OBJECTIVE: Reasons for failing to initiate prescribed insulin (primary nonadherence) are poorly understood. We investigated barriers to insulin initiation following a new prescription. RESEARCH ...DESIGN AND METHODS: We surveyed insulin-naïve patients with poorly controlled type 2 diabetes, already treated with two or more oral agents who were recently prescribed insulin. We compared responses for respondents prescribed, but never initiating, insulin (n = 69) with those dispensed insulin (n = 100). RESULTS: Subjects failing to initiate prescribed insulin commonly reported misconceptions regarding insulin risk (35% believed that insulin causes blindness, renal failure, amputations, heart attacks, strokes, or early death), plans to instead work harder on behavioral goals, sense of personal failure, low self-efficacy, injection phobia, hypoglycemia concerns, negative impact on social life and job, inadequate health literacy, health care provider inadequately explaining risks/benefits, and limited insulin self-management training. CONCLUSIONS: Primary adherence for insulin may be improved through better provider communication regarding risks, shared decision making, and insulin self-management training.
We previously generated a knock-in mouse line with a cocaine-insensitive dopamine transporter (DAT-CI mice). These mice lost several behavioral responses to cocaine, but retained their response to ...amphetamine. DAT-CI mice are hyperdopaminergic due to reduced DAT function, and may thus be a good model for studying attention deficit hyperactivity disorder (ADHD). These mice had been behaviorally characterized while they were on a mixed genetic background. However as the colony was propagated over time, the mixed genetics were shifted toward a pure C57Bl/6J background — via a common breeding scheme known as “backcrossing.” Several phenotypes appeared to have changed during this time frame. In this study, we investigated whether backcrossing altered the hyperlocomotive phenotype and behavioral responses to amphetamine, a drug used to treat ADHD.
C57-congenic DAT-CI mice had high spontaneous locomotor activity that could be suppressed by low doses of amphetamine. Furthermore, their locomotion was not stimulated by very high doses of amphetamine (20mg/kg). After the reversion to a mixed genetic background by breeding with the 129 strain, the C57:129 hybrid DAT-CI mice displayed reduced basal locomotor activity compared to the C57-congenic mutant mice, and regained locomotor stimulation by high-dose amphetamine. The calming effect of amphetamine at low doses was retained in both strains. In summary, reduced DAT function in DAT-CI mice leads to a hyperdopaminergic state, and an ADHD-like phenotype in both strains. The data show that the genetic background of DAT-CI mice affects their locomotor phenotypes and their responses to amphetamine. Since the differences in genetic background between the strains of mice have a significant impact on the ADHD-like phenotype and the response to amphetamine, further study with these strains could identify the genetic underpinnings affecting the severity of ADHD-related symptoms and the treatment response.
► A triple mutant knock-in of the dopamine transporter results in hyperlocomotion in mice. ► The hyperlocomotive behavior is suppressed by a range of doses of amphetamine. ► The basal and amphetamine-induced locomotion is modulated by the mouse strain used. ► The C57 strain of knock-in mice has higher symptom severity, and does not habituate.
In many lentic ecosystems, hydroperiod, or the duration of inundation, controls animal community composition and biomass. Although hydroperiod-imposed differences in wetland animal communities could ...cause differences in animal-driven nutrient supply, hydroperiod has not been considered as a template for investigating patterns of animal-driven nutrient cycling. Here, we use nutrient excretion rates (NH
4
-N and SRP) and biomasses of pelagic and benthic invertebrates and salamanders and nutrient uptake rates in a simulation model to estimate animal-driven nutrient supply and pond-level demand along a hydroperiod gradient of 12 subalpine ponds in the U.S. Rocky Mountains that are vulnerable to climate change. We found that animal biomass increased with hydroperiod duration and biomass predicted animal-driven supply contributions among hydroperiod classifications (temporary-permanent). Consequently, community-wide supply was greatest in permanent ponds. Animal-driven N supply exceeded demand in permanent and semi-permanent ponds, whereas P supply equaled demand in both. Conversely, temporary ponds had large deficits in N and P supply due to lower community biomass and hydroperiod-induced constraints on dominant suppliers (oligochaetes and chironomids). The distribution of taxon-specific supply also differed among hydroperiods, with supply dominated by a few taxa in permanent ponds and supply more evenly distributed among temporary pond taxa. The absence or lower biomass of dominant suppliers in temporary ponds creates nutrient deficits and possible limitation of productivity. Thus, as climate warming causes hydroperiods to become increasingly temporary and indirectly prompts biomass declines and compositional shifts, animal-driven nutrient supply will decrease and strong nutrient limitation may arise due to loss of animal-driven supply.
