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Biomedical subjects

S Davis

Publications and source records attributed to S Davis.

At least 73 records · Page 4Linked to original sources

Night shift work, light at night, and risk of breast cancer.

BACKGROUND: Exposure to light at night may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin by the pineal gland, which, in turn, could increase the release of estrogen by the ovaries. This study investigated whether such exposure is associated with an increased risk of breast cancer in women. METHODS: Case patients (n = 813), aged 20-74 years, were diagnosed from November 1992 through March 1995; control subjects (n = 793) were identified by random-digit dialing and were frequency matched according to 5-year age groups. An in-person interview was used to gather information on sleep habits and bedroom lighting environment in the 10 years before diagnosis and lifetime occupational history. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression, with adjustment for other potential risk factors. RESULTS: Breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest (OR = 1.14 for each night per week; 95% CI = 1.01 to 1.28). Risk did not increase with interrupted sleep accompanied by turning on a light. There was an indication of increased risk among subjects with the brightest bedrooms. Graveyard shiftwork was associated with increased breast cancer risk (OR = 1.6; 95% CI = 1.0 to 2.5), with a trend of increased risk with increasing years and with more hours per week of graveyard shiftwork (P =.02, Wald chi-squared test). CONCLUSION: The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer.

Adult↗

Residential magnetic fields, light-at-night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women.

Exposure to 60-Hz magnetic fields may increase breast cancer risk by suppressing the normal nocturnal rise in melatonin. This 1994-1996 Washington State study investigated whether such exposure was associated with lower nocturnal urinary concentration of 6-sulfatoxymelatonin in 203 women aged 20-74 years with no history of breast cancer. Each woman was interviewed and provided data on the following for a 72-hour period at two different seasons of the year: 1) magnetic field and ambient light measured every 30 seconds in her bedroom, 2) personal magnetic field measured at 30-second intervals, and 3) complete nighttime urine samples on three consecutive nights. Lower nocturnal urinary 6-sulfatoxymelatonin level was associated with more hours of daylight, older age, higher body mass index, current alcohol consumption, and current use of medications classified as beta blockers, calcium channel blockers, or psychotropics. After adjustment for these factors, higher bedroom magnetic field level was associated with significantly lower urinary concentration of 6-sulfatoxymelatonin during the same night, primarily in women who used these medications and during times of the year with the fewest hours of darkness. These results suggest that exposure to nighttime residential 60-Hz magnetic fields can depress the normal nocturnal rise in melatonin.

Adrenergic beta-Antagonists↗

Engineered underdominance allows efficient and economical introgression of traits into pest populations.

A novel form of underdominance is suggested as a mechanism that is able to drive desired genes into pest populations through the release of transgenic individuals over one or more generations. Such a mechanism is urgently needed by those working to reduce the impact of malaria by releasing strains of Anopheles, the vector of the disease, that are not susceptible to malaria parasites. We use simple population genetics models to quantify the benefits conferred when heterozygous genotypes, arising from matings between introduced and wild individuals, are not viable. In a randomly mating population, underdominant systems accelerate introgression of desired alleles and allow the release of individuals to be discontinued once the frequency of transgenic alleles attains a threshold. A set of two constructs, which together are selectively neutral but lethal when one is carried without the other, are found to produce dynamics that are characteristic of underdominant systems. When these constructs are carried on non-homologous chromosomes, then the ratio of released to natural born individuals need only be greater than 3:100 for introgression to occur. Furthermore, the threshold for the gene frequencies over which the introduced genes are expected to become fixed upon discontinuing the release of transgenic individuals is surprisingly low. The location of the threshold suggests that the introduced genes are expected to spread in space, at least locally. For the first time, the prospect of a practical drive mechanism for the genetic manipulation of pest populations is raised.

Alleles↗

Reproductive changes in fluctuating house mouse populations in southeastern Australia.

House mice (Mus domesticus) in the Victorian mallee region of southeastern Australia show irregular outbreaks. Changes in reproductive output that could potentially drive changes in mouse numbers were assessed from 1982 to 2000. Litter size in females is positively correlated with body size. When standardized to an average size female, litter size changes seasonally from highest in spring to lowest in autumn and winter. Litter size is depressed throughout breeding seasons that begin when the abundance of mice is high, but is similar in breeding seasons over which the abundance of mice increases rapidly or remains low. Breeding begins early and is extended on average by about five weeks during seasons when mouse abundance increases rapidly. The size at which females begin to reproduce is larger during breeding seasons that begin when mouse abundance is high. An extended breeding season that begins early in spring is necessary for the generation of a house mouse plague, but it is not in itself sufficient. Reproductive changes in outbreaks of house mice in Australia are similar but not identical to reproductive changes that accompany rodent population increases in the Northern Hemisphere. We conclude that food quality, particularly protein, is a probable mechanism driving these reproductive changes, but experimental evidence for field populations is conflicting.

