ABSTRACT
Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampus-dependent learning and memory. Canonically, this has been ascribed to an enhancing effect on neuronal excitability and synaptic plasticity in the CA1 region. However, it is the pyramidal neurons in the subiculum that form the primary efferent pathways conveying hippocampal information to other areas of the brain, and yet the effect of BDNF on these neurons has remained unexplored. We present new data that BDNF regulates neuronal excitability and cellular plasticity in a much more complex manner than previously suggested. Subicular pyramidal neurons can be divided into two major classes, which have different electrophysiological and morphological properties, different requirements for the induction of plasticity, and different extrahippocampal projections. We found that BDNF increases excitability in one class of subicular pyramidal neurons yet decreases excitability in the other class. Furthermore, while endogenous BDNF was necessary for the induction of synaptic plasticity in both cell types, BDNF enhanced intrinsic plasticity in one class of pyramidal neurons yet suppressed intrinsic plasticity in the other. Taken together, these data suggest a novel role for BDNF signaling, as it appears to dynamically and bidirectionally regulate the output of hippocampal information to different regions of the brain.
Subject(s)
Action Potentials/drug effects , Brain-Derived Neurotrophic Factor/pharmacology , Hippocampus/cytology , Neurons/classification , Neurons/drug effects , Animals , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials/drug effects , Male , Mice , Patch-Clamp TechniquesABSTRACT
A new tuberculosis vaccine is needed to replace or enhance BCG, which induces variable protection against Mycobacterium tuberculosis pulmonary infections in adults. Development of new TB vaccine candidates is severely hampered by the lack of a correlate of immunity, unproven animal models, and limited funding opportunities. One candidate, MVA85A, recently failed to meet its efficacy endpoint goals despite promising early-phase trial data. As a result, some in the field believe we should now shift our focus away from product development and toward a research-oriented approach. Here, we outline our suggestions for this research-oriented strategy including diversification of the candidate pipeline, expanding measurements of immunity, improving pre-clinical animal models, and investing in combination pre-clinical/experimental medicine studies. As with any evolution, this change in strategy comes at a cost but may also represent an opportunity for advancing the field.
Subject(s)
Mycobacterium tuberculosis/immunology , Tuberculosis Vaccines/immunology , Tuberculosis Vaccines/isolation & purification , Tuberculosis/prevention & control , Animals , Biomarkers/analysis , Biomedical Research/trends , Disease Models, Animal , Drug Discovery/trends , Humans , Tuberculosis/immunologyABSTRACT
BACKGROUND: Emergence from anaesthesia is often accompanied by signs of delirium, including fluctuating mental status and inattention. The evolution of these signs of delirium requires investigation since delirium in the post-anaesthesia care unit (PACU) may be associated with worse outcomes. METHODS: Adult patients emerging from anaesthesia were assessed for agitated emergence in the operating room using the Richmond Agitation-Sedation Scale (RASS). The Confusion Assessment Method for the Intensive Care Unit was then used to evaluate delirium signs at PACU admission and during PACU stay at 30 min, 1 h, and discharge. Signs consistent with delirium were classified as hyperactive vs hypoactive based upon a positive CAM-ICU assessment and the concomitant RASS score. Multivariable logistic regression was utilized to assess potential risk factors for delirium during PACU stay including age, American Society of Anesthesiologists classification, and opioid and benzodiazepine exposure. RESULTS: Among 400 patients enrolled, 19% had agitated emergence. Delirium signs were present at PACU admission, 30 min, 1 h, and PACU discharge in 124 (31%), 59 (15%), 32 (8%), and 15 (4%) patients, respectively. In patients with delirium signs, hypoactive signs were present in 56% at PACU admission and in 92% during PACU stay. Perioperative opioids were associated with delirium signs during PACU stay (P=0.02). CONCLUSIONS: A significant proportion of patients develop delirium signs in the immediate postoperative period, primarily manifesting with a hypoactive subtype. These signs often persist to PACU discharge, suggesting the need for structured delirium monitoring in the PACU to identify patients potentially at risk for worse outcomes in the postoperative period.