Short-term associations between extreme heat events and adverse health outcomes are well-established in epidemiologic studies. However, the use of different exposure definitions across studies has ...limited our understanding of extreme heat characteristics that are most important for specific health outcomes or subpopulations.
Logic regression is a statistical learning method for constructing decision trees based on Boolean combinations of binary predictors. We describe how logic regression can be utilized as a data-driven approach to identify extreme heat exposure definitions using health outcome data. We evaluated the performance of the proposed algorithm in a simulation study, as well as in a 20-year time-series analysis of extreme heat and emergency department visits for 12 outcomes in the Atlanta metropolitan area.
For the Atlanta case study, our novel application of logic regression identified extreme heat exposure definitions that were associated with several heat-sensitive disease outcomes (e.g., fluid and electrolyte imbalance, renal diseases, ischemic stroke, and hypertension). Exposures were often characterized by extreme apparent minimum temperature or maximum temperature over multiple days. The simulation study also demonstrated that logic regression can successfully identify exposures of different lags and duration structures when statistical power is sufficient.
Logic regression is a useful tool for identifying important characteristics of extreme heat exposures for adverse health outcomes, which may help improve future heat warning systems and response plans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Using multipollutant models to understand combined health effects of exposure to multiple pollutants is becoming more common. However, complex relationships between pollutants and differing degrees ...of exposure error across pollutants can make health effect estimates from multipollutant models difficult to interpret.
We aimed to quantify relationships between multiple pollutants and their associated exposure errors across metrics of exposure and to use empirical values to evaluate potential attenuation of coefficients in epidemiologic models.
We used three daily exposure metrics (central-site measurements, air quality model estimates, and population exposure model estimates) for 193 ZIP codes in the Atlanta, Georgia, metropolitan area from 1999 through 2002 for PM2.5 and its components (EC and SO4), as well as O3, CO, and NOx, to construct three types of exposure error: δspatial (comparing air quality model estimates to central-site measurements), δpopulation (comparing population exposure model estimates to air quality model estimates), and δtotal (comparing population exposure model estimates to central-site measurements). We compared exposure metrics and exposure errors within and across pollutants and derived attenuation factors (ratio of observed to true coefficient for pollutant of interest) for single- and bipollutant model coefficients.
Pollutant concentrations and their exposure errors were moderately to highly correlated (typically, > 0.5), especially for CO, NOx, and EC (i.e., "local" pollutants); correlations differed across exposure metrics and types of exposure error. Spatial variability was evident, with variance of exposure error for local pollutants ranging from 0.25 to 0.83 for δspatial and δtotal. The attenuation of model coefficients in single- and bipollutant epidemiologic models relative to the true value differed across types of exposure error, pollutants, and space.
Under a classical exposure-error framework, attenuation may be substantial for local pollutants as a result of δspatial and δtotal with true coefficients reduced by a factor typically < 0.6 (results varied for δpopulation and regional pollutants).
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract
Regulated antisense RNA (asRNA) expression has been employed successfully in Gram-positive bacteria for genome-wide essential gene identification and drug target determination. However, ...there have been no published reports describing the application of asRNA gene silencing for comprehensive analyses of essential genes in Gram-negative bacteria. In this study, we report the first genome-wide identification of asRNA constructs for essential genes in Escherichia coli. We screened 250 000 library transformants for conditional growth inhibitory recombinant clones from two shotgun genomic libraries of E. coli using a paired-termini expression vector (pHN678). After sequencing plasmid inserts of 675 confirmed inducer sensitive cell clones, we identified 152 separate asRNA constructs of which 134 inserts came from essential genes, while 18 originated from nonessential genes (but share operons with essential genes). Among the 79 individual essential genes silenced by these asRNA constructs, 61 genes (77%) engage in processes related to protein synthesis. The cell-based assays of an asRNA clone targeting fusA (encoding elongation factor G) showed that the induced cells were sensitized 12-fold to fusidic acid, a known specific inhibitor. Our results demonstrate the utility of the paired-termini expression vector and feasibility of large-scale gene silencing in E. coli using regulated asRNA expression.
Female Sexual Function and Pelvic Floor Disorders HANDA, Victoria L; CUNDIFF, Geoffrey; CHANG, Howard H ...
Obstetrics and gynecology (New York. 1953),
05/2008, Letnik:
111, Številka:
5
Journal Article
Recenzirano
Odprti dostop
To investigate the hypothesis that pelvic floor disorders are associated with female sexual problems, independently of other related factors.
