Amino acid sequence variations resulting from single-nucleotide polymorphisms (SNPs) were identified using a novel mass spectrometric method. This method obtains 99+% protein sequence coverage for human hemoglobin in a single LC-microspray tandem mass spectrometry (microLC-MS/MS) experiment. Tandem mass spectrometry data was analyzed using a modified version of the computer program SEQUEST to identify the sequence variations. Conditions of sample preparation, chromatographic separation, and data collection were optimized to correctly identify amino acid changes in six variants of human hemoglobin (Hb C, Hb E, Hb D-Los Angeles, Hb G-Philadelphia, Hb Hope, and Hb S). Hemoglobin proteins were isolated and purified, dehemed, (S)-carboxyami-domethylated, and then subjected to a combination proteolytic digestion to obtain a complex peptide mixture with multiple overlaps in sequence. Reversed-phase chromatographic separation of peptides was achieved on-line with MS utilizing a robust fritless microelectrospray interface. Tandem mass spectrometry was performed on an ion trap mass spectrometer using automated data-dependent MS/MS procedures. Tandem mass spectra were collected from the five most abundant ions in each scan using dynamic and isotopic exclusion to minimize redundancy. The spectra were analyzed by a version of the SEQUEST algorithm modified to identify amino acid substations resulting from SNPs.

BACKGROUND

Postoperative atrial fibrillation (AF) is a common complication of cardiac surgery and has been associated with increased incidence of other complications and increased hospital length of stay (LOS). Prevention of AF is a reasonable clinical goal, and, consequently, many randomized trials have evaluated the effectiveness of pharmacological and nonpharmacological interventions for prevention of AF. To better understand the role of various prophylactic therapies against postoperative AF, a systematic review of evidence from randomized trials was performed.

RESULTS

Fifty-two randomized trials (controlled by placebo or routine treatment) of beta-blockers, sotalol, amiodarone, or pacing were identified by systematic literature search. The 3 drug treatments each prevented AF with the following odds ratios (ORs): beta-blockers, 0.39 (95% CI, 0.28 to 0.52); sotalol, 0.35 (95% CI, 0.26 to 0.49); and amiodarone, 0.48 (95% CI, 0.37 to 0.61). Pacing was also effective; for biatrial pacing, the OR was 0.46 (95% CI, 0.30 to 0.71). The influence of pharmacological interventions on LOS was as follows: -0.66 day (95% CI, 2.04 to 0.72) for beta-blockers; -0.40 day (95% CI, 0.87 to 0.08) for sotalol; and -0.91 day (95% CI, 1.59 to -0.23) for amiodarone. The influence for biatrial pacing was -1.54 day (95% CI, -2.85 to -0.24). The incidence of stroke was 1.2% in all the treatment groups combined and 1.4% in controls (OR, 0.90; 95% CI, 0.46 to 1.74).

CONCLUSIONS

Beta-blockers, sotalol, and amiodarone all reduce risk of postoperative AF with no marked difference between them. There is evidence that use of these drugs will reduce LOS. Biatrial pacing is a promising new treatment opportunity. There was no evidence that reducing postoperative AF reduces stroke; however, data on stroke are incomplete.

We report results of a multiple regression analysis examining associations between aggregate daily mortality counts and environmental variables in Los Angeles County, California for the period 1970 to 1979. Mortality variable included total deaths not due to accidents and violence (M), deaths due to cardiovascular causes (CV), and deaths due to respiratory causes (Resp). The environmental variables included five pollutants averaged over Los Angeles County--total oxidants (Ox), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and KM (a measure of particulate optical reflectance). Also included were three metereological variables measured at the Los Angeles International Airport--temperature (Temp), relative humidity (RH), and extinction coefficient (Bext), the latter estimated from noontime visual range. To reduce the possibility of spurious correlations arising from the shared seasonal cycles of mortality and environmental variables, seasonal cycles were removed from the data by applying a high-pass filter. Cross-correlation functions were examined to determine the lag structure of the data prior to specifying and fitting the multiple regression models relating mortality and the environmental variables. The results demonstrated significant associations of M (or CV) with Ox at lag 1, temperature, and NO2, CO, or KM. Each of the latter three variables were strongly associated with daily mortality but also were highly correlated with one another in the high-frequency band, making it impossible to uniquely estimate their separate relationships to mortality. The results of this study show that small but significant associations exist in Los Angeles County between daily mortality and three separate environmental factors: temperature, primary motor vehicle-related pollutants (e.g., CO, KM, NO2), and photochemical oxidants.

