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Migratory species are the most important commercial fishes in the Amazon. They are also now the most threatened directly by some combination of overfishing, floodplain deforestation, and dam construction. Limited governmental monitoring and implemented regulations impede adequate management of the fisheries at adequate scale. We summarize the current stock status of the three most heavily exploited long-distance migratory species, which are two goliath catfishes (Brachyplatystoma rousseauxii and B. vaillantii) and the characiform Colossoma macropomum. In addition, we analyze impacts beyond overfishing on these species. Our results indicate: (i) the overfishing trends for these important species are either ominous or indicate the verge of collapse of the commercial fisheries based on them, and (ii) a dangerous synergy between overfishing, hydroelectric dams, and floodplain deforestation further challenge fisheries management of migratory species in the Amazon. We propose eight direct governmental actions as a proactive approach that addresses the main impacts on the fisheries. We consider that the most practical way to assess and manage overfishing of migratory species in the short run in an area as large as the main commercial fishing area in the Amazon is at market sites where enforced regulations can control fish catch. The management of the three species considered here has implications beyond just their sustainability. Their management would represent a paradigm shift where the governments assume their legal responsibilities in fishery management. These responsibilities include regulation enforcement, data collecting, inter-jurisdictional cooperation to protect migratory species at realistic life history scales, mitigation of the Madeira dams to assure goliath catfish passage to the largest western headwater region, and recognition of monitoring and managing wetland deforestation for the protection of fish and other aquatic and terrestrial biodiversity.

BACKGROUND:Asthma is associated with an increased cardiovascular disease (CVD) risk in adults, but the impact of asthma and atopic conditions on CVD risk in children is less well established. We hypothesized that children in the Childhood Origins of Asthma (COAST) Cohort with asthma and atopic conditions would have early carotid arterial injury. METHODS:The COAST study is a longitudinal birth cohort of children at increased risk of developing asthma. Children underwent ultrasonography measuring far wall right carotid bifurcation (RCB) and common carotid artery (RCCA) intima-media thickness (IMT; a measure of arterial injury). Multivariable linear regression models adjusted for age, gender, race, blood pressure, and body-mass index were used to assess associations of asthma and markers of arterial injury. RESULTS:The 89 participants were a mean (standard deviation) 15.3 (0.6) years old and 42% were female; 28 asthmatics had atopic disease, 34 asthmatics were without other atopic disease, and 15 non-asthmatics had atopic disease. This study population was compared to 12 controls (participants free of asthma or atopic disease). Compared to controls (589 μm), those with atopic disease (653 μm, p = 0.07), asthma (649 μm, p = 0.05), or both (677 μm, p = 0.005) had progressively higher RCB IMT values (ptrend = 0.011). In adjusted models, asthmatic and/or atopic participants had significantly higher RCB IMT than those without asthma or atopic disease (all p≤0.03). Similar relationships were found for RCCA IMT. CONCLUSION:Adolescents with asthma and other atopic diseases have an increased risk of subclinical arterial injury compared to children without asthma or other atopic disease.

To prevent obesity, it is important to assess dietary habits through self-reported energy intake (EI) in children. We investigated how EI is associated with body mass index and which elements of dietary habits and status are associated with EI among African-American (AA) children.We assessed and included data from 218 10-14-year-old AA children in Baltimore, MD, USA. EI was calculated using a food frequency questionnaire. The basal metabolic rate (BMR) was used as the predicted minimal rate of energy expenditure of children. A fully adjusted multiple logistic regression was used to determine the prevalence of obesity (≥ 95th BMI-for-age percentile) among the quartiles of EI/BMR ratio using the third quartile for the reference. The differences in the age-adjusted mean EI/BMR among the categories of dietary habits, social support, and socio economic status were analyzed using a general linear model.Children with the lowest EI/BMR had significantly higher adjusted odds ratio (aOR) of obesity as compared to those in the third quartile of EI/BMR (boys aOR 4.3; 95% confidence interval 1.08, 20 and girls aOR 4.1; 1.02, 21). In girls, the adjusted mean EI/BMR in the group that prepared food less than the means (3.8 times/week) was significantly lower than the group that prepared food over the means (P = 0.03). Further, the group that reported eating breakfast under 4 times/week indicated an adjusted mean EI/BMR lower than the group that ate breakfast over 5 times/week in both sexes.When EI was under-reported with reference to BMR, we may observe high prevalence of obesity. Further, food preparation by children and frequent consumption of breakfast may instill food cognition with usual dietary habits. Therefore, holistic assessments including dietary habits are required to examine self-reported food intake especially among overweight/obese children.