Subject(s)
Anesthesia Recovery Period , Anesthesia, General , Delirium/epidemiology , Postoperative Complications/epidemiology , Adult , Aged , Critical Care , Female , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , New Orleans/epidemiology , Prospective Studies , Psychomotor Agitation/epidemiology , Risk FactorsABSTRACT
Methods for the spatial estimation of risk of harm to soil by erosion by water and wind and by soil organic matter decline are explored. Rates of harm are estimated for combinations of soil type and land cover (as a proxy for hazard frequency) and used to estimate risk of soil erosion and loss of soil organic carbon (SOC) for 1 km(2)pixels. Scenarios are proposed for defining the acceptability of risk of harm to soil: the most precautionary one corresponds to no net harm after natural regeneration of soil (i.e. a 1 in 20 chance of exceeding an erosion rate of <1 tha(-1)y(-1) and SOC content decline of 0 kg t(-1)y(-1) for mineral soils and a carbon stock decline of 0 tha(-1)y(-1) for organic soils). Areas at higher and lower than possible acceptable risk are mapped. The veracity of boundaries is compromised if areas of unacceptable risk are mapped to administrative boundaries. Errors in monitoring change in risk of harm to soil and inadequate information on risk reduction measures' efficacy, at landscape scales, make it impossible to use or monitor quantitative targets for risk reduction adequately. The consequences for priority area definition of expressing varying acceptable risk of harm to soil as a varying probability of exceeding a fixed level of harm, or, a varying level of harm being exceeded with a fixed probability, are discussed. Soil data and predictive models for rates of harm to soil would need considerable development and validation to implement a priority area approach robustly.
Subject(s)
Carbon/analysis , Conservation of Natural Resources/methods , Environmental Monitoring , Soil/chemistry , Risk AssessmentABSTRACT
PURPOSE: Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. METHODS: We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%). RESULTS: Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% (92-100%) of study days beginning 1.0 (1.0-1.0) day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients, and 42/43 (98%) of cognitive plus physical therapy patients on 17% (10-26%), 67% (46-87%), and 75% (59-88%) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up. CONCLUSIONS: This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.
Subject(s)
Cognitive Behavioral Therapy/methods , Cognitive Dysfunction/therapy , Critical Illness/rehabilitation , Exercise Therapy/methods , Intensive Care Units/statistics & numerical data , Adult , Aged , Feasibility Studies , Female , Humans , Male , Middle Aged , Occupational Therapy/methods , Pilot Projects , Quality of Life , Surveys and Questionnaires , Treatment OutcomeABSTRACT
BACKGROUND: Recent work demonstrated the value of antigen-specific antibody indices (AI and C-value) to detect intrathecal antibody production against Sarcocystis neurona for antemortem diagnosis of equine protozoal myeloencephalitis (EPM). OBJECTIVES: The study was conducted to assess whether the antigen-specific antibody indices can be reduced to a simple serum : cerebrospinal fluid (CSF) titer ratio to achieve accurate EPM diagnosis. ANIMALS: Paired serum and CSF samples from 128 horses diagnosed by postmortem examination. The sample set included 44 EPM cases, 35 cervical-vertebral malformation (CVM) cases, 39 neurologic cases other than EPM or CVM, and 10 non-neurologic cases. METHODS: Antibodies against S. neurona were measured in serum and CSF pairs using the SnSAG2 and SnSAG4/3 (SnSAG2, 4/3) ELISAs, and the ratio of each respective serum titer to CSF titer was determined. Likelihood ratios and diagnostic sensitivity and specificity were calculated based on serum titers, CSF titers, and serum : CSF titer ratios. RESULTS: Excellent diagnostic sensitivity and specificity was obtained from the SnSAG2, 4/3 serum : CSF titer ratio. Sensitivity and specificity of 93.2 and 81.1%, respectively, were achieved using a ratio cutoff of ≤100, whereas sensitivity and specificity were 86.4 and 95.9%, respectively, if a more rigorous cutoff of ≤50 was used. Antibody titers in CSF also provided good diagnostic accuracy. Serum antibody titers alone yielded much lower sensitivity and specificity. CONCLUSIONS AND CLINICAL IMPORTANCE: The study confirms the value of detecting intrathecal antibody production for antemortem diagnosis of EPM, and they further show that the antigen-specific antibody indices can be reduced in practice to a simple serum : CSF titer ratio.