1. The role of the myoplasmic free Ca2+ concentration ([Ca2+]i) in the reduction of muscle force following contractions with stretch was investigated in single fibres from mouse toe muscle. Muscle fibres were either stretched by 25% of their optimum length (Lo) for ten tetani (Protocol I) or stretched by 50% of Lo for between ten and thirty tetani (Protocol II). Indo-1 was used to measure [Ca2+]i. 2. In each protocol the stretch series was compared with isometric controls; the stretch series always resulted in greater changes in muscle properties than in the isometric controls. The observed changes were (i) reduced tetanic force, (ii) reduced tetanic [Ca2+]i, (iii) increased resting [Ca2+]i and (iv) the greater relative reduction in force at low stimulus frequencies (30 and 50 Hz) compared with high (100 Hz). These changes were maintained for up to 60 min. 3. Stretching a resting muscle fibre had no effect on the subsequent [Ca2+]i or force. 4. Following Protocol I 10 mM caffeine restored tetanic force to pre-stretch levels. Tetanic [Ca2+]i vs. force curves were constructed pre- and post-stretch and showed that neither the maximum Ca(2+)-activated force nor the Ca2+ sensitivity of the muscle fibres post-stretch was significantly different from control. The force reduction, therefore, appears to be the result of reduced tetanic [Ca2+]i. 5. The more severe stretching regimen of Protocol II resulted in a much greater reduction in force than Protocol I. Ten millimolar caffeine did not restore control force. Comparison of the [Ca2+]i-force relationships pre- and post-stretch showed that the reduction in tetanic force was caused by a combination of a reduced tetanic [Ca2+]i, reduced maximum Ca(2+)-activated force and reduced Ca2+ sensitivity. 6. Following both protocols the resting [Ca2+]i showed a small rise which persisted for at least 60 min. This elevated [Ca2+]i was associated with a reduction in the pump rate of the sarcoplasmic reticulum Ca2+ pump. 7. This study establishes that reduced Ca2+ release and reduced Ca2+ sensitivity contribute to the reduction in force generating capacity of single mammalian muscle fibres following active stretches.

OBJECTIVE

To determine the prevalence and prognostic significance of hyperglycemia among critically ill nondiabetic children.

METHODS

We performed a retrospective cohort study using point-of-care blood glucose measurements, hospital administrative databases, and a computerized information system; 942 nondiabetic patients admitted to our Pediatric Intensive Care Unit (PICU) from October 2000 to September 2003 were included. The prevalence of hyperglycemia was based on initial PICU glucose measurement, highest value within 24 hours, and highest value measured during PICU stay up to 10 days after the first measurement. Primary outcome was in-hospital death with PICU lengths of stay (LOS) as secondary outcome.

RESULTS

Through the use of three cutoff values (120 mg/dL, 150 mg/dL, and 200 mg/dL), the prevalence of hyperglycemia was 16.7% to 75.0%. The relative risk (RR) for dying increased for maximum glucose within 24 hours >150 mg/dL (RR, 2.50; 95% confidence interval (CI), 1.26 to 4.93) and highest glucose within 10 days >120 mg/dL (RR, 5.68; 95% CI, 1.38 to 23.47). LOS was decreased for admission glucose >120 mg/dL and 150 mg/dL but increased for all threshold values for maximum glucose within 10 days.

CONCLUSIONS

Hyperglycemia occurs frequently among critically ill nondiabetic children and is correlated with a greater in-hospital mortality rate and longer LOS.