Fulvestrant is a selective estrogen receptor antagonist. Based on the measured growth inhibition of 60 human cancer cell lines (NCI60) in the presence of fulvestrant, as well as the baseline gene expression of the 60 cell lines, a gene expression score that predicts response to fulvestrant was developed. The score is based on 414 genes, 103 of which show increased expression in sensitive cell lines, while 311 show increased expression in the non-responding cell lines. The sensitivity genes primarily sense signaling through estrogen receptor alpha, whereas the resistance genes modulate the PI3K signaling pathway. The latter genes suggest that resistance to fulvestrant can be overcome by drugs targeting the PI3K pathway. The level of this gene expression score and its correlation with fulvestrant response was measured in a panel of 20 breast cancer cell lines. The predicted sensitivity matched the measured sensitivity well (CC = -0.63, P = 0.003). The predictor was applied to tumor biopsies obtained from a Phase II clinical trial. The sensitivity of each patient to treatment with fulvestrant was predicted based on the RNA profile of the biopsy taken before neoadjuvant treatment and without knowledge of the subsequent response. The prediction was then compared to clinical response to show that the responders had a significantly higher sensitivity prediction than the non-responders (P = 0.01). When clinical covariates, tumor grade and estrogen receptor H-score, were included in the prediction, the difference in predicted senstivity between responders and non-responders improved (P = 0.003). Using a pre-defined cutoff to separate patients into predicted sensitive and predicted resistant yielded a positive predictive value of 88% and a negative predictive value of 100% when compared to clinical data. We conclude that pre-screening patients with the new gene expression predictor has the potential to identify those postmenopausal women with locally advanced, estrogen-receptor-positive breast cancer most likely to respond to fulvestrant.

BACKGROUND: There are an estimated 9.4 million cases of foodborne illness each year. Consumers have a key role in preventing foodborne illness, but differences in the practice of food safety behaviors exist, increasing risk for certain groups in the population. Identifying groups who are more likely to practice risky food safety behaviors can assist in development of interventions to reduce the disease burden of foodborne illnesses. The purpose of this investigation was to examine the relationships of health indicators and psychosocial factors with self-reported food safety behaviors. METHODS AND FINDINGS: Data were collected via questionnaire from 153 African Americans who attend churches in Baltimore City. Individuals reported high overall concern with food safety (mean score: 0.80±0.49 on a scale of -1 to +1) and practiced food safety behaviors with moderate overall frequency (mean score: 5.26±4.01 on a scale of -12 to +12), with considerable variation in reported frequencies depending on the food safety behavior. After adjusting for demographic variables, food safety behaviors were significantly associated with BMI and psychosocial variables. Riskier food safety behaviors were associated with higher body mass index (BMI) (β = -0.141 95%CI (-0.237, -0.044), p = 0.004). Self-efficacy for healthy eating (standard β [std. β] = 0.250, p = 0.005) and healthy eating intentions (std. β = 0.178, p = 0.041) were associated with better food safety behaviors scores. CONCLUSIONS: These results show important relationships between weight-related health indicators, psychosocial factors and food safety behaviors that have not previously been studied. Interventions tailored to higher-risk populations have the potential to reduce the burden of food-related illnesses. Additional studies are needed to further investigate these relationships with larger and more diverse samples.

