Depression and Handgrip Strength Among U.S. Adults Aged 60 Years and Older from NHANES 2011-2014.

OBJECTIVES: Sarcopenia is a gradual loss of muscle mass and strength that occurs with aging. This muscle deterioration is linked to increased morbidity, disability, and other adverse outcomes. Although reduced handgrip strength can be considered a marker of sarcopenia and other aging-related decline in the elderly, there is limited research on this physical health problem in at-risk groups with common biopsychosocial conditions such as depression. Our primary objective was to ascertain level of combined handgrip strength and its relationship with depression among adults aged 60 years and older. DESIGN: Unadjusted and adjusted linear regression models were conducted with a cross-sectional survey dataset. SETTING: Secondary dataset from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). PARTICIPANTS: Community-dwelling, non-institutionalized adults ≥60 years old (n=3,421). MEASUREMENTS: The predictor variables included a positive screen for clinically relevant depression (referent=PHQ-9 score <10). The criterion variable of combined handgrip strength (kg) was determined using a dynamometer. RESULTS: Mean age and BMI were 69.9 years (51.5% female) and 28.8 kg/m2, respectively. Mean combined handgrip strength in the overall cohort was 73.5 and 46.6 kg in males and females, respectively. Three hundred thirty-six (9.8%) reported symptoms of depression. In unadjusted and fully adjusted models, depression was significantly associated with reduced handgrip strength (B = -0.26±0.79 and B = -0.19±0.08, respectively; p<0.001). CONCLUSION: Our findings demonstrate handgrip strength has a significant inverse association with depression. Future longitudinal studies should investigate the causal processes and potential moderators and mediators of the relationships between depression and reduced handgrip strength. This information may further encourage the use of depression and handgrip strength assessments and aid in the monitoring and implementation of health care services that address both physical and mental health limitations among older adult populations.

Smoking Predicting Physical Activity in an Aging America.

OBJECTIVES: Tobacco smoking and physical inactivity are among leading behavioral risk factors for ill health in older adults. This study considers how smoking is associated with physical activity. DESIGN: Using a Life-Course model, data are analyzed regarding this relationship, controlling for, and interacted with, life-course and other factors. Daily smokers and sometimes smokers were hypothesized to engage in less leisure-time physical activity than those who never smoked, while those who stopped smoking were expected to do more than never smokers. Analyses were performed using SAS-Callable SUDAAN. SETTING AND PARTICIPANTS: Secondary data from ten years of a national sample of adults aged 18 and over of the National Health Interview Survey, 2001-2010, are used (N = 264,945, missing data excluded, of 282,313 total cases). MEASUREMENTS: Daily smokers, occasional smokers, and smoking quitters are compared to never smokers with regard to requisite physical activity (150 minutes per week of moderate, 100 of vigorous, and/or 50 of strengthening activity). Life-course measures include birth cohorts, age, and year of survey, as well as gender, race/ethnicity, and education. RESULTS: Overall, hypotheses are supported regarding daily smokers and quitters; but the hypothesis is strongly rejected among sometimes smokers, who are much more likely to do requisite physical activity. Findings differ by age, sometimes smokers age 65 and over being less likely to do physical activity. Findings among all men are similar to the overall findings, while those among all women are similar to those for older respondents. Associations of smoking status with physical activity vary greatly by race/ethnicity. CONCLUSIONS: Daily smokers may be most in need of both smoking cessation and leisure-time physical activity interventions. Smoking-cessation efforts may pay greater physical activity benefits among women and the aged, while smoking-reduction efforts may provide better outcomes among men. Smoking reduction efforts may pay more exercise benefits among African-Americans and Hispanics.

Cell-specific and developmental expression of lectican-cleaving proteases in mouse hippocampus and neocortex.

