Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS-induced maturation of DCs and reprograms DCs toward a tolerance-promoting phenotype. Our results showed that DCs exposed to H. pylori in vitro or in vivo failed to induce T cell effector functions. Instead, they efficiently induced expression of the forkhead transcription factor FoxP3, the master regulator of Tregs, in naive T cells. Depletion of DCs in mice infected with H. pylori during the neonatal period was sufficient to break H. pylori-specific tolerance. DC depletion resulted in improved control of the infection but also aggravated T cell-driven immunopathology. Consistent with the mouse data, DCs infiltrating the gastric mucosa of human H. pylori carriers exhibited a semimature DC-SIGN(+)HLA-DR(hi)CD80(lo)CD86(lo) phenotype. Mechanistically, the tolerogenic activity of H. pylori-experienced DCs was shown to require IL-18 in vitro and in vivo; DC-derived IL-18 acted directly on T cells to drive their conversion to Tregs. CD4(+)CD25(+) Tregs from infected wild-type mice but not Il18(-/-) or Il18r1(-/-) mice prevented airway inflammation and hyperresponsiveness in an experimental model of asthma. Taken together, our results indicate that tolerogenic reprogramming of DCs ensures the persistence of H. pylori and protects against allergic asthma in a process that requires IL-18.

We have compared the lipo-oligosaccharide (LOS) biosynthesis loci from 11 Campylobacter jejuni strains expressing a total of 8 different ganglioside mimics in their LOS outer cores. Based on the organization of the genes, the 11 corresponding loci could be classified into three classes, with one of them being clearly an intermediate evolutionary step between the other two. Comparative genomics and expression of specific glycosyltransferases combined with in vitro activity assays allowed us to identify at least five distinct mechanisms that allow C. jejuni to vary the structure of the LOS outer core as follows: 1) different gene complements; 2) phase variation because of homopolymeric tracts; 3) gene inactivation by the deletion or insertion of a single base (without phase variation); 4) single mutation leading to the inactivation of a glycosyltransferase; and 5) single or multiple mutations leading to "allelic" glycosyltransferases with different acceptor specificities. The differences in the LOS outer core structures expressed by the 11 C. jejuni strains examined can be explained by one or more of the five mechanisms described in this work.

The association between soyfood intake and breast cancer risk is controversial. Most of the epidemiologic studies published on this topic in the 1990s were not designed to specifically address this question. We conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County to further investigate the role of soy. Our primary objective was to quantify breast cancer risks associated with intake of soy during adolescence and adult life among Asian-American women. During 1995-1998, we successfully interviewed 501 breast cancer patients and 594 control subjects. Intake of soy among Asian-Americans is still relatively high; the median intake was 12 mg isoflavones/day, approximately one-third of that reported in a recent study in Shanghai, China. The risk of breast cancer was significantly inversely associated with soy intake during adolescence and adult life. After adjusting for age, specific Asian ethnicity, education, migration history and menstrual and reproductive factors, women who reported soy intake at least once per week during adolescence showed a statistically significantly reduced risk of breast cancer. There was also a significant trend of decreasing risk with increasing soy intake during adult life. When we considered soy intake during both adolescence and adult life, subjects who were high-soy consumers during both time periods showed the lowest risk (OR=0.53, 95% CI=0.36-0.78) compared with those who were low consumers during both time periods. Risk of breast cancer was intermediate among subjects who were high-soy consumers during adolescence and low-soy consumers during adult life (OR=0.77, 95% CI=0.51-1.10). Based on a relatively small number of subjects, the risk did not appear to differ between those who were low consumers during adolescence and high consumers during adult life. Results remained similar after adjustment for other potential confounders including other dietary and non-dietary risk factors for breast cancer. These results show that high soy intake in childhood in Asian-Americans is associated with reduced breast cancer risk. Risk may be further reduced by intake as an adult.

