BackgroundIn the past decade fish farming has become an important economic activity in the Occidental Brazilian Amazon, where the number of new fish farms is rapidly increasing. One of the primary concerns with this phenomenon is the contribution of fishponds to the maintenance and increase of the anopheline mosquito population, and the subsequent increase in human malaria burden. This study reports the results of a 2-year anopheline abundance survey in fishponds and natural water bodies in a malaria-endemic area in northwest Brazil. The objective of this study was to investigate the contribution of natural water bodies (rivers, streams, creeks, ponds, and puddles) and artificial fishponds as breeding sites for Anopheles spp. in Mâncio Lima, Acre and to investigate the effect of limnological and environmental variables on Anopheles spp. larval abundance.MethodsNatural water bodies and fishponds were sampled at eight different times over 2 years (early, mid and late rainy season, dry season) in the Amazonian town of Mâncio Lima, Acre. Anopheline larvae were collected with an entomological dipper, and physical, chemical and ecological characteristics of each water body were measured. Management practices of fishpond owners were ascertained with a systematic questionnaire.ResultsFishponds were four times more infested with anopheline larvae than natural water bodies. Electrical conductivity and the distance to the nearest house were both significant inverse predictors of larval abundance in natural water bodies. The density of larvae in fishponds raised with increasing border vegetation. Fishponds owned by different farmers varied in the extent of anopheline larval infestation but ponds owned by the same individual had similar infestation patterns over time. Commercial fishponds were 1.7-times more infested with anopheline larvae compared to fishponds for family use.ConclusionsThese results suggest that fishponds are important breeding sites for anopheline larvae, and that adequate management activities, such as removal of border vegetation could reduce the abundance of mosquito larvae, most importantly Anopheles darlingi.

Since 2015 Brazil has experienced the social repercussions of the Zika virus epidemic, thus raising a debate about: difficulties of diagnosis; healthcare access for children with Zika Congenital Syndrome (ZCS); the search for benefits by affected families; social and gender inequalities; and a discussion on reproductive rights, among others. The objective of this article is to analyse access to specialized health services for the care of children born with ZCS in three North-eastern states of Brazil. This is an exploratory cross-sectional study which analyses recorded cases of microcephaly at the municipal level between 2015 and 2017. Most of the cases of ZCS were concentrated on the Northeast coast. Rio Grande do Norte and Paraiba had the highest incidence of microcephaly in the study period. The states of Bahia, Paraiba and Rio Grande do Norte were selected for their high incidence of microcephaly due to the Zika Virus. Socio-territorial vulnerability was stratified using access to microcephaly diagnosis and treatment indicators. The specialized care network was mapped according to State Health Secretaries Protocols. A threshold radius of 100 km was stablished as the maximum distance from municipalities centroids to specialised health care for children with microcephaly. Prenatal coverage was satisfactory in most of the study area, although availability of ultrasound equipment was uneven within states and health regions. Western Bahia had the lowest coverage of ultrasound equipment and lacked health rehabilitation services. ZCS's specialized health services were spread out over large areas, some of which were outside the affected patients' home municipalities, so displacements were expensive and very time consuming, representing an extra burden for the affected families. This study is the first to address accessibility of children with microcephaly to specialised health care services and points to the urgent need to expand coverage of these services in Brazil, especially in the northeastern states, which are most affected by the epidemic.

1572 Background: The rising global burden of breast cancer (BC) in developing countries demands innovative interventions to accelerate progress in cancer control and prevention. Given the high rates of aggressive young onset breast cancer in Brazil, we sought to examine genetic susceptibility to the disease in the State of Bahia in the Northeast of Brazil, which has the largest population of African descendants. Methods: We screened cases, high-risk breast cancer patients with and without family history of breast cancer, and controls (cancer-free women) for twenty-eight breast cancer susceptibility genes using a validated targeted capture and multiplex sequencing approach – the BROCA panel. Each participant gave informed consent under IRB approved protocols and provided clinical-pathological and epidemiological data. Results: A total of 292 consecutive and unrelated individuals (173 cases and 119 controls) were included. Nearly 2/3rds of the cases (116/173) and about 90% of the controls (108/119) self-reported as African-descendant. Mutations considered pathogenic were identified in 37 (21.4%) cases and in one control (0.84%, RAD51C c.266insA), OR = 27.75 and p = 0.008. The mutated genes in cases were BRCA1 (in 12 patients), BRCA2 (10), ATM (3), PALB2 (3), BRIP1 (3), BRCA2/ BARD1 (1), FAM175A (1), FANCM (1), NBN (1), SLX4 (1) and TP53 (1). Three recurrent mutations accounted for 12.4% (9/37) of the total: 3 BRCA1 c.3331_3334delCAAG (known European mutation), 3 BRCA1 c.211A > G (known Galician mutation), and 3 PALB2c.1671_1674delTATT (novel mutation). Conclusions: Mutations in BRCA1 and BRCA2 (64.85%) or another breast cancer gene (35.15%) occur in one in five high-risk breast cancer patients in the largest study of Northeastern Brazil to date, and a significant proportion were recurrent mutations of European origin, which can be explained by the admixture pattern of the Brazilian population. This result underscores the importance of using multigene panel in cancer genetic epidemiologic research of understudied populations where unexpected findings, such as the recurrent and novel variant in PALB2 c.1671_1674delTATT, can be detected.

