Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes

Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.

Varenicline, an alpha-4 beta-2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking

Abstract Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.

Dietary modification for women after breast cancer treatment : a narrative review

Diet is thought to account for about 25% of cancers in developed countries. It is well documented that the risks associated with both the breast cancer itself and its treatments are important for women previously treated for breast cancer. Women are at risk of recurrence of the primary disease and prone to develop treatment-induced co-morbidities, some of which are thought to be modified by diet. With a view to making dietary recommendations for the breast cancer patients we encounter in our clinical nursing research, we mined the literature to scope the most current robust evidence concerning the role of the diet in protecting women against the recurrence of breast cancer and its potential to ameliorate some of the longer-term morbidities associated with the disease. We found that the evidence about the role of the diet in breast cancer recurrence is largely inconclusive. However, drawing on international guidelines enabled us to make three definitive recommendations. Women at risk of breast cancer recurrence, or who experience co-morbidities as a result of treatment, should limit their exposure to alcohol, moderate their nutritional intake so it does not contribute to postmenopausal weight gain, and should adhere to a balanced diet. Nursing education planned for breast cancer patients about dietary issues should ideally be individually tailored, based on a good understanding of the international recommendations and the evidence underpinning them

Factors influencing health promotion activities in midlife and older Australian women with a chronic disease

Background: Chronic diseases including type 2 diabetes are a leading cause of morbidity and mortality in midlife and older Australian women. There are a number of modifiable risk factors for type 2 diabetes and other chronic diseases including smoking, nutrition, physical activity and overweight and obesity. Little research has been conducted in the Australian context to explore the perceived barriers to health promotion activities in midlife and older Australian women with a chronic disease. Aims: The primary aim of this study was to explore women’s perceived barriers to health promotion activities to reduce modifiable risk factors, and the relationship of perceived barriers to smoking behaviour, fruit and vegetable intake, physical activity and body mass index. A secondary aim of this study was to investigate nurses’ perceptions of the barriers to action for women with a chronic disease, and to compare those perceptions with those of the women. Methods: The study was divided into two phases where Phase 1 was a cross sectional survey of women, aged over 45 years with type 2 diabetes who were attending Diabetes clinics in the Primary and Community Health Service of the Metro North Health Service District of Queensland Health (N = 22). The women were a subsample of women participating in a multi-model lifestyle intervention, the ‘Reducing Chronic Disease among Adult Australian Women’ project. Phase 2 of the study was a cross sectional online survey of nurses working in Primary and Community Health Service in the Metro North Health Service District of Queensland Health (N = 46). Pender’s health promotion model was used as the theoretical framework for this study. Results: Women in this study had an average total barriers score of 32.18 (SD = 9.52) which was similar to average scores reported in the literature for women with a range of physical disabilities and illnesses. The leading five barriers for this group of women were: concern about safety; too tired; not interested; lack of information about what to do; with lack of time and feeling I can’t do things correctly the equal fifth ranked barriers. In this study there was no statistically significant difference in average total barriers scores between women in the intervention group and those is the usual care group of the parent study. There was also no significant relationship between the women’s socio-demographic variables and lifestyle risk factors and their level of perceived barriers. Nurses in the study had an average total barriers score of 44.48 (SD = 6.24) which was higher than all other average scores reported in the literature. The leading five barriers that nurses perceived were an issue for women with a chronic disease were: lack of time and interferes with other responsibilities the leading barriers; embarrassment about appearance; lack of money; too tired and lack of support from family and friends. There was no significant relationship between the nurses’ sociodemographic and nursing variables and the level of perceived barriers. When comparing the results of women and nurses in the study there was a statistically significant difference in the median total barriers score between the groups (p < 0.001), where the nurses perceived the barriers to be higher (Md = 43) than the women (Md = 33). There was also a significant difference in the responses to the individual barriers items in fifteen of the eighteen items (p < 0.002). Conclusion: Although this study is limited by a small sample size, it contributes to understanding the perception of midlife and older women with a chronic disease and also the perception of nurses, about the barriers to healthy lifestyle activities that women face. The study provides some evidence that the perceptions of women and nurses may differ and argues that these differences may have significant implications for clinical practice. The study recommends a greater emphasis on assessing and managing perceived barriers to health promotion activities in health education and policy development and proposes a conceptual model for understanding perceived barriers to action.

Young children as regenerative tissue donors : considering the need for legal reform in light of divergent ethical approaches

In Australia, young children who lack decision-making capacity can have regenerative tissue removed to treat another person suffering from a severe or life-threatening disease. While great good can potentially result from this as the recipient’s life may be saved, ethical unease remains over the ‘use’ of young children in this way. This paper examines the ethical approaches that have featured in the debate over the acceptability and limits of this practice, and how these are reflected in Australia’s legal regime governing removal of tissue from young children. This analysis demonstrates a troubling dichotomy within the Australia’s laws that requires decision-makers to adopt inconsistent ethical approaches depending on where a donor child is situated. It is argued that this inconsistency in approach warrants legal reform of this ethically sensitive issue.

Prevalence of malnutrition in Parkinson's disease : a systematic review

Parkinson's disease (PD) patients may be at higher risk of malnutrition because of the symptoms associated with the disease and the side effects of the medication used to manage it. A decline in nutritional status is associated with many adverse outcomes related to health and quality of life. It is not clear, however, to what extent this population is currently affected by malnutrition. The objective of this review was to systematically assess the methodology and outcomes of studies reporting the prevalence of malnutrition in PD patients. Studies that attempted to classify participants with PD into nutritional risk and/or malnutrition categories using body mass index, weight change, anthropometric measures, and nutritional screening and assessment scores were included. The prevalence of malnutrition ranged from 0% to 24% in PD patients, while 3–60% of PD patients were reported to be at risk of malnutrition. There was a large degree of variation among studies in the methods chosen, the definition of malnutrition using those methods, and the detail in which the methodological protocols were reported. The true extent of malnutrition in the PD population has yet to be accurately quantified. It is important, however, to screen for malnutrition at the time of PD diagnosis.