Evaluation of architectural distortion with contrast-enhanced mammography.

Architectural distortion (AD) is the third most common abnormality detected on mammograms. In the absence of an accurate non-invasive tool to evaluate ADs, clinical management often requires surgical excision for histological diagnosis. This problem is expected to worsen with the growing use of digital breast tomosynthesis (DBT) and the resultant increasing detection of ADs. There is therefore a great clinical need for a diagnostic imaging tool to complement non-enhanced mammography for the evaluation of AD. Contrast-enhanced mammography (CEM) is an emerging breast imaging method that uses contrast media and the principle of dual-energy subtraction to evaluate vascularity of suspicious breast lesions. CEM, a cost-effective alternative to breast magnetic resonance imaging (MRI), can be used to evaluate AD by juxtaposing CEM images with non-enhanced mammograms for comparison. In this review, the authors aim to provide readers with an overview of the interpretation of AD on CEM using imaging examples. Relevant imaging features of CEM and their respective significance will be matched with information from a literature review. Finally, the authors would like to highlight the added value of CEM in relevant clinical applications in the assessment of AD.

Cardiometabolic risks during anabolic hormone supplementation in older men.

OBJECTIVE: To determine the cardiometabolic risks of testosterone and growth hormone (GH) replacement therapy to youthful levels during aging. DESIGN AND METHODS: A double-masked, partially placebo controlled study in 112 men 65-90 years-old was conducted. Transdermal testosterone (5 g vs. 10 g/day) using a Leydig Cell Clamp and subcutaneous recombinant GH (rhGH) (0 vs. 3 vs. 5 µg/kg/day) were administered for 16-weeks. Measurements included testosterone and IGF-1 levels, body composition by DEXA, and cardiometabolic risk factors (upper body fat, blood pressure, insulin sensitivity, fasting triglycerides, HDL-cholesterol, and serum adiponectin) at baseline and after 16 weeks of treatment. RESULTS: Some cardiometabolic factors improved (total and trunk fat, triglycerides, HDL-cholesterol) and others worsened (systolic blood pressure, insulin sensitivity index [QUICKI], adiponectin). Cardiometabolic risk composite scores (CRCSs) improved (-0.69 ± 1.55, P < 0.001). In multivariate analyses, QUICKI, triglycerides, and HDL-cholesterol contributed 33%, 16%, and 14% of the variance in CRCS, respectively. Pathway analyses indicated that changes in fat and lean mass were related to individual cardiometabolic variables and CRCS in a complex manner. Changes in BMI, reflecting composite effects of changes in fat and lean mass, were more robustly associated with cardiometabolic risks than changes in fat mass or LBM individually. CONCLUSIONS: Testosterone and rhGH administration was associated with diverse changes in individual cardiometabolic risk factors, but in aggregate appeared not to worsen cardiometabolic risk in healthy older men after 4-months. The long-term effects of these and similar anabolic therapies on cardiovascular events should be investigated in populations with greater functional limitations along with important health disabilities including upper body obesity and other cardiometabolic risks.

Leptin predicts a decline in moderate to vigorous physical activity in minority female children at risk for obesity.

UNLABELLED: What is already known about this subject Physical activity declines as children enter puberty. Leptin is cross-sectionally associated with physical activity, but there are conflicting findings on the magnitude and direction of this association. Leptin concentrations fluctuate during puberty, and may impact energy balance. What this study adds Leptin predicts the decline in physical activity during the start of puberty independent of central adiposity. Based on a median split of leptin, girls with low leptin levels have higher levels of physical activity than girls with high leptin levels at the start of puberty. Leptin levels at the start of puberty may provide a biological basis for the age-related physical activity decline in girls. BACKGROUND: Leptin may influence moderate to vigorous physical activity (MVPA) at the start of puberty. The direction and magnitude of this association are unclear. OBJECTIVES: To determine the effect of baseline leptin on MVPA over 1 year in minority girls at high risk for obesity. METHODS: Data came from TRANSITIONS, a longitudinal observational study on the age-related MVPA decline. Fifty peripubertal girls aged 8-11 years at baseline participated. Baseline leptin (ng mL(-1) ) was collected via a duplicated assay using a double antibody radio immune assay. MVPA (min d(-1) ) was measured using accelerometers for at least four 10-h days on a quarterly basis for up to 1 year. RESULTS: Continuous leptin was negatively related to MVPA (P = 0.001) independent of central adiposity at baseline and predicted the MVPA decline over 1 year (P = 0.002). For descriptive purposes, baseline leptin was dichotomized at the sample median into 'high leptin' and 'low leptin' categories to determine whether MVPA trajectories differed between these groups. Girls with 'low leptin' at baseline had significantly higher levels of MPVA at baseline, visit 1 and visit 2 compared to girls with 'high leptin'. CONCLUSIONS: High leptin levels predicted nearly a 12.6% decline in MVPA over 1 year. These findings provide support for the biological basis of declining MVPA as girls enter puberty.

