An Emerging Role for Epigenetic Dysregulation in Arsenic Toxicity and Carcinogenesis

Competing Interests Declaration: The authors declare they have no competing financial interests. Abbreviations: AHCY, S-adenosylhomocysteine hydrolase; APL, acute promyelocytic leukemias; As, inorganic arsenic; AS3MT, arsenic (+3 oxidation state) methyltransferase; ChIP-on-chip, chromatin immunoprecipitation-on-chip; ChIP-seq, chromatin immunoprecipitation-sequencing; DEFB1, defensin, beta 1; DNMTs, DNA methyltransferases; H3K4me3, H3K4 tri-methylation; H3K9me2, H3K9 di-methylation; H3K27me3, H3K27 tri-methylation; HATs, histone acetyltransferases; HDACs, histon

Estimating identification uncertainties in CITES ‘look-alike’ species

Achieving sustainability in international wildlife trade encompasses a series of challenges, such as identification uncertainty for taxonomically complex groups. Although CITES has developed a ‘look-alike’ policy to collectively manage trade in morphologically similar species and thus facilitate enforcement, its effective application with regards to the export quota system is questionable. We used a multidisciplinary approach to provide an understating of the trade in a taxonomically complex genus of Malagasy chameleons. An online systematic survey of trade was undertaken to identify which species of Calumma have been the subject of trade. A matching task was employed to calculate identification error rates among species in the genus. Results suggest that the online market for Calumma is thriving, including species with long-standing zero quotas. Identification error rates varied widely, reaching high levels of error for some species pairs here identified as ‘look-alike’ species. Findings suggest manual identification technique has varying reliability, potentially resulting in misidentification by stakeholders within the trade. Such errors have negative consequences for both chameleon conservation and the long-term socio-economic development of Madagascar. An understanding of the patterns of identification error can help tailor future management and policy plans

Evaluating social outcomes of HIV/AIDS interventions: a critical assessment of contemporary indicator frameworks

Introduction: Contemporary HIV-related theory and policy emphasize the importance of addressing the social drivers of HIV risk and vulnerability for a long-term response. Consequently, increasing attention is being given to social and structural interventions, and to social outcomes of HIV interventions. Appropriate indicators for social outcomes are needed in order to institutionalize the commitment to addressing social outcomes. This paper critically assesses the current state of social indicators within international HIV/AIDS monitoring and evaluation frameworks. Methods: We analyzed the indicator frameworks of six international organizations involved in efforts to improve and synchronize the monitoring and evaluation of the HIV/AIDS response. Our analysis classifies the 328 unique indicators according to what they measure and assesses the degree to which they offer comprehensive measurement across three dimensions: domains of the social context, levels of change and organizational capacity. Results and discussion: The majority of indicators focus on individual-level (clinical and behavioural) interventions and outcomes, neglecting structural interventions, community interventions and social outcomes (e.g. stigma reduction; community capacity building; policy-maker sensitization). The main tool used to address social aspects of HIV/AIDS is the disaggregation of data by social group. This raises three main limitations. Indicator frameworks do not provide comprehensive coverage of the diverse social drivers of the epidemic, particularly neglecting criminalization, stigma, discrimination and gender norms. There is a dearth of indicators for evaluating the social impacts of HIV interventions. Indicators of organizational capacity focus on capacity to effectively deliver and manage clinical services, neglecting capacity to respond appropriately and sustainably to complex social contexts. Conclusions: Current indicator frameworks cannot adequately assess the social outcomes of HIV interventions. This limits knowledge about social drivers and inhibits the institutionalization of social approaches within the HIV/AIDS response. We conclude that indicator frameworks should expand to offer a more comprehensive range of social indicators for monitoring and evaluation and to include indicators of organizational capacity to tackle social drivers. While such expansion poses challenges for standardization and coordination, we argue that the complexity of interventions producing social outcomes necessitates capacity for flexibility and local tailoring in monitoring and evaluation

Cohort profile: Risk and risk factors for female breast cancer after treatment for childhood and adolescent cancer: an internationally pooled cohort.