Mounting evidence has demonstrated that a specialized extracellular matrix exists in the mammalian brain and that this glycoprotein-rich matrix contributes to many aspects of brain development and function. The most prominent supramolecular assemblies of these extracellular matrix glycoproteins are perineuronal nets, specialized lattice-like structures that surround the cell bodies and proximal neurites of select classes of interneurons. Perineuronal nets are composed of lecticans, a family of chondroitin sulfate proteoglycans that includes aggrecan, brevican, neurocan, and versican. These lattice-like structures emerge late in postnatal brain development, coinciding with the ending of critical periods of brain development. Despite our knowledge of the presence of lecticans in perineuronal nets and their importance in regulating synaptic plasticity, we know little about the development or distribution of the extracellular proteases that are responsible for their cleavage and turnover. A subset of a large family of extracellular proteases (called a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTS]) is responsible for endogenously cleaving lecticans. We therefore explored the expression pattern of two aggrecan-degrading ADAMTS family members, ADAMTS15 and ADAMTS4, in the hippocampus and neocortex. Here, we show that both lectican-degrading metalloproteases are present in these brain regions and that each exhibits a distinct temporal and spatial expression pattern. Adamts15 mRNA is expressed exclusively by parvalbumin-expressing interneurons during synaptogenesis, whereas Adamts4 mRNA is exclusively generated by telencephalic oligodendrocytes during myelination. Thus, ADAMTS15 and ADAMTS4 not only exhibit unique cellular expression patterns but their developmental upregulation by these cell types coincides with critical aspects of neural development.

Coselection for resistance to multiple late-generation human therapeutic antibiotics encoded on tetracycline resistance plasmids captured from uncultivated stream and soil bacteria.

AIMS: Transmissible plasmids captured from stream and soil bacteria conferring resistance to tetracycline in Pseudomonas were evaluated for linked resistance to antibiotics used in the treatment of human infections. METHODS AND RESULTS: Cells released from stream sediments and soils were conjugated with a rifampicin-resistant, plasmid-free Pseudomonas putida recipient and selected on tetracycline and rifampicin. Each transconjugant contained a single 50-80 kb plasmid. Resistance to 11 antibiotics, in addition to tetracycline, was determined for the stream transconjugants using a modification of the Stokes disc diffusion antibiotic susceptibility assay. Nearly half of plasmids conferred resistance to six or more antibiotics. Resistance to streptomycin, gentamicin, and/or ticarcillin was conferred by a majority of the plasmids, and resistance to additional human clinical use antibiotics such as piperacillin/tazobactam, ciprofloxacin and aztreonam was observed. MICs of 16 antibiotics for representative sediment and soil transconjugants revealed large increases, relative to the Ps. putida recipient, for 11 of 16 antibiotics tested, including the expanded spectrum antibiotics cefotaxime and ceftazidime, as well as piperacillin/tazobactam, lomefloxacin and levofloxacin. CONCLUSIONS: Resistance to multiple antibiotics-including those typically used in clinical Pseudomonas and enterobacterial infections-can be conferred by transmissible plasmids in streams and soils. SIGNIFICANCE AND IMPACT OF STUDY: Selective pressure exerted by the use of one antibiotic, such as the common agricultural antibiotic tetracycline, may result in the persistence of linked genes conferring resistance to important human clinical antibiotics. This may impact the spread of resistance to human use antibiotics even in the absence of direct selection.

Astrocyte-derived kynurenic acid modulates basal and evoked cortical acetylcholine release.

We tested the hypothesis that fluctuations in the levels of kynurenic acid (KYNA), an endogenous antagonist of the alpha7 nicotinic acetylcholine (ACh) receptor, modulate extracellular ACh levels in the medial prefrontal cortex in rats. Decreases in cortical KYNA levels were achieved by local perfusion of S-ESBA, a selective inhibitor of the astrocytic enzyme kynurenine aminotransferase II (KAT II), which catalyses the formation of KYNA from its precursor L-kynurenine. At 5 mm, S-ESBA caused a 30% reduction in extracellular KYNA levels, which was accompanied by a two-threefold increase in basal cortical ACh levels. Co-perfusion of KYNA in the endogenous range (100 nm), which by itself tended to reduce basal ACh levels, blocked the ability of S-ESBA to raise extracellular ACh levels. KYNA perfusion (100 nm) also prevented the evoked ACh release caused by d-amphetamine (2.0 mg/kg). This effect was duplicated by the systemic administration of kynurenine (50 mg/kg), which resulted in a significant increase in cortical KYNA formation. Jointly, these data indicate that astrocytes, by producing and releasing KYNA, have the ability to modulate cortical cholinergic neurotransmission under both basal and stimulated conditions. As cortical KYNA levels are elevated in individuals with schizophrenia, and in light of the established role of cortical ACh in executive functions, our findings suggest that drugs capable of attenuating the production of KYNA may be of benefit in the treatment of cognitive deficits in schizophrenia.

