Late onset sepsis (LOS) is a major contributor to neonatal morbidity and mortality, especially in premature infants. Distortions in the establishment of normal gut microbiota, commensal microbes that colonize the digestive tract, might increase the risk of LOS via disruption of the mucosal barrier with resultant translocation of luminal contents. Correlation of distortions of the intestinal microbiota with LOS is a necessary first step to design novel microbiota-based screening approaches that might lead to early interventions to prevent LOS in high risk infants. Using a case/control design nested in a cohort study of preterm infants, we analyzed stool samples that had been prospectively collected from ten preterm infants with LOS and from 18 matched controls. A 16S rRNA based approach was utilized to compare microbiota diversity and identify specific bacterial signatures that differed in their prevalence between cases and controls. Overall α-diversity (Chao1) was lower in cases two weeks before (p<0.05) but not one week before or at the time of diagnosis of LOS. Overall microbiota structure (Unifrac) appeared distinct in cases 2 weeks and 1 week before but not at diagnosis (p<0.05). Although we detected few operational taxonomic units (OTUs) unique or enriched in cases, we found many OTUs common in controls that were lacking in cases (p<0.01). Bifidobacteria counts were lower in cases at all time points. Our results support the hypothesis that a distortion in normal microbiota composition, and not an enrichment of potential pathogens, is associated with LOS in preterm infants.

BACKGROUND

Right heart failure (RHF) is not an infrequent complication of left ventricular assist device (LVAD) implantation. Few studies have examined outcomes for LVAD patients who subsequently develop RHF. This study details one center's experience with RHF in chronic congestive heart failure (CHF) patients.

METHODS

One hundred eight patients with chronic CHF >>or=6 months) who underwent HeartMate LVAD implantation were identified during June 1996 to July 2004. Acute heart failure patients requiring LVADs were excluded to eliminate the impact of confounding non-cardiac factors. RHF was defined as the need for a subsequent right ventricular assist device (RVAD),>>or=14 days of intravenous inotropes/pulmonary vasodilators, or both. Forty-two (38.9%) RHF patients were identified. Fourteen of these required RVAD insertion. Outcome parameters included early (<or=30-day) mortality, intensive care unit (ICU) length of stay (<em>LOS</em>), incidence of re-operation for bleeding and acute renal failure, and stroke, bridge-to-transplantation rate and post-transplantation survival rate.

RESULTS

More female patients developed RHF than not (73.3% vs 26.7%, p = 0.003). RHF patients had a higher early mortality rate, greater ICU LOS, higher rates of re-operation for bleeding and renal failure, and lower bridge-to-transplantation rate than non-RHF patients (19.0% vs 6.2%, p = 0.039; 23.8 +/- 23.7 vs 9.6 +/- 7.1 days, p < 0.001; 38.9% vs 18.3%, p = 0.026; 61.0% vs 22.6%, p < 0.001; 65.0% vs 89.9%, p = 0.003; respectively). Fourteen (33.3%) RHF patients required RVAD insertion. Elevated intra-operative central venous pressure (CVP) was found to be an independent predictor of post-LVAD RHF. Overall bridge-to-transplantation rate for the entire study cohort was 73.1%.

CONCLUSIONS

The development of RHF after LVAD insertion confers significant morbidity and mortality. Judicious application of inotropes and pulmonary vasodilators and timely RVAD insertion, if necessary, should be maintained. Further investigations evaluating pre- and intra-operative risk factors for the development of RHF are warranted.

We recently demonstrated that Campylobacter jejuni produces a capsular polysaccharide (CPS) that is the major antigenic component of the classical Penner serotyping system distinguishing Campylobacter into >60 groups. Although the wide variety of C. jejuni serotypes are suggestive of structural differences in CPS, the genetic mechanisms of such differences are unknown. In this study we sequenced biosynthetic cps regions, ranging in size from 15 to 34 kb, from selected C. jejuni strains of HS:1, HS:19, HS:23, HS:36, HS:23/36 and HS:41 serotypes. Comparison of the determined cps sequences of the HS:1, HS:19 and HS:41 strains with the sequenced strain, NCTC11168 (HS:2), provides evidence for multiple mechanisms of structural variation including exchange of capsular genes and entire clusters by horizontal transfer, gene duplication, deletion, fusion and contingency gene variation. In contrast, the HS:23, HS:36 and HS:23/36 cps sequences were highly conserved. We report the first detailed structural analysis of 81-176 (HS:23/36) and G1 (HS:1) and refine the previous structural interpretations of the HS:19, HS:23, HS:36 and HS:41 serostrains. For the first time, we demonstrate the commonality and function of a second heptose biosynthetic pathway for Campylobacter CPS independent of the pathway for lipooligosaccharide (LOS) biosynthesis and identify a novel heptosyltransferase utilized by this alternate pathway. Furthermore, we show the retention of two functional heptose isomerases in Campylobacter and the sharing of a phosphatase for both LOS and CPS heptose biosynthesis.