Subject(s)
Antibodies, Protozoan/blood , Encephalomyelitis/veterinary , Enzyme-Linked Immunosorbent Assay/veterinary , Horse Diseases/parasitology , Protozoan Proteins/immunology , Sarcocystis/immunology , Sarcocystosis/veterinary , Animals , Antibodies, Protozoan/cerebrospinal fluid , Encephalomyelitis/cerebrospinal fluid , Encephalomyelitis/parasitology , Horse Diseases/diagnosis , Horses , Predictive Value of Tests , Protozoan Proteins/cerebrospinal fluid , Sarcocystosis/blood , Sarcocystosis/cerebrospinal fluid , Sarcocystosis/parasitology , Sensitivity and SpecificityABSTRACT
Microbial pollution in surface waters is a concern throughout the world, with both public health and economic implications. One contributing source to such pollution is stormwater runoff, often treated using various types of stormwater control measures. However, relatively little is known regarding microbe sequestration in constructed stormwater wetlands (CSWs), one type of commonly installed stormwater control measure. In this study, indicator bacteria concentrations in both the water and sediment of a CSW were evaluated at multiple locations. Results suggested that fecal coliform concentrations in stormwater runoff decrease through the system, with relatively consistent concentrations noted throughout the second half of the wetland. This potentially indicates a baseline concentration of fecal coliform is present due to internal processes such as animal activity and microbial persistence. However, wetland sediments showed little E. coli present during most sampling events, with minimal patterns existing with respect to sediment sampling location. CSW designs should promote optimization of hydraulic retention time and minimization of stormwater velocities to promote sedimentation and degradation of microbes by way of wetland treatment functions.
Subject(s)
Escherichia coli/isolation & purification , Feces/microbiology , Water Microbiology , Wetlands , Humans , Soil Microbiology , Waste Disposal, FluidABSTRACT
The prevalence of ten antibiotic resistance genes (ARGs) was evaluated in a total of 616 Escherichia coli isolates from swine manure, swine lagoon effluent, and from soils that received lagoon effluent on a commercial swine farm site in Sampson County, North Carolina (USA). Isolates with ARGs coding for streptomycin/spectinomycin (aadA/strA and strB), tetracycline (tetA and tetB), and sulfonamide (sul1) occurred most frequently (60.6-91.3%). The occurrence of E. coli isolates that carried aadA, tetA, tetB, and tetC genes was significantly more frequent in soil samples (34.0-97.2%) than in isolates from lagoon samples (20.9-90.6%). Furthermore, the frequency of isolates that contain genes coding for aadA and tetB was significantly greater in soil samples (82.6-97.2%) when compared to swine manure (16.8-86.1%). Isolates from the lagoon that carried tetA, tetC, and sul3 genes were significantly more prevalent during spring (63.3-96.7%) than during winter (13.1-67.8%). The prevalence of isolates from the lagoon that possessed the strA, strB, and sul1 resistance genes was significantly more frequent during the summer (90.0-100%) than during spring (66.6-80.0%). The data suggest that conditions in the lagoon, soil, and manure may have an impact on the occurrence of E. coli isolates with specific ARGs. Seasonal variables seem to impact the recovery isolates with ARGs; however, ARG distribution may be associated with mobile genetic elements or a reflection of the initial numbers of resistant isolates shed by the animals.