PURPOSE The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer was established in 2018 to address gaps in knowledge of risk and risk factors for breast cancer subsequent to childhood/adolescent cancer by pooling individual patient data from seven cohorts. Initially, the pooled cohort will focus on three clinically relevant questions regarding treatment-related subsequent breast cancer risk in female survivors, which are the risk related to low-dose radiotherapy exposure to the chest, specific chemotherapy agents and attained age. PARTICIPANTS The consortium database includes pooled data on 21 892 female survivors from seven cohorts in North America and Europe with a primary cancer diagnosis at <21 years of age, and survival ≥5 years from diagnosis. FINDINGS TO DATE This is a newly established pooled study. The cohort profile summarised the data collected from each included cohort, including childhood cancer diagnosis information and treatment details (ie, radiotherapy fields and cumulative doses, and chemotherapy agents and cumulative doses for each agent). Included cohorts' follow-up started 1951-1981 and ended 2013-2021, respectively, for a median follow-up duration of 24.3 (IQR 18.0-32.8) years since primary cancer diagnosis. The median age at primary cancer diagnosis was 5.4 (IQR 2.5-11.9) years. And the median attained age at last follow-up was 32.2 (IQR 24.0-40.4) years. In all, 4240 (19.4%) survivors were treated with radiotherapy to the chest and 9308 (42.5%) with anthracyclines. At the end of the follow-up, 835 females developed a first subsequent breast cancer, including 635 invasive breast cancer only, 184 carcinomas in situ only (172 ductal carcinomas in situ and 12 lobular carcinomas in situ), and 16 with both an invasive and in situ diagnosis at the same moment. The cumulative incidences of subsequent breast cancer (both invasive and in situ) 25 and 35 years after primary cancer diagnosis were 2.2% and 6.2%, respectively. FUTURE PLANS The consortium is intended to serve as a model and robust source of childhood/adolescent cancer survivor data for elucidating other knowledge gaps on subsequent breast cancer risk, and risk of other subsequent malignancies (including data on males) in the future

External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials

Should weight loss and maintenance programmes be designed differently for men? A systematic review of long-term randomised controlled trials presenting data for men and women: The ROMEO project.

We systematically reviewed the randomised controlled trial (RCT) evidence for long-term (≥12 months) weight management interventions for obese men in contrast to women to help understand whether programmes should be designed differently for men. We searched 11 databases up to October 2014. Twenty-two RCTs reported data separately for men and women in weight loss or weight maintenance interventions. We found men were under-represented in RCTs of weight loss interventions open to both sexes. Men comprised 36% of participants (4771 from 13,305 participants). Despite this, men were 11% (95% CI 8-14%, p<0.001) more likely to be trial completers compared to women. The trials did not report service user consultation and none were designed to investigate whether men and women responded differently to given interventions. Our meta-analysis of 13 trials showed no significant difference in weight loss between men and women, either for weight loss in kg (p=0.90) or percentage weight loss (p=0.78), although men tended to lose more weight with intensive low fat reducing diets, with or without meal replacements, and structured physical activity/exercise programmes than women. Orlistat was less beneficial for men for weight maintenance. Individual support and tailoring appeared more helpful for men than women. We found evidence that men and women respond differently to, and have different preferences for, varying types of weight management programme. We suggest that it is important to understand men's views on weight loss, as this is likely to also improve the uptake and effectiveness of programmes for men

Use and commercialization of Podocnemis expansa (Schweiger 1812) (Testudines: Podocnemididae) for medicinal purposes in two communities in North of Brazil

<p>Abstract</p> <p>Background</p> <p>Throughout Brazil a large number of people seek out reptiles for their meat, leather, ornamental value and supposed medicinal importance. However, there is a dearth of information on the use of reptiles in folk medicine. In North Brazil, the freshwater turtle, <it>Podocnemis expansa</it>, is one of the most frequently used species in traditional medicines. Many products derived from <it>P. expansa </it>are utilized in rural areas and also commercialized in outdoor markets as a cure or treatment for different diseases. Here we document the use and commercialization of <it>P. expansa </it>for medicinal purposes in the state of Pará, Northern Brazil.</p> <p>Methods</p> <p>Data were gathered through interview-questionnaires, with some questions left open-ended. Information was collected in two localities in Pará State, North of Brazil. In the City of Belém, data was collected through interviews with 23 herbs or root sellers (13 men and 10 women). Attempts were made to interview all animal merchants in the markets visited. In fishing community of the Pesqueiro Beach, interviews were done with 41 inhabitants (23 men and 18 women) and during the first contacts with the local population, we attempted to identify local people with a specialized knowledge of medicinal animal usage.</p> <p>Results</p> <p><it>P. expansa </it>was traded for use in traditional medicines and cosmetics. Fat and egg shells were used to treat 16 different diseases. Turtle fat was the main product sold. The demand for these products is unknown. However, the use of this species in folk medicine might have a considerable impact on wild population, and this must be taken into account for the conservation and management of this species.</p> <p>Conclusion</p> <p>Our results indicated that the use and commercialization of <it>P. expansa </it>products for medicinal purposes is common in North of Brazil. More studies regarding the use and commerce of Brazilian turtles are urgently needed in order to evaluate the real impact of such activities on natural populations. We hope that our findings about the trade and use of <it>P. expansa </it>in folk medicine will motivate further studies on the use of animals in folk medicine and its implications for conservation.</p

European code against cancer 4th edition: 12 ways to reduce your cancer risk

This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer