Barriers and facilitators of using dementia community support services provided by an Alzheimers organisation: Perceptions of informal caregivers receiving services.

Known barriers prevent informal caregivers of a person with dementia using community services; however, there is a dearth of knowledge on how organisations can overcome these barriers. This study examined caregivers' perceptions of the barriers and facilitators of service use with regards to their membership to one Alzheimers organisation and their recommendations for improvements. In-depth interviews were conducted with 19 informal caregivers. Thematic analysis revealed personal and organisational barriers to service use, and associated recommendations. Six recommendations were made for dementia service organisations: (a) be proactive and arrange regular scheduled meetings with clients; (b) utilise consistent, trusting, empathic support personnel who can build strong relationships with clients; (c) provide support groups; (d) tailor support; (e) ensure expert knowledge and numerous channels of information delivery to clients, the general public and health professionals and (f) actively promote the organisation and services offered. This study provides novel insights into how a community organisation can overcome client barriers to service use. In addition, the study reveals caregivers perceived value of an Alzheimers organisation, argued to be an essential service, but until now clients' perceptions of the value received have not been explored.

Women and men's use of coercive control in intimate partner violence.

This study examined the relationship between coercive control and intimate partner violence (IPV) for men and women and for targets and perpetrators. One hundred and seventy-two participants (85 men, 87 women) recruited from three samples reported on their own and their partner's behavior. IPV was measured using the Revised Conflict Tactics Scale (CTS2). Coercive control was measured using modified items from the Psychological Maltreatment of Women Inventory (PMWI). Coercive control was associated with IPV, and this relationship was similar for men and women across the three samples. In fact, coercive control was predominantly reciprocal in nature, with women and men reporting both receiving and perpetrating controlling behaviors. Overall, coercive controlling behaviors were characteristic of individuals within violent relationships, regardless of their physical abuse status. The experience of violence, rather than gender, was the best predictor of coercive control.

Legalization of recreational cannabis: Facilitators and barriers to switching from an illegal to a legal source.

Illicit markets persist in places where recreational cannabis has been legalized. This study aimed to identify perceived facilitators/barriers of switching from an illicit to a licit cannabis source. Using a cross-sectional qualitative approach, 529 students, from one New Zealand university, completed a survey investigating the facilitators/barriers to switching through two open-ended questions. Perceived facilitators for switching included: safety (63.1%); price (42.7%); legal, no risk of convictions (35.3%); increased accessibility (32.3%); product diversity (14.2%). Perceived barriers included: price (66.4%); judgement (36%); regulation (28.9%); loyalty to current supplier (27.2%); reduced accessibility (13.2%). The findings provide recommendations for policies aimed at tipping people in favor of a licit over an illicit source. Avoiding arrest/convictions, and easier access, were not primary facilitators for switching. Thus, providing a licit market might be insufficient in the absence of other competitive factors, such as communicating improved product safety. Competitive pricing and regulation (tetrahydrocannabinol strength/quantity limits) were also barriers. Given legal markets aimed at minimizing harm are constrained with competing in these areas, it is significant that our findings identified other barriers which could be overcome, including limiting surveillance and quantity limits and positioning stores to preserve anonymity. The findings also highlight that loyalty to current illicit suppliers will be a significant barrier.

Control of Recreational Cannabis in a New Zealand University Sample: Perceptions of Informal and Formal Controls.

An increasing number of countries have, or are moving towards, reforming cannabis policies. New Zealand is also moving in this direction and the government will hold a referendum on the legalization of recreational cannabis in September 2020. To inform imminent public and political discussions it is important to understand how current cannabis use is controlled. Research suggests that cannabis law has been ineffective in NZ. Internationally, informal controls, rather than the law, have been found to shape cannabis use by creating a threshold for normalization, but the attitudes shaping this threshold are unknown. This study aimed to examine drug acceptability attitudes, specifically students' attitudes towards the illegal use of cannabis and their attitudes towards peers who abstain, sometimes use, or are heavy users of cannabis, to identify the factors that control cannabis use. Using a mixed methods approach, university students recruited their peers (N = 535) to complete a pen and paper survey investigating perceptions towards 3 cannabis user prototypes (abstainers, moderate users, heavy users), concern for legality of cannabis use, and the integration of cannabis into the student culture (perceptions of peers' use, ease of acquisition, and availability). Perceptions of peers' lifetime and regular use were 82% and 38.5%, respectively. Participants rated cannabis as easy to acquire and likely to be available at a typical student social occasion. The majority stated that the law does not deter use (92.7%); participants perceived the law to be soft and that they are unlikely to get caught. Participants' descriptions of the 3 cannabis user prototypes revealed a threshold for normalization. For instance, abstaining was perceived to be associated with positive attributes (such as being studious), linked to being less sociable, and linked to being less likely to be judged. Moderate use of cannabis was perceived to be normal and sociable. Heavy use was perceived to be associated with having negative attributes, such as being addicted, unhealthy, and an underachiever, and negative drug labels. Our findings revealed that cannabis use is not controlled by the law, but by informal thresholds of control. Moderate cannabis use is accepted whereas heavy cannabis use is not. We extended research by identifying the attitudes shaping these thresholds, in particular that negative outcomes associated with heavy use deters the normalization of this behavior. We argue that policy must be informed by, and build on, these informal controls. The negative perceptions associated with heavy use also raise concerns regarding the well-being of heavy users, and coupled with the ineffectiveness of cannabis law, lend support towards a health model for regulating cannabis. Furthermore, insights into the negative perceptions associated with heavy use could inform health interventions on the types of concerns that will resonate with users.

Perpetration of Alcohol-Related Aggression by Male and Female College Students: An Examination of Overt and Relational Aggression.

Existing literature exemplifies the relationship between alcohol and overt aggression, especially for adult males. Less clear is the relationship between alcohol and aggression among male and female college students, in particular, the nature of this aggression and the co-occurrence of drinking and aggression on the same day (temporal proximity). This study examines the chronic and temporal nature of males' and females' alcohol-related aggression among college students. Two hundred fourteen students completed a web-based 7-day event-level survey measuring alcohol consumption and perpetration of physical aggression, verbal aggression, anger, and relational aggression over 4 weeks, resulting in 4,256 observations (days). The global analysis revealed students who are heavy drinkers are more likely to perpetrate all four forms of aggression, whereas the event-level analysis revealed that specific forms of aggression are associated with drinking at the time, while other forms were not linked to drinking occasions. Cross-tabulation revealed males and females were more likely to use verbal and physical aggression when drinking. For females, drinking was also associated with relational aggression and anger. Despite often being overlooked in research on aggression during emerging adulthood, relational aggression was prevalent. Discrepancies between the global and temporal analysis revealed factors other than alcohol might explain the relationship between chronic alcohol consumption and specific forms of aggression. This is one of the first event-level studies to show the temporal relationship between alcohol and relational aggression. The distinctions in the current study, exemplifying the diversity of alcohol-related aggression, are critical for understanding aggressive behavior, potential gender differences, and for developing interventions. The temporal relationship between alcohol and aggression suggests health interventions should target drinking and aggression simultaneously.

Lifestyle determinants of behavioural outcomes triggered by direct-to-consumer advertising of prescription medicines: a cross-sectional study.

OBJECTIVE: Direct-to-consumer advertising of prescription medicines encourages individuals to search for or request advertised medicines, can stimulate taking medications rather than making lifestyle behaviour changes, and may target individuals with poorer demographic and socioeconomic status and riskier health-related behaviours. This study thus explored whether responses to medicine advertising vary as a function of lifestyle behaviours, and demographic and socioeconomic factors. METHODS: Data were collected through an online survey of a nationally representative sample of 2,057 adults in New Zealand. Multivariate binary logistic regressions were used to explore whether lifestyle behaviours, including nutritional habits, alcohol consumption, illegal drug consumption, physical activity, attitudes towards doing exercise, as well as demographic and socioeconomic status were associated with self-reported behavioural responses to medicine advertising. RESULTS: Individuals who had unhealthier lifestyle behaviours were more likely to respond to medicine advertising. CONCLUSIONS: The findings raise concerns regarding the misuse or overuse of medications for diseases that may otherwise be improved by a healthier lifestyle. Implications for public health: To improve public health and wellbeing of society, we call for regulatory changes regarding advertising of medicines. Where applicable, lifestyle changes should be advertised as potential substitutes for the advertised medicines. Interprofessional collaboration is also recommended to educate individuals and convey the value of health behaviour changes.

