Evaluation of daily environmental cleaning and disinfection practices in veterans affairs acute and long-term care facilities: A mixed methods study.

OBJECTIVES: To describe daily environmental cleaning and disinfection practices and their associations with cleaning rates while exploring contextual factors experienced by healthcare workers involved in the cleaning process. METHODS: A convergent mixed methods approach using quantitative observations (ie, direct observation of environmental service staff performing environmental cleaning using a standardized observation form) and qualitative interviews (ie, semistructured interviews of key healthcare workers) across 3 Veterans Affairs acute and long-term care facilities. RESULTS: Between December 2018 and May 2019 a total of sixty-two room observations (N = 3602 surfaces) were conducted. The average observed surface cleaning rate during daily cleaning in patient rooms was 33.6% for all environmental surfaces and 60.0% for high-touch surfaces (HTS). Higher cleaning rates were observed with bathroom surfaces (Odds Ratio OR = 3.23), HTSs (OR = 1.57), and reusable medical equipment (RME) (OR = 1.40). Lower cleaning rates were observed when cleaning semiprivate rooms (OR = 0.71) and rooms in AC (OR = 0.56). In analysis stratified by patient presence (ie, present, or absent) in the room during cleaning, patient absence was associated with higher cleaning rates for HTSs (OR = 1.71). In addition, the odds that bathroom surfaces being cleaned more frequently than bedroom surfaces decreased (OR = 1.97) as well as the odds that private rooms being cleaned more frequently than semi-private rooms also decreased (OR = 0.26; 0.07-0.93). Between January and June 2019 eighteen qualitative interviews were conducted and found key themes (ie, patient presence and semiprivate rooms) as potential barriers to cleaning; this supports findings from the quantitative analysis. CONCLUSION: Overall observed rates of daily cleaning of environmental surfaces in both acute and long-term care was low. Standardized environmental cleaning practices to address known barriers, specifically cleaning practices when patients are present in rooms and semi-private rooms are needed to achieve improvements in cleaning rates.

A Mycobacterial Systems Resource for the Research Community.

Functional characterization of bacterial proteins lags far behind the identification of new protein families. This is especially true for bacterial species that are more difficult to grow and genetically manipulate than model systems such as Escherichia coli and Bacillus subtilis To facilitate functional characterization of mycobacterial proteins, we have established a Mycobacterial Systems Resource (MSR) using the model organism Mycobacterium smegmatis This resource focuses specifically on 1,153 highly conserved core genes that are common to many mycobacterial species, including Mycobacterium tuberculosis, in order to provide the most relevant information and resources for the mycobacterial research community. The MSR includes both biological and bioinformatic resources. The biological resource includes (i) an expression plasmid library of 1,116 genes fused to a fluorescent protein for determining protein localization; (ii) a library of 569 precise deletions of nonessential genes; and (iii) a set of 843 CRISPR-interference (CRISPRi) plasmids specifically targeted to silence expression of essential core genes and genes for which a precise deletion was not obtained. The bioinformatic resource includes information about individual genes and a detailed assessment of protein localization. We anticipate that integration of these initial functional analyses and the availability of the biological resource will facilitate studies of these core proteins in many Mycobacterium species, including the less experimentally tractable pathogens M. abscessus, M. avium, M. kansasii, M. leprae, M. marinum, M. tuberculosis, and M. ulceransIMPORTANCE Diseases caused by mycobacterial species result in millions of deaths per year globally, and present a substantial health and economic burden, especially in immunocompromised patients. Difficulties inherent in working with mycobacterial pathogens have hampered the development and application of high-throughput genetics that can inform genome annotations and subsequent functional assays. To facilitate mycobacterial research, we have created a biological and bioinformatic resource (https://msrdb.org/) using Mycobacterium smegmatis as a model organism. The resource focuses specifically on 1,153 proteins that are highly conserved across the mycobacterial genus and, therefore, likely perform conserved mycobacterial core functions. Thus, functional insights from the MSR will apply to all mycobacterial species. We believe that the availability of this mycobacterial systems resource will accelerate research throughout the mycobacterial research community.