D.F., a patient with severe visual form agnosia, has been the subject of extensive research during the past decade. The fact that she could process visual input accurately for the purposes of guiding action despite being unable to perform visual discriminations on the same visual input inspired a novel interpretation of the functions of the two main cortical visual pathways or 'streams'. Within this theoretical context, the authors proposed that D.F. had suffered severe bilateral damage to her occipitotemporal visual system (the 'ventral stream'), while retaining the use of her occipitoparietal visual system (the 'dorsal stream'). The present paper reports a direct test of this idea, which was initially derived from purely behavioural data, before the advent of modern functional neuroimaging. We used functional MRI to examine activation in her ventral and dorsal streams during object recognition and object-directed grasping tasks. We found that D.F. showed no difference in activation when presented with line drawings of common objects compared with scrambled line drawings in the lateral occipital cortex (LO) of the ventral stream, an area that responded differentially to these stimuli in healthy individuals. Moreover, high-resolution anatomical MRI showed that her lesion corresponded bilaterally with the location of LO in healthy participants. The lack of activation with line drawings in D.F. mirrors her poor performance in identifying the objects depicted in the drawings. With coloured and greyscale pictures, stimuli that she can identify more often, D.F. did show some ventral-stream activation. These activations were, however, more widely distributed than those seen in control participants and did not include LO. In contrast to the absent or abnormal activation observed during these perceptual tasks, D.F. showed robust activation in the expected dorsal stream regions during object grasping, despite considerable atrophy in some regions of the parietal lobes. In particular, an area in the anterior intraparietal sulcus was activated more for grasping an object than for just reaching to that object, for both D.F. and controls. In conclusion, we have been able to confirm directly that D.F.'s visual form agnosia is associated with extensive damage to the ventral stream, and that her spared visuomotor skills are associated with visual processing in the dorsal stream.

BACKGROUND

The emergence of next generation sequencing (NGS) has provided the means for rapid and high throughput sequencing and data generation at low cost, while concomitantly creating a new set of challenges. The number of available assembled microbial genomes continues to grow rapidly and their quality reflects the quality of the sequencing technology used, but also of the analysis software employed for assembly and annotation.

RESULTS

In this work, we have explored the quality of the microbial draft genomes across various sequencing technologies. We have compared the draft and finished assemblies of 133 microbial genomes sequenced at the Department of Energy-Joint Genome Institute and finished at the Los Alamos National Laboratory using a variety of combinations of sequencing technologies, reflecting the transition of the institute from Sanger-based sequencing platforms to NGS platforms. The quality of the public assemblies and of the associated gene annotations was evaluated using various metrics. Results obtained with the different sequencing technologies, as well as their effects on downstream processes, were analyzed. Our results demonstrate that the Illumina HiSeq 2000 sequencing system, the primary sequencing technology currently used for de novo genome sequencing and assembly at JGI, has various advantages in terms of total sequence throughput and cost, but it also introduces challenges for the downstream analyses. In all cases assembly results although on average are of high quality, need to be viewed critically and consider sources of errors in them prior to analysis.

CONCLUSIONS

These data follow the evolution of microbial sequencing and downstream processing at the JGI from draft genome sequences with large gaps corresponding to missing genes of significant biological role to assemblies with multiple small gaps (Illumina) and finally to assemblies that generate almost complete genomes (Illumina+PacBio).

The evidence for a protective effect of vegetables, fruits, and legumes against prostate cancer is weak and inconsistent. We examined the relationship of these food groups and their constituent foods to prostate cancer risk in a multicenter case-control study of African-American, white, Japanese, and Chinese men. Cases (n = 1619) with histologically confirmed prostate cancer were identified through the population-based tumor registries of Hawaii, San Francisco, and Los Angeles in the United States and British Columbia and Ontario in Canada. Controls (n = 1618) were frequency-matched to cases on ethnicity, age, and region of residence of the case, in a ratio of approximately 1:1. Dietary and other information was collected by in-person home interview; a blood sample was obtained from control subjects for prostate-specific antigen determination. Odds ratios (OR) were estimated using logistic regression, adjusting for age, geographic location, education, calories, and when indicated, ethnicity. Intake of legumes (whether total legumes, soyfoods specifically, or other legumes) was inversely related to prostate cancer (OR for highest relative to lowest quintile for total legumes = 0.62; P for trend = 0.0002); results were similar when restricted to prostate-specific antigen-normal controls or to advanced cases. Intakes of yellow-orange and cruciferous vegetables were also inversely related to prostate cancer, especially for advanced cases, among whom the highest quintile OR for yellow-orange vegetables = 0.67 (P for trend = 0.01) and the highest quintile OR for cruciferous vegetables = 0.61 (P for trend = 0.006). Intake of tomatoes and of fruits was not related to risk. Findings were generally consistent across ethnic groups. These results suggest that legumes (not limited to soy products) and certain categories of vegetables may protect against prostate cancer.