Animals↗

Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits.

We injected a combination of the beta-amyloids (Abetas) Abeta40 and Abeta43 to "seed" formation of amyloid deposits in the dorsal dentate gyrus of rats in vivo, on the basis of a theory of Jarrett and Landsbury (1993). Rats were tested on several different learning tasks, and synaptic transmission and plasticity were assessed in vivo. Between 7 and 16 weeks after injection, we found aggregated amyloid material, reactive astrocytosis, microgliosis, and cell loss around the sites of injection. Rats were impaired specifically in working memory type tasks in accordance with the type of memory deficit observed in the early stages of Alzheimer's disease. Synaptic transmission and long-term potentiation, a candidate cellular mechanism for memory, were severely impaired in vivo. Injections of the same dose of fragments individually did not induce these effects. These findings suggest that aggregated amyloid material induces cognitive deficits similar to those observed in the early phases of Alzheimer's disease via an alteration in neuronal transmission and plasticity.

Alzheimer Disease↗

Ecological conceptual models: a framework and case study on ecosystem management for South Florida sustainability.

The Everglades and South Florida ecosystems are the focus of national and international attention because of their current degraded and threatened state. Ecological risk assessment, sustainability, and ecosystem and adaptive management principles and processes are being used nationally as a decision and policy framework for a variety of types of ecological assessments. The intent of this study is to demonstrate the application of these paradigms and principles at a regional scale. The effects-directed assessment approach used in this study consists of a retrospective, eco-epidemiological phase to determine the causes for the current conditions and a prospective predictive risk-based assessment using scenario analysis to evaluate future options. Embedded in these assessment phases is a process that begins with the identification of goals and societal preferences which are used to develop an integrated suite of risk-based and policy relevant conceptual models. Conceptual models are used to illustrate the linkages among management (societal) actions, environmental stressors, and societal/ecological effects, and provide the basis for developing and testing causal hypotheses. These models, developed for a variety of landscape units and their drivers, stressors, and endpoints, are used to formulate hypotheses to explain the current conditions. They are also used as the basis for structuring management scenarios and analyses to project the temporal and spatial magnitude of risk reduction and system recovery. Within the context of recovery, the conceptual models are used in the initial development of performance criteria for those stressors that are determined to be most important in shaping the landscape, and to guide the use of numerical models used to develop quantitative performance criteria in the scenario analysis. The results will be discussed within an ecosystem and adaptive management framework that provides the foundation for decision making.

Animals↗

A three-item scale for the early prediction of stroke recovery.

BACKGROUND: Accurate assessment of prognosis in the first hours of stroke is desirable for best patient management. We aimed to assess whether the extent of ischaemic brain injury on magnetic reasonance diffusion-weighted imaging (MR DWI) could provide additional prognostic information to clinical factors. METHODS: In a three-phase study we studied 66 patients from a North American teaching hospital who had: MR DWI within 36 h of stroke onset; the National Institutes of Health Stroke Scale (NIHSS) score measured at the time of scanning; and the Barthel Index measured no later than 3 months after stroke. We used logistic regression to derive a predictive model for good recovery. This logistic regression model was applied to an independent series of 63 patients from an Australian teaching hospital, and we then developed a three-item scale for the early prediction of stroke recovery. FINDINGS: Combined measurements of the NIHSS score (p=0.01), time in hours from stroke onset to MR DWI (p=0.02), and the volume of ischaemic brain tissue on MR DWI (p=0.04) gave the best prediction of stroke recovery. The model was externally validated on the Australian sample with 0.77 sensitivity and 0.88 specificity. Three likelihood levels for stroke recovery-low (0-2), medium (3-4), and high (5-7)-were identified on the three-item scale. INTERPRETATION: The combination of clinical and MR DWI factors provided better prediction of stroke recovery than any factor alone, shortly after admission to hospital. This information was incorporated into a three-item scale for clinical use.