Subject(s)
Drug Resistance, Bacterial , Escherichia coli/drug effects , Escherichia coli/genetics , Genes, Bacterial , Manure/microbiology , Soil Microbiology , Water Microbiology , Animals , Escherichia coli/isolation & purification , Escherichia coli Proteins/genetics , North Carolina , Seasons , SwineABSTRACT
AIMS: The aim of this study was to identify and characterize the population of Enterococcus sp. in domestic wastewater as it flows through a constructed wetland. METHODS AND RESULTS: Four hundred and eighty-four Enterococcus isolates were collected from the inlet, various sites within and from the outlet of a plastic lined constructed wetland in College Station, TX. The wetland treated septic tank effluent that passed sequentially through two 1.89 m(3) septic tanks and a 1.89 m(3) pump tank allowing 48 l doses at a 24 l min(-1) rate. The Enterococcus isolates were identified to species using the commercial Biolog system. The 484 Enterococcus isolates were comprised of ten different species, including Enterococcus faecalis (30.6%), Enterococcus pseudoavium (24.0%), Enterococcus casseliflavus (12.8%), Enterococcus faecium (11.2%), Enterococcus mundtii (7.9%), Enterococcus gallinarum (6.2%), Enterococcus dispar (3.7%), Enterococcus hirae (2.1%), Enterococcus durans and Enterococcus flavescens both 0.8%. Of the 88 isolates collected from the inlet, only 9.1% of the isolates were identified as Ent. faecalis and Ent. pseudoavium (36.4%) was identified as the predominant species. Whereas of the 74 isolates collected from the outlet, the predominant species were identified as Ent. faecalis (29.7%). Species identification varied among sites within the wetland, but often Ent. faecalis was the predominant species. CONCLUSIONS: Our data suggest that while Ent. faecalis is the predominant species of Enterococcus found in domestic wastewater, the populations may shift during treatment as the wastewater flows through the constructed wetland. SIGNIFICANCE AND IMPACT OF THE STUDY: We found that shifts in Enterococcus species composition occurred during domestic wastewater treatment. This has implications for the identification of faecal pollution based on the presence of specific bacterial types associated with domestic wastewater.
Subject(s)
Enterococcus/physiology , Water Microbiology , Wetlands , Bacterial Load , Enterococcus/isolation & purification , Phenotype , Sewage/microbiology , Waste Disposal, Fluid/methods , Water/chemistryABSTRACT
The current paper examines the realities of women delivering in resource-poor settings, and recommends cost-effective, scalable strategies for making these deliveries safer. Ninety-five percent of maternal deaths occur in poor settings, and the largest proportion of these deaths are women who deliver at home, far away from health care facilities, and without financial access to skilled providers. This situation will improve only when policymakers and programme planners refocus their attention on service delivery and financing interventions, with the potential to reach the largest portion of women living in places where mortality is the highest. We suggest three feasible interventions that can potentially minimise both demand and supply side problems of safe delivery: (1) misoprostol to treat postpartum haemorrhage, an easy to use and heat stable technology to reduce the leading cause of maternal deaths; (2) alternative providers, such as clinical officers, trained to offer emergency obstetric care services; (3) financing safe delivery through vouchers or other mechanisms that can be implemented in poor settings and made attractive to the donor community through output-based assistance (OBA).