Does patent ductus arteriosus affect feed tolerance in preterm neonates?

Patent ductus arteriosus (PDA), especially PDA with sepsis, has been reported as a risk factor for feed intolerance in preterm neonates. In this study, the start to full feeds interval was found to be longest in preterm neonates (

Is surgical ligation of patent ductus arteriosus necessary? The Western Australian experience of conservative management.

BACKGROUND: Surgical ligation of patent ductus arteriosus (PDA) is widely practised in preterm infants despite no clear evidence that this improves outcomes. Geographical isolation meant that ductal ligation was not an option in King Edward Memorial Hospital until recently. OBJECTIVE: A retrospective data analysis to test the hypothesis that outcomes of infants with persistent PDA were no worse than those of infants with no significant duct or a duct that closed after medical treatment. PATIENTS AND METHODS: A total of 252 infants (gestation < or =28 weeks) born between 1 January 2000 and 30 June 2002 were divided into three groups: group 1, no significant PDA (n = 154); group 2, significant PDA which closed after medical treatment (n = 65); group 3, significant PDA remaining patent after medical treatment (n = 33). A significant PDA was defined by a left atrium to aortic root ratio of >1.4 or a ductal diameter >1.5 mm with a left to right shunt. RESULTS: Twenty four (10%) infants died at median (interquartile range) 15.5 (9-35) days. After adjustment for gestational age, relative to group 1, the infants from group 3 were at a 4.02 times increased risk of death (95% confidence interval 1.12 to 14.51). There was no significant difference between groups in the incidence of chronic lung disease, chronic lung disease or death, necrotising enterocolitis, intraventricular haemorrhage, duration of oxygen, or hospital stay. CONCLUSION: Mortality was higher in infants with a persistent PDA, but other morbidities were not significantly different. A randomised trial is needed to determine whether surgical ligation will reduce mortality in such infants.

Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach.

BACKGROUND: Numerous case reports have linked clozapine to the development of diabetes mellitus and hyperlipidemia in patients with schizophrenia. However, investigators have been unable to clearly demonstrate this association when compared with a control group receiving conventional antipsychotics. METHODS: Medical and pharmacy claims from the Iowa Medicaid program were used to compare incidence rates for diabetes, hyperlipidemia, and hypertension in 552 patients receiving clozapine and 2461 patients receiving conventional antipsychotics (eg, haloperidol, chlorpromazine hydrochloride), with the use of a retrospective cohort design. Logistic regression was used to compare incidence rates adjusting for age, sex, and duration of available follow-up. RESULTS: No significant differences in overall incidence rates for diabetes, hyperlipidemia, or hypertension were observed in patients receiving clozapine vs conventional antipsychotics. However, among younger patients (aged 20-34 years), clozapine administration was associated with a significantly increased relative risk of diabetes (2.5 [95% confidence interval, 1.2-5.4]) and hyperlipidemia (2.4 [95% confidence interval, 1.1-5.2]), but not hypertension (0.9 [95% confidence interval, 0.4-2.0]). CONCLUSIONS: These data suggest that clozapine may not be an independent cause of diabetes or hyperlipidemia, but instead acts as an effect modifier in susceptible populations by increasing weight or affecting insulin secretion and resistance. This finding requires confirmation in other settings and patient populations and with the other atypical antipsychotics (risperidone, olanzapine, and quetiapine fumarate). The potential long-term medical and economic implications of the early induction of diabetes and hyperlipidemia in patients with schizophrenia warrant further study.