Students Who Limit Their Drinking, as Recommended by National Guidelines, Are Stigmatized, Ostracized, or the Subject of Peer Pressure: Limiting Consumption Is All But Prohibited in a Culture of Intoxication.

There is an unquestionable need to address drinking patterns in subcultures where excessive drinking is normative. Regulatory bodies advocate moderating alcohol consumption but it is unclear whether individuals have agency to do so, particularly when excessive consumption is the norm. This study aimed to address this gap by examining student's perceptions of limiting consumption, as recommended by government guidelines, in one university in New Zealand. Using a qualitative social science approach, university students surveyed and interviewed their heavy-drinking peers (n = 201) to investigate perceptions of 3 drinking behaviors (Heavy, Moderation, and Abstinence). Thematic analysis revealed that students who drink heavily are labeled positively and viewed as sociable (Dr Froth, Liver of Steel, Trooper, Champion, Hero, Good Alcoholic, popular, a friend). Students who limit drinking, on the other hand, were viewed similar to those who abstain, labeled using explicit, emotive, and derogative terminology (eg, Fag, Vagina, Grandma, Weirdo, Coward, Killjoy) and excluded, ostracized, or the subject of peer pressure. They were also expected to provide a justification for moderating their drinking (eg, being an athlete, broke). Although individuals who moderated their consumption were perceived to have strong willpower and maturity (eg, self-aware, brave, sophisticated), these positive attributes were mentioned less frequently and involved less emotive language than were labels linking moderation to a negative social identity. The method employed in this study provided a frank insight into a student culture of intoxication and the barriers facing students who try to drink in moderation. Our findings reveal that limiting consumption, even occasionally, threatens students' social identity and inclusion in the student drinking culture. These results suggest that individualistic harm minimization strategies are unlikely to be effective. Instead, the findings underscore the need to develop alternative cultures emphasizing extracurricular activities which may facilitate students' agency to go against the norm and moderate their drinking.

Supporting a sugar tax in New Zealand: Sugar sweetened beverage ('fizzy drink') consumption as a normal behaviour within the obesogenic environment.

BACKGROUND: Excessive intake of sugar sweetened beverages (SSBs) is a preventable cause of death. While some countries have implemented a tax on SSBs, other countries, such as New Zealand, rely on industry self-regulation and individual responsibility, such as referring to labels, to control one's own sugar intake from SSBs. The present study examines whether SSB consumers consciously control their diet and therefore interventions such as better labelling might be effective, or alternatively, whether SSB consumers engage in a general pattern of unhealthy eating, and in which case government regulation would be advisable. AIM: To explore self-reported dietary consumption and conscious healthy eating behaviours of New Zealand consumers who had consumed SSBs over a 24 hour period. METHOD: A cross-sectional survey of a representative sample of 2007 New Zealanders, measuring their food and beverage intake over a 24 hour period and self-reported intentions to eat healthily. Within this was a measurement of SSB consumption in the 24 hour period. RESULTS: Multivariable logistic regression revealed that compared to non-SSB consumers, SSB consumers were more likely to have eaten the following: confectionery; fast food; pre-prepared food; biscuits, cakes or pastries; takeaways; ice-cream/dessert. SSB consumption was also associated with a lower likelihood of referring to food labels, less conscious effort to eat healthily, and to less likely to avoid: sugar; fat; calories; food additives; pre-prepared food. SSB consumers were also less likely to have eaten breakfast, or made a meal at home made from scratch. CONCLUSION: SSB consumers were more likely than non-SSB consumers to demonstrate a general pattern of unhealthy eating and were less likely to report consciously controlling their diet. The findings raise significant concerns regarding the efficacy of individual and industry self-regulation and lend support to stronger government targeted interventions.