Activities of Daily Living↗

Impact of overlapping recruitment on linkage analysis of complex disorders: simulation studies.

Evidence for significant linkage in complexly inherited disorders usually necessitates independent, replicative studies. This study investigates the implications of including in the replicative studies families already used to suggest linkage in initial linkage analysis. We generated 1,000 unlinked replicates of 100 nuclear families with a complexly inherited disease but with no linkage to the markers analyzed. We then used a standard nonparametric linkage method to analyze these data. From the original 1,000 replicates of the original data set, one set was chosen as it yielded suggestive, but falsely positive, linkage results (LOD score = 3.4). Variable numbers of randomly selected families from this positive replicate (n = 100 families) were used to replace families in replicates of the original (unlinked) data set, and linkage analysis repeated. Overlap of families from the "positive data set" did increase the LOD scores for "unlinked data sets." While a small amount of overlap (replacement) between a positive linkage result and the replication sample is unlikely in practice to alter results, our study suggests that steps should be taken to ensure that overlap is minimized. The implications of this overlapping recruitment on replicative linkage studies are discussed.

Family Health↗

Comparison of normal infants and infants with cystic fibrosis using forced expiratory flows breathing air and heliox.

SUMMARY. The detection of early airway disease in infants with cystic fibrosis (CF) may lead to earlier intervention and an improved prognosis. We hypothesized that the ratio of maximal expiratory flows while breathing a mixture of helium and oxygen (heliox) and air, referred to as density dependence (DD), would identify early airway disease in infants with CF who have normal lung function. We also hypothesized that these infants with CF might be better differentiated from normal infants when the flows breathing heliox are compared instead of room air flows. We evaluated 10 infants with CF and 21 infants without CF and with normal lung function, defined as a forced vital capacity (FVC) and forced expiratory flows between 25-75% of expired volume (FEF(25-75)) of greater than 70% predicted (z-score > -2.0). Full forced expiratory maneuvers by the rapid thoracic compression technique were obtained while breathing room air and then heliox. Flow at 50% and 75% of expired volume (FEF(50), FEF(75)), FEF(25-75), and FVC were calculated from the flow volume curve with patients and control subjects breathing each gas mixture. The ratio of heliox to air flow at FEF(50) and FEF(75) was calculated (DD(50), DD(75)), and the point where the two flow-volume curves crossed (V(iso) V') was also measured. DD parameters did not distinguish the infants with CF from the infants without CF; length-adjusted FEF(50) breathing air was significantly lower in the infants with CF compared to the infants without CF (P < 0.05). Length-adjusted flows breathing heliox did not distinguish the two groups. We conclude that the lower FEF(50) value may reflect early airway obstruction in healthy infants with CF, and that measurements obtained with the less dense gas mixture did not improve detection of airway disease in this age group.

Air↗

Effect of concurrent anxiety on response to sertraline and imipramine in patients with chronic depression.

Anxiety commonly complicates the clinical presentation of depression and has been associated with poorer long-term outcome, but little information is available on the clinical correlates, and comparative effect on treatment response, of subsyndromic or secondary anxiety. Patients diagnosed with chronic major or double depression were randomized to 12 weeks of double-blind treatment with either sertraline or imipramine in a 2:1 ratio. A high anxiety subgroup was operationally defined by a HAM-D anxiety/somatization factor score > or = 7. The effect of study treatment was measured utilizing the HAM-D, CGI, HAM-D anxiety/somatization factor, as well as a quality of life measure (Q-LES-Q) and a measure of psychosocial functioning (the MOS-SF-36). Two hundred nine patients were treated with imipramine and 426 patients were treated with sertraline. Thirty-six percent of the total met criteria for the high anxiety subgroup. According to Kaplan-Meier probability estimates, patients with significant concurrent anxiety symptoms were more likely to respond by 12 weeks (66.4%) than those without significant anxiety symptoms (54.2%). There was no significant difference in response rates for sertraline vs. imipramine. Both drugs were effective at treating high baseline levels of anxiety, with 60% of sertraline patients and 58% of imipramine patients having 50% or greater reduction from baseline in HAM-D anxiety/somatization factor scores, and only 4.6% and 9.9%, respectively, reporting treatment-emergent worsening in anxiety at study endpoint. Despite the chronicity of depressive illness, acute treatment with both sertraline and imipramine significantly improved psychosocial and quality of life measures. High baseline levels of anxiety did not reduce overall antidepressant response but did somewhat delay the onset of response to sertraline or imipramine in patients with chronic depression.

