentation at the onset of clinical disease and contribute to effector myelin destruction.

OBJECTIVE

Although several standardized definitions for AKI have been developed, no consensus exists regarding which to use in children. This study applied the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria to an anonymized cohort of hospitalizations extracted from the electronic medical record to compare AKI incidence and outcomes in intensive care unit (ICU) and non-ICU pediatric populations.

METHODS

Observational, electronic medical record-enabled study of 14,795 hospitalizations at the Lucile Packard Children's Hospital between 2006 and 2010. AKI and AKI severity stage were defined by the pRIFLE, AKIN, and KDIGO definitions according to creatinine change criteria; urine output criteria were not used. The incidences of AKI and each AKI stage were calculated for each classification system. All-cause, in-hospital mortality and total hospital length of stay (LOS) were compared at each subsequent AKI stage by Fisher exact and Kolmogorov-Smirnov tests, respectively.

RESULTS

AKI incidences across the cohort according to pRIFLE, AKIN, and KDIGO were 51.1%, 37.3%, and 40.3%. Mortality was higher among patients with AKI across all definitions (pRIFLE, 2.3%; AKIN, 2.7%; KDIGO, 2.5%; P<0.001 versus no AKI [0.8%-1.0%]). Within the ICU, pRIFLE, AKIN, and KDIGO demonstrated progressively higher mortality at each AKI severity stage; AKI was not associated with mortality outside the ICU by any definition. Both in and outside the ICU, AKI was associated with significantly higher LOS at each AKI severity stage across all three definitions (P<0.001). Definitions resulted in differences in diagnosis and staging of AKI; staging agreement ranged from 76.7% to 92.5%.

CONCLUSIONS

Application of the three definitions led to differences in AKI incidence and staging. AKI was associated with greater mortality and LOS in the ICU and greater LOS outside the ICU. All three definitions demonstrated excellent interstage discrimination. While each definition offers advantages, these results underscore the need to adopt a single, universal AKI definition.

The COVID-19 started from Wuhan city in China, slowly spread across the globe after December 2019. Due to movement of people from one city to other cities, one country to other countries, infection spreads and COVID-19 became a pandemic. Efforts were made at local, regional and national levels to lockdown the movement of people and to keep infected one in quarantine or isolation to stop the spread of COVID-19. The traffic, market and small industries were closed, as a result pronounced decline in the concentrations of particulate matters (PM) were observed. Normally these sources contribute to the high concentrations of particulate matters (PM_2.5) which represents air quality of a location. In this short communication, we present analysis of PM_2.5 of major cities (New York, Los Angeles, Zaragoza, Rome, Dubai, Delhi, Mumbai, Beijing and Shanghai) around the world suffered severely with the COVID-19. Our analysis shows decline in PM_2.5 concentration due to lockdown, mainly due to less movement of people to keep "social distancing" to control the spread of CORONA-19. The low concentrations of PM_2.5 reflect the efforts made in the cities to curb the spread of infection, that improve air quality.

OBJECTIVE

We assessed whether the few findings to date suggesting weak relationships between education and health-related variables among Hispanics are indicative of a more widespread pattern.

METHODS

We used logistic regression models to examine education differentials (i.e., education gradients) in health behaviors and outcomes among White and Mexican-origin adults, adolescents, and infants. We gathered information from 3 data sets: the Los Angeles Family and Neighborhood Survey, the Fragile Families and Child Wellbeing Study, and the National Health Interview Survey.

RESULTS

In contrast with patterns for Whites, education was weakly associated or not associated with numerous health-related variables among the US Mexican-origin population. Among adults, Mexican immigrants were especially likely to have weaker education gradients than Whites.

CONCLUSIONS

The weak relationships between education and health observed among individuals of Mexican origin may have been the result of several complex mechanisms: social gradients in health in Mexico that differ from those in the United States, selective immigration according to health and socioeconomic status, and particular patterns of integration of Mexican immigrants into US society.