The biology of cortical granules.

An egg-that took weeks to months to make in the adult-can be extraordinarily transformed within minutes during its fertilization. This review will focus on the molecular biology of the specialized secretory vesicles of fertilization, the cortical granules. We will discuss their role in the fertilization process, their contents, how they are made, and the molecular mechanisms that regulate their secretion at fertilization. This population of secretory vesicles has inherent interest for our understanding of the fertilization process. In addition, they have import because they enhance our understanding of the basic processes of secretory vesicle construction and regulation, since oocytes across species utilize this vesicle type. Here, we examine diverse animals in a comparative approach to help us understand how these vesicles function throughout phylogeny and to establish conserved themes of function.

Organic carbon flow in the Ob, Yenisey Rivers and Kara Sea of the Arctic region.

Stable carbon isotope and elemental C/N ratios of the organic fraction of a set of samples along a transect in the Ob and Yenisey Rivers into the Kara Sea in the Arctic were measured. Previously, the concentrations of 239,240Pu and 137Cs in these same samples had been determined. The coupled measurements were carried out to assess possible connectivity between organic carbon flow into the Kara Sea and transport of radioactive nuclides in this marine environment. Organic carbon flow into the Kara Sea is influenced significantly by terrigenous sources carried by the Ob and Yenisey Rivers. The carbon isotope-organic carbon relationship provides evidence that a rich source of terrigenous carbon exists in the riverine system. A weak, but significant relationship between stable carbon isotope ratio and 137Cs suggests that most of the 137Cs is derived from riverine particles, as compared to Pu which is also derived from in situ scavenging within the water column.

Ocean storage of nuclear wastes? Experiences from the Russian Arctic.

An international demonstration (RD&D) project for ocean storage of radioactive wastes should be proposed, to study the feasibility of the concept of ocean storage of nuclear waste. This international project should utilize the scientific, engineering and technical capabilities of selected universities, oceanographic institutions, NGOs and industries. This project would need to be an independent (non-governmental) study, utilizing the capabilities of selected universities, oceanographic institutions, environmental NGOs (Non-Governmental Organizations) and industries. Scientists and engineers first need to conduct an engineering, environmental, and economic feasibility study of the concept. The goal of the project would be to determine if ocean-based storage reduced the risks to the environment and public health to a greater degree than land-based storage. This would require comparing the risks and factors involved and making the data and information available to anyone, anywhere, anytime on the internet. The mere presence of an investigation of the ocean storage option could facilitate scientific and engineering competition between the two options, could subsequently reduce environmental and public risks and provide better protection and cost benefits in the system utilized. One of the primary concerns of the scientific community would be related to the sensitivity and precision of the monitoring of individaul containers on the ocean bottom. An advantage of the land-based option is that if there is a release, its presence could be detected at very low levels and be contained in the storage facility. On the ocean bottom, a release from a container might not be easily detected due to dispersion. Therefore the containment system would have to be a system within a system with monitoring between the two providing greater protection. Ocean storage may have greater technical and political hurdles than land-based options, but it may provide greater protection over time, because it negates the threat of terrorism, it therefore merit further study. In the future if the use of nuclear energy and nuclear wastes increases, the global society could benefit from this international project, because it could reduce environmental and public health risks and promote energy independence.

The geographic distribution of population health and contaminant body burden in gulf of Mexico oysters.