The study population included 301 adult women seeking ...outpatient gynecologic and urogynecologic care. Pelvic floor disorders were assessed with the Pelvic Floor Disorders Inventory-20 (PFDI-20) and the pelvic organ prolapse quantification examination. Sexual function was assessed with the Personal Experiences Questionnaire. Using ordinal regression analysis, we identified characteristics and conditions associated with decreased libido, infrequent orgasm, decreased arousal, and dyspareunia.
Sexual function was poorer among 78 women (26%) without a current sexual partner than among 223 with a partner (P<.01). Among the 223 with a current partner, women with a high Pelvic Floor Disorders Inventory score were significantly more likely to report decreased arousal (P<.01), infrequent orgasm (P<.01), and increased dyspareunia (P<.01). A similar pattern was observed for the urinary, colorectal-anal, and prolapse scales of the Pelvic Floor Disorders Inventory, although some associations were marginally significant. Stage III-IV prolapse was significantly associated with infrequent orgasm (P=.02), but other sexual complaints were not more common with increasing prolapse stage.
Pelvic floor symptoms are significantly associated with reduced sexual arousal, infrequent orgasm, and dyspareunia. We conclude that sexual function is worse in women with symptomatic prolapse but not in women with asymptomatic prolapse.
II.
The mechanisms underlying reactive hyperemia (RH) responses in microvessels are poorly understood. Previous assessment tools have not been capable of directly visualizing microvessels during ...physiological stimulation in humans. Optical coherence tomography (OCT) is capable of imaging and quantifying subcutaneous microvessels as small as ~30 µm. In this study we use OCT to visualize and quantify skin microvascular changes in response to RH for the first time in humans. We also assessed the reproducibility of this technique. OCT and laser Doppler flowmetry (LDF) were used simultaneously to scan cutaneous microvessels in 10 young healthy subjects on 2 days. We applied a speckle decorrelation algorithm to assess OCT images and calculated flow rate, speed, diameter, and density parameters. Measures were obtained at rest (baseline) and 30-s following a 5-min cuff inflation (RH). All data were compared between days. The RH stimulus significantly increased (
< 0.0001) OCT-derived microvascular diameter (37.6 ± 3.4 vs. 44.5 ± 5.2 µm), flow rate (82.4 ± 23.4 vs. 240.1 ± 58.6 pl/s), speed (48 ± 5.7 vs. 101.5 ± 17.1 µm/s), density (5.1 ± 1.7 vs. 14.6 ± 2.6%), and also LDF-derived flux (12.3 ± 5.7 vs. 31.6 ± 9.1 perfusion units). At baseline, OCT-derived diameter (
= 0.55), flow rate (
= 0.64), speed (
= 0.55), and density (
= 0.75) showed significant between-day correlations (
< 0.05), as did LDF results (
= 0.74). In response to RH, OCT-derived diameter (
= 0.63) and density (
= 0.64) showed significant correlations (
< 0.05), whereas flow rate (
= 0.45), speed (
= 0.43), and LDF (
= 0.26) were less reproducible. Our study is novel in that it establishes the feasibility of using OCT to visualize and quantify microvascular structure and function responses to RH in humans.
This study describes the first evidence in humans that optical coherence tomography provides direct visualization and comprehensive quantification of cutaneous microvascular hemodynamics as a response to reactive hyperemia. This imaging technique will greatly improve human cutaneous microvascular assessment in physiological and clinical settings.
A fundamental goal of evolutionary ecology is to understand how asymmetric competition influences phenotype expression, yet few studies have quantified the relative effects of intra- and ...interspecific competition on phenotypes. We examined the effects of intra- and interspecific larval competition on both discrete and continuous phenotype expression of the facultatively paedomorphic mole salamander (
Ambystoma talpoideum
). We manipulated the density and frequency of larval
A. talpoideum
and a common competitor, the spotted salamander (
A. maculatum
), in experimental mesocosms within a response surface design. The production of discrete ontogenetic morphs (metamorphs, paedomorphs, and overwintering larvae) was affected more by intraspecific than interspecific competition, but the effect varied between morphs. Paedomorph and metamorph production were more strongly affected by intraspecific than interspecific competition, while the production of overwintering larvae was affected by each type of competition approximately equally. Paedomorphs largely occurred only at low conspecific densities, overwintering larvae primarily occurred at high overall densities, and metamorph production peaked at intermediate densities of con- and heterospecifics. Density-dependent intraspecific competition had stronger effects on body size and growth rates than interspecific competition for both metamorphs and overwintering larvae, whereas interspecific competition more strongly affected paedomorph size. Overall, these results support the hypothesis that intraspecific competition influences both continuous and discrete phenotypic expression more strongly than interspecific competition. Fluctuating strengths of each type of competition can affect variation in life history strategies by influencing discrete ontogenetic pathways via individual body sizes, leading to differential morph production and fitness within and among morphs.
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