Stigma profoundly affects the lives of people with HIV/AIDS. Fear of being identified as having HIV or AIDS may discourage a person from getting tested, from accessing medical services and medications, and from disclosing their HIV status to family and friends. In the present study, we use focus groups to identify the most salient domains of stigma and the coping strategies that may be common to a group of diverse, low-income women and men living with HIV in Los Angeles, CA (n = 48). We also explore the impact of stigma on health and healthcare among HIV positive persons in our sample. Results indicate that the most salient domains of stigma include: blame and stereotypes of HIV, fear of contagion, disclosure of a stigmatized role, and renegotiating social contracts. We use the analysis to develop a framework where stigma is viewed as a social process composed of the struggle for both internal change (self-acceptance) and reintegration into the community. We discuss implications of HIV-related stigma for the mental and physical health of HIV-positive women and men and suggestions for possible interventions to address stigma in the healthcare setting.

OBJECTIVE

To examine how deep chest surgical site infections following coronary artery bypass graft (CABG) surgery impact hospital inpatient length of stay (LOS), costs, and mortality.

METHODS

A large, Midwestern community medical center.

METHODS

All CABG patients who developed deep chest infection (n = 41) were compared to a set of control subjects (n = 160) systematically selected as every tenth uninfected CABG patient. Clinical data were abstracted from patient records, and cost information was obtained from the cost accounting database of the hospital.

RESULTS

Variables that significantly increased the risk of deep chest surgical site infection included obesity (odds ratio [OR], 11; p = 0. 0001), renal insufficiency (OR, 8.9; p = 0.0001), connective tissue disease (OR, 25.4; p = 0.0003), reexploration for bleeding (OR, 8.2; p = 0.0015), and the timing of antibiotic prophylaxis >> 60 min before incision; OR, 5.3; p = 0.0128). Within 1 year postoperatively, patients with deep chest surgical site infection had a mortality rate of 22%, vs 0.6% for uninfected patients (p = 0.0001). Infected patients also incurred an average of 20 additional hospital days (p = 0.0001). Univariate analysis indicated that patients who developed deep chest surgical site infection incurred $20,012 in additional costs in the first year (p = 0.0001). Infected patients who died incurred on average $60,547 more than infected patients who survived (p = 0.034). Multivariate analysis confirmed the magnitude of the estimate of the cost for deep chest surgical site infection ($18, 938; p = 0.0001).

CONCLUSIONS

Deep chest surgical site infections following CABG surgery are associated with significant increases in LOS, hospitalization costs, and mortality. These results suggest the need for improved infection control measures to reduce deep chest surgical site infection rates.

OBJECTIVE

Latinas and African-Americans with breast cancer, especially those of lower socioeconomic status and acculturation, have been underrepresented in studies assessing treatment satisfaction, decision-making, and quality of life. A study was designed to recruit a large and representative sample of these subgroups.

METHODS

Incident cases were selected by rapid case ascertainment (RCA) in the Los Angeles Surveillance, Epidemiology, and End Results Registry from 2005 to 2006, with oversampling of Latinas and African-Americans. Patients were mailed a questionnaire and $10 incentive 5 to 6 months after diagnosis; nonrespondents were contacted by telephone. Multivariate analysis was used to assess possible response bias. The RCA definition of Hispanic origin was validated by self-reports. The Short Acculturation Scale for Hispanics index for Latina respondents was used.

RESULTS

One thousand six hundred and ninety-eight eligible breast cancer cases were selected and 1,223 participated, for a response rate of 72.0%, which varied little by race/ethnicity. Age, race/ethnicity, and clinical factors were not associated with response; however, respondents were slightly more likely to be married and from higher socioeconomic status census tracts than nonrespondents. The RCA definition of Hispanic identity was highly sensitive (94.6%) and specific (90.0%). Lower acculturation was associated with lower education and literacy among Latinas.

CONCLUSIONS

High response rates among all subgroups were achieved due to the use of RCA, an incentive, extensive telephone follow-up, a native Spanish-speaking interviewer, and a focused questionnaire. The low acculturation index category identified a highly vulnerable subgroup. This large sample representing subgroups with greater problems will provide a basis for developing better interventions to assist these women.