As part of NOAA's National Status and Trends Mussel Watch Program, oysters were sampled along the Gulf of Mexico coast each winter from 1986 to 1993 (The present analysis deals with 1986-1993 Mussel Watch data; the Mussel Watch project itself continues at this printing) and analyzed for trace metal, polynuclear aromatic hydrocarbons and pesticide body burden, plus a series of biological variables designed to assess population status and health. We identified contaminant and biological variables in which large-scale spatial processes played an important role in establishing population values by examining the likelihood that neighboring bays tended to have populations with body burdens or population attributes more similar than expected by chance. Local or watershed-dependent factors, such as land use and freshwater inflow, are important in controlling the bay-to-bay variation in body burden in most contaminants. However, the bay-to-bay variations in body burden of some metals (As, Cd, Hg, Ni, Se) appear to be principally influenced by larger-scale climatic factors. These metals and the biological variable shell length demonstrated a strong degree of similarity between bays over a large regional area reminiscent of the pattern shown by climatic factors, such as temperature and precipitation. In contrast, among the organics, none of the PAHs showed even a moderately strong climatic signal. Among the pesticides, only two did (dieldrin, total DDTs). These pesticides and the biological variables, reproductive stage and Perkinsus marinus prevalence and infection intensity, had spatial patterns that suggested both a local and a regional influence to their geographic distributions. This same pattern is exhibited by freshwater runoff. Metal contaminants also behaved distinctively compared to organics in the temporal influence of climate in establishing the interannual variability in body burden. For the organics, trends in interannual variability were strongly influenced by climate, whereas spatial trends were not. In contrast, most metals were unaffected by climatic forcing both spatially and temporally. However, all of the metals having a spatial pattern strongly influenced by climate (As, Cd, Hg, Ni, Se) also exhibited interannual variations related to variations in climate.

Trace contaminant concentrations in the Kara Sea and its adjacent rivers, Russia.

Trace organic (chlorinated pesticides, PCBs, PAHs and dioxins/furans) and trace metal concentrations were measured in surficial sediment and biological tissues (i.e., worms, crustaceans, bivalve molluscs, and fish livers) collected from the Russian Arctic. Total DDT, chlordane, PCB and PAH concentrations ranged from ND to 1.2, ND to <0.1, ND to 1.5 and <20-810 ng g(-1), respectively, in a suite of 40 surficial sediment samples from the Kara Sea and the adjacent Ob and Yenisey Rivers. High sedimentary concentrations of contaminants were found in the lower part of the Yenisey River below the salt wedge. Total dioxins/furans were analysed in a subset of 20 sediment samples and ranged from 1.4 to 410 pg g(-1). The highest trace organic contaminant concentrations were found in organisms, particularly fish livers. Concentrations as high as 89 ng g(-1) chlordane; 1010 ng g(-1) total DDTs; 460 ng g(-1) total PCBs; and 1110 ng g(-1) total PAH, were detected. A subset of 11 tissue samples was analysed for dioxins and furans with total concentrations ranging from 12 to 61 pg g(-1). Concentrations of many trace organic and metal contaminants in the Kara Sea appear to originate from riverine sources and atmospheric transport from more temperate areas. Most organic contaminant concentrations in sediments were low; however, contaminants are being concentrated in organisms and may pose a health hazard for inhabitants of coastal villages.

Information gained from linking SEER Cancer Registry Data to state-level hospital discharge abstracts. Surveillance, Epidemiology, and End Results.

OBJECTIVES: Our goal was to link patients from the Iowa Surveillance, Epidemiology, and End Results (SEER) Registry to their respective inpatient discharge abstracts from an Iowa Health Care Cost and Utilization Project (HCUP)-formatted database and evaluate whether this linkage provides information related to cancer treatment variation. METHODS: Computer algorithms linked patients from the Iowa SEER Registry to discharge abstracts using 5 variables consistently defined between the databases (hospital identification, date of birth, admission date, discharge date, and zip code). Abstracts were reviewed for validity, and links not passing face validity were excluded. SUBJECTS: Our sample contained 7,296 patients with early-stage breast cancer (I, IIa, IIb) with surgery from the Iowa SEER Registry from 1989 through 1994 with contacts only with Iowa hospitals. RESULTS: Inpatient discharges abstracts were linked to 86.4% of the patients in our sample. More than 96% of the linked discharges for Medicare patients had a corresponding Medicare claim. Over 45% of the linked patients were not covered by Medicare. Comorbidity indexes were comparable to other published sources. Significant differences in diagnosis, comorbidities, and treatment were found across third-party payers. CONCLUSIONS: This linkage provides a valuable source of comorbidity and insurance data and perhaps the only source of secondary clinical information for the uninsured. This linkage is best suited for cancers requiring inpatient stays for treatment and for those states where border crossing for treatment is low.