An epidemiologic study of Los Angeles Marathon (LAM) applicants was conducted to investigate the relationship between self-reported infectious episodes (IE), training data, and LAM participation. Eight days before the LAM, 4926 of 12,200 applicants were randomly selected, and sent a pilot-tested four page questionnaire, which was received 7 days after the LAM. The 2311 respondents were found to be 2.0 yr older and 7.6 min faster than other LAM finishers (p less than .01). Univariate and multivariate analyses (logistic regression) were conducted to test the relationship between IE and km/wk of running (6 total categories). The final model tested controlled for age, marital status, reported sickness in other members of the runner's home, perceived feelings of stress in response to personal training regimens, and the suppressive effect of sickness on regular training. In runners training greater than or equal to 97 vs less than 32 km/wk, the odds ratio (OR) for IE during the 2 month period prior to the LAM was 2.0 (95% confidence interval (CI) 1.2-3.4). A test for trend showed an increase in OR with increase in km/wk category (p = .04) which was largely explained by the increased odds of reported sickness in the greater than or equal to 97 km/wk category. Of the 1828 LAM participants without IE before the LAM, 236 (12.9%) reported IE during the week following the LAM vs 3 of 134 (2.2%) similarly experienced runners who did not participate, OR = 5.9 (95% CI 1.9-18.8). These data suggest that runners may experience increased odds for IE during heavy training or following a marathon race.

MicroRNAs profoundly impact hematopoietic cells by regulating progenitor cell-fate decisions, as well as mature immune effector function. However to date, microRNAs that regulate hematopoietic stem cell (HSC) function have been less well characterized. Here we show that microRNA-125b (miR-125b) is highly expressed in HSCs and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1(lo)CD34(-) lymphoid-balanced and the Slamf1(neg)CD34(-) lymphoid-biased cell subsets within the multipotent HSC (CD34-KLS) fraction. Mature peripheral blood cells derived from the miR-125b-overexpressing HSC are skewed toward the lymphoid lineage. Consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoid-biased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13. The antiapoptotic effect of miR-125b is more pronounced in the lymphoid-biased HSC subset because of their intrinsic higher baseline levels of apoptosis. These effects of miR-125b are associated with the development of lymphoproliferative disease, marked by expansion of CD8(+) T lymphocytes. Taken together, these data reveal that miR-125b regulates HSC survival and can promote lymphoid-fate decisions at the level of the HSC by preferentially expanding lymphoid-balanced and lymphoid-biased HSC.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, culminating in severe motor symptoms, including resting tremor, rigidity, bradykinesia, and postural instability. In addition to motor deficits, there are a variety of nonmotor symptoms associated with PD. These symptoms generally precede the onset of motor symptoms, sometimes by years, and include anosmia, problems with gastrointestinal motility, sleep disturbances, sympathetic denervation, anxiety, and depression. Previously, we have shown that mice with a 95% genetic reduction in vesicular monoamine transporter expression (VMAT2-deficient, VMAT2 LO) display progressive loss of striatal dopamine, L-DOPA-responsive motor deficits, alpha-synuclein accumulation, and nigral dopaminergic cell loss. We hypothesized that since these animals exhibit deficits in other monoamine systems (norepinephrine and serotonin), which are known to regulate some of these behaviors, the VMAT2-deficient mice may display some of the nonmotor symptoms associated with PD. Here we report that the VMAT2-deficient mice demonstrate progressive deficits in olfactory discrimination, delayed gastric emptying, altered sleep latency, anxiety-like behavior, and age-dependent depressive behavior. These results suggest that the VMAT2-deficient mice may be a useful model of the nonmotor symptoms of PD. Furthermore, monoamine dysfunction may contribute to many of the nonmotor symptoms of PD, and interventions aimed at restoring monoamine function may be beneficial in treating the disease.