The beneficial effects of growth hormone on wound healing in severely burned children were studied. Forty patients who were 2 to 18 years old, with 40% or more total body surface area (TBSA) and 20% or more TBSA full-thickness flame or scald burns, were randomized in a double-blind study to receive placebo or 0.1 mg/kg/day recombinant human growth hormone (rHGH) until the first donor site healed or to receive 0.2 mg/kg/day rHGH or placebo from admission throughout hospitalization. Patients receiving 0.2 mg/kg/day rHGH demonstrated significantly higher serum IGF-1 levels at 4.8 +/- 1.7 U/mL compared to placebos at 1.6 +/- 0.4 U/mL (p less than 0.05) and a significant decrease in donor-site healing times compared to placebo (p less than 0.05). Length of hospital stay (LOS/%TBSA) was decreased from 0.80 +/- 0.10 days/%TBSA burned in the placebo group to 0.54 +/- 0.04 days/%TBSA burned in the 0.2 mg/kg/day treatment group (p less than 0.05). This translates, for the average 60% TBSA burned patient, to a decrease in LOS from 46 to 32 days.

To assess the impact of the aging population on the occurrence of fragility fractures, we examined hospital discharges for hip fracture among U.S. women and men aged 45 years and older from 1993 through to 2003. The number of hospitalizations declined by 5%, and age-adjusted rates fell by over 20% for both women and men during this period.

BACKGROUND

Although the aging of the population should mean an increasing burden of fragility fractures, several recently published reports suggest regional declines in the incidence of hip fracture. We investigated trends in hospital discharges and utilization for hip fractures across the USA from 1993 to 2003.

METHODS

Hospital discharges from the Nationwide Inpatient Sample from 1993 through to 2003 were analyzed for numbers of primary diagnosis of hip fracture and associated average length of stay (LOS) and charges among women and men aged 45 years and older. Age-specific rates were constructed using national census data.

RESULTS

Over the 11-year study period the number of hospitalizations for hip fractures decreased by 5%, from 296,000 to 281,000. The numbers of discharges declined by 16,600 (7.4%) for women and increased by 1900 (2.6%) among men. However, age-adjusted rates for both women and men fell by about 20%. Average hospital LOS was reduced by about 35% for both sexes, resulting in decreases in days of care of 42 and 33% for women and men, respectively. At the same time, average inflation-adjusted charges for each hospitalization grew by 35% for women and 38% for men, and increasing proportions of patients were discharged to continuing institutional care. During the study interval the total number of prescriptions per year for bisphosphonate anti-resorptive agents grew from under 0.5 to 30 million.

CONCLUSIONS

Despite the increasing size of the older segment of the U.S. population, hospitalizations for hip fractures are not increasing. With declining lengths of stay there has been a reduced demand on hospital resources, although with average charges per hospitalization rising and more patients being discharged to other institutions for continuing care the economic consequences of hip fracture continue to increase.

There are well-replicated, independent lines of evidence supporting a role for corticotropin-releasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We studied the association of CRHR1 genotypes with the phenotype of antidepressant treatment response in 80 depressed Mexican-Americans in Los Angeles who completed a prospective randomized, placebo lead-in, double-blind treatment of fluoxetine or desipramine, with active treatment for 8 weeks. Subjects were included into the study if they had a diagnosis of depression without other confounding medical or psychiatric diagnoses or treatments. All patients were followed weekly and assessed for changes in the Hamilton rating scales for anxiety (HAM-A) and depression (HAM-D). Inclusion criteria in the study included a HAM-D of 18 or higher. Because CRHR1 affects both depression and anxiety. Patients were classified into a high-anxiety (HA) group if their HAM-A score was 18 or higher and in a low-anxiety (LA) group if their HAM-A score was less than 18. Utilizing the haplotype-tag single-nucleotide polymorphisms rs1876828, rs242939 and rs242941, we tested for haplotypic association between CRHR1 and 8-week response to daily antidepressant treatment. In the HA group (n=54), homozygosity for the GAG haplotype was associated with a relative 70% greater reduction in HAM-A scores compared to heterozygous (63.1+/-4.5 vs 37.1+/-6.9%, respectively, P=0.002). For HAM-D, GAG haplotype homozygosity was associated with a 31% greater reduction in scores after treatment compared to heterozygous (67.3+/-4.3 vs 51.2+/-6.0%, respectively, P=0.03). In those with lower-anxiety levels at screening, there were no associations between CRHR1 genotype and percent change in HAM-A or HAM-D. These findings of increased response to antidepressants in highly anxious patients homozygous for the GAG haplotype of CRHR1 need to be independently validated and replicated. Such work would support the hypotheses that response to antidepressant treatment is heterogeneous and that the CRHR1 gene and possibly other genes in stress-inflammatory pathways are involved in response to antidepressant treatment. These findings also suggest that variations in the CRHR1 gene may affect response to CRHR1 agonists or antagonists. All data are deposited in www.pharmgkb.org.