Reducing off target viral delivery in ovarian cancer gene therapy using a protease-activated AAV2 vector platform.

Gene therapy is a promising strategy for treating metastatic epithelial ovarian cancer (EOC). However, efficient vector targeting to tumors is difficult and off-target effects can be severely detrimental. Most vector targeting approaches rely on surface receptors overexpressed on some subpopulation of cancer cells. Unfortunately, there is no universally expressed cell surface biomarker for tumor cells. As an alternative, we developed an adeno-associated virus (AAV) based "Provector" whose cellular transduction can be activated by extracellular proteases, such as matrix metalloproteinases (MMP) that are overexpressed in the tumor microenvironments of the most aggressive forms of EOC. In a non-tumor bearing mouse model, the Provector demonstrates efficient de-targeting of healthy tissues, especially the liver, where viral delivery is <1% of AAV2. In an orthotopic HeyA8 tumor model of EOC, the Provector maintains decreased off-target delivery in the liver and other tissues but with no loss in tumor delivery. Notably, approximately 10% of the injected Provector is still detected in the blood at 24 h while >99% of injected AAV2 has been cleared from the blood by 1 h. Furthermore, mouse serum raised against the Provector is 16-fold less able to neutralize Provector transduction compared to AAV2 serum neutralizing AAV2 transduction (1:200 vs 1:3200 serum dilution, respectively). Thus, the Provector appears to generate less neutralizing antibodies than AAV2. Importantly, serum against AAV2 does not neutralize the Provector as well as AAV2, suggesting that pre-existing antibodies against AAV2 would not negate the clinical application of Provectors. Taken together, we present an EOC gene delivery vector platform based on AAV with decreased off-target delivery without loss of on-target specificity, and greater immunological stealth over the traditional AAV2 gene delivery vector.

Reorientation of health services: enablers and barriers faced by organisations when increasing health promotion capacity.

Issue addressed Primary healthcare settings are important providers of health promotion approaches. However, organisational challenges can affect their capacity to deliver these approaches. This review identified the common enablers and barriers health organisations faced and it aimed to explore the experiences health organisations, in particular Aboriginal organisations, had when increasing their health promotion capacity. Methods A systematic search of peer-reviewed literature was conducted. Articles published between 1990-2014 that focused on a health care-settings approach and discussed factors that facilitated or hindered an organisation's ability to increase health promotion capacity were included. Results Twenty-five articles met the inclusion criteria. Qualitative (n=18) and quantitative (n=7) study designs were included. Only one article described the experiences of an Aboriginal health organisation. Enablers included: management support, skilled staff, provision of external support to the organisation, committed staffing and financial resources, leadership and the availability of external partners to work with. Barriers included: lack of management support, lack of dedicated health promotion staff, staff lacking skills or confidence, competing priorities and a lack of time and resources allocated to health promotion activities. Conclusions While the literature highlighted the importance of health promotion work, barriers can limit the delivery of health promotion approaches within primary healthcare organisations. A gap in the literature exists about how Aboriginal health organisations face these challenges. So what? Primary healthcare organisations wanting to increase their health promotion capacity can pre-empt the common barriers and strengthen identified enablers through the shared learnings outlined in this review.

Role of Tetra Amino Acid Motif Properties on the Function of Protease-Activatable Viral Vectors.

