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AbstractThis article explores a program designed to encourage a structure of local development committees (LDCs) to galvanize possibilities for residents’ exercise of political agency to engender social learning for shared decision-making for development through higher education in Haiti. It also examines a grassroots effort among a group of rural Haitian farmers to develop a local response to changing agricultural conditions aimed at improving their crop production and yields. We compare and contrast our findings concerning these endeavors with those of a government-sponsored LDC program implemented in Jamaica in recent years. We conclude that one of our Haitian cases, which paradoxically did not involve a formal LDC, stimulated ordinary and transformative learning in support of what Polanyi called a polycentric order among the farmers involved (Mezirow, J., 2000, Learning to think like an adult, in J. Mezirow, ed, Learning as transformation: critical perspectives on a theory in progress, San Francisco, CA: Jossey-Bass Publishers, pp. 3–33; Polanyi, M., 1965, The Logic of Liberty: Reflections and rejoinders, Chicago: University of Chicago Press. Original work published 1951).

Background: The most effective agents in the treatment of breast cancer have a common side effect, the hair loss. Some studies reported a reduction of hair loss with the use of the scalp cooling device. Indeed, it decreases the drug accumulation in the hair follicles. We report our preliminary experience with a scalp cooling device in reducing chemotherapy-induced alopecia and related distress in breast cancer patients undergoing adjuvant chemotherapy. Methods: Hair loss grading and treatment tolerability were evaluated during chemotherapy every 21 days and 3 weeks after the last cycle of chemotherapy via Dean's scale by patients and operators and a comfort analogic scale by patients. We administered the Hospital Anxiety and Depression Scale questionnaire at the baseline and at the end of treatment to assess the distress related to chemotherapy- induced alopecia. Results: Among the 46 patients identified, 27 accepted the device. The eligible chemotherapy regimens included docetaxel+cyclophosphamide (TC), doxorubicin+cyclophosphamide (AC) and paclitaxel (P) weekly+trastuzumab (T). 24 pts (89%) completed the treatment; 3 pts (11%) treated with AC prematurely interrupted use of the scalp-cooling device due to inefficacy. After the last cycle of chemotherapy, the number of patient who perceived a HL < grade 2 was 16 (59%). The hair retention reported by operators has been higher (78%). 81.5% of patients well tolerated the treatment. Conclusion: In our study, the scalp-cooling device reduced chemotherapy-induced alopecia in taxane- based chemotherapy. Furthermore, it suggests a discordance in hair loss perception between patients and operators.

ABSTRACTPolycystic ovary syndrome (PCOS) is a common disorder with a high phenotypic variability. Frequently, it is associated with a mild to moderate insulin resistance (IR) caused by an interaction between polygenic diathesis and the environment. However, PCOS may be a complication of an underlying syndrome of severe IR such as insulin receptor autoantibodies, mutations in the insulin receptor or in the signalling pathway downstream from the insulin receptor or, most frequently, a defect in function or in the development of the subcutaneous adipose tissue. Such conditions are clinically characterized by lipodystrophy. Lipodystrophy in some cases is produced by a single-gene defect. In our experience, PCOS secondary to a missense mutation in the LMNA gene, known as familial partial lipodystrophy type 2 (FPLD2), is the most frequent form of PCOS secondary to severe IR due to genetically determined lipodystrophy. These forms should be identified as they benefit from tailored therapies.

The aim of the present study was to evaluate the activity and tolerability of low-dose oral ethinylestradiol and luteinizing hormone-releasing hormone analogue with concomitant low-dose acetylsalicylic acid for advanced castrate-resistant prostate cancer. Of the 32 enrolled patients, a prostate-specific antigen response was observed in 19 (59.3%). The median progression-free survival was 9.4 months. Treatment was generally well tolerated, and no grade 3/4 toxicity was observed.

ABSTRACTBackground: Several randomized phase III trials in neuroendocrine tumors (NETs) showed the clinical role of new targeted agents and their impact on tumor response and outcome of whose patients affected by advanced NET. In this study, we summarize the available clinical data related to clinical efficacy of targeted therapies in the treatment of advanced NETs. Methods: A meta-analysis of randomized studies in accordance with the PRISMA guidelines was performed after searching the databases of PubMed, the Cochrane Library, and the ASCO University Meeting for relevant publications. Results: One thousand 9 hundred and 8 cases were included in the meta-analysis; among these, 1012 were in the experimental arm and 896 were in the control arm. The pooled analysis of the use of target agents in NETs revealed significantly increased of progression free survival compared to control group (hazard ratio = 0.59, 95% CI:0.42-0.84; P = 0.003). Subgroup analysis of patients according to tumor site showed a difference in favor of pancreatic neuroendocrine tumors. Moreover, targeted therapies improved the overall survival (hazard ratio = 0.79, 95%CI: 0.63-0.98; P = 0.03), and response rate (hazard ratio = 3.33, 95% CI 2.02-5.49; P < 0.00001) in all types of NETs. Conclusion: Our analysis supports the routine use of targeted agents for treatment of neuroendocrine tumors with particular regards to the pancreatic neuroendocrine tumors.