We used wide angle x-ray scattering (WAXS) from stacks of oriented lipid bilayers to measure chain orientational order parameters and lipid areas in model membranes consisting of mixtures of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/cholesterol and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/cholesterol in fluid phases. The addition of 40% cholesterol to either DOPC or DPPC changes the WAXS pattern due to an increase in acyl chain orientational order, which is one of the main properties distinguishing the cholesterol-rich liquid-ordered (Lo) phase from the liquid-disordered (Ld) phase. In contrast, powder x-ray data from multilamellar vesicles does not yield information about orientational order, and the scattering from the Lo and Ld phases looks similar. An analytical model to describe the relationship between the chain orientational distribution and WAXS data was used to obtain an average orientational order parameter, S(x-ray). When 40% cholesterol is added to either DOPC or DPPC, S(x-ray) more than doubles, consistent with previous NMR order parameter measurements. By combining information about the average chain orientation with the chain-chain correlation spacing, we extended a commonly used method for calculating areas for gel-phase lipids to fluid-phase lipids and obtained agreement to within 5% of literature values.

BACKGROUND

Depression contributes to disability and there are ethnic/racial disparities in access and outcomes of care. Quality improvement (QI) programs for depression in primary care improve outcomes relative to usual care, but health, social and other community-based service sectors also support clients in under-resourced communities. Little is known about effects on client outcomes of strategies to implement depression QI across diverse sectors.

OBJECTIVE

To compare the effectiveness of Community Engagement and Planning (CEP) and Resources for Services (RS) to implement depression QI on clients' mental health-related quality of life (HRQL) and services use.

METHODS

Matched programs from health, social and other service sectors were randomized to community engagement and planning (promoting inter-agency collaboration) or resources for services (individual program technical assistance plus outreach) to implement depression QI toolkits in Hollywood-Metro and South Los Angeles.

METHODS

From 93 randomized programs, 4,440 clients were screened and of 1,322 depressed by the 8-item Patient Health Questionnaire (PHQ-8) and providing contact information, 1,246 enrolled and 1,018 in 90 programs completed baseline or 6-month follow-up.

METHODS

Self-reported mental HRQL and probable depression (primary), physical activity, employment, homelessness risk factors (secondary) and services use.

RESULTS

CEP was more effective than RS at improving mental HRQL, increasing physical activity and reducing homelessness risk factors, rate of behavioral health hospitalization and medication visits among specialty care users (i.e. psychiatrists, mental health providers) while increasing depression visits among users of primary care/public health for depression and users of faith-based and park programs (each p < 0.05). Employment, use of antidepressants, and total contacts were not significantly affected (each p>> 0.05).

CONCLUSIONS

Community engagement to build a collaborative approach to implementing depression QI across diverse programs was more effective than resources for services for individual programs in improving mental HRQL, physical activity and homelessness risk factors, and shifted utilization away from hospitalizations and specialty medication visits toward primary care and other sectors, offering an expanded health-home model to address multiple disparities for depressed safety-net clients.

The aim of this study was to determine the prognostic implications of the pretreatment level of Th17 cells compared with regulatory T-cell status in prostate cancer patients receiving active whole cell immunotherapy. Ten-color flow cytometry was used to analyze IL-17-producing CD4(+) T-cells in the peripheral blood of hormone-resistant non-bone metastatic prostate cancer patients prior to immunotherapy with an allogeneic whole-cell vaccine. Surface expression of the chemokine receptors CCR4 and CCR6 was used to further subdivide IL-17-producing cells into subsets with distinct homing properties. The frequency of circulating regulatory T-cells (Tregs), defined as CD3(+)CD4(+)CD127(lo)Foxp3(+)CD25(+) was compared in the same patients. The frequency of CCR4(-)IL-17(+)CD4(+) T-cells prevaccination inversely correlated with time to disease progression (TTP) in 23 prostate cancer patients. Furthermore, responder (R) patients with statistically significant reductions in PSA velocity (PSAV) in response to the immunotherapy (n = 9), showed a Th17 profile similar to healthy male controls and significantly different from non-responder (NR) patients (n = 14) (i.e., those without any significant reduction in PSAV). In contrast, the frequency of Tregs in peripheral blood in PSA-R (n = 11) and -NR (n = 14) patients was similar (but in both cases, significantly higher than in age-matched healthy men). Accordingly, there was no significant correlation between frequency of Tregs and TTP in these late-stage prostate cancer patients undergoing active immunotherapy. These data imply an important role for IL-17-producing helper T-cells in cancer immunology and highlight their potential use as a pretreatment screen to ensure appropriate treatment is offered to hormone-resistant prostate cancer patients.