Protease-activatable viruses (PAV) based on adeno-associated virus have previously been generated for gene delivery to pathological sites characterized by elevated extracellular proteases. "Peptide locks", composed of a tetra-aspartic acid motif flanked by protease cleavage sequences, were inserted into the virus capsid to inhibit virus-host cell receptor binding and transduction. In the presence of proteases, the peptide locks are cleaved off the capsid, restoring the virus' ability to bind cells and deliver cargo. Although promising, questions remained regarding how the peptide locks prevented cell binding. In particular, it was unclear if the tetra-amino acid (4AA) motif blocks receptor binding via electrostatic repulsion or steric obstruction. To explore this question, we generated a panel of PAVs with lock designs incorporating altered 4AA motifs, each wielding various chemical properties (negative, positive, uncharged polar, and hydrophobic) and characterized the resultant PAV candidates. Notably, all mutants display reduced receptor binding and decreased transduction effciency in the absence of proteases, suggesting simple electrostatics between heparin and the D4 motif do not play an exclusive role in obstructing virus-receptor binding. Even small hydrophobic (A4) and uncharged polar (SGGS) motifs confer a reduction in heparin binding compared to the wild type. Furthermore, both uncharged polar N4 and Q4 mutants (comparable in size to the D4 and E4 motifs respectively, but lacking the negative charge) demonstrate partial ablation of heparin binding. Collectively, these results support a possible dual mechanism of PAV lock operation, where steric hindrance and electrostatics make nonredundant contributions to the disruption of virus-receptor interactions. Finally, because of high virus titer production and superior capsid stability, only the negatively charged 4AA motifs remain viable design choices for PAV construction. Future studies probing the structure-function relationship of PAVs will further expand its promise as a gene delivery vector able to target diseased tissues exhibiting elevated extracellular proteases.

Testing for Hendra virus: difficulties experienced by veterinarians in Queensland prior to 2011.

OBJECTIVE: To identify the perceived barriers to Hendra virus (HeV) management by private equine veterinarians in Queensland. DESIGN: An exploratory qualitative study of private equine veterinarians registered and working in coastal Queensland. METHODS: A questionnaire that included eight open-ended questions about the management of HeV was used in face-to-face in-depth interviews with 21 veterinary personnel working in equine or mixed private practice between Far North and South-East Queensland in 2009-10. The qualitative data was entered and analysed thematically using QSR's International's Nvivo 9 qualitative data analysis software. RESULTS: This study revealed key issues associated with HeV testing: (1) inadequate knowledge of testing procedures and laboratory diagnostic pathways; (2) difficulty in accessing laboratory services; (3) responsibility for cost of collection and transport of specimen; and (4) the role of government. Participants perceived these issues as reducing potential HeV case management efficiency. CONCLUSION: Although HeV management plans have been modified in part since 2009-10, this study highlights the importance of considering the perspectives of private veterinary practitioners in any biosecurity protocols.

MlAG12: a Triticum timopheevii-derived powdery mildew resistance gene in common wheat on chromosome 7AL.

Wheat powdery mildew is an economically important disease in cool and humid environments. Powdery mildew causes yield losses as high as 48% through a reduction in tiller survival, kernels per head, and kernel size. Race-specific host resistance is the most consistent, environmentally friendly and, economical method of control. The wheat (Triticum aestivum L.) germplasm line NC06BGTAG12 possesses genetic resistance to powdery mildew introgressed from the AAGG tetraploid genome Triticum timopheevii subsp. armeniacum. Phenotypic evaluation of F(3) families derived from the cross NC06BGTAG12/'Jagger' and phenotypic evaluation of an F(2) population from the cross NC06BGTAG12/'Saluda' indicated that resistance to the 'Yuma' isolate of powdery mildew was controlled by a single dominant gene in NC06BGTAG12. Bulk segregant analysis (BSA) revealed simple sequence repeat (SSR) markers specific for chromosome 7AL segregating with the resistance gene. The SSR markers Xwmc273 and Xwmc346 mapped 8.3 cM distal and 6.6 cM proximal, respectively, in NC06BGTAG12/Jagger. The multiallelic Pm1 locus maps to this region of chromosome 7AL. No susceptible phenotypes were observed in an evaluation of 967 F(2) individuals in the cross NC06BGTAG12/'Axminster' (Pm1a) which indicated that the NC06BGTAG12 resistance gene was allelic or in close linkage with the Pm1 locus. A detached leaf test with ten differential powdery mildew isolates indicated the resistance in NC06BGTAG12 was different from all designated alleles at the Pm1 locus. Further linkage and allelism tests with five other temporarily designated genes in this very complex region will be required before giving a permanent designation to this gene. At this time the gene is given the temporary gene designation MlAG12.