Background: There are an estimated 9.4 million cases of foodborne illness each year. Consumers have a key role in preventing foodborne illness, but differences in the practice of food safety behaviors exist, increasing risk for certain groups in the population. Identifying groups who are more likely to practice risky food safety behaviors can assist in development of interventions to reduce the disease burden of foodborne illnesses. The purpose of this investigation was to examine the relationships of health indicators and psychosocial factors with self-reported food safety behaviors. Methods and Findings: Data were collected via questionnaire from 153 African Americans who attend churches in Baltimore City. Individuals reported high overall concern with food safety (mean score: 0.80±0.49 on a scale of -1 to +1) and practiced food safety behaviors with moderate overall frequency (mean score: 5.26±4.01 on a scale of -12 to +12), with considerable variation in reported frequencies depending on the food safety behavior. After adjusting for demographic variables, food safety behaviors were significantly associated with BMI and psychosocial variables. Riskier food safety behaviors were associated with higher body mass index (BMI) (β =20.141 95%CI (20.237, 20.044), p = 0.004). Self-efficacy for healthy eating (standard β [std. β] = 0.250, p = 0.005) and healthy eating intentions (std. β = 0.178, p = 0.041) were associated with better food safety behaviors scores. Conclusions: These results show important relationships between weight-related health indicators, psychosocial factors and food safety behaviors that have not previously been studied. Interventions tailored to higher-risk populations have the potential to reduce the burden of food-related illnesses. Additional studies are needed to further investigate these relationships with larger and more diverse samples. [ABSTRACT FROM AUTHOR]

BackgroundCanonical α/β T-cell receptors (TCRs) bind to human leukocyte antigen (HLA) displaying antigenic peptides to elicit T cell-mediated cytotoxicity. TCR-engineered T-cell immunotherapies targeting cancer-specific peptide-HLA complexes (pHLA) are generating exciting clinical responses, but owing to HLA restriction they are only able to target a subset of antigen-positive patients. More recently, evidence has been published indicating that naturally occurring α/β TCRs can target cell surface proteins other than pHLA, which would address the challenges of HLA restriction. In this proof-of-concept study, we sought to identify and engineer so-called HLA-independent TCRs (HiTs) against the tumor-associated antigen mesothelin.MethodsUsing phage display, we identified a HiT that bound well to mesothelin, which when expressed in primary T cells, caused activation and cytotoxicity. We subsequently engineered this HiT to modulate the T-cell response to varying levels of mesothelin on the cell surface.ResultsThe isolated HiT shows cytotoxic activity and demonstrates killing of both mesothelin-expressing cell lines and patient-derived xenograft models. Additionally, we demonstrated that HiT-transduced T cells do not require CD4 or CD8 co-receptors and, unlike a TCR fusion construct, are not inhibited by soluble mesothelin. Finally, we showed that HiT-transduced T cells are highly efficacious in vivo, completely eradicating xenografted human solid tumors.ConclusionHiTs can be isolated from fully human TCR-displaying phage libraries against cell surface-expressed antigens. HiTs are able to fully activate primary T cells both in vivo and in vitro. HiTs may enable the efficacy seen with pHLA-targeting TCRs in solid tumors to be translated to cell surface antigens.

Syncytin-1 is a member of human endogenous retroviral W gene family (HERVW1). Known to be expressed in human placental trophoblast, syncytin-1 protein mediates the fusion of cytotrophoblasts for the formation of syncytiotrophoblasts, the terminally differentiated form of trophoblast lineage. In addition, in vitro studies indicate that syncytin-1 possessed nonfusogenic functions such as those for immune suppression, cell cycle regulation and anti-apoptotic activities. Overexpression of syncytin-1 has been observed in various malignant tissues including breast, endometrial and ovarian cancers. It was reported that syncytin-1 gene expression is associated with dynamic changes of DNA hypomethylation in the 5' LTR. In this study, applying the real-time PCR, Western blot analysis and immunohistochemistry methods, we demonstrate a constitutive expression of syncytin-1 in normal pancreas tissues as well as normal tissues adjacent to cancer lesions. Moreover, a reduced expression is found in the pancreatic adenocarcinoma tissues. The expression levels of syncytin-1 are not correlated with the stage, historical grade and gender, but inversely correlated with patients' age. Furthermore, COBRA and bisulfite sequencing results indicated that the lower expression of syncytin-1 is correlated with the hypermethylation of two CpG dinucleotides in the 5' LTR of syncytin-1 gene. The nonfusogenic function of syncytin-1 in normal pancreas as well as its role(s) in the pathogenesis and progression of pancreatic cancers remains to be investigated. Identification of the two CpG dinucleotides around transcription start site as key epigenetic elements has provided valuable information for further studies on the epigenetic regulation of syncytin-1 in pancreatic cancer cells.