Subject(s)
Health Services Accessibility/economics , Home Childbirth/economics , Maternal Mortality/trends , Postpartum Hemorrhage/prevention & control , Developing Countries , Female , Home Childbirth/adverse effects , Home Childbirth/statistics & numerical data , Humans , Medically Underserved Area , Misoprostol/therapeutic use , Oxytocics/therapeutic use , Postpartum Hemorrhage/drug therapy , Postpartum Hemorrhage/mortality , Poverty , PregnancyABSTRACT
Phylogenetic relationships in the USDA Vigna germplasm collection are somewhat unclear and their genetic diversity has not been measured empirically. To reveal interspecific phylogenetic relationships and assess their genetic diversity, 48 accessions representing 12 Vigna species were selected, and 30 gene-derived markers from legumes were employed. Some high-quality amplicons were sequenced. Indels (insertion/deletions) were discovered from the sequence alignments that were specific identifiers for some Vigna species. With regard to revealing polymorphisms, intron-spanning markers were more effective than exon-derived markers. These gene-derived markers were more successful in revealing interspecific polymorphisms than intraspecific polymorphisms at both the DNA fragment and sequence levels. Two different dendrograms were generated from DNA fragment data and sequence data, respectively. The results from these two dendrograms supported each other and showed similar phylogenetic relationships among the Vigna species investigated. The accessions clustered into four main groups and 13 subgroups. Each subgroup represents a subgenus or a species. Phylogenetic analysis revealed that an accession might be misclassified in our collection. The putative misclassified accession was further supported by seed morphology. Limited intraspecific genetic diversity was revealed by these gene-derived markers and/or sequences. The USDA Vigna germplasm collection currently consists of multiple species with many accessions further classified into specific subspecies, but very few subspecies of the total subspecies available exist within the collection. Based on our results, more attention should be paid to the subspecies, wild forms and/or botanical varieties for future curation in order to expand the genetic diversity of Vigna germplasm in the USDA collection.
Subject(s)
Fabaceae/classification , Fabaceae/genetics , Alleles , Base Sequence , DNA Primers/genetics , DNA, Plant/genetics , Fabaceae/embryology , Genetic Markers , Genetic Variation , Molecular Sequence Data , Phenotype , Phylogeny , Pigmentation/genetics , Seeds/anatomy & histology , Sequence Homology, Nucleic Acid , Species Specificity , United StatesABSTRACT
Antibiotic resistance analysis (ARA), frequency of sampling, and seasonality were evaluated in a rural Virginia watershed dominated by cattle. The selected watershed (Mill Creek) was 3767 ha in size, included two small communities (one sewered and one unsewered), and several farms that when combined contained over 3800 beef and dairy cattle. Monthly monitoring of fecal coliforms at two sampling sites in Mill Creek from January to December, 2001, revealed that the recreational standard (1000 colony forming units, CFUs/100 ml) was exceeded a total of eight times for a 33% violation rate at each site. In addition, stream samples were collected weekly for 4 consecutive weeks during seasonal high flows (March) and seasonal low flows (September-October), plus daily for 7 consecutive days within the weekly schedules for a combined total of 60 stream samples (30 at each of two sites). The recreational standard was exceeded once during seasonal high flow and nine times during seasonal low flow. Microbial source tracking (MST) was performed by ARA to assess the impact of cattle on water quality within the different sampling routines. The resistance patterns of 2880 water isolates and 1158 known source (host-origin) isolates were determined with seven antibiotics at 28 different concentrations. The 1158 isolate database was reduced to 562 unique isolates when clonal ARA patterns were removed. This database of 562 unique isolates had an average rate of correct classification (ARCC) of 95.4%, and several statistical procedures confirmed the library as accurate and representative. Sixty-five percent of 50 challenge-set isolates from sources, but not samples, used in the library were correctly identified. The 562 unique pattern database was used to classify Escherichia coli isolates from water samples into six host source categories. The ARA results showed that cattle were the major source of pollution in the stream and cattle were the dominant source in over 60% of the water samples. Sampling frequency and seasonality had no effect on the MST results, as cattle dominated both seasons and samplings. Deer were a minor contributor in the summer (high water demand), and geese were a minor contributor in the winter when migratory flocks were observed moving through the watershed. An unexpected human allocation was found, especially under seasonal high flow conditions. The exact origin of this human allocation is not known. This project demonstrated that a host-origin library, based on a phenotypic method, could be developed for a well-defined watershed and was both representative of the sources in the watershed and performed reasonably well against a challenge set.