OBJECTIVE

The long-term durability of Guglielmi detachable coil (GDC) embolization of cerebral aneurysms is still unknown. The purpose of this study was to evaluate the anatomical evolution of neck remnants in aneurysms treated with GDCs.

METHODS

Of 455 aneurysms treated with GDCs from 1990 to 1998 at the University of California at Los Angeles Medical Center, 178 aneurysms (39%) had residual necks postembolization. Long-term follow-up angiograms were obtained in 73 of these aneurysms in 71 patients. The mean duration of angiographic follow up was 17.3 months. Twenty-four of the aneurysms were small with small necks, 24 were small with wide necks, 15 were large, and 10 were giant aneurysms. In small aneurysms with small necks, postembolization angiography revealed 12 aneurysms (50%) with progressive thrombosis, eight (33%) unchanged, and four (17%) with recanalization. In small aneurysms with wide necks, six (25%) had progressive thrombosis, eight (33%) remained unchanged, and 10 (42%) had recanalization. In large aneurysms, two (13%) were unchanged and 13 (87%) had recanalization. Of the giant aneurysms only one (10%) remained unchanged and nine (90%) had recanalization. Overall, 18 aneurysms (25%) exhibited progressive thrombosis, 19 (26%) remained unchanged, and 36 (49%) displayed recanalization on follow-up angiography. During the last 2 years of the study, the recanalization rate decreased and a higher rate of progressive thrombosis was noted in aneurysms with small necks. These positive changes are related to important new technical developments.

CONCLUSIONS

Treatment with GDCs appears to be effective and the results permanent in most small aneurysms with small necks. However, there are important technical limitations in the current GDC technology that prevent recanalization in wide-necked or large or giant aneurysms.

Several simplified membrane models featuring coexisting liquid disordered (Ld) and ordered (Lo) lipid phases have been developed to mimic the heterogeneous organization of cellular membranes, and thus, aid our understanding of the nature and functional role of ordered lipid-protein nanodomains, termed "rafts". In spite of their greatly reduced complexity, quantitative characterization of local lipid environments using model membranes is not trivial, and the parallels that can be drawn to cellular membranes are not always evident. Similarly, various fluorescently labeled lipid analogs have been used to study membrane organization and function in vitro, although the biological activity of these probes in relation to their native counterparts often remains uncharacterized. This is particularly true for raft-preferring lipids ("raft lipids", e.g. sphingolipids and sterols), whose domain preference is a strict function of their molecular architecture, and is thus susceptible to disruption by fluorescence labeling. Here, we analyze the phase partitioning of a multitude of fluorescent raft lipid analogs in synthetic Giant Unilamellar Vesicles (GUVs) and cell-derived Giant Plasma Membrane Vesicles (GPMVs). We observe complex partitioning behavior dependent on label size, polarity, charge and position, lipid headgroup, and membrane composition. Several of the raft lipid analogs partitioned into the ordered phase in GPMVs, in contrast to fully synthetic GUVs, in which most raft lipid analogs mis-partitioned to the disordered phase. This behavior correlates with the greatly enhanced order difference between coexisting phases in the synthetic system. In addition, not only partitioning, but also ligand binding of the lipids is perturbed upon labeling: while cholera toxin B binds unlabeled GM1 in the Lo phase, it binds fluorescently labeled GMI exclusively in the Ld phase. Fluorescence correlation spectroscopy (FCS) by stimulated emission depletion (STED) nanoscopy on intact cellular plasma membranes consistently reveals a constant level of confined diffusion for raft lipid analogs that vary greatly in their partitioning behavior, suggesting different physicochemical bases for these phenomena.

BACKGROUND

The prevalence of autistic disorder (AD), a serious developmental condition, has risen dramatically over the past two decades, but high-quality population-based research addressing etiology is limited.

OBJECTIVE

We studied the influence of exposures to traffic-related air pollution during pregnancy on the development of autism using data from air monitoring stations and a land use regression (LUR) model to estimate exposures.