Roles for host immune response in carcinogenesis are not well defined. Recent studies have shown that microbially driven inflammation can lead to colon cancer and that prior transfer of regulatory lymphocytes expressing CD4 and CD25 prevents the innate inflammatory events that lead to colon cancer in mice. To further examine the ability of regulatory lymphocytes to inhibit carcinogenesis, 129/SvEv Rag-2-deficient mice were inoculated by gastric gavage with Helicobacter hepaticus, an enteric bacterial pathogen of mice. Mice were then treated at 1, 3, or 12 months after infection with adoptive transfer of CD4(+)CD45RB(lo)CD25(+)-regulatory cells. Mice dosed with regulatory cells at 4 or 12 weeks after H. hepaticus infection had reduced severity of inflammatory bowel disease and significantly lower risk of colon cancer during the 8 month observation period, compared with infected mice that had not received cells. This suggested that regulatory cells were able to interrupt the ongoing innate immune events in the stepwise progression to cancer. Transfer of regulatory cells into chronically infected mice with established cancer reduced severity of colitis, epithelial dysplasia, and cancer, but did not eliminate all tumors. Regulatory cells lacking anti-inflammatory cytokine interleukin (IL)-10 were unable to inhibit inflammatory bowel disease, dysplasia, or cancer, showing that IL-10 was required for the protective effects of lymphocytes in this setting. Taken together, the data suggest that IL-10-mediated suppression of host innate inflammatory response was pivotal in interrupting carcinogenesis. Regulatory lymphocytes and cytokines may have implications for novel therapies for colon cancer in humans.

OBJECTIVE

Hospital hyperglycemia, in individuals with and without diabetes, has been identified as a marker of poor clinical outcome in cardiac surgery patients. However, the impact of perioperative hyperglycemia on clinical outcome in general and noncardiac surgery patients is not known.

METHODS

This was an observational study with the aim of determining the relationship between pre- and postsurgery blood glucose levels and hospital length of stay (LOS), complications, and mortality in 3,184 noncardiac surgery patients consecutively admitted to Emory University Hospital (Atlanta, GA) between 1 January 2007 and 30 June 2007.

RESULTS

The overall 30-day mortality was 2.3%, with nonsurvivors having significantly higher blood glucose levels before and after surgery (both P < 0.01) than survivors. Perioperative hyperglycemia was associated with increased hospital and intensive care unit LOS (P < 0.001) as well as higher numbers of postoperative cases of pneumonia (P < 0.001), systemic blood infection (P < 0.001), urinary tract infection (P < 0.001), acute renal failure (P = 0.005), and acute myocardial infarction (P = 0.005). In multivariate analysis (adjusted for age, sex, race, and surgery severity), the risk of death increased in proportion to perioperative glucose levels; however, this association was significant only for patients without a history of diabetes (P = 0.008) compared with patients with known diabetes (P = 0.748).

CONCLUSIONS

Perioperative hyperglycemia is associated with increased LOS, hospital complications, and mortality after noncardiac general surgery. Randomized controlled trials are needed to determine whether perioperative diabetes management improves clinical outcome in noncardiac surgery patients.

Perceived stigma in clinical settings may discourage HIV-infected individuals from accessing needed health care services. Having good access to care is imperative for maintaining the health, well being, and quality of life of persons living with HIV/AIDS (PLWHAs). The purpose of this prospective study, which took place from January 2004 through June 2006, was to evaluate the relationship between perceived stigma from a health care provider and access to care among 223 low income, HIV-infected individuals in Los Angeles County. Approximately one fourth of the sample reported perceived stigma from a health care provider at baseline, and about one fifth reported provider stigma at follow up. We also found that access to care among this population was low, as more than half of the respondents reported difficulty accessing care at baseline and follow up. Perceived stigma was found to be associated with low access to care both at baseline (odds ratio [OR] = 3.29; 95% confidence interval [CI] = 1.55, 7.01) and 6-month follow up (2.85; 95% CI = 1.06, 7.65), even after controlling for sociodemographic characteristics and most recent CD4 count. These findings are of particular importance because lack of access or delayed access to care may result in clinical presentation at more advanced stages of HIV disease. Interventions are needed to reduce perceived stigma in the health care setting. Educational programs and modeling of nonstigmatizing behavior can teach health care providers to provide unbiased care.

OBJECTIVE

High rates of mastectomy and marked regional variations have motivated lingering concerns about overtreatment and failure to involve women in treatment decisions. We examined the relationship between patient involvement in decision making and type of surgical treatment for women with breast cancer.