No association between alcohol supplementation and autoantibodies to DNA damage in postmenopausal women in a controlled feeding study.

Alcohol consumption is linked to increased breast cancer risk. Since oestrogens increase breast cancer risk, possibly through oxidative damage, and we have shown that alcohol consumption increases serum oestrogens, we tested whether moderate alcohol supplementation increased oxidative DNA damage among healthy postmenopausal women not on hormone replacement therapy in a randomized controlled crossover study. We used serum 5-hydroxymethyl-2-deoxyuridine (5-HMdU) autoantibodies (aAbs) as a marker of oxidative DNA damage. The results showed no evidence for increased or decreased levels of oxidative DNA damage among women who consumed 15 g or 30 g alcohol per day for 8 weeks compared with women in the 0 g alcohol group. We conclude that among healthy women, it is possible that an 8-week trial of moderate alcohol supplementation might be too short to make enough 5-HMdU aAbs to compare differences by alcohol dose. In future studies, a panel of biomarkers for DNA damage should be used.

Moderate alcohol consumption and levels of antioxidant vitamins and isoprostanes in postmenopausal women.

BACKGROUND: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, the mechanisms mediating this association are speculative. OBJECTIVE: The Postmenopausal Women's Alcohol Study was designed to explore the effects of moderate alcohol consumption on potential risk factors for breast cancer. In the present analysis, we evaluated the relationship of alcohol consumption with antioxidant nutrients and a biomarker of oxidative stress. DESIGN: Participants (n=53) consumed a controlled diet plus each of three treatments (15 or 30 g alcohol/day or a no-alcohol placebo beverage), during three 8-week periods in random order. We measured the antioxidants, vitamin E (alpha (alpha)- and gamma (gamma)-tocopherols), selenium, and vitamin C in fasting blood samples which were collected at the end of diet periods, treated and frozen for assay at the end of the study. We also measured 15-F(2t)-IsoP isoprostane, produced by lipid peroxidation, which serves as an indicator of oxidative stress and may serve as a biomarker for conditions favorable to carcinogenesis. RESULTS: After adjusting for BMI (all models) and total serum cholesterol (tocopherol and isoprostane models) we observed a significant 4.6% decrease (P=0.02) in alpha-tocopherol and a marginally significant 4.9% increase (P=0.07) in isoprostane levels when women consumed 30 g alcohol/day (P=0.06 and 0.05 for overall effect of alcohol on alpha-tocopherol and isoprostanes, respectively). The other antioxidants were not significantly modified by the alcohol treatment. CONCLUSIONS: These results suggest that moderate alcohol consumption increases some biomarkers of oxidative stress in postmenopausal women.

Effects of moderate alcohol consumption on folate and vitamin B(12) status in postmenopausal women.