METHODS

Children of mothers who gave birth in Los Angeles, California, who were diagnosed with a primary AD diagnosis at 3-5 years of age during 1998-2009 were identified through the California Department of Developmental Services and linked to 1995-2006 California birth certificates. For 7,603 children with autism and 10 controls per case matched by sex, birth year, and minimum gestational age, birth addresses were mapped and linked to the nearest air monitoring station and a LUR model. We used conditional logistic regression, adjusting for maternal and perinatal characteristics including indicators of SES.

RESULTS

Per interquartile range (IQR) increase, we estimated a 12-15% relative increase in odds of autism for ozone [odds ratio (OR) = 1.12, 95% CI: 1.06, 1.19; per 11.54-ppb increase] and particulate matter ≤ 2.5 µm (OR = 1.15; 95% CI: 1.06, 1.24; per 4.68-μg/m3 increase) when mutually adjusting for both pollutants. Furthermore, we estimated 3-9% relative increases in odds per IQR increase for LUR-based nitric oxide and nitrogen dioxide exposure estimates. LUR-based associations were strongest for children of mothers with less than a high school education.

CONCLUSIONS

Measured and estimated exposures from ambient pollutant monitors and LUR model suggest associations between autism and prenatal air pollution exposure, mostly related to traffic sources.

OBJECTIVE

To examine the association between severity of visual field loss (VFL) and self-reported health-related quality of life (HRQOL) in a population-based sample.

METHODS

Population-based cross-sectional study.

METHODS

Participants in the Los Angeles Latino Eye Study (LALES) underwent a comprehensive ophthalmic examination including visual field testing by the Humphrey Automated Field Analyzer II (Swedish Interactive Thresholding Algorithm [SITA] Standard 24-2) [Carl Zeiss Meditec, Dublin, California, USA]. Mean deviation (MD) scores were used to determine severity of VFL both as a continuous variable and stratified by severity: no VFL (MD>>or= -2 decibels [dB]), mild VFL (-6 dB < MD < -2 dB), and moderate to severe VFL (MD < -6 dB). HRQOL was assessed by the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) and the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). Linear regression analyses and analysis of covariance were used to assess the relationship between HRQOL scores and VFL.

RESULTS

Of the 5,213 participants included in this study, 18% had unilateral mild, 1.5% unilateral moderate to severe, 19% bilateral mild, and 6.5% bilateral moderate to severe VFL. Worse NEI-VFQ-25 and SF-12 HRQOL scores were associated with VFL in a linear manner. Four- to 5-dB differences in VFL were associated with a five-point difference in the NEI-VFQ-25 composite and most subscale scores. Persons with VFL had the greatest difficulty with driving activities, dependency, mental health, distance vision, and peripheral vision.

CONCLUSIONS

HRQOL is diminished even in persons with relatively mild VFL on the basis of MD scores. Prevention and management of persons with VFL may be important in preventing or reducing poor HRQOL related to difficulties in driving, distance and peripheral vision activities, and a sense of dependency.

OBJECTIVE

Providing active assistance to complete desired arm movements is a common technique in upper extremity rehabilitation after stroke. Such active assistance may improve recovery by affecting somatosensory input, motor planning, spasticity or soft tissue properties, but it is labor intensive and has not been validated in controlled trials. The purpose of this study was to investigate the effects of robotically administered active-assistive exercise and compare those with free reaching voluntary exercise in improving arm movement ability after chronic stroke.

METHODS

Nineteen individuals at least one year post-stroke were randomized into one of two groups. One group performed 24 sessions of active-assistive reaching exercise with a simple robotic device, while a second group performed a task-matched amount of unassisted reaching. The main outcome measures were range and speed of supported arm movement, range, straightness and smoothness of unsupported reaching, and the Rancho Los Amigos Functional Test of Upper Extremity Function.

CONCLUSIONS

There were significant improvements with training for range of motion and velocity of supported reaching, straightness of unsupported reaching, and functional movement ability. These improvements were not significantly different between the two training groups. The group that performed unassisted reaching exercise improved the smoothness of their reaching movements more than the robot-assisted group.

CONCLUSIONS

Improvements with both forms of exercise confirmed that repeated, task-related voluntary activation of the damaged motor system is a key stimulus to motor recovery following chronic stroke. Robotically assisting in reaching successfully improved arm movement ability, although it did not provide any detectable, additional value beyond the movement practice that occurred concurrently with it. The inability to detect any additional value of robot-assisted reaching may have been due to this pilot study's limited sample size, the specific diagnoses of the participants, or the inclusion of only individuals with chronic stroke.