Objective:This study was designed to assess the steroid profiling by liquid chromatography coupled with tandem mass spectrometry in PCOS women with different phenotypes.Design:Cross-sectional study.Setting:University hospital of Bologna, Italy.Patients and Methods:A total of 156 PCOS women and 141 controls comparable for age were investigated. All underwent a steroid profiling by liquid chromatography coupled with tandem mass spectrometry. Metabolic parameters were also investigated and hirsutism was measured by the modified Ferriman-Gallwey (mF-G) score.Results:Three distinct phenotypes were initially defined according to the combination of hirsutism (mF-G ≥ 8) and/or high testosterone (T) (HA), oligo-amenorrhea (OA), and polycystic ovarian morphology (PCOm); OA + PCOm (n = 43), HA + OA (n = 65), and HA + OA + PCOm (n = 45). T, androstenedione (A), and free androgen index (FAI) levels progressively increased in the 3 PCOS phenotypes with respect to the controls, with the highest values in the HA + OA + PCOm phenotype. The various combinations of hirsutism, high T, high A, and high FAI made it possible to categorize the 3 original phenotypes into 8 hyperandrogenic subgroups, characterized by divergent additional steroid profile and metabolic pattern. A total of 90% of patients with PCOS thus proved hyperandrogenic. Interestingly, half the PCOS women originally classified as having the OA-PCOm phenotype were categorized in a hyperandrogenic subgroup. No significant correlation was found between T, A, and the mF-G score. In contrast, significant correlation was found between A and both T and FAI.Conclusions:This study provides evidence that, by including a steroid profile in the definition of hyperandrogenemia, the majority of women with PCOS are hyperandrogenic, although a clinical and biochemical heterogeneity exists. In addition, these data demonstrate that hirsutism and high androgen levels cannot be used indifferently to define hyperandrogenism.

This article discusses the roles, challenges and opportunities of non-Indigenous academics working at the interface of Indigenous and non-Indigenous knowledges. Sustainability scientists have both questioned and advocated for cross-cultural research, and in this article we reflect on what working across different ways of knowing entails for non-Indigenous researchers at the professional, personal and epistemological level. Grounded on our experiences of on-going engagement with Indigenous communities, this article explores multiple pathways of taking Indigenous knowledges seriously while working in “Western” academic settings. In doing so, it highlights issues around the role and responsibility of non-Indigenous researchers in decolonising the (re)production of knowledges and the multiple contexts in which this can take place in sustainability science. It then deals with some of the challenges and ethical dilemmas we have encountered along the way, mainly with regards to issues of representation, translation in a broader sense, participation, and authority. Finally, this article discusses some of the epistemological consequences of engaging in such work, and how despite being fraught with tensions and contradictions, it can help to foster spaces of plural co-existence.

This paper analyzes the Kayapó's struggle against large-scale hydroelectric development in the Brazilian Amazon. Whereas environmental justice efforts that were launched in the 1980s against a similar dam project were met with success, efforts in the past several years to halt the Belo Monte dam, to date, have not stopped licensing or construction. And in spite of the rise of regional and international indigenous movements, environmental awareness, and the democratic turn in Brazil, the building continues. This paper examines the different processes the Kayapó have used to address environmental justice issues, especially their deployment of identity politics as a resistance strategy to achieve recognitional justice. As the new wave of “participation” as an environmental governance norm places most emphasis on procedural forms of justice, a focus on procedure, such as the participation offered in Environmental Impact Assessment processes, does not adequately address and sometimes masks underlying issues of recognitional injustice. I show that these policies to ensure participation have had uneven impacts, and Kayapó strategies rooted in identity politics have had mixed results in achieving desired goals for justice. At the same time large-scale organized activist and resistance provide a productive counterspace for marginalized communities to create a public record of their concerns, even if the effectiveness of the protests have varied over time. While a continued robust civil society is promising, it remains a concern that despite the rise procedural forms of justice, recognitional justice remains elusive for the Kayapó.