BACKGROUND: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, a causal relationship has not been established, and the mechanisms mediating this association are speculative. Alcohol may act through altered status of folate and vitamin B(12), two vitamins required for DNA methylation and nucleotide synthesis, and thus cell integrity. Although the effects of heavy alcohol intake on folate and vitamin B(12) status have been well-documented, few studies have addressed the effects of moderate alcohol intake in a controlled setting. OBJECTIVE: The objective of this study was to determine the effects of moderate alcohol intake on folate and vitamin B(12) status in healthy, well-nourished, postmenopausal women. DESIGN: The study design was a randomized, diet-controlled crossover intervention. Postmenopausal women (n=53) received three 8-week alcohol treatments in random order: 0, 15, and 30 g/day. Treatment periods were preceded by 2-5-week washout periods. Blood collected at baseline and week 8 of each treatment period was analyzed for serum folate, vitamin B(12), homocysteine (HCY), and methylmalonic acid (MMA) concentrations. RESULTS: After adjusting for body mass index (BMI), a significant 5% decrease was observed in mean serum vitamin B(12) concentrations from 0 to 30 g of alcohol/day (461.45+/-30.26 vs 440.25+/-30.24 pg/ml; P=0.03). Mean serum HCY concentrations tended to increase by 3% from 0 to 30 g of alcohol/day (9.44+/-0.37 vs 9.73+/-0.37 micromol/l; P=0.05). Alcohol intake had no significant effects on serum folate or MMA concentrations. CONCLUSIONS: Among healthy, well-nourished, postmenopausal women, moderate alcohol intake may diminish vitamin B(12) status.

Setting standards in the evaluation of community-based health promotion programmes--a unifying approach.

Community-based health promotion often emphasizes elements of empowerment, participation, multidisciplinary collaboration, capacity building, equity and sustainable development. Such an emphasis may be viewed as being in opposition to equally powerful notions of evidence-based decision making and accountability, and with funders' and government decision-makers' preoccupation with measuring outcomes. These tensions may be fuelled when community practitioners and lay participants feel evaluations are imposed upon them in a manner that fails to appreciate the uniqueness of their community, its programme, and practitioners' skills and experience. This paper attempts to provide an approach that depicts evaluation as being mutually beneficial to both funders/government and practitioners. First, a values stance for health promotion, termed a 'salutogenic' orientation, is proposed as a foundation for the evaluation of community-based health promotion. Secondly, we discuss possible objects of interest, the first component of an evaluation. We then discuss the spirit of the times and its implications for community-based health promotion. Finally, we address the key question of setting standards. A typology of standards is presented. Arbitrary, experiential and utility standards are based on perceived needs and priorities of practitioners, lay participants or professional decision-makers. Historical, scientific and normative standards are driven by empirical, objective data. Propriety and feasibility standards are those wherein the primary concern is for consideration of resources, policies, legislation and administrative factors. The 'model' standards approach is presented as an exemplar of a combined approach that incorporates elements of each of the other standards. We argue that the 'optimal' standard for community-based health promotion depends on the setting and the circumstances. There is no 'magic bullet', 'one-size-fits-all' or 'best' standard. Further, we argue that standards should be set from an inclusive, salutogenic orientation. This approach offers a means of creating a situation in which policy-makers and funders are more supportive of evaluation designs that fit with community realities, and community stakeholders are more capable and consistent in rigorously evaluating community-based health promotion programmes and policies.

Oolong tea increases metabolic rate and fat oxidation in men.

According to traditional Chinese belief, oolong tea is effective in the control of body weight. Few controlled studies, however, have been conducted to measure the impact of tea on energy expenditure (EE) of humans. A randomized cross-over design was used to compare 24-h EE of 12 men consuming each of four treatments: 1) water, 2) full-strength tea (daily allotment brewed from 15 g of tea), 3) half-strength tea (brewed from 7.5 g tea) and 4) water containing 270 mg caffeine, equivalent to the concentration in the full-strength tea treatment. Subjects refrained from consuming caffeine or flavonoids for 4 d prior to the study. Tea was brewed each morning; beverages were consumed at room temperature as five 300 mL servings. Subjects received each treatment for 3 d; on the third day, EE was measured by indirect calorimetry in a room calorimeter. For the 3 d, subjects consumed a typical American diet. Energy content of the diet was tailored to each subject's needs as determined from a preliminary measure of 24-h EE by calorimetry. Relative to the water treatment, EE was significantly increased 2.9 and 3.4% for the full-strength tea and caffeinated water treatments, respectively. This increase over water alone represented an additional expenditure of 281 and 331 kJ/d for subjects treated with full-strength tea and caffeinated water, respectively. In addition, fat oxidation was significantly higher (12%) when subjects consumed the full-strength tea rather than water.