This population-based study was undertaken to obtain information on age-, sex-, and race-specific incidence of nonarteritic and arteritic anterior ischemic optic neuropathy for the State of Missouri and for Los Angeles County, California. Among subjects who were 50 or older the estimated mean annual incidence rates per 100,000 population were 2.30 for nonarteritic anterior ischemic optic neuropathy and 0.36 for arteritic anterior ischemic optic neuropathy. White individuals appear to be at significantly higher risk of developing nonarteritic anterior ischemic optic neuropathy than black or Hispanic individuals, suggesting possible genetic predisposition.

Introduction: COVID-19 pandemic, declared on March 11, 2020, constitute an extraordinary health, social and economic global challenge. The impact on people's mental health is expected to be high. This paper sought to systematically review community-based studies on depression conducted during the COVID-19 and estimate the pooled prevalence of depression.

Method: We searched for cross-sectional, community-based studies listed on PubMed or Web of Science from January 1, 2020 to May 8, 2020 that reported prevalence of depression. A random effect model was used to estimate the pooled proportion of depression.

<strong class="sub-title"> Results: </strong> A total of 12 studies were included in the meta-analysis, with prevalence rates of depression ranging from 7.45% to 48.30%. The pooled prevalence of depression was 25% (95% CI: 18% - 33%), with significant heterogeneity between studies (<i>I</i> ^<i>2</i> = 99.60%, <i>p</i> < .001).

Conclusions: Compared with a global estimated prevalence of depression of 3.44% in 2017, our pooled prevalence of 25% appears to be 7 times higher, thus suggesting an important impact of the COVID-19 outbreak on people's mental health. Addressing mental health during and after this global health crisis should be placed into the international and national public health agenda to improve citizens' wellbeing.

Introducción: La pandemia de COVID-19, declarada el 11 de marzo de 2020, representa un reto global extraordinario a nivel sanitario, social y económico. Se espera un impacto alto en la salud mental de las personas. Este artículo tiene como objetivo realizar una revisión sistemática de estudios transversales basados en muestras comunitarias que proporcionaban la prevalencia de depresión durante la crisis del COVID-19.

Método: Se realizó una búsqueda de estudios comunitarios publicados en Pubmed y Web of Science desde el 1 de enero del 2020 al 8 de mayo del 2020 y que informaron prevalencia de depresión. Se usó un modelo de efectos aleatorios para estimar la proporción agrupada de depresión.

<strong class="sub-title"> Resultados: </strong> Un total de 12 estudios fueron incluidos en el meta-análisis, con prevalencias de depresión que oscilaban entre 7,45% y 48,30%. La prevalencia agrupada de depresión fue de 25% (95% CI: 18%-33%), con heterogeneidad significativa entre estudios (<i>I</i> ^<i>2</i> = 99,60%, <i>p</i> < 0,001).

Conclusiones: En comparación con una estimación global de depresión en 2017 del 3,44%, nuestra prevalencia agrupada del 25% es 7 veces mayor, sugiriendo un impacto importante del brote de COVID-19 en la salud mental de las personas. El abordaje de la salud mental durante y después de esta crisis global sanitaria debe ser parte de las agendas de salud pública nacionales e internacionales para mejorar el bienestar de los ciudadanos.

Keywords: COVID-19; Depression; community-based studies; meta-analysis; prevalence.

OBJECTIVE

To determine the extent that demographics, clinical characteristics, comorbidities, and complications contribute to the risk of in-hospital mortality and morbidity in acute stroke.

METHODS

Data of consecutive patients admitted to 14 stroke units cooperating within the Berlin Stroke Register were analyzed. The association of demographics, clinical characteristics, comorbidities, and complications with the risk of in-hospital death and poor outcome at discharge was assessed, and independent attributable risks were calculated, applying average sequential attributable fractions.

RESULTS

In a 3-year period, 16,518 consecutive patients with ischemic or hemorrhagic stroke were documented. In-hospital mortality was 5.4%, and 45.7% had a poor outcome (modifed Rankin Scale score ≥3). In patients with length of stay (LOS) ≤7 days, 37.5% of in-hospital deaths were attributed to stroke severity, 23.1% to sociodemographics (age and prestroke disability), and 28.9% to increased intracranial pressure (iICP) and other complications. In those with LOS >7 days, age and stroke severity accounted for 44.1%, whereas pneumonia (12.2%), other complications (12.6%), and iICP (8.3%) contributed to one-third of in-hospital deaths. For poor outcome, attributable risks were similar for prestroke disability, stroke severity, pneumonia, and other complications regardless of the patient's LOS.