METHODS

All women with ductal carcinoma-in-situ and a 20% random sample of women with invasive breast cancer aged 79 years and younger who were diagnosed in 2002 and reported to the Detroit and Los Angeles Surveillance, Epidemiology, and End Results registries were identified and surveyed shortly after receipt of surgical treatment (response rate, 77.4%; n = 1,844).

RESULTS

Mean age was 60.1 years; 70.2% of the women were white, 18.0% were African American, and 11.8% were from other ethnic groups. Overall, 30.2% of women received mastectomy as initial treatment. Most women reported that they made the surgical decision (41.0%) or that the decision was shared (37.1%); 21.9% of patients reported that their surgeon made the decision with or without their input. Among white women, only 5.3% of patients whose surgeon made the decision received mastectomy compared with 16.8% of women who shared the decision and 27.0% of women who made the decision (P < .001, adjusted for clinical factors, predisposing factors, and number of surgeons visited). However, this association was not observed for African American women (Wald test 10.0, P = .041).

CONCLUSIONS

Most women reported that they made or shared the decision about surgical treatment. More patient involvement in decision making was associated with greater use of mastectomy. Racial differences in the association of involvement with receipt of treatment suggest that the decision-making process varies by racial groups.

During 2002, the Los Angeles County Department of Health Services (LACDHS) investigated three community outbreaks of skin infections associated with methicillin-resistant Staphylococcus aureus (MRSA). MRSA commonly has occurred in health-care settings; however, recent investigations of community-associated MRSA (CA-MRSA) have identified infection in various settings, including correctional facilities, athletic teams, and others (CDC, unpublished data, 2002). This report describes investigations of CA-MRSA in Los Angeles County.

BACKGROUND

The premise underlying regionalization of trauma care is that larger volumes of trauma patients cared for in fewer institutions will lead to improved outcomes. However, whether a relationship exists between institutional volume and trauma outcomes remains unknown.

OBJECTIVE

To evaluate the association between trauma center volume and outcomes of trauma patients.

METHODS

Retrospective cohort study.

METHODS

Thirty-one academic level I or level II trauma centers across the United States participating in the University Healthsystem Consortium Trauma Benchmarking Study.

METHODS

Consecutive patients with penetrating abdominal injury (PAI; n = 478) discharged between November 1, 1997, and July 31, 1998, or with multisystem blunt trauma (minimum of head injury and lower-extremity long-bone fractures; n = 541) discharged between June 1 and December 31, 1998.

METHODS

Inpatient mortality and hospital length of stay (<em>LOS</em>), comparing high-volume (>650 trauma admissions/y) and low-volume (</=650 admissions/y) centers.

RESULTS

After multivariate adjustment for patient characteristics and injury severity, the relative odds of death was 0.02 (95% confidence interval [CI], 0.002-0.25) for patients with PAI admitted with shock to high-volume centers compared with low-volume centers. No benefit was evident in patients without shock (P =.50). The adjusted odds of death in patients with multisystem blunt trauma who presented with coma to a high-volume center was 0.49 (95% CI, 0.26-0.93) vs low-volume centers. No benefit was observed in patients without coma (P =.05). Additionally, a shorter LOS was observed in patients with PAI and New Injury Severity Scores of 16 or higher (difference in adjusted mean LOS, 1.6 days [95% CI, -1.5 to 4.7 days]) and in all patients with multisystem blunt trauma admitted to higher-volume centers (difference in adjusted mean LOS, 3.3 days [95% CI, 0.91-5.70 days]).

CONCLUSIONS

Our results indicate that a strong association exists between trauma center volume and outcomes, with significant improvements in mortality and LOS when volume exceeds 650 cases per year. These benefits are only evident in patients at high risk for adverse outcomes.

UNASSIGNED

Establishment of the infant microbiome has lifelong implications on health and immunity. Gut microbiota of breastfed compared with nonbreastfed individuals differ during infancy as well as into adulthood. Breast milk contains a diverse population of bacteria, but little is known about the vertical transfer of bacteria from mother to infant by breastfeeding.

UNASSIGNED

To determine the association between the maternal breast milk and areolar skin and infant gut bacterial communities.