Correlates of partner violence for incarcerated women and men.

This study examines partner violence within an incarcerated sample of women and men. Specifically, it focused on the relationship between explicit and implicit attitudes to the perpetration and victimization of violence. Findings revealed that violence was bidirectional, with males and females equally likely to report being the perpetrator or victim of violence. The attitudes and beliefs associated with violence were similar regardless of gender, type of violence (physical or psychological), or whether individuals were the victim or perpetrator of violence. Hostility to women was the most significant factor associated with perpetrating and condoning partner violence. Hostility to women in combination with implicit beliefs condoning violence were the strongest predictors for suffering physical violence. Victims' self-reported communication problems uniquely predicted their suffering of psychological violence. The explanation for and consequences of these results are discussed.

'At-risk' individuals' responses to direct to consumer advertising of prescription drugs: a nationally representative cross-sectional study.

OBJECTIVES: The factors determining individuals' self-reported behavioural responses to direct to consumer advertising of prescription drugs were explored with an emphasis on 'at-risk' individuals' responses. DESIGN: Nationally representative cross-sectional survey. SETTING: Community living adults in New Zealand. PARTICIPANTS: 2057 adults (51% women). PRIMARY OUTCOME MEASURES: Self-reported behavioural responses to drug advertising (asking a physician for a prescription, asking a physician for more information about an illness, searching the internet for more information regarding an illness and asking a pharmacist for more information about a drug). METHODS: Multivariate logistic regressions determined whether participants' self-reported behavioural responses to drug advertising were predicted by attitudes towards advertising and drug advertising, judgements about safety and effectiveness of advertised drugs, self-reported health status, materialism, online search behaviour as well as demographic variables. RESULTS: Identifying as Indian and to a less extent Chinese, Maori and 'other' ethnicities were the strongest predictors of one or more self-reported responses (ORs 1.76-5.00, Ps<0.05). Poorer self-reported health status (ORs 0.90-0.94, all Ps<0.05), favourable attitude towards drug advertising (ORs 1.34-1.61, all Ps<0.001) and searching for medical information online (ORs 1.32-2.35, all Ps<0.01) predicted all self-reported behavioural outcomes. Older age (ORs 1.01-1.02, Ps<0.01), less education (OR 0.89, P<0.01), lower income (ORs 0.89-0.91, Ps<0.05) and higher materialism (ORs 1.02-1.03, Ps<0.01) also predicted one or more self-reported responses. CONCLUSIONS: Taken together, the findings suggest individuals, especially those who are 'at-risk' (ie, with poorer self-reported health status, older, less educated, lower income and ethnic minorities), may be more vulnerable to drug advertising and may make uninformed decisions accordingly. The outcomes raise significant concerns relating to the ethicality of drug advertising and suggest a need for stricter guidelines to ensure that drug advertisements provided by pharmaceutical companies are ethical.

Cholesterol-sensing receptors, liver X receptor alpha and beta, have novel and distinct roles in osteoclast differentiation and activation.

UNLABELLED: The liver X receptor (alpha,beta) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXRalpha-/-, LXRbeta-/-, and LXRalpha-/-beta-/- mice show that both LXRalpha and beta are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. INTRODUCTION: The liver X receptors (alpha,beta) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. MATERIALS AND METHODS: pQCT was performed on both male and female LXRalpha-/-, LXRbeta-/-, LXRalpha-/-beta-/-, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. RESULTS: At the mRNA level, LXRbeta was more highly expressed than LXRalpha in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXRalpha-/- mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXRbeta-/- mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. CONCLUSIONS: Our findings show that both LXRs influence cellular function within the bone, with LXRalpha having an impact on osteoclast activity, primarily in cortical bone, whereas LXRbeta modulates trabecular bone turnover.

Reduced fertility and inability of oocytes to resume meiosis in mice deficient of the Lxr genes.