CONCLUSIONS

Approximately two-thirds of early death and poor outcome in acute stroke is attributed to nonmodifiable predictors, whereas main modifiable factors are early complications such as iICP, pneumonia, or other complications, on which stroke unit treatment should focus to further improve the prognosis of acute stroke.

CD11c(hi) dendritic cells (DC) play an essential role during the initiation of cell-mediated immunity. Recently, CD11c(lo)CD45RB(hi) DC with regulatory properties have been described. However, the origins of regulatory DC are poorly understood. Here, we show that spleen-derived stromal cells promote selective development of CD11c(lo)CD45RB(+) IL-10-producing regulatory DC from lineage-negative c-kit(+) progenitor cells. These DC have the capacity to suppress T cell responses and induce IL-10-producing regulatory T cells in vitro and to induce antigen-specific tolerance in vivo. Furthermore, stromal cells from mice infected with Leishmania donovani more effectively supported differentiation of these highly potent regulatory DC. The ability of tissue stromal cells to direct the development of DC with a regulatory phenotype thus provides a new mechanism for local immune regulation.

Isogenic ftsZ, ftsQ, ftsA, pbpB, and ftsE cell division mutants of Escherichia coli were compared with their parent strain in temperature shift experiments. To improve detection of phenotypic differences in division behavior and cell shape, the strains were grown in glucose-minimal medium with a decreased osmolality (about 100 mosM). Already at the premissive temperature, all mutants, particularly the pbpB and ftsQ mutants, showed an increased average cell length and cell mass. The pbpB and ftsQ mutants also exhibited a prolonged duration of the constriction period. All strains, except ftsZ, continued to initiate new constrictions at 42 degrees C, suggesting the involvement of FtsZ in an early step of the constriction process. The new constrictions were blunt in ftsQ and more pronounced in ftsA and pbpB filaments, which also had elongated median constrictions. Whereas the latter strains showed a slow recovery of cell division after a shift back to the permissive temperature, ftsZ and ftsQ filaments recovered quickly. Recovery of filaments occurred in all strains by the separation of newborn cells with an average length of two times LO, the length of newborn cells at the permissive temperature. The increased size of the newborn cells could indicate that the cell division machinery recovers too slowly to create normal-sized cells. Our results indicate a phenotypic resemblance between ftsA and pbpB mutants and suggest that the cell division gene products function in the order FtsZ-FtsQ-FtsA, PBP3. The ftsE mutant continued to constrict and divide at 42 degrees C, forming short filaments, which recovered quickly after a shift back to the permissive temperature. After prolonged growth at 42 degree C, chains of cells, which eventually swelled up, were formed. Although the ftsE mutant produced filaments in broth medium at the restrictive temperature, it cannot be considered a cell division mutant under the presently applied conditions.

BACKGROUND

The US Centers for Disease Control and Prevention (CDC) strongly recommend comprehensive risk counceling and services for people living with HIV (PLH); yet, there are no evidence-based counseling protocols.

OBJECTIVE

To examine the effect of a 15-session, individually delivered, cognitive behavioral intervention on a diverse sample of PLH at risk of transmitting to others.

METHODS

This was a multisite, 2-group, randomized, controlled trial.

METHODS

Nine hundred thirty-six HIV-infected participants considered to be at risk of transmitting HIV of 3818 persons screened were randomized into the trial. Participants were recruited in Los Angeles, Milwaukee, New York, and San Francisco.

METHODS

Fifteen 90-minute individually delivered intervention sessions were divided into 3 modules: stress, coping, and adjustment; safer behaviors; and health behaviors. The control group received no intervention until the trial was completed. Both groups completed follow-up assessments at 5, 10, 15, 20, and 25 months after randomization.

METHODS

Transmission risk, as measured by the number of unprotected sexual risk acts with persons of HIV-negative or unknown status, was the main outcome measure.

RESULTS

Overall, a significance difference in mean transmission risk acts was shown between the intervention and control arms over 5 to 25 months (chi2 = 16.0, degrees of freedom = 5; P = 0.007). The greatest reduction occurred at the 20-month follow-up, with a 36% reduction in the intervention group compared with the control group.