Diet interviews of subject pairs: how different persons recall eating the same foods.

OBJECTIVE: To compare qualitative descriptions of the same food items eaten by different persons using 24-hour dietary recall interviews. DESIGN: Eleven pairs of subjects were interviewed twice using 24-hour dietary recalls such that each member of the pair described the same day's foods. Each pair shared a home and ate at least 2 meals together daily. After each interview, subjects were asked to identify the foods reported during the interview that they observed the other member of their pair consuming and to note when a particular food was the only item of that type available in the house. Qualitative descriptions of the foods were compared, differences in descriptions were noted, and calculations were made of the potential energy error produced if a subject erred in reporting a food item. SUBJECTS/SETTING: Subjects were randomly selected from a database of persons who have participated in other studies at the Beltsville Human Nutrition Research Center. Ten pairs were husbands and wives and 1 pair was sisters. Each pair reported eating at least 2 meals per day together. Dietary recall interviews were done at the Research Center and were conducted by a trained dietitian in a quiet room free of distractions. RESULTS: Discrepancies in qualitative food descriptions were identified for every subject pair interviewed. Men were found to be more likely to omit food items than women, snack items were more likely to be omitted than meal items, meat items were likely to be described inaccurately, and first interviews were likely to contain more errors than second interviews. APPLICATIONS/CONCLUSIONS: This analysis shows which types of food items are most likely to be omitted or inaccurately described, and that dietetics professionals may improve the accuracy of dietary intake interviews by asking questions related to meat, milk, and snacks very carefully. The analysis also showed reductions in recall inconsistencies from the first recall to the second recall, suggesting that the learning associated with repeated interviews may be helpful in accurately identifying what a person consumes.

Serum hormones and the alcohol-breast cancer association in postmenopausal women.

BACKGROUND: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. METHODS: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. RESULTS: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. CONCLUSIONS: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.

Field-by-field evaluation of intraoperative transoesophageal echocardiography interpretative skills.

A quality assurance system is essential for the credibility and structured growth of anaesthesiology-based transoesophageal echocardiography (TEE) programmes. We have developed software (Q/A Kappa), involving a 400-line source code, capable of directly reporting kappa correlation coefficient values, using external reviewer interpretations as the 'gold standard', and thereby allowing systematic assessment of the validity of intraoperative echocardiographic interpretation. This paper presents assessment of the validity of 240 intraoperative anaesthesiologists' echocardiographic interpretations, and, in addition, the results of field testing of this prototypical software. Data, derived from consecutive cardiac surgery patients, consisted of standardized two-dimensional transoesophageal echocardiographic, colour flow and Doppler imaging sequences. Intraoperative and off-line 'gold standard' TEE interpretations were compared for 19 fields or variables using the Q/A Kappa program. The kappa correlation coefficients were highly variable and dependent on the examination field, ranging from 0.08 for apical regional wall motion scores to 1.00 for tricuspid regurgitation grade, left atrial measurement, aortic valve anatomy and left ventricular long axis and short axis global function. The correlation coefficients were also operator dependent. These data (480 interpretations) were also manually integrated into the equation required for calculation of values of the variable kappa correlation coefficient. The relationship between Q/A Kappa-derived values and manually calculated values was highly significant (p < 0.001; r = 1.0). The implications and possible explanations of the results for particular examination fields are discussed. This study also demonstrates successful seamless functioning of this software program from data entry, segmentation into tables and valid statistical analysis. These findings suggest that it is practical to provide sophisticated continuous quality improvement TEE data on a routine basis.

Androgens regulate bone resorption activity of isolated osteoclasts in vitro.