Purpose There is a paucity of data on the spectrum and prevalence of pathogenic variants among women of African ancestry in the Northeast region of Brazil. Methods We performed BROCA panel sequencing to identify inherited loss-of-function variants in breast cancer susceptibility genes among 292 Brazilian women referred to a single institution cancer risk assessment program. Results The study included a convenient cohort of 173 women with invasive breast cancer (cases) and 119 women who were cancer-free at the time of ascertainment. The majority of the women self-reported as African-descended (67% for cases and 90.8% for unaffected volunteers). Thirty-seven pathogenic variants were found in 36 (20.8%) patients. While the spectrum of pathogenic variants was heterogeneous, the majority (70.3%) of the pathogenic variants were detected in high-risk genes BRCA1, BRCA2, PALB2, and TP53. Pathogenic variants were also found in the ATM, BARD1, BRIP1, FAM175A, FANCM, NBN, and SLX4 genes in 6.4% of the affected women. Four recurrent pathogenic variants were detected in 11 patients of African ancestry. Only one unaffected woman had a pathogenic variant in the RAD51C gene. Different risk assessment models examined performed well in predicting risk of carrying germline loss-of-function variants in BRCA1 and/or BRCA2 in breast cancer cases. Conclusion The high prevalence and heterogenous spectrum of pathogenic variants identified among self-reported African descendants in Northeast Brazil is consistent with studies in other African ancestry populations with a high burden of aggressive young onset breast cancer. It underscores the need to integrate comprehensive cancer risk assessment and genomic testing in the management of newly diagnosed Black women with breast cancer across the African Diaspora, enabling improved cancer control in admixed underserved and understudied populations.

Background: PARP1/2 inhibitors (PARPi) are active anti-cancer agents in BRCA1 or BRCA2 mutation carriers (BRCA) with advanced breast or ovarian cancer. However, not all BRCA-tumors respond to PARP blockade, and eventually all develop acquired resistance. Little is known about clinically relevant mechanisms of PARPi resistance in BRCA-breast cancer. Here, we sought to identify biomarkers correlating with primary and acquired resistance to PARPi using PDX derived from both the early disease and the metastatic setting. Methods: We have developed a panel of PDX from patients harboring germline BRCA1 or BRCA2 mutations, namely from 12 primary and advanced breast cancer and 1 high-grade serous metastatic ovarian cancer (HGSOC). The antitumor activity of the PARP1/2 inhibitor olaparib as single agent (50 mg/kg) was assessed in all models. To study the mechanisms of acquired resistance, the olaparib-sensitive PDXs were exposed to olaparib for >100 days, until individual tumors regrew. The tumor's capacity to repair DNA double strand breaks was estimated by quantification of the BRCA1 and RAD51 nuclear foci in the S-phase of the cell cycle. We investigated the correlation between the tumor's BRCA1/RAD51 foci formation and sensitivity to olaparib, and also identified potential genetic modifiers of PARPi sensitivity by targeted sequencing. Results: Four out of 13 PDX (31%) treated with single agent olaparib exhibited tumor regression or disease stabilization. Nuclear BRCA1/RAD51 foci formation correlated with PARPi resistance in six BRCA1 PDX models investigated, either with primary or acquired resistance. No reversions in BRCA1/2 mutations were identified as the mechanism of olaparib resistance. We identified four potential genetic modifiers of PARPi sensitivity and the corresponding validating studies will be presented. Conclusions: Among our BRCA PDX, reactivation of HR functionality is a frequent event that is associated with PARPi resistance and seems to occur through mechanisms other than secondary mutations in BRCA1/2 in contrast to what it has been reported for HGSOC. Citation Format: Cruz C, Bustos Ld, Gris A, Palafox M, Castroviejo M, Llop A, Morancho B, Diez O, Gutiérrez S, Caratú G, Prudkin L, Bruna A, Caldas C, O'Connor MJ, Rubio IT, Arribas J, Baselga J, Cortes J, Serra V, Balmaña J. PARP inhibition in breast and ovarian patient-derived tumor xenografts (PDX) harboring germline BRCA1/2 mutations unveils mechanisms of primary and acquired resistance that restore homologous recombination (HR). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-07-05.

Background Almost 20% of the US population are housing insecure (HI) due to inadequate living conditions, imbalanced costs to income, nonsustainable shelter, or overcrowding. Housing insecure and physical trauma share similar risk factors, but their direct association is not well elucidated. The objective of our study was to determine the prevalence of HI in survivors of traumatic injury. Methods We conducted a prospective cohort study at an urban, level 1 trauma center. A survey on social determinants of health was administered to adult patients, and demographic, injury specifics, and clinical outcomes data were collected. HI was defined by affirmative answers to questions related to history of homelessness or concern about sustainable shelter. The cohort was stratified by HI; groups were compared using the Mann-Whitney U and Fisher exact tests, as appropriate. Results Of 116 study participants, four were excluded due to missing data. Of the 112, 42 (37.8%) reported HI and most were black (69%) males (73.8%). There were no demographic differences between groups. Conversely, HI patients had a higher rate of penetrating traumatic injury (34.1% vs 14.5%, P-value = .03) and were significantly less educated compared to secure participants ( P-value = .03) [no degree (26.2% vs 10.3%), high school degrees (21.4% vs 41.2%)] with concomitant illicit drug use (63.4% vs 27.9%, P < .001), and history of addiction (52.4% vs 7.2%, P < .001). Conclusion HI far exceeds national averages in our cohort. Although difficult to ascertain a cause-effect relationship, HI may be a modifiable risk factor for trauma that negatively influences outcomes.

No abstract

No abstract