CONCLUSIONS

Cognitive behavioral intervention programs can effectively reduce the potential of HIV transmission to others among PLH who report significant transmission risk behavior.

BACKGROUND

Total hip arthroplasty is a common surgical procedure but little is known about longitudinal trends.

OBJECTIVE

To examine demographics and outcomes of patients undergoing primary and revision total hip arthroplasty.

METHODS

Observational cohort of 1,453,493 Medicare Part A beneficiaries who underwent primary total hip arthroplasty and 348,596 who underwent revision total hip arthroplasty. Participants were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes for primary and revision total hip arthroplasty between 1991 and 2008.

METHODS

Changes in patient demographics and comorbidity, hospital length of stay (LOS), mortality, discharge disposition, and all-cause readmission rates.

RESULTS

Between 1991 and 2008, the mean age for patients undergoing primary total hip arthroplasty increased from 74.1 to 75.1 years and for revision total hip arthroplasty from 75.8 to 77.3 years (P < .001). The mean number of comorbid illnesses per patient increased from 1.0 to 2.0 for primary total hip arthroplasty and 1.1 to 2.3 for revision (P < .001). For primary total hip arthroplasty, mean hospital LOS decreased from 9.1 days in 1991-1992 to 3.7 days in 2007-2008 (P = .002); unadjusted in-hospital and 30-day mortality decreased from 0.5% to 0.2% and from 0.7% to 0.4%, respectively (P < .001). The proportion of primary total hip arthroplasty patients discharged home declined from 68.0% to 48.2%; the proportion discharged to skilled care increased from 17.8% to 34.3%; and 30-day all-cause readmission increased from 5.9% to 8.5% (P < .001). For revision total hip arthroplasty, similar trends were observed in hospital LOS, in-hospital mortality, discharge disposition, and hospital readmission rates.

CONCLUSIONS

Among Medicare beneficiaries who underwent primary and revision hip arthroplasty between 1991 and 2008, there was a decrease in hospital LOS but an increase in the rates of discharge to postacute care and readmission.

Health-related information from multiple sources was collected on 334 women living in two predominantly white, affluent retirement communities near Los Angeles as part of a case-control study of a serious chronic disease (cancer of the breast) conducted in 1977-1978. There was no evidence on interview of cases preferentially recalling more drug use or past diseases than controls. Agreement between interview and medical record for all disease conditions studied as well as for height, weight, and most menstrual and reproductive variables was of the order of 90% or better. Age at last menstrual period as reported on inerview did not correspond particularly well with that recorded on the medical record. Agreement between data sources for ever/never drug use varied considerably with the type of drug studied, from a low of 69% for use of barbiturates and related drugs to a high of 87% for use of antihypertensive medications. Estrogen usage information was collected in detail. Better correspondence was observed between medical record and interview than between either medical and pharmacy records or interview and pharmacy records.

Five homosexual men dying at UCLA Center for the Health Sciences, Los Angeles, with acquired immunodeficiency and Pneumocystis pneumonia, Kaposi's sarcoma, or cryptosporidiosis since May 1981 have all had mycobacteria of the Mycobacterium avium-intracellulare complex cultured from tissues taken just before death or at postmortem examination. Each man had histological evidence of disseminated mycobacterial infection. Acid-fast organisms were seen in macrophages in the lung, spleen, and lymph nodes in all cases and in a variety of additional organs in two cases. Other severe infections were always found at postmortem examination--cytomegalovirus, cryptosporidiosis, and Pneumocystis. Disseminated M avium-intracellulare infection has been so striking in homosexual males dying with acquired immunodeficiency at our institution that we believe a vigorous search for mycobacteria should be made in all such patients. Empiric therapy for mycobacterial infection may be justified in selected cases of immunodeficiency before a specific microbiological diagnosis.