For many years it has been recognized that sex steroids have profound effects on bone metabolism. The current perception is that estrogen decreases bone resorption and androgen increases bone deposition. To investigate the potential for androgens to directly modulate bone resorption, we have examined avian osteoclast and human and mouse osteoclast-like cells for androgen responsiveness. There was a dose-dependent decrease in resorption activity in response to alpha-dihydrotestosterone (alpha-DHT), beta-DHT, testosterone, or the synthetic androgen RU1881. This decrease was blocked by cotreatment with the specific androgen antagonist hydroxyflutamide. Further examination of avian osteoclasts revealed that the cells exhibited specific and saturable nuclear binding of tritiated RU1881 and that alpha-DHT stimulated the activity of the androgen response element as measured by using a chloramphenicol acetyltransferase reporter plasmid. In addition, avian osteoclasts responded to androgen treatment with elevated production and secretion of transforming growth factor beta, a well documented response to androgen exposure in other cell systems. Treatment with either alpha-DHT or beta-DHT for 24 hours resulted in a significant dose-dependent decrease in secretion of cathepsin B and tartrate-resistant acid phosphatase. This response to beta-DHT, a stereoisomer of alpha-DHT that is inactive in other androgen receptor-dependent systems, supports the hypothesis that the osteoclast androgen receptor has unusual ligand-binding properties. Taken together, these results confirm the presence of functional androgen receptors in these cells and support the conclusion that osteoclasts are able to respond directly to androgens in vitro and thus are potential androgen target cells in vivo.

Effects of margarine compared with those of butter on blood lipid profiles related to cardiovascular disease risk factors in normolipemic adults fed controlled diets.

Effects of butter and 2 types of margarine on blood lipid and lipoprotein concentrations were compared in a controlled diet study with 23 men and 23 women. Table spreads, added to a common basal diet, provided 8.3% of energy as fat. Diets averaged 34.6% of energy as fat and 15.5% as protein. Each diet was fed for 5 wk in a 3 x 3 Latin-square design. One margarine (TFA-M) approximated the average trans monoene content of trans fatty acid-containing margarines in the United States (17% trans fatty acids by dry wt). The other margarine (PUFA-M) was free of trans unsaturated fatty acids; it contained approximately twice the polyunsaturated fatty acid content of TFA-M (49% compared with 27% polyunsaturated fatty acids). The tub-type margarines had similar physical properties at ambient temperature. Fasting blood lipids and lipoproteins were determined in 2 samples taken from the subjects during the fifth week of each dietary treatment. Compared with butter, total cholesterol was 3.5% lower (P=0.009) after consumption of TFA-M and 5.4% lower (P< 0.001) after consumption of PUFA-M. Similarly, LDL cholesterol was 4.9% lower (P=0.005) and 6.7% lower (P< 0.001) after consumption of TFA-M and PUFA-M, respectively. Neither margarine differed from butter in its effect on HDL cholesterol or triacylglycerols. Thus, consumption of TFA-M or PUFA-M improved blood lipid profiles for the major lipoproteins associated with cardiovascular risk when compared with butter, with a greater improvement with PUFA-M than with TFA-M.

Plasma lipoprotein (a) levels in men and women consuming diets enriched in saturated, cis-, or trans-monounsaturated fatty acids.

Studies that have shown adverse effects of trans-unsaturated fatty acids on plasma lipoprotein (a) [Lp(a)] levels have used levels of trans-fatty acid that are higher than those in the average U.S. diet. This study was conducted to clarify the effects on Lp(a) of trans-fatty acids levels commonly found in U.S. diets. Lp(a) levels were measured in a double-blind study of 29 men and 29 women who ate 4 controlled diets in random order for 6 weeks each. Fatty acids represented 39% to 40% of energy. The diets were: (1) Oleic (16.7% of energy as oleic acid); (2) Moderate trans (3.8% of energy as trans-monoenes, approximately the trans content of the U.S. diet); (3) High trans (6.6% of energy as trans-monoenes); (4) Saturated (16.2% of energy as lauric plus myristic plus palmitic acids). The Saturated diet lowered Lp(a) levels significantly (by 8% to 11%). Compared to the Oleic diet, the trans diets had no adverse effect on Lp(a) levels when all subjects were considered collectively. A subset with initially high levels of Lp(a) (> or = 30 mg/dL), however, responded to the High trans diet with a slight (5%) increase in Lp(a) levels relative to the Oleic and Moderate trans diets. Thus, in amounts commonly found in the typical U.S. diet, saturated fatty acids consistently decrease Lp(a) concentrations. The adverse effects of replacing cis- with trans-fatty acids are only suggestive and are restricted to high trans intakes in subjects with high Lp(a) levels.