Adrenergic Uptake Inhibitors↗

Regulated expression of the neuronal calcium sensor-1 gene during long-term potentiation in the dentate gyrus in vivo.

Neuronal calcium sensor-1 (NCS-1), the mammalian homologue of frequenin, is a member of a highly conserved family of neuron-specific calcium-binding proteins which has been implicated in exocytosis and in multiple calcium-signalling pathways, suggesting a potential involvement in mechanisms of neuronal plasticity. Here, using in situ hybridization, we report an increased induction of the mRNA encoding NCS-1 in dentate granule cells following the induction of long-term potentiation in the awake rat. We show that NCS-1 mRNA levels are increased 1 and 3 h after long-term potentiation in an N-methyl-D-aspartate receptor-dependent manner, returning to baseline expression levels by 6 h. Electroconvulsive stimulation also induced NCS-1 mRNA transcription in the dentate gyrus, but at the different time of 6 h post-seizure, returning to baseline by 12 h. These results show that regulated expression of the NCS-1 gene is part of the transcriptional response associated with activity-dependent neuronal plasticity in vivo and suggest a molecular mechanism capable of mediating a functional change in synapse sensitivity to calcium and calcium-signalling pathways after long-term potentiation.

Animals↗

Functional consequences of repeated (+/-)3,4-methylenedioxymethamphetamine (MDMA) treatment in rhesus monkeys.

Six rhesus monkeys were trained to stable performance on neuropsychological tests of memory, reinforcer efficacy, reaction time and bimanual motor coordination. Three monkeys were then exposed to a high-dose, short course regimen of (+/-)3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") (4 days, 10 mg/kg i.m., b.i.d.). Following treatment, concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) were reduced by approximately 50% in the treated animals, and this effect persisted for approximately three months post-MDMA. Behavioral performance was disrupted during acute MDMA treatment but returned to baseline within one week following treatment. MDMA also produced persistent alterations in late peak latencies of brainstem auditory evoked potentials (BSAEP), lasting three months post-MDMA. Both CSF 5-HIAA concentrations and evoked potential latencies were normalized four months after treatment. These findings indicate that serotonergic alterations associated with MDMA use may result in persisting changes in brain function.

Animals↗

Combined magnetic resonance imaging and single-photon emission tomography scanning in the discrimination of Alzheimer's disease from age-matched controls.

OBJECTIVE: To compare the utility of temporal lobe magnetic resonance imaging (MRI) and single-photon emission tomography (SPET) scanning in discriminating between subjects with Alzheimer's disease (AD) and age-matched controls. METHODS: Thirty subjects with NINCDS-ADRDA AD (23 probable AD, 5 possible AD, 2 definite AD) and 22 age- and sex-matched controls underwent T1-weighted coronal MRI scanning (0.3 T) and technetium 99m-HMPAO SPET scanning. MRI scans were analyzed using a digitizer system with volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and whole cerebral cortex calculated. From SPET scans, regional cerebral blood flow (rCBF) was assessed in anterior and posterior frontal, parietal, occipital, and mesial temporal cortex using a region of interest analysis with the cerebellum as a reference area. RESULTS: Using MRI, the areas that best separated groups were left hippocampal and left amygdala volume, resulting in correct classification (patient vs. control) in 79% of cases (sensitivity 77%, specificity 82%). Exactly the same proportion of subjects were correctly classified by SPET, with the most discriminating rCBF changes being left parietal and right posterior frontal. Combining information from both scans improved the proportion of correctly classified subjects in a discriminant function to 90% (sensitivity 93%, specificity 86%; only 2 AD and 3 controls misclassified). All AD subjects had abnormalities on MRI and/or SPET (sensitivity for combined examinations 100%), while abnormalities on both MRI and SPET had a positive predictive value of 100% for dementia (including the detection of one control subject who later had dementia). Significant correlations between MRI and SPET measures were seen in control subjects but not in patients. CONCLUSION: Both 0.3 T MRI and single rotating gamma camera SPET were equally useful in separating AD subjects from age-matched controls, although the combination of both significantly enhanced discrimination. In particular, all AD subjects had abnormalities on either MRI or SPET and both techniques may have an important role in assisting with clinical diagnosis, though replication in other centers and examination of differentiation of AD from other causes of dementia need to be examined.