Direct molecular interaction of a conserved yolk granule protein in sea urchins.

The regulation of yolk storage in oocytes and subsequent utilization in embryos is critical for embryogenesis. In sea urchins, the major yolk protein is made in the intestines, transported to the ovaries and accumulated in developing oocytes within membrane-bound vesicles comprising approximately 10% of the mass of an egg. Here, a non-yolk protein that accumulates specifically in yolk granules is reported. This protein was identified by cDNA cloning and, by use of antibodies to the recombinant protein, it was shown that this molecule is stored selectively in yolk granules of oocytes and embryos. No accumulation was seen in the accessory cells, testis, or intestines. In situ ribonucleic acid (RNA) hybridizations showed that the transcript accumulated only in oocytes, and was more highly concentrated in young oocytes. However, later in oogenesis, the messenger ribonucleic acid (mRNA) levels decreased significantly so that no signal was detectable in mature haploid eggs or at any later stage in development. However, by immunofluorescence and western blot analysis, the 30 kDa band was present throughout development. The predicted sequence of this protein shows that it is a member of the bep, HLC-32, EBP family of sea urchin proteins, but as it does not accumulate at the cell surface, nor in the hyaline layer in the two species studied here, as do other members of the family, it has been referred to as YP30 (30 kDa protein of the yolk platelet). To address its potential function, yeast two-hybrid analysis was performed to screen for proteins that potentially interact with YP30. It was found that it binds itself, and forms strongly interacting dimers. It is hypothesized that YP30 participates in the packaging and storage of major yolk protein during oogenesis, or in the utilization of the major yolk protein in development.

The marginal benefits of invasive treatments for acute myocardial infarction: does insurance coverage matter?

This paper applies instrumental variable (IV) techniques and estimates the average benefits of invasive surgical treatments for marginal acute myocardial infarction (AMI) patients by insurance coverage. The study uses data from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project (HCUP), State Inpatient Databases for the state of Washington, for years 1988-1993. We observed differences in average benefits for marginal patients across insurance subpopulations that cannot be explained by differences in measured clinical circumstances. Our empirical results show that the insurance subpopulations with the greatest estimated marginal benefits are those with the lowest expected payment generosity to providers. Because of the relatively weak explanatory power of our instruments for three insurance subpopulations, and because many of the parameter estimates across the insurance subpopulations are not statistically different from each other, policy recommendations should be approached cautiously. However, our application of IV techniques to AMI patients demonstrates the usefulness of this approach to estimate treatment effects across patient populations (e.g., across types of insurance coverage) for medical conditions of interest to policymakers. These estimates may help determine whether treatments are overutilized or underutilized.

Immunodominance among EBV-derived epitopes restricted by HLA-B27 does not correlate with epitope abundance in EBV-transformed B-lymphoblastoid cell lines.

Using synthetic peptides, the HLA-B27-restricted CTL response to EBV in asymptomatic virus carriers has been mapped to four epitope regions in EBV latent cycle Ags. One of these peptide-defined epitopes (RRIYDLIEL) tends to be immunodominant and is recognized in the context of all three B27 subtypes studied, B*2702, B*2704, and B*2705. The other peptide-defined epitopes induce responses only in the context of one subtype, the immunogenic combinations being RRARSLSAERY/B*2702, RRRWRRLTV/B*2704, and FRKAQIQGL/B*2705. We used immunoaffinity chromatography to isolate the naturally presented viral peptides associated with these MHC class I molecules on the surface of EBV-transformed B-LCL. Using CTL reconstitution assays in conjunction with mass spectrometry, we established that the naturally processed and presented peptides are identical with the previously identified synthetic sequences. Despite the subtype-specific immunogenicity of three of the four epitopes, all four epitope peptides were found in association with each of the three different HLA-B27 subtypes. Indeed, those peptides that failed to induce a response in the context of a particular HLA-B27 subtype were frequently presented at greater abundance by that subtype than were the immunogenic peptides. Furthermore, among the peptides that did induce a response, immunodominance did not correlate with epitope abundance; in fact the immunodominant RRIYDLIEL epitope was least abundant, being present at less than one copy per cell. The relationship of this unexpected finding to the persistence of EBV is discussed.