Metabolic pathways of clostridia for producing butanol.

Worldwide demand for energy has been the impetus for research to produce alcohol biofuels from renewable resources. This review focuses on the biosynthesis of butanol, which is regarded to be superior to ethanol as a fuel. Although acetone/butanol fermentation is one of the oldest large-scale fermentation processes, butanol yield by anaerobic fermentation remains sub-optimal. Metabolic engineering provides a means for fermentation improvements. Consequently, a comprehensive assessment of the intermediary enzymes involved in butanol formation from carbohydrates by the saccharolytic bacterium, Clostridium acetobutylicum and other closely allied clostridia was performed to provide guidelines for potentially enhancing butanol productivity. The activity of the enzymes, their regulation and contribution to the metabolic pathways was reviewed. Published kinetic data for each important enzymatic reaction were assessed. For most enzymatic reactions, the systematic investigation of the kinetic data and the properties of the enzymes led to the development of rate equations that were able to describe activity as the function of the substrates, products, and allosteric effectors.

Traumatic lumbar artery arteriovenous fistula: preclinically detected by 16-multidetector-row computed tomography and post-processing techniques.

We report a 21-year-old woman with a penetrating abdominal wound. Injuries of the abdominal aorta and alimentary tract were found during emergency surgery. The patient had a follow-up computed tomography (CT) scan 3 months after surgery. Arterial-phase 16-row multidetector computed tomography (MDCT) showed a suspicious dilated vessel adjacent to the repaired aorta on 5-mm transverse images. A fistula between a lumbar artery and the inferior vena cava was clearly demonstrated on images reformatted with two- (2D) and three-dimensional (3D) techniques. The patient suffered from symptoms of high-output heart failure 8 months after surgery.

Effects of perceived peer isolation and social support availability on the relationship between body mass index and depressive symptoms.

OBJECTIVE: To examine relationships between body mass index (BMI) and psychological correlates in Chinese school adolescents during the period of economic transition. DESIGN: Baseline data of 1655 Chinese adolescents aged 11-15 y were retrieved from a longitudinal smoking cessation and health promotion program in Wuhan, China. Assessments of body weight and height, depressive symptoms, perceived peer isolation (PPI) and perceived availability of social support (PASS) were collected. RESULTS: Based on the International Obesity Task Force (IOTF) age-and sex-specific BMI cutoffs, 12.5% of boys and 9.2% of girls were overweight. In girls, high BMI was significantly related to higher self-reported depressive symptoms, and was dominantly mediated by PPI. On the contrary, high BMI boys reported significantly lower levels of PPI although high PPI level aggravated depressive symptoms. For both girls and boys, the observed effect of PPI on the relationship between BMI and depressive symptoms was sustained only in low PASS boys and girls. CONCLUSIONS: The present study revealed different effects of PPI on the association of BMI and depressive symptoms between boys and girls, which were buffered by levels of PASS. The findings of this study may contribute to our understanding of the influences of psychological correlates in pediatric overweight in the Eastern cultural environment.

Strain improvement to enhance the production of recombinant penicillin acylase in high-cell-density Escherichia coli cultures.

Using fed-batch operation for high-cell-density cultivation, efforts are frequently made for optimization of culture parameters, particularly feeding strategy. The current study also emphasized the importance of selecting strains for the production of recombinant proteins in high-cell-density cultures. With Escherichia coli penicillin acylase (PAC) as a target protein, the host/vector system of MDdeltaP7 harboring pTrcKnPAC2902 and pKS12 was designed for optimization of fed-batch cultivation for recombinant protein production. The host, MDdeltaP7, potentially had a high translational and periplasmic processing efficiency for pac expression. On the other hand, the vector, pTrcKnPAC2902, was genetically constructed for pac overexpression. Coexistence of the other vector, pKS12, significantly enhanced PAC production by improving cell physiology and reducing the amount of inclusion body formation upon pac overexpression. An extremely high volumetric PAC activity at 37,500 U/L was obtained with the use of the developed host/vector system under optimum fed-batch culture conditions.