Subject(s)
Bacteria/isolation & purification , Drug Resistance, Microbial , Fresh Water/microbiology , Water Pollution/analysis , Animals , Animals, Domestic , Cattle , Rural Health , Seasons , Sewage/microbiology , Virginia , Water Pollutants/analysisABSTRACT
AIMS: Carbon source utilization profiles as a phenotypic fingerprinting methodology for determining sources of faecal pollution in water were evaluated. METHODS AND RESULTS: Three hundred and sixty-five Enterococcus isolates were collected from known faecal sources in four different geographical regions and were identified to species with the commercial Biolog system. Discriminant analysis (DA) was used to identify the substrate-containing wells that best classified the 365 isolates by source. By using 30 of the 95 wells for the analysis, the average rate of correct classification (ARCC) by source was 92.7% for a human vs non-human two-way classification when isolates from all regions were combined into one library. Corresponding ARCCs for other classification schemes were 81.9% for a four-way classification of human vs livestock vs wildlife vs domestic pets, and 85.7% for a three-way classification without human isolates. When three individual libraries were made based on classification of sources within Enterococcus species, the ARCC was 95.3% for the Ent. faecalis library, 95.8% for the Ent. gallinarum library and 94.7% for the Ent. mundtii library. Thirty Enterococcus isolates (unknown sources) were obtained from each of three stream sites where a specific source of pollution was apparent; 90.0% of the isolates from a human-suspected source were classified as human, 86.6% were classified as livestock from a livestock-suspected site, and 93.3% were classified as wildlife from a wildlife-suspected site. CONCLUSIONS: Phenotypic fingerprinting with carbon source utilization profiles provided levels of correct classification by sources from an Enterococcus library that were in the upper range of those reported in the literature. ARCCs for three Enterococcus species-specific libraries were very high and may be the best approach for further developing this concept and methodology. SIGNIFICANCE ANC IMPACT OF THE STUDY: The results, based on a modest Enterococcus library and a preliminary field validation test, demonstrated the potential for carbon source utilization profiles to be employed as a phenotypic method for determining sources of faecal pollution in water.
Subject(s)
Bacterial Typing Techniques/methods , Enterococcus/classification , Feces/microbiology , Water Microbiology , Water Pollution , Animals , Carbon/metabolism , Enterococcus/isolation & purification , Enterococcus/metabolism , Environmental Monitoring/methods , Humans , Phenotype , Sewage/microbiology , Species Specificity , WaterABSTRACT
Genetic association studies investigating the role of the +118A allele of the human mu-opioid receptor gene in risk for alcohol dependency have produced inconsistent findings, possibly because of the failure to recognize sampling methodology difficulties inherent in association studies of polygenic disorders. We examined the frequency of the AA genotype and A allele in several groups of substance-dependent cases, unrestricted controls, and super controls screened for the use of alcohol and cigarettes. Our findings and analyses suggest that the OPRM1 +118 polymorphism is a general risk gene for substance dependence, but is not specific to a particular substance. The nature of the conferred risk is likely to be in use of multiple substances, but it is not yet determined if the risk could be expressed in severity of use of any particular substance. The contribution of the gene to risk for substance dependence is small, and is detected most easily in studies that use control samples that are screened for all forms of substance dependence.