Renin-angiotensin system (RAS) inhibition can attenuate the effects of aging on renal function and structure; however, its effect on mitochondrial aging is unknown. To investigate whether an angiotensin-converting enzyme inhibitor (enalapril) or an angiotensin II receptor blocker (losartan) could mitigate age-associated changes in kidney mitochondria, male Wistar rats (14 mo old) received during 8 mo water containing either enalapril (10 mg/kg/day) (Enal), or losartan (30 mg/kg/day) (Los), or no additions (Old). Four-month-old untreated rats (Young) were also studied. In Old rats mitochondrial respiratory control, ADP/O, nitric oxide synthase activity, and uncoupling protein 2 levels were lower (46, 42, 27, and 76%, respectively), and Mn-SOD activity was higher (70%) than in Young, Enal, and Los rats. In Old rats mitochondrial hydrogen peroxide production was higher than in both Young (197%) and Enal or Los (40%) rats. In Old rats, kidney GSH/GSSG was lower than in both Young (80%) and Enal (57%) or Los (68%) rats. In Old rats electron microscopy showed effacement of microvilli in tubular epithelial cells, ill-defined mitochondrial cristae, lower mitochondrial numbers, and enhanced number of osmiophilic bodies relative to Young, Enal, or Los rats. In conclusion, enalapril and losartan can protect against both age-related mitochondrial dysfunction and ultrastructural alterations, underscoring the role of RAS in the aging process. An association with oxidative stress modulation is suggested.

OBJECTIVE

Although there is considerable evidence that alcohol consumption facilitates assaultive violence, the extent to which alcohol outlets in a community influence assaultive violence remains controversial.

METHODS

To assess the geographic association between city-specific rates of assaultive violence and alcohol-outlet density, an ecologic analysis of the 74 larger cities in Los Angeles County was conducted for the 1990 reporting year.

RESULTS

Sociodemographic factors alone accounted for 70% (R2 = .70) of the variance in the rate of assaultive violence in a multiple regression model. Adding the variable for alcohol-outlet density to the model yielded a significant positive slope. The magnitude of this relation indicates that in a typical Los Angeles County city (50,000 residents, 100 outlets, 570 offenses per year), one outlet was associated with 3.4 additional assaultive violence offenses in 1990.

CONCLUSIONS

These findings indicate that higher levels of alcohol-outlet density are geographically associated with higher rates of assaultive violence. This association is independent of measured confounders, including city-level measures of unemployment, ethnic/racial makeup, income, age structure, city size, household size, and female-headed households.

Increased risk of prostate cancer in men with a family history of the disease has been observed consistently in epidemiologic studies. However, most studies have been confined to white men; little is known about familial aggregation of prostate cancer in populations with unusually high incidence, such as African Americans, or in populations with low incidence, such as Asian-Americans. The authors report results from a population-based case-control study of prostate cancer among blacks, whites, and Asian-Americans in the United States and Canada. Controls were matched to cases on age (5-year groups), ethnicity (black, white, Chinese-American, Japanese-American), and region of residence (Los Angeles, San Francisco, Hawaii, Vancouver, Toronto). In the combined group of participants, 5% of controls and 13% of cases reported a father, brother, or son with prostate cancer. These prevalences were somewhat lower among Asian-Americans than among blacks or whites. A positive family history was associated with a statistically significant two- to threefold increase in risk in each of the three ethnic groups. The overall odds ratio associated with such a family history, adjusted for age and ethnicity, was 2.5 (95% confidence interval 1.9-3.3). This odds ratio varied by neither ethnicity nor age of the participants. Sera from 1,087 controls were used to examine the relations between family history and serum concentrations of androgens and prostate-specific antigen. The concentrations of sex hormone-binding globulin were slightly higher in men with than without a positive family history. Prostate-specific antigen concentrations were unrelated to family history.