Effect of pH on high-temperature production of bacterial penicillin acylase in Escherichia coli.

High-temperature-oriented production of bacterial penicillin acylase (PAC), which is usually expressed at low temperatures (less than 30 degrees C), was demonstrated in this study via heterologous expression of the Providencia rettgeri (P. rettgeri) pac gene in Escherichia coli (E. coli). While it is possible to produce PAC at a temperature as high as 37 degrees C, the environmental condition (specifically, culture pH) critically affected culture performance. Production of PAC at 37 degrees C was feasible only when culture pH was close to neutral (i.e., 6.5-7.5). Outside this pH range, cell physiology for the host/vector system was seriously affected, resulting in poor culture performance. In acidic culture environments, temperature significantly affected the pac expression level and specific PAC activity decreased with an increase in culture temperature. In basic culture environments, cell growth was seriously inhibited though the pac expression level was minimally affected by temperature. Such unusual types of pH and temperature effects on pac expression were never reported for bacterial PACs. The results suggest that culture pH should be precisely controlled for the current host/vector systems being applied on the overproduction of P. rettgeri PAC in E. coli at high temperatures.

Adolescent smoking in Wuhan, China: baseline data from the Wuhan Smoking Prevention Trial.

BACKGROUND: This study reports the prevalence of adolescent smoking in the urban and rural areas of Wuhan, China, the capital of Hubei Province, on the Yangtze River in central China. METHODS: Smoking behavior was examined by age, gender, and urbanicity as part of the Wuhan Smoking Prevention Trial. Subjects included 6994 seventh- to ninth-grade students attending 22 randomly selected schools in urban and rural districts. Outcome measures included lifetime smoking, past-30-day smoking, established smoking (>100 cigarettes in lifetime), and susceptibility to smoking (absence of a firm commitment not to smoke). RESULTS: Lifetime smoking prevalence was 47% among boys and 18% among girls. Past-30-day smoking prevalence was 16% among boys and 4% among girls. Established smoking prevalence was 2% among boys and 0% among girls. The prevalence of susceptibility to smoking was 31% among boys and 10% among girls. Smoking increased significantly with age (p<.0005). Susceptibility was more prevalent in rural areas than in urban areas (p<.05), but there were no urban-rural differences in lifetime, past 30-day smoking, or established smoking. Trend analyses revealed that smoking increased with age more rapidly among boys than among girls (p<.05). Smoking was more prevalent among rural boys than among urban boys, but it was more prevalent among urban girls than among rural girls (p<.05). CONCLUSIONS: Adolescent smoking is a significant public health problem in China. Boys are at particularly high risk, as are girls living in urban areas. Effective smoking prevention programs for adolescents, as well as restrictions on tobacco industry marketing and youth access to tobacco, are needed to prevent tobacco-related morbidity and mortality in China.

DegP-coexpression minimizes inclusion-body formation upon overproduction of recombinant penicillin acylase in Escherichia coli.

We demonstrated the enhancement of recombinant penicillin acylase (PAC) production in Escherichia coli by increasing the intracellular concentration of the periplasmic protease DegP. Using appropriate host/vector systems (e.g., HB101 harboring pTrcKnPAC2902 or MDDeltaP7 harboring pTrcKnPAC2902) in which the expression of the pac gene was regulated by the strong trc promoter, the overproduction of PAC was often limited by periplasmic processing and inclusion bodies composed of protein aggregates of PAC precursors were formed in the periplasm. The amount of these periplasmic inclusion bodies was significantly reduced and PAC activity was significantly increased upon coexpression of DegP. The specific PAC activity reached an extremely high level of 674 U/L/OD(600) for MDDeltaP7 harboring pTrcKnPAC2902 and pKS12 under optimum culture conditions. However, such improvement in the production of PAC was not observed for the expression systems (e.g., MDDeltaP7 harboring pCLL2902) in which the periplasmic processing was not the step limiting the production of PAC. The results suggest that DegP could in vivo assist the periplasmic processing though the enzyme is shown to be not absolutely required for the formation of active PAC in E. coli. In addition, the steps limiting the production of PAC are identified and the reasons for the formation of PAC inclusion bodies are discussed here.

Analytic approaches for assessing long-term treatment effects. Examples of empirical applications and findings.