Oxidative modification of LDL increases its atherogenicity, and 15-lipoxygenase (15-LO) has been implicated in the process. To address this issue, we generated transgenic rabbits that expressed 15-LO in a macrophage-specific manner and studied their susceptibility to atherosclerosis development when they were fed a high-fat, high-cholesterol (HFHC) diet (Teklad 0533 rabbit diet 7009 with 10% corn oil and 0.25% cholesterol) for 13.5 wk. Transgenic and nontransgenic rabbits developed similar degrees of hypercholesterolemia and had similar levels of triglyceride, VLDL, LDL, and HDL. Quantitative morphometric analysis of the aortic atherosclerosis indicated that the transgenic animals (n = 19) had significantly smaller lesion areas (9.8+/-6.5%, mean+/-SD) than their littermate controls (n = 14, 17.8+/-15.0%) (P < 0.05). In a subgroup (n = 9) of transgenic rabbits that received the HFHC diet plus the antioxidant N',N '-diphenyl-phenylenediamine (1%), the extent of lesion involvement (9.8+/-7.5%) did not differ from the subgroup (n = 10) that received the regular HFHC diet (9.7+/-5.9%). Since the results were unexpected, we repeated the experiments. Again, we found that the nontransgenic littermates (n = 12) had more extensive lesions (11.6+/-10.6%) than the transgenic rabbits (n = 13; 9.5+/-7.8%), although the difference was not significant. In a third set of experiments, we crossed 15-LO transgenic rabbits with Watanabe heritable hyperlipidemic (WHHL) rabbits and found that the lesion area in the 15-LO transgenic/heterozygous WHHL rabbits (n = 14) was only about one third (7.7+/-5.7%) that found in nontransgenic heterozygous WHHL littermate controls (n = 11, 20.7+/-19.4%) (P < 0.05). These data suggest that overexpression of 15-LO in monocytes/macrophages protects against lipid deposition in the vessel wall during early atherogenesis in these rabbit models of atherosclerosis.

BACKGROUND

The Veterans Health Administration, the American Cancer Society, and the American Geriatrics Society recommend colorectal cancer screening for older adults unless they are unlikely to live 5 years or have significant comorbidity that would preclude treatment.

OBJECTIVE

To determine whether colorectal cancer screening is targeted to healthy older patients and is avoided in older patients with severe comorbidity who have life expectancies of 5 years or less.

METHODS

Cohort study.

METHODS

Veterans Affairs (VA) medical centers in Minneapolis, Minnesota; Durham, North Carolina; Portland, Oregon; and West Los Angeles, California, with linked national VA and Medicare administrative claims.

METHODS

27 068 patients 70 years or older who had an outpatient visit at 1 of 4 VA medical centers in 2001 or 2002 and were due for screening.

METHODS

The main outcome was receipt of fecal occult blood testing (FOBT), colonoscopy, sigmoidoscopy, or barium enema in 2001 or 2002, on the basis of national VA and Medicare claims. Charlson-Deyo comorbidity scores at the start of 2001 were used to stratify patients into 3 groups ranging from no comorbidity (score of 0) to severe comorbidity (score>> or =4), and 5-year mortality was determined for each group.

RESULTS

46% of patients were screened from 2001 through 2002. Only 47% of patients with no comorbidity were screened despite having life expectancies greater than 5 years (5-year mortality, 19%). Although the incidence of screening decreased with age and worsening comorbidity, it was still 41% for patients with severe comorbidity who had life expectancies less than 5 years (5-year mortality, 55%). The number of VA outpatient visits predicted screening independent of comorbidity, such that patients with severe comorbidity and 4 or more visits had screening rates similar to or higher than those of healthier patients with fewer visits.

CONCLUSIONS

Some tests may have been performed for nonscreening reasons. The generalizability of findings to persons who do not use the VA system is uncertain.

CONCLUSIONS

Advancing age was inversely associated with colorectal cancer screening, whereas comorbidity was a weaker predictor. More attention to comorbidity is needed to better target screening to older patients with substantial life expectancies and avoid screening older patients with limited life expectancies. primary funding source: VA Health Services Research and Development.

OBJECTIVE

To assess the ability of internists to identify functional disabilities reported by their patients.

METHODS

Comparison of responses by physicians and a random sample of their patients to a 12-item questionnaire about physical and social function.

METHODS

A hospital-based internal medicine group practice in Boston, Massachusetts, and selected office-based internal medicine practices in Los Angeles, California.

METHODS

Five staff physicians, three general internal medicine fellows, and 34 internal medicine residents in the hospital-based practice and 178 of their patients. Seventy-six physicians in the office-based practices and 230 of their patients.

RESULTS

Physicians underestimated or failed to recognize 66% of disabilities reported by patients. Patient-reported disabilities were underestimated or unrecognized more often in the hospital-based practice than in the office-based practices (75% compared with 60%, P less than 0.05). Physicians overstated functional impairment in 21% of paired responses in which patients reported no disability.

CONCLUSIONS

Physicians often underestimate or fail to recognize functional disabilities that are reported by their patients. They overstate functional impairment to a lesser degree. Because these discrepancies may adversely affect patient care and well-being, medical educators and clinicians should pay more attention to the assessment of patient function.