BACKGROUND

Intraoperative fluid therapy regimens using oesophageal Doppler monitoring (ODM) to optimize stroke volume (SV) (goal-directed fluid therapy, GDT) have been associated with a reduction in length of stay (LOS) and complication rates after major surgery. We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge (RfD) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients.

METHODS

In this double-blinded controlled trial, 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically 'fit' (n=123) or 'unfit' (n=56) on the basis of their performance during a cardiopulmonary exercise test. Within these fitness strata, patients were randomized to receive a standard fluid regimen with or without ODM-guided intraoperative GDT.

RESULTS

GDT patients received an average of 1360 ml of additional intraoperative colloid. The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls. Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance (median 6.8 vs 4.9 days, P=0.09, and median 8.8 vs 6.7 days, P=0.09, respectively). Fit GDT patients had an increased RfD (median 7.0 vs 4.7 days; P=0.01) and LOS (median 8.8 vs 6.0 days; P=0.01) compared with controls.

CONCLUSIONS

Intraoperative SV optimization conferred no additional benefit over standard fluid therapy. In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome.

BACKGROUND

UK NIHR CRN 7285, ISRCTN 14680495. http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7285.

OBJECTIVE

To evaluate the hypothesis that poor adherence to highly active antiretroviral treatment (HAART) would be more strongly related to cognitive impairment among older than among younger HIV-seropositive adults.

METHODS

A volunteer sample of 431 HIV-infected adult patients prescribed self-administered HAART was recruited from community agencies and university-affiliated infectious disease clinics in the Los Angeles area.

METHODS

Neurocognitive measures included tests of attention, information processing speed, learning/memory, verbal fluency, motor functioning, and executive functioning. Medication adherence was measured using microchip-embedded pill bottle caps (Medication Event Monitoring System) and self-report. Latent/structural analysis techniques were used to evaluate factor models of cognition and adherence.

RESULTS

Mean adherence rates were higher among older >>or=50 years) than younger (<50 years) HIV-positive adults. However, latent/structural modeling demonstrated that neurocognitive impairment was associated with poorer medication adherence among older participants only. When cognitive subdomains were examined individually, executive functioning, motor functioning, and processing speed were most strongly related to adherence in this age group. CD4 count and drug problems were also more strongly associated with adherence among older than younger adults.

CONCLUSIONS

Older HIV-positive individuals with neurocognitive impairment or drug problems are at increased risk of suboptimal adherence to medication. Likewise, older adults may be especially vulnerable to immunological and neurocognitive dysfunction under conditions of suboptimal HAART adherence. These findings highlight the importance of optimizing medication adherence rates and evaluating neurocognition in the growing population of older HIV-infected patients.

During the course of an experimentally induced Ebola virus (EBOVA) infection of cynomolgus macaques, peripheral blood mononuclear cells were isolated and characterized by multi-color flow cytometry. Both CD4+ and CD8+ lymphocyte counts decreased 60-70% during the first 4 days after infection. Among CD8+ lymphocytes, this decline was greatest among the CD8(lo) population, which was composed mostly of CD3- CD16+ NK cells. In contrast, the number of CD20+ B lymphocytes in the blood did not significantly change during the course of the infection. Phenotypic analysis of T lymphocyte subsets by flow cytometry failed to show evidence of a robust immune response to the infection. Apoptosis could be detected as early as day 2 postinfection among the CD8+ and CD16+ subsets of lymphocytes. Increased expression of CD95 (Fas) suggests that apoptosis may be induced via signaling through the Fas/Fas-L cascade. In contrast, the number of HLA-DR+ cells increased tenfold in the blood during the course of infection. These data suggest that EBOV may block dendritic cell maturation after infection, thereby inhibiting activation of lymphocytes and eliminating those subsets that are most likely to be capable of mounting an effective response to the virus.