Analytic approaches, including the structural equation model (autoregressive panel model), hierarchical linear model, latent growth curve model, survival/event history analysis, latent transition model, and time-series analysis (interrupted time series, multivariate time-series analysis) are discussed for their applicability to data of different structures and their utility in evaluating temporal effects of treatment. Methods are illustrated by presenting applications of the various approaches in previous studies examining temporal patterns of treatment effects. Recent advancements in these longitudinal modeling approaches and the accompanying computer software development offer tremendous flexibility in examining long-term treatment effects through longitudinal data with varying numbers and intervals of assessment and types of measures. A multimethod assessment will contribute to a more complete understanding of the complex phenomena of the long-term courses of substance use and its treatment.

An approach for enhancing heterologous production of Providencia rettgeri penicillin acylase in Escherichia coli.

Heterologous production of Providencia rettgeri penicillin acylase (PAC) was optimized in Escherichia coli. Several factors, including carbon, temperature, and host effects, were identified to be critical for the enzyme overproduction. The optimum culture conditions for the enzyme production vary for different host/vector systems. With the optimization, both volumetric and specific PAC activities could be significantly improved by more than 50-fold compared to the native expression in P. rettgeri. The heterologous production could be possibly limited by translation or posttranslational steps, depending on the culture temperature and host/vector system. To our knowledge, this is the first evidence demonstrating the limiting step for the production of P. rettgeri PAC and the existence of the P. rettgeri PAC precursor.

Novel strategy for efficient screening and construction of host/vector systems to overproduce penicillin acylase in Escherichia coli.

A novel and simple method of using penicillin for screening of mutant strains with a high penicillin acylase (PAC) activity was developed. Random mutagenesis was conducted using a PAC-producing strain resistant to 6-aminopenicillanic acid (6-APA) as the parent strain and mutants were screened with penicillin at a high concentration. Results suggest that mutants with a high minimum inhibitory concentration for penicillin (MIC(penG)) usually overproduce PAC. Both volumetric and specific PAC activities of a mutant, MD7, were significantly higher than those of the parent strain, HBPAC101 harboring pCLL2902. The mutation(s) resulting in the enhanced expression was mapped on the host chromosome rather than the plasmid. In addition, the mutant strain of MDDeltaP7, derived by elimination of the harbored plasmid in MD7, was demonstrated to be efficient in production of PAC by using the expression plasmids for which expression of the pac gene is limited by translation. An extremely high specific PAC activity of more than 350 U/L/OD(600) was reached upon cultivation of MDDeltaP7 harboring pTrcKnPAC2902 in a bioreactor. As such, the strategy is effective in terms of constructing PAC overproducers and improving the process yield for production of PAC.

Effect of SecB chaperone on production of periplasmic penicillin acylase in Escherichia coli.

The effect of SecB chaperone on production of periplasmic penicillin acylase (PAC) in Escherichia coli was investigated. It appears that formation of PAC required the function of SecB chaperone and the amount of SecB required was at a basal level. The secB mutant was defective in production of PAC, and the impairment could be complemented by extrachromosomally supplementing SecB in trans. The function of SecB might be primarily stabilizing the cytoplasmic PAC precursors. Overproduction of SecB chaperone usually resulted in an increase in the amount of PAC precursors without enhancing PAC activity. In addition, most of the PAC precursors were located in the periplasm, suggesting that formation of active PAC was likely limited by periplasmic processing steps.

Manipulation of carbon assimilation with respect to expression of the pac gene for improving production of penicillin acylase in Escherichia coli.

A strategy of genetically manipulating carbon assimilation with respect to expression of the pac gene was employed for overproduction of recombinant penicillin acylase (PAC). Two expression plasmids of pCLL2902 and pCLL3201, which contain the pac coding region but differ in the pac regulatory region, were constructed for the production experiments. Expression of the pac gene was subjected to phenyl acetic acid (PAA-) induction and glucose catabolite repression for pCLL3201, whereas it was subjected to neither of the two transcriptional regulations for pCLL2902. The specific PAC activity for strains harboring pCLL2902 was significantly higher than that for strains harboring pCLL3201 due to an improved transcription efficiency. In addition, no inclusion bodies were observed upon production of PAC using the current expression systems. The results suggest that using the native pac promoter instead of a strong promoter such as tac for regulation is a feasible approach for production of PAC. The impact of the current expression systems is also significant from a process viewpoint since, using strains harboring pCLL2902, not only could glucose replace PAA as a carbon source of Escherichia coli cultures for production of PAC but also the volumetric PAC activity was highly improved.

Genetic manipulation to identify limiting steps and develop strategies for high-level expression of penicillin acylase in Escherichia coli.