UNASSIGNED

In a prospective, longitudinal study, bacterial composition was identified with sequencing of the 16S ribosomal RNA gene in breast milk, areolar skin, and infant stool samples of 107 healthy mother-infant pairs. The study was conducted in Los Angeles, California, and St Petersburg, Florida, between January 1, 2010, and February 28, 2015.

UNASSIGNED

Amount and duration of daily breastfeeding and timing of solid food introduction.

UNASSIGNED

Bacterial composition in maternal breast milk, areolar skin, and infant stool by sequencing of the 16S ribosomal RNA gene.

UNASSIGNED

In the 107 healthy mother and infant pairs (median age at the time of specimen collection, 40 days; range, 1-331 days), 52 (43.0%) of the infants were male. Bacterial communities were distinct in milk, areolar skin, and stool, differing in both composition and diversity. The infant gut microbial communities were more closely related to an infant's mother's milk and skin compared with a random mother (mean difference in Bray-Curtis distances, 0.012 and 0.014, respectively; P < .001 for both). Source tracking analysis was used to estimate the contribution of the breast milk and areolar skin microbiomes to the infant gut microbiome. During the first 30 days of life, infants who breastfed to obtain 75% or more of their daily milk intake received a mean (SD) of 27.7% (15.2%) of the bacteria from breast milk and 10.3% (6.0%) from areolar skin. Bacterial diversity (Faith phylogenetic diversity, P = .003) and composition changes were associated with the proportion of daily breast milk intake in a dose-dependent manner, even after the introduction of solid foods.

UNASSIGNED

The results of this study indicate that bacteria in mother's breast milk seed the infant gut, underscoring the importance of breastfeeding in the development of the infant gut microbiome.

An interactive system for computer analysis of nucleic acid and protein sequences has been developed for the Los Alamos DNA Sequence Database. It provides a convenient way to search or verify various sequence features, e.g., restriction enzyme sites, protein coding frames, and properties of coded proteins. Further, the comprehensive analysis package on a large-scale database can be used for comparative studies on sequence and structural homologies in order to find unnoted information stored in nucleic acid sequences.

OBJECTIVE

To develop and validate a brief instrument--the Perceived Efficacy in Patient-Physician Interactions Questionnaire (PEPPI)--to measure older patients' self-efficacy in obtaining medical information and attention to their medical concerns from physicians.

METHODS

Two consecutive validation surveys.

METHODS

Eleven senior multipurpose centers in Los Angeles County California.

METHODS

A convenience sample of 163 community-dwelling older persons (Survey 1: n=59, mean age=77.1 years, 76.3% female; Survey 2: n=104, mean age=77.4 years, 57.7% female).

METHODS

The 10-item PEPPI, subscales of the Patient Satisfaction Questionnaire, the Medical Outcomes Study (MOS) Coping Scale, the Mastery Scale, and global self-reported health and restricted activity days items.

RESULTS

The full 10-item and a 5-item short form of PEFPI demonstrated Cronbach's alphas of 0.91 and 0.83, respectively. PEPPI demonstrated discriminant and convergent validity as hypothesized, correlating negatively with avoidant coping (r=-.27, P=.001) and positively with active coping (r=.17, P=.03) and with patient satisfaction with physician interpersonal manner (r=.49, P < .0001) and communication (r=.51, P < .0001) (values from the overall sample). Further, in the second survey, PEPPI correlated positively with self-reported health (r=.42, P < .0001), education (r = .24, P=.01) and self-mastery (r=.29, P=.01) and negatively with restricted activity days (r=-.25, P=.01). PEPPI-5 demonstrated correlations similar in magnitude, direction, and statistical significance.

CONCLUSIONS

In either the 5- or 10-item version, PEPPI is a valid and reliable measure of older patients' perceived self-efficacy in interacting with physicians. This instrument may be useful in measuring the impact of empowerment interventions to increase older patients' personal sense of effectiveness in obtaining needed health care.

OBJECTIVE

To investigate the outcomes after prolonged empirical antibiotic administration to premature infants in the first week of life, and concluding subsequent late onset sepsis (LOS), necrotizing enterocolitis (NEC), and death.

METHODS

Study infants were ≤ 32 weeks gestational age and ≤ 1500 g birth weight who survived free of sepsis and NEC for 7 days. Multivariable logistic regression was conducted to determine independent relationships between prolonged initial empirical antibiotic therapy (≥ 5 days) and study outcomes that control for birth weight, gestational age, race, prolonged premature rupture of membranes, days on high-frequency ventilation in 7 days, and the amount of breast milk received in the first 14 days of life.