BACKGROUND

Human endometrium is a highly regenerative tissue. We hypothesized that the source of endometrial stromal and vascular regeneration is a resident stromal stem/progenitor cell population. Putative human endometrial stromal stem/progenitor cells have been identified using clonal assays, a retrospective functional stem cell assay. Therefore, the aim of this study was to screen potential stem cell markers for the prospective isolation of human endometrial stromal stem/progenitor cells and to determine their capacity to identify colony-forming stromal cells.

METHODS

Single-cell suspensions of human endometrial stromal cells were sorted using fluorescence-activated cell sorting into positive and negative populations based on STRO-1, CD133, CD90 or CD146 expression for clonal assays. All markers were immunolocalized in human endometrium.

RESULTS

Small populations (2-9%) of human endometrial stromal cells expressed each of the markers. Only CD146(+) cells were enriched for colony-forming cells, and CD90(hi) cells showed a trend for greater enrichment compared with CD90(lo) cells. STRO-1 and CD146 were localized to perivascular cells of the endometrium. CD90 was strongly expressed by functionalis stroma and perivascular cells, but only weakly expressed in the basalis stroma. CD133 was expressed by epithelial cells of the endometrium, rather than by stroma or perivascular cells.

CONCLUSIONS

This study identified CD146 as a marker of colony-forming human endometrial stromal cells supporting the concept that human endometrium contains a population of candidate stromal stem/progenitor cells.

Dietary patterns may be influenced by the availability and accessibility within stores of different types of foods. However, little is known about the amount of shelf space used for healthy and unhealthy foods in different types of stores. We conducted measurements of the length of shelf space used for fruits, vegetables, and snack foods items in 419 stores in 217 urban census tracts in southern Louisiana and in Los Angeles County. Although supermarkets offered far more shelf space of fruits and vegetables than did other types of stores, they also devoted more shelf space to unhealthy snacks (mean 205 m for all of these items combined) than to fruits and vegetables (mean 117 m, p < 0.001). After supermarkets, drug stores devoted the most shelf space to unhealthy items. The ratio of the total shelf space for fruits and vegetables to the total shelf space for these unhealthy snack items was the lowest (0.10 or below) and very similar in convenience stores, drug stores, and liquor stores, was in a middle range (0.18 to 0.30) in small food stores, and was highest in medium-sized food stores (0.40 to 0.61) and supermarkets (0.55 to 0.72). Simple measurements of shelf space can be used by researchers to characterize the healthfulness of the food environment and by policymakers to establish criteria for favorable policy treatment of stores.

The passage of California's Proposition 187 in 1994 intensified debate over health care access for the undocumented population. Under Proposition 187, physicians would have been required to report the undocumented immigrants to immigration authorities. Even before 187, some undocumented may have been wary to come in contact with the medical care system. This paper examines whether concerns about one's immigration status serves as a deterrent to seeking care. These concerns may be resurfacing, with changes under the 1996 welfare reform legislation and related amendments that affect eligibility of non-citizen immigrants for public programs and states' ability to provide care to undocumented immigrants. Therefore, representative in-person surveys of undocumented Latinos were conducted in Houston, El Paso, Fresno, and Los Angeles in neighborhoods with significant concentrations of Latinos. It was found that 39% of the undocumented adult immigrants expressed fear about receiving medical services because of undocumented status. Those reporting fear were likelier to report inability acquiring medical and dental care, prescription drugs, and eyeglasses. Hence it can be concluded that concern about immigration status decreases the likelihood of receiving care.

BACKGROUND

Development of acute kidney injury (AKI) during the perioperative period is associated with increases in morbidity and mortality. Our aim was to evaluate the incidence and determinants of postoperative AKI after major noncardiac surgery in patients with previously normal renal function.

METHODS

This retrospective cohort study was carried out in the multidisciplinary Post-Anaesthesia Care Unit (PACU) with five intensive care beds. The study population consisted of 1166 patients with no previous renal insufficiency who were admitted to these intensive care unit (ICU) beds over 2 years. After admission patients were followed for the development of AKI, defined as proposed by The Acute Kidney Injury Network (increment of serum creatinine [greater than or equal to] 0.3 mg/dL or 50% from baseline within 48 hours or urine output < 0.5 mL/kg/hr for>> 6 hours despite fluid resuscitation when applicable). Patient preoperative characteristics, intraoperative management and outcome were evaluated for associations with acute kidney injury using an univariate and multiple logistic regression model.