Abstract: We evaluated the effect of transdermal norethisterone acetate (NETA) versus oral medroxyprogesterone acetate (MPA) on the lipids of 28 postmenopausal women taking hormonal replacement therapy for climacteric symptoms. All the 28 patients were using conventional patches releasing 0.050 mg of estradiol per day continuously. However, while one group of 14 patients received transdermal NETA (0.25 mg/day) for 14 days of the cycle, the other group of 14 patients received oral MPA (10 mg/day) for the same number of days. The patients were randomly allocated to one of the two groups. The treatment cycles were repeated for 12 months. There was no significant difference between the two treatment groups for compliance and for incidence of side effects. Both hormonal replacement therapies were equally effective in relieving climacteric symptoms. All the patients underwent serum lipid assays twice, the first time before starting treatment and then again during the progestogen phase of the 12th and last cycle. Serum total cholesterol (TC), low-density lipoprotein (LDL-C), and triglyceride levels did not change significantly during both treatments. Transdermal estradiol associated with oral MPA significantly reduced high-density lipoprotein (HDL-C) by 17.9 (p < 0.05) and significantly increased LDL-C/HDL-C and TC/HDL-C risk ratios by 61.7 (p < 0.05) and 33.1 (p < 0.05), respectively. In contrast, administration of the transdermal NETA did not significantly affect HDL-C levels (– 1.9 of decrease) and, consequently, the risk ratios were minimally altered, with 3.3 and 6.0 increases for TC/HDL-C and LDL-C/HDL-C, respectively. There was a statistically significant difference (p < 0.05) in HDL-C net changes between MPA and NETA treatments (+ 8.5 and - 8.0 mg/dl, respectively). We can therefore conclude that the association of transdermal NETA with transdermal estradiol elicits a relatively benign impact on lipoprotein profile in comparison to oral MPA association

To compare the influence of spontaneous and surgical menopause on bone loss, we measured with dual x-ray absorptiometry (DXA) the spinal bone mineral density (BMD) in 513 women recruited at the Menopause Clinic at Ferrara University Hospital. One hundred one women were premenopausal with regular menstrual cycles; 185 women were perimenopausal with irregular periods or with absence of menstruation for <11 months; 160 women had spontaneous menopause with at least 12 months of amenorrhea; 67 women had a surgical menopause (hysterectomy with bilateral oophorectomy) prior to which they had regular menstruation. To minimize the age bias on BMD, all postmenopausal patients were selected to have the age range at menopause corresponding with the chronological age range (45–53 years) of premenopausal women used as reference. Moreover, to evaluate the influence of time since menopause on BMD, all postmenopausal women were stratified in five categories according to time lapsed since their last menses or oophorectomy. BMD values of spontaneous and surgical menopause do not appear to differ significantly (0.908 4pM 0.146 and 0.885 ± 0.129 g/cm2, mean ± SD). However, the difference between the menopausal groups becomes evident when BMD results take into account the interval since menopause. After 61–144 months of amenorrhea, women who had undergone spontaneous menopause had a cumulative bone loss of 21.8 in comparison with premenopausal BMD, whereas women who had undergone surgical menopause had a bone loss of 25.8. The yearly percentage of bone loss values of surgical menopause (ranging from 3.72 to 7.93) settled to ∼1 per year after 5 years from oophorectomy, whereas the percentage values of spontaneous menopause (ranging from 1.75 to 4.65) settled to 1 per year after 3 years since the last menses. The difference between bone loss rates of spontaneous and surgical menopause, evaluated by comparison of regression coefficients (— 0.027 and —0.051, respectively) of linear regressions of BMD values on time since menopause, was statistically significant (p≤ 0.001). Odds ratio (OR) of osteopenia (as Tscore, ≥ — 1) was significantly higher in surgical menopause (OR, 10.36; CI, 24.69–4.34) compared with spontaneous menopause (OR, 7.11; CI, 14.73–3.43). Our data support the evidence that women undergoing bilateral oophorectomy while still menstruating are at a higher risk of osteopenia than women undergoing menopause spontaneously.

To assess the effect of daily dietary supplementation of soy protein isolate powder on hot flushes in postmenopausal women.

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Introduction: Recently the combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the aromatase inhibitor exemestane has been shown to double the progression-free survival rate in advanced breast cancer. However, the effect of the interrelated pathways of hypoxia-inducible factor-1α (HIF-1α) and mTOR signaling, both of which are associated with a more aggressive breast cancer phenotype and endocrine resistance, on response in the neoadjuvant setting is unknown. We, therefore, have investigated the influence of these pathways with the aim of better defining those patients most likely to benefit from an endocrine-based therapy associated with/without mTOR inhibitors. Patients and Methods: A total of 107 women with T2-4 N0-1 and estrogen receptor-positive breast cancer were randomly assigned to 6 months of primary letrozole (2.5 mg/daily) (LET) or LET plus oral “metronomic” cyclophosphamide (50mg/daily) (LET-CYC). Phospo-mTOR and HIF-1α were evaluated in tumor specimens collected before and after treatment using a tissue microarray format. Results: LET-based therapy induced a downregulation of phospho-mTOR and HIF-1α expression (P = .0001 and P < .004, respectively). The reduction of HIF-1α expression observed was positively correlated with phospho-mTOR reduction (P < .03); however, no treatment interaction between the two proteins was detected. HIF-1α expression was significantly modulated by the treatment (P < .004) with a reduction both in the LET arm (45%, n = 36/80) (P = .05) and LET-CYC arm (55%, n = 44/80) (P = .04). HIF-1α reduction showed a relationship with clinical response confined in LET arm only (P < .03). Conclusions: In this neoadjuvant population, LET was able to modulate the phospho-mTOR and HIF-1α pathways and may define a subpopulation of nonresponders who may be most likely to benefit from mTOR inhibitors.