RESULTS

Of the 365 premature infants who survived 7 days free of sepsis or NEC, 36% received prolonged initial empirical antibiotics, which was independently associated with subsequent outcomes: LOS (OR, 2.45 [95% CI, 1.28-4.67]) and the combination of LOS, NEC, or death (OR, 2.66 [95% CI, 1.12-6.3]).

CONCLUSIONS

Prolonged administration of empirical antibiotics to premature infants with sterile cultures in the first week of life is associated with subsequent severe outcomes. Judicious restriction of antibiotic use should be investigated as a strategy to reduce severe outcomes for premature infants.

BACKGROUND

Rats selectively bred for high intake of a sweet saccharin solution (HiS) consume more ethanol than their low-saccharin intake (LoS) counterparts. The HiS phenotype may be a predictor of abuse of other drugs via other routes of administration.

OBJECTIVE

HiS and LoS, male and female rats were tested for acquisition of IV cocaine and heroin self-administration under a fixed-ratio 1 (FR1) schedule, and cocaine-reinforced behavior was examined under a progressive-ratio (PR) schedule.

METHODS

Four groups of rats (HiS males and females and LoS males and females) were trained to self-administer IV cocaine (0.2 mg/kg), and another four groups were trained to self-administer heroin (0.015 mg/kg) using an automated autoshaping procedure. Rats were allowed 30 days to reach a criterion whereby a mean of 100 (cocaine) or 20 (heroin) infusions were self-administered during 6-h sessions over 5 consecutive days.

RESULTS

The HiS female rats acquired cocaine self-administration significantly more rapidly than the LoS rats, and females of both phenotypes met the acquisition criteria more rapidly than males. In both HiS and LoS cocaine groups a greater percentage of females (compared with males) met the acquisition criteria within 30 days. The only cocaine group in which 100% met the criterion was the HiS females. The female (compared with male) heroin groups showed a more rapid rate of acquisition, but there was no difference due to saccharin phenotype. In each of the four heroin groups 100% of all rats met the criteria within 30 days. Results of the PR schedule in the HiS females and males and LoS females indicated significantly higher break points in the HiS females (compared with HiS males), but there were no differences in females due to phenotype.

CONCLUSIONS

Female rats selectively bred for higher saccharin intake show more rapid and successful acquisition of IV self-administration of a low dose of cocaine than those bred for low saccharin intake. Female rats (compared with males) consistently showed accelerated rates of acquisition and maintenance (PR) of cocaine self-administration and acquisition of heroin self-administration.

B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have been shown to promote multiple myeloma (MM) cell growth. We show that the main site of production for BAFF and APRIL is the bone marrow (BM) environment, and that production is mainly by monocytes and neutrophils. In addition, osteoclasts produce very high levels of APRIL, unlike BM stromal cells. Myeloma cells (MMCs) express TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor), the receptor of BAFF/APRIL, at varying levels. TACI expression is a good indicator of a BAFF-binding receptor. Expression data of purified MMCs from 65 newly diagnosed patients have been generated using Affymetrix microarrays and were analyzed by supervised clustering of groups with higher (TACI(hi)) versus lower (TACI(lo)) TACI expression levels. Patients in the TACI(lo) group had clinical parameters associated with bad prognosis. A set of 659 genes was differentially expressed between TACI(hi) and TACI(lo) MMCs. This set makes it possible to efficiently classify TACI(hi) and TACI(lo) MMCs in an independent cohort of 40 patients. TACI(hi) MMCs displayed a mature plasma cell gene signature, indicating dependence on the BM environment. In contrast, the TACI(lo) group had a gene signature of plasmablasts, suggesting an attenuated dependence on the BM environment. Taken together, our findings suggest using gene expression profiling to identify the group of patients who might benefit most from treatment with BAFF/APRIL inhibitors.

OBJECTIVE

To compare physical and mental health outcomes of chronically ill adults, including elderly and poor subgroups, treated in health maintenance organization (HMO) and fee-for-service (FFS) systems.