RESULTS

A total of 1597 patients were admitted to the PACU and of these, 1166 met the inclusion criteria. Eighty-seven patients (7.5%) met AKI criteria. Univariate analysis identified age, American Society of Anesthesiologists (ASA) physical status, emergency surgery, high risk surgery, ischemic heart disease, congestive heart disease and Revised Cardiac Risk Index (RCRI) score as independent preoperative determinants for AKI in the postoperative period. Multivariate analysis identified ASA physical status, RCRI score, high risk surgery and congestive heart disease as preoperative determinants for AKI in the postoperative period. Patients that developed AKI had higher Simplified Acute Physiology Score (SAPS) II and Acute Physiology and Chronic Health Evaluation (APACHE) II, higher PACU length of stay (LOS), higher PACU mortality, higher hospital mortality and higher mortality at 6 months follow-up. AKI was an independent risk factor for hospital mortality (OR 3.12, 95% CI 1.41 to 6.93, P = 0.005).

CONCLUSIONS

This study shows that age, emergency and high risk surgery, ischemic heart disease, congestive heart disease, ASA physical status and RCRI score were considered risk factors for the development of AKI, in patients needing intensive care after surgery. AKI has serious impact on PACU length of stay and mortality. AKI was an independent risk factor for hospital mortality.

Waters adjacent to the County of Los Angeles (CA) receive untreated runoff from a series of storm drains year round. Many other coastal areas face a similar situation. To our knowledge, there has not been a large-scale epidemiologic study of persons who swim in marine waters subject to such runoff. We report here results of a cohort study conducted to investigate this issue. Measures of exposure included distance from the storm drain, selected bacterial indicators (total and fecal coliforms, enterococci, and Escherichia coli), and a direct measure of enteric viruses. We found higher risks of a broad range of symptoms, including both upper respiratory and gastrointestinal, for subjects swimming (a) closer to storm drains, (b) in water with high levels of single bacterial indicators and a low ratio of total to fecal coliforms, and (c) in water where enteric viruses were detected. The strength and consistency of the associations we observed across various measures of exposure imply that there may be an increased risk of adverse health outcomes associated with swimming in ocean water that is contaminated with untreated urban runoff.

Participants of the Multiethnic Cohort Study in Hawaii and Los Angeles, California, a representative sample of African-American, Native Hawaiian, Latino, Japanese-American, and White adults, completed a baseline questionnaire in 1993-1996 assessing dietary supplement use during the past year as well as demographic, dietary, and other lifestyle factors. Factors associated with supplement use were examined among those who reported an absence of chronic disease (n = 100,196). Use of any of eight supplements at least once per week during the past year ranged from 44% among Hawaiian men to 75% among Japanese-American and White women. Multivitamins were the most frequently reported supplement; 48% of the men and 56% of the women reported regular use. Dietary supplement use was high across all ethnic groups, although levels and length of regular use varied. In all gender-specific ethnic groups, supplement use tended to increase with age, education, physical activity, fruit intake, and dietary fiber intake and to decrease with obesity, smoking, and dietary fat intake. Participants whose lifestyles were healthier were more likely to use dietary supplements. Therefore, it may be difficult to separate the effects of supplement use from other lifestyle factors when studying disease etiology.

Leukotrienes have physiological roles in innate immune responses and pathological roles in inflammatory diseases, such as asthma, allergic rhinitis and atherosclerosis. Anti-leukotriene therapy has proven benefits in the treatment of respiratory disease, either through the inhibition of leukotriene synthesis or the selective antagonism of leukotriene receptors. The first committed step in the synthesis of leukotrienes is the oxidation of arachidonic acid (AA) by 5-lipoxygenase (5-LO), and the integral membrane protein 5-lipoxygenase-activating protein (FLAP) is an essential partner of 5-LO for this process. FLAP was molecularly identified via a photoaffinity probe and an affinity gel based on MK-886, a selective leukotriene inhibitor that has no activity against broken-cell preparations of 5-LO. Several FLAP inhibitors showed efficacy in early clinical trials in asthma but were not developed commercially for unpublished reasons. Recently, the FLAP (ALOX5AP) gene has been linked to risk for myocardial infarction, stroke and restenosis, reigniting pharmaceutical interest in this target. In addition, the recent determination of the crystal structure of inhibitor-bound FLAP offers exciting potential for novel FLAP inhibitor design.