T-cell development follows a defined set of stage-specific differentiation steps. However, molecular and cellular events occurring at early stages of human T-cell development remain to be fully elucidated. To address this, human umbilical cord blood (UCB) hematopoietic stem cells (HSCs) were induced to differentiate to the T lineage in OP9-DL1 cocultures. A developmental program involving a sequential and temporally discrete expression of key differentiation markers was revealed. Quantitative clonal analyses demonstrated that CD34(+)CD38(-) and CD34(+)CD38(lo) subsets of UCB contain a similarly high T-lineage progenitor frequency, whereas the frequency in CD34(+)CD38(+/hi) cells was 5-fold lower. Delta-like/Notch-induced signals increased the T-cell progenitor frequency of CD34(+)CD38(-/lo) cells differentiated on OP9-DL1, and 2 distinct progenitor subsets, CD34(+)CD45RA(+)CD7(++)CD5(-)CD1a(-) (proT1) and CD34(+)CD45RA(+)CD7(++)CD5(+)CD1a(-) (proT2), were identified and their thymus engrafting capacity was examined, with proT2 cells showing a 3-fold enhanced reconstituting capacity compared with the proT1 subset. Furthermore, in vitro-generated CD34(+)CD7(++) progenitors effectively engrafted the thymus of immunodeficient mice, which was enhanced by the addition of an IL-7/IL-7 antibody complex. Taken together, the identification of T-progenitor subsets readily generated in vitro may offer important avenues to improve cellular-based immune-reconstitution approaches.

Roads present formidable barriers to dispersal. We examine movements of two highly mobile carnivores across the Ventura Freeway near Los Angeles, one of the busiest highways in the United States. The two species, bobcats and coyotes, can disappear from habitats isolated and fragmented by roads, and their ability to disperse across the Ventura Freeway tests the limits of vertebrates to overcome anthropogenic obstacles. We combine radio-telemetry data and genetically based assignments to identify individuals that have crossed the freeway. Although the freeway is a significant barrier to dispersal, we find that carnivores can cross the freeway and that 5-32% of sampled carnivores crossed over a 7-year period. However, despite moderate levels of migration, populations on either side of the freeway are genetically differentiated, and coalescent modelling shows their genetic isolation is consistent with a migration fraction less than 0.5% per generation. These results imply that individuals that cross the freeway rarely reproduce. Highways and development impose artificial home range boundaries on territorial and reproductive individuals and hence decrease genetically effective migration. Further, territory pile-up at freeway boundaries may decrease reproductive opportunities for dispersing individuals that do manage to cross. Consequently, freeways are filters favouring dispersing individuals that add to the migration rate but little to gene flow. Our results demonstrate that freeways can restrict gene flow even in wide-ranging species and suggest that for territorial animals, migration levels across anthropogenic barriers need to be an order of magnitude larger than commonly assumed to counteract genetic differentiation.

OBJECTIVE

Forgetting to take medications is an important cause of nonadherence. This study evaluated factors associated with forgetting to take medications in a large cohort of persons with systemic lupus erythematosus (SLE) participating in the University of California, San Francisco Lupus Outcomes Study (LOS). Relationships among adherence problems and service utilization (outpatient visits, emergency department visits, and hospitalizations) were also evaluated.