METHODS

A 4-year observational study of 2235 patients (18 to 97 years of age) with hypertension, non-insulin-dependent diabetes mellitus (NIDDM), recent acute myocardial infarction, congestive heart failure, and depressive disorder sampled from HMO and FFS systems in 1986 and followed up through 1990. Those aged 65 years and older covered under Medicare and low-income patients (200% of poverty) were analyzed separately.

METHODS

Offices of physicians practicing family medicine, internal medicine, endocrinology, cardiology, and psychiatry, in HMO and FFS systems of care. Types of practices included both prepaid group (72% of patients) and independent practice association (28%) types of HMOs, large multispecialty groups, and solo or small, single-specialty practices in Boston, Mass, Chicago, Ill, and Los Angeles, Calif.

METHODS

Differences between initial and 4-year follow-up scores of summary physical and mental health scales from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) for all patients and practice settings.

RESULTS

On average, physical health declined and mental health remained stable during the 4-year follow-up period, with physical declines larger for the elderly than for the nonelderly (P<.001). In comparisons between HMO and FFS systems, physical and mental health outcomes did not differ for the average patient; however, they did differ for subgroups of the population differing in age and poverty status. For elderly patients (those aged 65 years and older) treated under Medicare, declines in physical health were more common in HMOs than in FFS plans (54% vs 28%; P<.001). In 1 site, mental health outcomes were better (P<.05) for elderly patients in HMOs relative to FFS but not in 2 other sites. For patients differing in poverty status, opposite patterns of physical health (P<.05) and for mental health (P<.001) outcomes were observed across systems; outcomes favored FFS over HMOs for the poverty group and favored HMOs over FFS for the nonpoverty group.

CONCLUSIONS

During the study period, elderly and poor chronically ill patients had worse physical health outcomes in HMOs than in FFS systems; mental health outcomes varied by study site and patient characteristics. Current health care plans should carefully monitor the health outcomes of these vulnerable subgroups.

BACKGROUND

There is a dearth of validated information about lesbian and bisexual women's health. To better understand some of these issues, we used population-based data to assess variations in health behaviors, health status, and access to and use of health care based on sexual orientation.

METHODS

Our study population was drawn from a population-based sample of women, the 1997 Los Angeles County Health Survey. Participants reported their sexual orientation and these analyses included 4697 women: 4610 heterosexual women, 51 lesbians, and 36 bisexual women. We calculated adjusted relative risks to assess the effect of sexual orientation on important health issues.

RESULTS

Lesbians and bisexual women were more likely than heterosexual women to use tobacco products and to report any alcohol consumption, but only lesbians were significantly more likely than heterosexual women to drink heavily. Lesbians and bisexual women were less likely than heterosexual women to have health insurance, more likely to have been uninsured for health care during the preceding year, and more likely to have had difficulty obtaining needed medical care. During the preceding 2 years, lesbians, but not bisexual women, were less likely than heterosexual women to have had a Papanicolaou test and a clinical breast examination.

CONCLUSIONS

In this first population-based study of lesbian and bisexual women's health, we found that lesbians and bisexual women were more likely than heterosexual women to have poor health behaviors and worse access to health care. These findings support our hypothesis that sexual orientation has an independent effect on health behaviors and receipt of care, and indicate the need for the increased systematic study of the relationship between sexual orientation and various aspects of health and health care. Arch Fam Med. 2000;9:1043-1051

OBJECTIVE

The Pittsburgh Sleep Quality Index (PSQI) is widely used to assess subjective sleep disturbances in psychiatric, medical, and healthy adult and older adult populations. Yet, validation of the PSQI single-factor scoring has not been carried out.

METHODS

The PSQI was administered as a self-report questionnaire. Using a cross-validation approach, scores from the PSQI were analyzed with exploratory and confirmatory factor analyses.

METHODS

San Diego, Denver, and Los Angeles community-based clinics.

METHODS

Community-dwelling depressed and nondepressed adults older that 60 years of age (N = 417)

RESULTS

Results yielded a 3-factor scoring model that obtained a measure of perfect fit and was significantly better fitted than either the original single-factor model or a 2-factor model. Components of the 3 factors were characterized by the descriptors sleep efficiency, perceived sleep quality, and daily disturbances.

CONCLUSIONS

These findings validate the factor structure of the PSQI and demonstrate that a 3-factor score should be used to assess disturbances in three separate factors of subjective sleep reports.