Breast cancer represents a heterogeneous group of diseases with varied biological features, behavior, and response to therapy; thus, management of breast cancer relies on the availability of robust predictive and prognostic factors to support therapy decision-making. Traditionally, neoadjuvant treatment for breast cancer was preserved for locally advanced, converting an inoperable to a surgical resectable cancer. Neoadjuvant trials, additionally, offer: 1) the opportunity to evaluate new treatment options in a faster way and with fewer patients than large adjuvant trials; 2) to identify and validate the prognostic and predictive value of a marker with its association with clinical outcome in relation to the administered treatment. In this setting, thanks to new, affordable technologies which help to detail the molecular profiles of tumors, new trial designs based on new target therapies, like window-of-opportunity, are also suggested, as they represent the chance to identify tumor sensitivity or to overcome tumor resistance to the treatment used, based on its interaction with tumor biology in early tumor stages. However, clinicians and researchers should pay particular attention: In this setting, the safety of patients is paramount, given the exposure of potentially curable patients to investigational agents with limited safety experience, the definition of the study population and the study design, such as adaptive strategies, should limit patient exposure to ineffective agents, and intensify safety monitoring in the course of the treatment. Here, issues related to outcome determination in breast cancer, including some critical points of view, are presented.

Background and aim Epithelial ovarian cancer (EOC) is characterized by few early symptoms, presentation at an advanced stage and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. Recently, not only tumor antigens but also antibodies produced in response to the disease have been considered as biomarkers for early detection of EOC. Kallikrein-related peptidases (KLK) are secreted serine proteases implicated in tumor progression. A recent study has demonstrated that the serum KLK5 (sKLK5) concentration is elevated in patients with EOC, but the existence of a humoral immune response to KLK5 has not been studied. Moreover, the presence of sKLK5 in other ovarian diseases has not been clearly determined. The aim of this study was to examine the serological existence of anti-KLK5 antibodies, bound to KLK5 into circulating immune complexes (KLK5-lgM and KLK5-lgG ICs) or free antibodies (IgM and IgG), in healthy women and in patients with benign ovarian masses, borderline tumors and EOC. In the same patients we also assessed the levels of sKLK5.Materials and methods Serum samples were obtained from 50 healthy women, 50 patients with benign ovarian masses, 1 7 patients with borderline ovarian tumors, and 50 patients with EOC, before any surgical or chemotherapeutic treatment. Patients with a past or concomitant history of malignancy were excluded from the study. KLK5-lgM and KLK5-lgG ICs were detected with a sandwich ELISA using a polyclonal anti-KLK5 antibody (R&D Systems, Minneapolis, MN, USA) in capture and an anti-hlgM-HRP antibody (Sigma Aldrich Inc, St Louis, MO, USA) or anti-hlgG-HRP antibody (Sigma) in detection. Free anti-KLK5 IgM and IgG were detected with an indirect ELISA using recombinant human kallikrein 5 (R&D) in coating and anti-hlgM-HRP or anti-hlgG-HRP antibodies in detection. Finally, sKLK5 was detected with a sandwich ELISA, using a polyclonal anti-KLK5 antibody in capture and a biotinylated poyclonal anti-hK5 antibody (R&D) in detection.Results Elevated levels of KLK5-lgM and KLK5-lgG ICs were detected in 11% of patients with borderline tumors and 8% of patients with EOC, whereas elevated levels of free anti-KLK5 IgM and IgG were found in 1 7% of patients with borderline tumors and 8% of patients with EOC, resulting in a 100% specificity both in healthy women and patients with benign ovarian disease. Patients with EOC showed higher levels of sKLK5, whereas the protein was almost undetectable in women with other ovarian tumors (Kruskal-Wallis test: p<0.001). In particular, at 95% specificity in healthy controls, 52% of patients with EOC showed high sKLK5 levels. Interestingly, both the immune complexes and the free antibodies were elevated in patients with undetectable sKLK5 levels and borderline tumors with intraepithelial carcinoma.Conclusion Our results showed that sKLK5 is a potential new biomarker to be used in combination with other biomarkers for EOC detection. Moreover, the combination of sKLK5 and antibodies reactive to KLK5 might improve the sensitivity in EOC detection since these antibodies may be found in patients without detectable sKLK5 levels. In conclusion, the identification of an immune response that generally precedes the presence of high levels of circulating antigens may represent a novel useful tool for early EOC detection.