We have identified the bottleneck steps limiting expression of penicillin acylase (PAC) through comparison of the expression performance for various PAC-expression vectors constructed by genetically modulating the efficiencies of transcription and/or translation of the pac gene. To our knowledge, this is the first report demonstrating that expression of PAC could be limited by various steps, such as transcription, translation, and post-translational steps (i.e. translocation and periplasmic processing), depending on the host/vector systems. Results also indicate that the structure of the wild-type pac gene might not be optimal for direct use in production of PAC using recombinant DNA technology. To improve the gene expression, transcription was enhanced by manipulating certain DNA bases in the pac regulatory region, whereas translation was enhanced by enlarging the spacing between the ribosome binding site and the ATG initiation codon to increase the initiation efficiency. The information is useful in terms of developing genetic strategies for overproduction of recombinant PAC in Escherichia coli.

Cocaine use and high-risk sexual behavior among STD clinic patients.

BACKGROUND AND OBJECTIVES: Crack-smoking sexually transmitted disease (STD) patients are at high-risk for contracting HIV. GOAL OF THE STUDY: To examine the effects of cocaine use and other correlates on high-risk sexual behavior among STD clinic patients. STUDY DESIGN: This was a cross-sectional study of 1,490 consecutive patients attending three Los Angeles County STD clinics between 1992 and 1994. RESULTS: Logistic regression analysis found high-risk sexual activity was associated with being a male and being of younger age. Among women, high-risk sexual behavior was associated with crack cocaine use and a perceived need for help. Among the men in the study, ethnicity (being black) and having an arrest history were associated with high-risk behavior. CONCLUSIONS: Effective intervention strategies should address cocaine use among STD patients and provide them with referrals to drug treatment.

Optimization of the host/vector system and culture conditions for production of penicillin acylase in Escherichia coli.

Culture performance for the production of penicillin acylase (PAC) in a bioreactor was investigated using HB101 or ATCC11105 as the host and pCLL2902, pCLL3201 or pTrcKnPAC2902 as the expression plasmid. We observed that the production of PAC by HB101 harboring pCLL3201 was, similar to ATCC11105, induced by phenyl acetic acid (PAA) and catabolicaily repressed by glucose, whereas the production of PAC by HB101 harboring pCLL2902 did not require PAA for induction and was not repressed by glucose. PAC activity of HB101 harboring pCLL2902 was significantly higher than that of HB101 harboring pCLL3201. There was no significant effect of host or carbon source on the production of PAC using pCLL2902. The production of PAC by HB101 harboring pTrcKnPAC2902, in which the pac gene expression was controlled by the trc promoter system, was about the same as that by HB101 harboring pCLL2902, when the culture was appropriately induced with isopropyl beta-d-thiogalactopyranoside (IPTG). Therefore, the use of both pCLL2902 and pTrcKnPAC2902 could be expected to be feasible for industrial applications. However, optimization of IPTG induction for HB101 harboring pTrcKnPAC2902 might be required, since formation of inclusion bodies tends to limit the production of PAC in some cases.

Interaction effects of client and treatment program characteristics on retention: an exploratory analysis using hierarchical linear models.

This paper applied a hierarchical linear modeling approach to explore the interaction effects of treatment program and client characteristics on client retention in treatment for drug users. Program characteristics included services provision, funding sources, and staff-client gender congruence, and client characteristics included gender, age at admission, and drug use level prior to admission. The same model was applied separately to three modalities: residential, methadone maintenance, and outpatient drug-free programs. Data were obtained from 59 treatment programs and 3,764 of their clients who had discharge records. The most noteworthy significant interaction effect detected was program's funding source and client's gender on treatment retention in the outpatient drug-free modality. For example, female clients remained less time in the programs that accepted only public funding than in the programs that accepted both public and private funding. Male clients remained in the treatment an average of 25.3 fewer days than female clients in drug-free programs that only accepted public fund, but stayed about the same time as females if the programs received mixed funding.

Effects of a community-based prevention program on decreasing drug use in high-risk adolescents.

OBJECTIVES: This study investigated the secondary prevention effects of a substance abuse primary prevention program. METHODS: Logistic regression analyses were conducted on 4 waves of follow-up data from sixth- and seventh-grade baseline users of cigarettes, alcohol, and marijuana taking part in a school-based program in Indianapolis. RESULTS: The program demonstrated significant reductions in cigarette use at the initial follow-up (6 months) and alcohol use at the first 2 follow-ups (up to 1.5 years). Models considering repeated measures also showed effects on all 3 substances. CONCLUSIONS: Primary prevention programs are able to reach and influence high-risk adolescents in a nonstigmatizing manner.