Subject(s)
Alcoholism/genetics , Polymorphism, Genetic , Receptors, Opioid, mu/genetics , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Smoking , Substance-Related Disorders/geneticsABSTRACT
BACKGROUND: The clinical expression of AD likely occurs when the accumulation of degeneration in specific brain regions leads to the descent below a critical threshold of "brain reserve" beyond which normal cognitive function cannot be maintained. The association between head circumference (HC), a measure of brain reserve, and the incidence of probable AD was examined in a large nondemented cohort that has been followed since 1992 and its modification by APOE epsilon 4 genotype. METHODS: Fifty-nine incident cases of probable AD were identified from 1,869 initially nondemented individuals seen at the baseline examination (1992 to 1994) and followed for a mean of 3.8 years. Variables measured at baseline included age, education, gender, HC, height, weight, and score on the National Adult Reading Test-Revised. APOE was genotyped at the time of the first biennial examination (1994 to 1996) and was available for 1,111 individuals in the cohort. Cox proportional hazard regression was performed to estimate hazard ratios (HR) for probable AD for HC and other covariates. RESULTS: Incident cases were significantly older, less educated, shorter, and lighter, had lower estimated verbal IQ scores, and were more likely to have at least one APOE epsilon 4 allele than unaffected individuals. The HR associated with the lowest tertile of HC (<21.4 inches) adjusted for education, gender, and APOE epsilon 4 was 2.3 (95% CI 0.7 to 6.9, p = 0.16). The HR for one or two APOE epsilon 4 alleles was significant (HR = 4.8, 95% CI 1.8 to 12.9, p = 0.002). The combination of low HC and APOE epsilon 4 strongly predicted earlier onset of AD with HR = 14.1 (95% CI 3.0 to 65, p = 0.0007). CONCLUSIONS: Smaller HC, in the presence of the APOE epsilon 4 allele, hastens the age at onset of AD. These results support the brain reserve hypothesis and its importance in precipitating the clinical expression of AD among genetically predisposed individuals.
Subject(s)
Alzheimer Disease/epidemiology , Head/anatomy & histology , Aged , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Apolipoprotein E4 , Apolipoproteins E/genetics , Brain/pathology , Cephalometry , Female , Follow-Up Studies , Genotype , Humans , Incidence , Male , Predictive Value of TestsABSTRACT
OBJECTIVE: To investigate the effects of light to moderate alcohol consumption on cognitive performance. DESIGN AND SETTING: A cross-sectional analysis including older Japanese Americans in King County, WA, enrolled in the Kame Project, a population-based study of cognition, dementia, and aging. PARTICIPANTS: 1,836 cognitively intact participants aged 65 and older who participated in the baseline (1992-1994) examination. MEASUREMENT: Cognitive performance was measured using the Cognitive Abilities Screening Instrument, reaction time (simple and choice), and a measure of vocabulary (North American Adult Reading Test). RESULTS: Multivariate analyses were used to examine the relationship between cognitive performance and alcohol consumption at baseline with men and women together and then separately controlling for age, education, smoking, history of stroke, angina, hypertension, diabetes, and coronary heart disease. Findings showed lower cognitive test scores were observed for men who were either abstainers or in the heavy drinking group. For women, a linear relationship between alcohol consumption and cognitive performance was seen on two of the four measures of cognitive functioning. No significant difference in the association of drinking and cognitive function was identified within the different Japanese American subgroups. CONCLUSION: RESULTS suggest a possible positive relationship between light to moderate drinking and cognitive performance in an aging Japanese American population. Additional long-term prospective and cross-cultural studies are needed to determine the generalizability of these findings to other aging cohorts.
Subject(s)
Aging/psychology , Alcohol Drinking/psychology , Asian/psychology , Central Nervous System Depressants/pharmacology , Cognition/drug effects , Ethanol/pharmacology , Age Factors , Aged , Aged, 80 and over , Asian/statistics & numerical data , Cross-Sectional Studies , Female , Humans , Male , Neuropsychological Tests , Prospective Studies , Research Design , Sex Factors , Temperance/psychologyABSTRACT
PURPOSE: To evaluate and compare the in vitro antimicrobial activity of levofloxacin versus ciprofloxacin and ofloxacin against ocular isolates from patients with bacterial conjunctivitis. METHODS: The in vitro antimicrobial susceptibilities of ocular isolates to levofloxacin, ofloxacin, and ciprofloxacin were determined using both the agar disk diffusion and broth dilution methods. RESULTS: Disk diffusion susceptibility testing disclosed that 99% (100 of 101 isolates) of gram-negative isolates and 98% (127 of 129 isolates) of gram-positive isolates were susceptible to levofloxacin; 96% (97 of 101 isolates) of gram-negative isolates and 78% (100 of 129 isolates) of gram-positive isolates were susceptible to ofloxacin; and 94% (95 of 101 isolates) of gram-negative isolates and 61% (79 of 129 isolates) of gram-positive isolates were susceptible to ciprofloxacin. Broth dilution testing disclosed that 99% (72 of 73 isolates) of gram-negative isolates and 98% (111 of 113 isolates) of gram-positive isolates were susceptible to levofloxacin; 96% (70 of 73 isolates) of gram-negative isolates and 92% (104 of 113 isolates) of gram-positive isolates were susceptible to ofloxacin; and 95% (69 of 73 isolates) of gram-negative isolates and 82% (93 of 113 isolates) of gram-positive isolates were susceptible to ciprofloxacin. CONCLUSIONS: In this study, levofloxacin demonstrated superior in vitro activity against human bacterial conjunctival isolates compared with either ofloxacin or ciprofloxacin (levofloxacin > ofloxacin > ciprofloxacin).
Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Bacteria/isolation & purification , Ciprofloxacin/pharmacology , Colony Count, Microbial , Conjunctivitis, Bacterial/microbiology , Drug Evaluation , Drug Resistance, Microbial , Humans , Levofloxacin , Microbial Sensitivity Tests , Ofloxacin/pharmacologyABSTRACT
The VA Medical Center in Washington, DC, was the nexus for a number of computerization projects that were initiated by the Department of Veterans Affairs. The culmination of these initiatives is a software package that presents the complete electronic patient record in an easy-to-use graphic user interface. This record combines text data from the legacy data base, diagnostic images from patient procedures, electrocardiograms from a commercial server, an Internet connection, and a hospital web site with pertinent reference information. The information is available in over 1000 places in the hospital and can be accessed remotely using a remote access server. The computerization of the medical record has improved hospital efficiency, has made physician access to patient information more reliable, has opened new opportunities for patient education, and has given healthcare providers more time to care for patients.
Subject(s)
Medical Records Systems, Computerized , Telemedicine/trends , United States Department of Veterans Affairs , Diagnostic Imaging , Efficiency, Organizational , Hospital Information Systems , Humans , Internet , Patient Education as Topic , Software , United StatesABSTRACT
OBJECTIVE: In a sample of older Japanese American women, we aimed to: (1) describe the most commonly consumed soy foods, (2) estimate dietary soy isoflavone intake, (3) describe characteristics associated with dietary soy isoflavone intake, and (4) compare our estimates with previously published estimates in other Japanese samples. DESIGN: A 14-item soy food-frequency questionnaire was administered to older Japanese American women and responses were converted to quantitative estimates of soy isoflavones (genistein plus daidzein). Multiple regression was used to examine characteristics associated with dietary soy isoflavone intake, including self-reported lifestyle and cultural factors and dietary intake of various foods ascertained from a semi-quantitative food-frequency questionnaire. To compare our estimates with other samples, a review of the literature was conducted. SETTING/SUBJECTS: Data are from 274 women aged 65+ years, recruited from a longitudinal cohort study of Japanese Americans in King County, Washington State. RESULTS: The soy foods most commonly consumed were tofu (soybean curd), miso (fermented soybean paste) and aburaage (fried thin soybean curd). The mean intake of dietary soy isoflavones was 10.2 (standard deviation (SD), 12.4) mg day(-1), approximately a quarter to a half that of previously published estimates in Japanese samples. Dietary soy isoflavone intake was positively associated with speaking Japanese, the consumption of traditional Japanese dishes (kamaboko, manju and mochi), low-fat/non-fat milk and yellow/red vegetables, vitamin E supplement use, and walking several blocks each day. Dietary soy isoflavone intake was negatively associated with the consumption of butter. CONCLUSIONS: The estimated dietary soy isoflavone intake in Japanese American women living in King County, Washington State was about a quarter to a half that of women living in Japan. Dietary soy isoflavone intake was associated with speaking Japanese and healthy lifestyle and dietary habits.