Cytotoxic T-lymphocyte responses to a polymorphic Epstein-Barr virus epitope identify healthy carriers with coresident viral strains.

Cytotoxic T-lymphocyte (CTL) responses to Epstein-Barr virus (EBV) tend to focus on a few immunodominant viral epitopes; where these epitope sequences are polymorphic between EBV strains, host CTL specificities should reflect the identity of the resident strain. In studying responses in HLA-B27-positive virus carriers, we identified 2 of 15 individuals who had strong CTL memory to the pan-B27 epitope RRIYDLIEL (RRIY) from nuclear antigen EBNA3C but whose endogenous EBV strain, isolated in vitro, encoded a variant sequence RKIYDLIEL (RKIY) which did not form stable complexes with B27 molecules and which was poorly recognized by RRIY-specific CTLs. To check if such individuals were also carrying an epitope-positive strain (either related to or distinct from the in vitro isolate), we screened DNA from freshly isolated peripheral blood mononuclear cells for amplifiable virus sequences across the EBNA3C epitope, across a different region of EBNA3C with type 1-type 2 sequence divergence, and across a polymorphic region of EBNA1. This showed that one of the unexplained RRIY responders carried two distinct type 1 strains, one with an RKIY and one with an RRIY epitope sequence. The other responder carried an RKIY-positive type 1 strain and a type 2 virus whose epitope sequence of RRIFDLIEL was antigenically cross-reactive with RRIY. Of 15 EBV-seropositive donors analyzed by such assays, 12 appeared to be carrying a single virus strain, one was coinfected with distinct type 1 strains, and two were carrying both type 1 and type 2 viruses. This implies that a small but significant percentage of healthy virus carriers harbor multiple, perhaps sequentially acquired, EBV strains.

Market factors and the availability of community pharmacies.

The purpose of this study was to examine the relationships between the availability of community pharmacies and 4 types of market factors. A composite data set was created that linked, at the county level, data on: (1) type and number of pharmacies; (2) population characteristics; (3) payer variables; (4) health care system factors; and (5) competitive factors. In this exploratory study, secondary data were used to assess the association between the availability of community pharmacies and the influence of market factors. To assess the market influences on availability of community pharmacies, 2 regressions were performed. In 1 model, the number of community pharmacies per 10,000 population was the dependent variable, whereas the dependent variable in the other regression was the proportion of independently owned community pharmacies. The independent variables in each regression were the market factors--population characteristics, payer variables, health care system factors, and competitive variables. Squared terms were included for 8 of 15 market factors to account for nonlinearities in the relationships. Multiple market factors were correlated with both the number of community pharmacies and the proportion of independently owned pharmacies in an area. Several of the relationships were not linear and changed direction within the range of data. Counties with either a low or a high percentage of elderly people had fewer pharmacies and a lower proportion of independently owned pharmacies compared with counties with a moderate percentage of elderly people. Counties that were scarcely or highly rural had fewer community pharmacies but a higher proportion of independently owned pharmacies than counties that were moderately rural. Areas with a greater percentage of the population earning less than the poverty level had more pharmacies, especially independently owned ones. Fewer community pharmacies were found in areas with higher health maintenance organization penetration rates. The number of hospital admissions was positively associated with the number of pharmacies but negatively associated with the proportion of independently owned pharmacies. The availability of community pharmacies varies across the country. In light of the trend toward fewer independently owned pharmacies, potential problems in accessing pharmacy services could develop in certain areas, including those that are highly rural and those with a high percentage of people earning less than the poverty level. Future research and policy issues are identified.