Aged↗

An examination of methods for risk-adjustment of rehospitalization rates.

This study examines three methods of conducting risk-adjustment to determine if the choice of method results in different conclusions about comparative mental health center performance. The three methods of risk-adjustment are stratification-weighting, logistic regression without interaction effects, and logistic regression with interaction effects. The dependent variable of interest is psychiatric rehospitalization within 14-60 days of discharge to a community mental health center. Subjects are adults discharged in fiscal year 1998 from inpatient psychiatric care to a designated community mental health center in Oklahoma. Using each method, we examine the mental health centers to determine whether their rehospitalization rates are significantly greater than, less than, or not different from, expected. Results show that, for some agencies, method of risk adjustment leads to different conclusions about center performance. Results are discussed with respect to identifying the preferred method of risk-adjustment, study limitations, and next steps in developing risk-adjustment technology and applications.

Adult↗

A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories.

The induction of long-term potentiation (LTP) in the dentate gyrus of the hippocampus is associated with a rapid and robust transcription of the immediate early gene Zif268. We used a mutant mouse with a targeted disruption of Zif268 to ask whether this gene, which encodes a zinc finger transcription factor, is required for the maintenance of late LTP and for the expression of long-term memory. We show that whereas mutant mice exhibit early LTP in the dentate gyrus, late LTP is absent when measured 24 and 48 hours after tetanus in the freely moving animal. In both spatial and non-spatial learning tasks, short-term memory remained intact, whereas performance was impaired in tests requiring long-term memory. Thus, Zif268 is essential for the transition from short- to long-term synaptic plasticity and for the expression of long-term memories.

Anesthetics↗

High-resolution IR studies of hydrogen bonded clusters: large amplitude dynamics in (HCl)n.

Structural and dynamical information on small hydrogen-bonded systems is revealed by high-resolution IR spectroscopy of HCl dimer, trimer and tetramer. In (HCl)2, four combination bands tentatively assigned to the Van der Waals stretch nu 4 and geared band nu 5 vibrations are observed. The study focuses on two unexpected results: (i) all of the observed bands are built only on the bound HCl stretch nu 2, and (ii) the bands predominantly originate from the 9-fold less populated upper tunneling level of the ground state. Model 3D quantum calculations are presented to show that both these surprising trends originate from the large amplitude tunneling dynamics in the dimer. The (HCl)3 spectra are assigned and analyzed for multiple isotopomeric contributions. The spectral fit reveals large homogeneous line broadening indicating the excited state lifetime of approximately 1.6 ns and tentatively associated with dynamics of intramolecular vibrational energy distribution (IVR) induced trimer ring opening. Finally, first high-resolution data on the HCl stretch fundamental spectrum of (HCl)4 are presented.

Journal Article↗

Subfield-specific immediate early gene expression associated with hippocampal long-term potentiation in vivo.

It is not known whether NMDA receptor-dependent long-term potentiation (LTP) is mediated by similar molecular mechanisms in different hippocampal areas. To address this question we have investigated changes in immediate early gene and protein expression in two hippocampal subfields following the induction of LTP in vivo and in vitro. In granule cells of the dentate gyrus, LTP induced in vivo by tetanic stimulation of the perforant path was followed by strong induction of the immediate early genes (IEGs) Zif268, Arc and Homer. The increase in Zif268 mRNA was accompanied by an increase in protein expression. In contrast, we were unable to detect modulation of the IEGs Zif268, Arc, Homer and HB-GAM following induction of LTP by high-frequency stimulation of the commissural projection to CA1 pyramidal cells in vivo. In this pathway, we also failed to detect modulation of Zif268 protein levels. Zif268, Arc and Homer can be modulated in CA1 pyramidal cells approximately twofold after electroshock-induced maximal seizure, which demonstrates potential responsiveness to electrical stimuli. When LTP was induced in vitro neither CA1 pyramidal cells nor granule cells showed an increase in Zif268, Arc or Homer mRNA. However, in the slice preparation, granule cells have a different transcriptional state as basal IEG levels are elevated. These results establish the existence of subfield-specific transcriptional responses to LTP-inducing stimulation in the hippocampus of the intact animal, and demonstrate that in area CA1-enhanced transcription of Zif268, Arc and Homer is not required for the induction of late LTP.

Animals↗