Individual variability in lipoprotein cholesterol response to National Cholesterol Education Program Step 2 diets.

The effects of National Cholesterol Education Program (NCEP) Step 2 diets on plasma lipoprotein profiles in 72 men [mean (+/- SD) age: 44 +/- 15 y, range: 19-81 y] and 48 women (mean age: 50 +/- 21 y, range: 21-78 y) participating in five previously published studies were examined. Subjects were placed on a baseline diet similar to an average American diet (35-41% total fat, 13-16% saturated fat, 31-45 mg cholesterol/MJ) and then on an NCEP Step 2 diet (18-29% total fat, 4-7% saturated fat, 11-20 mg cholesterol/MJ) under isoenergetic conditions. All food and drink were provided. Compared with the baseline diet, consumption of the NCEP Step 2 diets was associated with significant decreases in concentrations of low-density-lipoprotein (LDL) cholesterol (-18.9% and -15.6%, respectively) and high-density-lipoprotein (HDL) cholesterol (-17.0% and -11.2%, respectively) in both men and women. Men with the apolipoprotein (apo) E 3,4 phenotype had a significantly greater decrease in LDL cholesterol (-24.2%) with the NCEP Step 2 diets than men with the apo E 3,3 phenotype (-17.7%). Men with the apo A-IV 1,2 phenotype tended to have less LDL cholesterol lowering (-12.8%) than men with the apo A-IV 1,1 phenotype (-19.6%), but this difference was not significant. No differences were seen by apo E and A-IV phenotype in women. A large variability in lipid response to the diet was observed, with changes in LDL cholesterol ranging from +3% to -55% in men and and from +13% to -39% in women. Forty-eight percent of the variability in LDL-cholesterol response (in mmol/L) to the diet could be accounted for by baseline LDL concentrations and age in men, and 13% by age in women.

Extragonadal sperm reserves, sperm-depletion rates, numbers of sperm per mating, and fertility with successive matings by intact or unilaterally vasectomized rats.

Because of the high rates of sperm production and large extragonadal sperm reserves of sexually rested male rats, mating trials are insensitive for detecting test-induced alterations in sperm production rates. Mating trials might be more sensitive if, independently of any experimental treatments under study, the number of sperm per mating was closer to the minimum requirements for normal fertility. The present study was undertaken to assess the impact of unilateral vasectomy and/or matings with up to three females in succession, for 1 hour each, on the number of sperm per mating and fertility, in comparison to corresponding values for males allowed unlimited matings with a receptive female overnight. Unilateral vasectomy did not affect sperm production, extragonadal sperm reserves, or removal of contralateral sperm during ejaculation (P > 0.05) but caused a 50% decrease in sperm numbers per mating. Sperm output, judged from numbers of residual extragonadal sperm in unmated and mated males, was excessive (290 x 10[6]) during conventional overnight mating with intact males and during the first and second hours of restricted mating (105 and 184 x 10(6) respectively, for intact males; one-half of these amounts for unilaterally vasectomized males). In contrast, sperm output during the third successive mating was minimal (nonmeasurable) but adequate, since pregnancy rates were similar for females mated first, second, or third in succession (P > 0.05). Since successive matings reduce the number of sperm per mating by natural methods, this approach may enhance the sensitivity of mating tests when applied for assessing the potential effects of experimental treatments on sperm production.