METHODS

The cohort consisted of 834 LOS participants who provided self-reported frequency of forgetting to take medications as directed. Predictors of adherence and service utilization patterns included self-reported sociodemographics, disease-related characteristics (e.g., disease activity, recent SLE flare), and mental health characteristics (Center for Epidemiologic Studies Depression Scale and cognitive function screen). Health care utilization patterns included the presence and quantity of visits to rheumatologists, primary care physicians, other care providers, emergency departments, and hospitalizations.

RESULTS

Forty-six percent of the LOS cohort reported forgetting to take medications at least some of the time. Depressive symptom severity was a strong predictor of adherence difficulties (odds ratio [OR] 1.04, 95% confidence interval [95% CI] 1.02-1.05; P < 0.0001) after accounting for all other predictors. Persons reporting adherence difficulties had significantly greater numbers of outpatient rheumatology and primary care visits, and were more likely to visit the emergency department (OR 1.45, 95% CI 1.04-2.04; P = 0.03).

CONCLUSIONS

Depression may be an important cause of medication adherence problems, and difficulties with adherence are significantly associated with high-cost service utilization, specifically emergency department visits. In an era of rapidly evolving treatments for lupus, identifying patients at risk for adherence problems may decrease medical expenditures and improve patient outcomes in SLE.

The lipooligosaccharide (LOS) of Haemophilus influenzae contains sialylated glycoforms, and a sialyltransferase, Lic3A, has been previously identified. We report evidence for two additional sialyltransferases, SiaA, and LsgB, that affect N-acetyllactosamine containing glycoforms. Mutations in genes we have designated siaA and lsgB affected only the sialylated glycoforms containing N-acetylhexosamine. A mutation in siaA resulted in the loss of glycoforms terminating in sialyl-N-acetylhexosamine and the appearance of higher molecular weight glycoforms, containing the addition of phosphoethanolamine, N-acetylgalactosamine, and N-acetylneuraminic acid. Chromosomal complementation of the siaA mutant resulted in the expression of the original sialylated LOS phenotype. A mutation in lic3A resulted in the loss of sialylation only in glycoforms lacking N-acetylhexosamine and had no effect on sialylation of the terminal N-acetyllactosamine epitope. A double mutant in siaA and lic3A resulted in the complete loss of sialylation of the terminal N-acetyllactosamine epitope and expression of the higher molecular weight sialylated glycoforms seen in the siaA mutant. Mutation of lsgB resulted in persistence of sialylated glycoforms but a reduction in N-acetyllactosamine containing glycoforms. A triple mutant of siaA, lic3A, and lsgB contained no sialylated glycoforms. These results demonstrate that the sialylation of the LOS of H. influenzae is a complex process involving multiple sialyltransferases.

BACKGROUND

Previous research has shown that breast and cervical cancer screening rates are low among Vietnamese women.

METHODS

Over a 24-month period, we implemented a media-led community education campaign to promote recognition, intention, receipt, and currency of routine checkups, clinical breast examinations, mammograms, and Pap tests among Vietnamese-American women in Alameda and Santa Clara Counties in northern California. Women in Los Angeles and Orange Counties in southern California served as controls. To evaluate its impact, pretest telephone interviews were conducted of 451 randomly selected women in the intervention area and 482 women in the control area and posttest interviews with 454 and 422 women, respectively.

RESULTS

At posttest, after controlling for demographic differences in the surveyed populations, the odds ratios for the intervention effect were statistically significant for having heard of a general checkup, Paptest, and clinical breast examination (CBE); planning to have a checkup, Pap test, CBE, and mammogram; and having had a checkup and Pap test. The intervention had no effect on being up to date for any of the tests.

CONCLUSIONS

A media-led education intervention succeeded in increasing recognition of and intention to undertake screening tests more than receipt of or currency with the tests.

BACKGROUND

A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States.

METHODS

Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time.

RESULTS

Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations.

CONCLUSIONS

While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their practice.