Dozens of human immunodeficiency virus-type 1 (HIV-1) vaccine candidates specifically designed to elicit cytotoxic T-lymphocyte (CTL) responses have entered the pipeline of clinical trials. Evaluating the immunogenicity and potential efficacy of these HIV-1 vaccine candidates is challenging in the face of the extensive viral genetic diversity of circulating strains. Standardized peptide reagents to define the magnitude and potential breadth of the T-cell response, especially to circulating strains of HIV-1, are needed. For this purpose we developed a biometric approach based on T-cell recognition pattern for defining standardized reagents. Circulating strains in the Los Alamos database were evaluated and standardized algorithms to define all potential T-cell epitopes (PTEs) were generated. While many unique PTEs could be identified, a finite number based upon prevalence of circulating strains in the database, which we define as vaccine-important PTEs (VIPs), were used to select a common standardized panel of HIV-1 peptides for CTL-based vaccine evaluation. The usability of PTE peptide set was manifested by detection of Nef-specific CTL responses in HIV-1 subtype B infections.

BACKGROUND

Mice lacking leukocyte type 12/15-lipoxygenase (12/15-LO) show reduced atherosclerosis in several models. 12/15-LO is expressed in a variety of cells, including vascular cells, adipocytes, macrophages, and cardiomyocytes. The purpose of this study was to determine which cellular source of 12/15-LO is important for atherosclerosis.

RESULTS

Bone marrow from 12/15-LO-/-/apoE-/- mice was transplanted into apoE-/- mice and vice versa. Deficiency of 12/15-LO in bone marrow cells protected apoE-/- mice fed a Western diet from atherosclerosis to the same extent as complete absence of 12/15-LO, although plasma 8,12-iso-iPF2alpha-IV, a measure of lipid peroxidation, remained elevated. 12/15-LO-/-/apoE-/- mice regained the severity of atherosclerotic lesion typical of apoE-/- mice after replacement of their bone marrow cells with bone marrow from apoE-/- mice. Peritoneal macrophages obtained from wild-type but not 12/15-LO-/- mice caused endothelial activation in the presence of native LDL. Absence of 12/15-LO decreased the ability of macrophages to form foam cells when exposed to LDL.

CONCLUSIONS

We conclude that macrophage 12/15-LO plays a dominant role in the development of atherosclerosis by promoting endothelial inflammation and foam cell formation.

Lifetime and current prevalence of Diagnostic Interview Schedule/DSM-III disorders were determined for a probability sample of homeless adults in the Skid Row area of Los Angeles. Compared with findings from a household sample, prevalence was substantially higher for every disorder assessed. Rates of major mental illnesses were the most disproportionately high. Substance abuse was more highly prevalent among older individuals and Native Americans, while schizophrenia was most highly prevalent among those subjects between 31 and 40 years of age. Rates of both substance abuse and schizophrenia were elevated among individuals who had been homeless many times or for long periods of time. It was estimated that 28% of subjects in this inner-city homeless sample were chronically mentally ill, a percentage that was consistent with results of well-designed studies employing nondiagnostic standardized measures of mental illness, but lower than results of studies relying on clinical judgment to assess the prevalence of specific disorders. There is a need for simultaneous attention to the social welfare and mental health needs of homeless mentally ill individuals.

Adult mammals cycle between periods of sleep and wakefulness. Recent assessments of these cycles in humans and other mammals indicate that sleep bout durations exhibit an exponential distribution, whereas wake bout durations exhibit a power-law distribution. Moreover, it was found that wake bout distributions, but not sleep bout distributions, exhibit scale invariance across mammals of different body sizes. Here we test the generalizability of these findings by examining the distributions of sleep and wake bout durations in infant rats between 2 and 21 days of age. In agreement with Lo et al., we find that sleep bout durations exhibit exponential distributions at all ages examined. In contrast, however, wake bout durations also exhibit exponential distributions at the younger ages, with a clear power-law distribution only emerging at the older ages. Further analyses failed to find substantial evidence either of short- or long-term correlations in the data, thus suggesting that the durations of current sleep and wake bouts evolve through time without memory of the durations of preceding bouts. These findings further support the notion that bouts of sleep and wakefulness are regulated independently. Moreover, in light of recent evidence that developmental changes in sleep and wake bouts can be attributed in part to increasing forebrain influences, these findings suggest the possibility of identifying specific neural circuits that modulate the changing complexity of sleep and wake dynamics during development.