Cholesterol precursors act as activators of the nuclear hormone receptor, liver X receptor (LXR). One of these LXR-activating ligands is meiosis activating sterol (MAS), which also induces resumption of meiosis in oocytes from mice in vitro. Whether LXR participates in the regulation of oocyte maturation and whether the expression of either one of the two paralogues of LXR (alpha and beta) affect fertility of mice has, however, not yet been clarified. Female mice lacking Lxra, Lxrb or both genes (Lxra(-/-), Lxrb(-/-) and Lxrab(-/-), respectively) conceive less frequently and have significantly fewer pups per litter as compared to wild type mice. Both Lxra and Lxrb mRNA were found to be expressed in mouse oocytes. The relative expression of, in particular, Lxrb was almost two orders of magnitude higher than in liver, brain and testis. A water-soluble LXR agonist caused naked oocytes, but not cumulus enclosed oocytes (CEO), from wild type mice to resume meiosis significantly more often than control oocytes. Follicle stimulating hormone (FSH) is a potent stimulator of meiosis in CEO from wild type mice, but was without effect in mice lacking both Lxr genes. Zymosterol, a MAS active substance, induced resumption of meiosis in oocytes from Lxrab(-/-) mice, but significantly less effectively than in oocytes from wild type mice. Taken together, LXRs seem to affect ovarian function, suggesting specific roles of cholesterol precursors in regulation of female reproduction.

The liver X receptor-{beta} is essential for maintaining cholesterol homeostasis in the testis.

The liver X receptor (LXR)alpha and -beta has been found to play a central role in maintaining cellular cholesterol homeostasis. In this study we comprehensively investigated the effect of deleting LXRalpha and -beta on testicular morphology and function. In the absence of LXRbeta, excessive cholesterol accumulated in the Sertoli cells from 2.5 months, resulting in severe cellular disruption and dysregulation of spermatogenesis by 10 months of age. This correlated with gene expression analyses that clearly indicated that LXRbeta was the dominant transcript in the testis Although the LXRalpha(-/-) testis was normal, the LXRalpha(-/-)beta(-/-) testis presented with a more severe phenotype than the LXRbeta(-/-) mice, and males were infertile by 4 months of age, indicating LXRalpha may partially rescue the testicular phenotype. Although Leydig cells did not accumulate excessive cholesterol, declining serum and intratesticular androgen levels with age suggested that these cells were in fact less functional. Treatment of a Sertoli cell line with the LXR agonist T0901317 led to increased expression of known LXR target genes like ATP binding cassette-G1 and sterol regulatory binding protein-1c; similar results were observed in wild-type testis after in vivo administration, suggesting the LXR is functioning in the same way as in other tissues. Ordinarily increased levels of cholesterol activate intracellular sensors to decrease these levels; however, the increasing amount of cholesterol in the Sertoli cells indicates improper control of cholesterol metabolism when LXRbeta is absent. Although the precise molecular mechanism at this time remains unclear, our study highlights the crucial role for LXRbeta in retaining cholesterol homeostasis in Sertoli cells.

The phenotype of the aromatase knockout mouse reveals dietary phytoestrogens impact significantly on testis function.

Estrogen is synthesized in the testis, both in Leydig cells and seminiferous epithelium, and its importance in spermatogenesis is highlighted by the phenotype of the aromatase knockout (ArKO) mouse. These mice are unable to synthesize endogenous estrogens. The males develop postmeiotic defects by 18 wk of age. We hypothesized that maintenance of spermatogenesis in younger animals may be mediated by exogenous estrogenic substances. Dietary soy meal, contained in almost all commercial rodent diets, provides a source of estrogenic isoflavones. We thus investigated spermatogenesis in wild-type and ArKO mice raised on a diet containing soy, compared with a soy-free diet, to elucidate the biological action of phytoestrogens on the testis. In ArKO mice, dietary phytoestrogens could partially prevent disruptions to spermatogenesis, in that they prevented the decline in germ cell numbers. They also seemed to maintain Sertoli cell function, and they blocked elevations in FSH. The impairment of spermatogenesis seen in soy-free ArKOs occurred in the absence of a decreased gonadotropic stimulus, suggesting that the effects of dietary phytoestrogens are independent of changes to the pituitary-gonadal axis. Our study highlights the importance of estrogen in spermatogenesis and shows that relatively low levels of dietary phytoestrogens have a biological effect in the testis.