Immunochemical studies of the lipo-oligosaccharides (LOS) of the Gram-negative bacteria Neisseria gonorrhoeae and Neisseria meningitidis have revealed some interesting structural characteristics of these LOS that might relate to their roles during pathogenesis. The carbohydrate moieties of the LOS of pathogenic Neisseria mimic carbohydrates present in glycosphingolipids of human cells. Firstly, an LOS component present among a number of Neisseria species is antigenically and/or chemically identical to lactoneoseries glycosphingolipids present in human cells. The lactoneoseries LOS becomes sialylated on Neisseria gonorrhoeae when they are grown in the presence of cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NANA), the nucleotide sugar for sialic acid. Examination of gonococci present in exudates from males with natural infection indicates that sialylation also occurs in vivo. The mechanism for this process apparently involves a bacterial sialyltransferase scavenging available host CMP-NANA ("host-modification" of LOS) and transferring the sialic acid to the lactoneoserieslike LOS. Strains of N. meningitidis and Haemophilus influenzae also express similarly sialylated LOS suggesting that this is a common mechanism of pathogenesis among these bacteria. Additional examples of LOS that mimic other glycosphingolipid series have been identified also and the fact that multiple series can be expressed in a single population of gonococci suggests that a diverse set of LOS can be presented to the host during infection. It is possible that this diverse set of LOS serve different functions for the bacteria in various hosts and/or environments during infection.

We examined how drugs, high-risk sexual behaviors, and socio-demographic variables are associated with recent HIV infection among men who have sex with men (MSM) in a case-control study. Interviewers collected risk factor data among 111 cases with recent HIV infection, and 333 HIV-negative controls from Chicago and Los Angeles. Compared with controls, cases had more unprotected anal intercourse (UAI) with both HIV-positive and HIV-negative partners. MSM with lower income or prior sexually transmitted infections (STI) were more likely to be recently HIV infected. Substances associated with UAI included amyl nitrate ("poppers"), methamphetamine, Viagra (or similar PDE-5 inhibitors), ketamine, and gamma hydroxybutyrate (GHB). Cases more frequently used Viagra, poppers, and methamphetamine during UAI compared with controls. In multivariate analysis, income, UAI with HIV-positive partners, Viagra, and poppers remained associated with recent HIV seroconversion. Better methods are needed to prevent HIV among MSM who engage in high-risk sex with concurrent drug use.

There is an urgent need to create novel models using human disease-relevant cells to study SARS-CoV-2 biology and to facilitate drug screening. As SARS-CoV-2 primarily infects the respiratory tract, we developed a lung organoid model using human pluripotent stem cells (hPSC-LOs). The hPSC-LOs, particularly alveolar type II-like cells, are permissive to SARS-CoV-2 infection, and showed robust induction of chemokines upon SARS-CoV-2 infection, similar to what is seen in COVID-19 patients. Nearly 25% of these patients also have gastrointestinal manifestations, which are associated with worse COVID-19 outcomes¹. We therefore also generated complementary hPSC-derived colonic organoids (hPSC-COs) to explore the response of colonic cells to SARS-CoV-2 infection. We found that multiple colonic cell types, especially enterocytes, express ACE2 and are permissive to SARS-CoV-2 infection. Using hPSC-LOs, we performed a high throughput screen of FDA-approved drugs and identified entry inhibitors of SARS-CoV-2, including imatinib, mycophenolic acid (MPA), and quinacrine dihydrochloride (QNHC). Treatment at physiologically relevant levels of these drugs significantly inhibited SARS-CoV-2 infection of both hPSC-LOs and hPSC-COs. Together, these data demonstrate that hPSC-LOs and hPSC-COs infected by SARS-CoV-2 can serve as disease models to study SARS-CoV-2 infection and provide a valuable resource for drug screening to identify candidate COVID-19 therapeutics.