Xenopus cell-free extracts to study the DNA damage response.

Cell-free systems derived from Xenopus eggs represent a powerful tool, intermediate between in vitro and in vivo model systems. Here, we describe protocols to prepare cell-free extracts recapitulating several aspects of the DNA damage response, including the DNA damage-dependent activation of ATM/ATR protein kinases and several DNA damage checkpoint signaling pathways that inhibit initiation of DNA replication. We provide protocols to prepare cell-free extracts, DNA templates, protein kinase substrates, and to perform checkpoint assays. In addition, we describe related methods that provide useful readouts of the DNA damage response.

Regulation of hepatic energy metabolism and gluconeogenesis by BAD.

The homeostatic balance of hepatic glucose utilization, storage, and production is exquisitely controlled by hormonal signals and hepatic carbon metabolism during fed and fasted states. How the liver senses extracellular glucose to cue glucose utilization versus production is not fully understood. We show that the physiologic balance of hepatic glycolysis and gluconeogenesis is regulated by Bcl-2-associated agonist of cell death (BAD), a protein with roles in apoptosis and metabolism. BAD deficiency reprograms hepatic substrate and energy metabolism toward diminished glycolysis, excess fatty acid oxidation, and exaggerated glucose production that escapes suppression by insulin. Genetic and biochemical evidence suggests that BAD's suppression of gluconeogenesis is actuated by phosphorylation of its BCL-2 homology (BH)-3 domain and subsequent activation of glucokinase. The physiologic relevance of these findings is evident from the ability of a BAD phosphomimic variant to counteract unrestrained gluconeogenesis and improve glycemia in leptin-resistant and high-fat diet models of diabetes and insulin resistance.

Dual role of proapoptotic BAD in insulin secretion and beta cell survival.

The proapoptotic BCL-2 family member BAD resides in a glucokinase-containing complex that regulates glucose-driven mitochondrial respiration. Here, we present genetic evidence of a physiologic role for BAD in glucose-stimulated insulin secretion by beta cells. This novel function of BAD is specifically dependent upon the phosphorylation of its BH3 sequence, previously defined as an essential death domain. We highlight the pharmacologic relevance of phosphorylated BAD BH3 by using cell-permeable, hydrocarbon-stapled BAD BH3 helices that target glucokinase, restore glucose-driven mitochondrial respiration and correct the insulin secretory response in Bad-deficient islets. Our studies uncover an alternative target and function for the BAD BH3 domain and emphasize the therapeutic potential of phosphorylated BAD BH3 mimetics in selectively restoring beta cell function. Furthermore, we show that BAD regulates the physiologic adaptation of beta cell mass during high-fat feeding. Our findings provide genetic proof of the bifunctional activities of BAD in both beta cell survival and insulin secretion.

Aromatase--a brief overview.

There is growing awareness that androgens and estrogens have general metabolic roles that are not directly involved in reproductive processes. These include actions on vascular function, lipid and carbohydrate metabolism, as well as bone mineralization and epiphyseal closure in both sexes. In postmenopausal women, as in men, estrogen is no longer solely an endocrine factor but instead is produced in a number of extragonadal sites and acts locally at these sites in a paracrine and intracrine fashion. These sites include breast, bone, vasculature, and brain. Within these sites, aromatase action can generate high levels of estradiol locally without significantly affecting circulating levels. Circulating C19 steroid precursors are essential substrates for extragonadal estrogen synthesis. The levels of these androgenic precursors decline markedly with advancing age in women, possible from the mid-to-late reproductive years. This may be a fundamental reason why women are at increased risk for bone mineral loss and fracture, and possibly decline of cognitive function, compared with men. Aromatase expression in these various sites is under the control of tissue-specific promotors regulated by different cohorts of transcription factors. Thus in principle, it should be possible to develop selective aromatase modulators (SAMs) that block aromatase expression, for example, in breast, but allow unimpaired estrogen synthesis in other tissues such as bone.