Background: Polychlorinated biphenyls (PCBs) are industrial chemicals that were used widely for approximately 50 years. Now banned, they are still ubiquitous because of their persistence in the ...environment, the food chain, and human fatty tissue. High in utero exposures cause developmental deficits accompanied by growth retardation. Studies examining intrauterine growth at lower exposures have been inconsistent, with most such investigations having relied on surrogate exposure indicators such as consumption of fish from contaminated bodies of water. Methods: In the 1960s, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20°C. At 5 years of age, detailed anthropometric measurements were made on children born in the years 1964-1967. We measured PCBs in specimens from 399 mothers using gas chromatography/electron capture detection. We conducted multiple linear regression to examine the relationship between these organochlorine concentrations and both intrauterine and 5-year growth, with adjustment for medical, lifestyle, sociodemographic, and specimen characteristics. Results: In male infants, higher total in utero PCB exposure was associated with reduced birth weight, head circumference, and weight-for-gestational age. An increase from the 10th to 90th percentile in total PCBs was related to 290 g lower birth weight, a 0.7-cm decrease in head circumference, and for weight for gestational age, a reduction in z-score of 0.6. In girls, smaller head circumference and shorter gestations were observed. In contrast, prenatal PCBs were associated with greater growth in 5-year-old girls, with no apparent effect in 5-year-old boys. Conclusions: Maternally mediated exposure to PCBs may be detrimental to fetal growth, particularly in boys. These effects apparently are not persistent. Interpretation of greater childhood growth of girls is unclear.
Concentrations of polybrominated diphenyl ethers (PBDEs) were determined in air samples from near suspected sources, namely an indoors computer laboratory, indoors and outdoors at an electronics ...recycling facility, and outdoors at an automotive shredding and metal recycling facility. The results showed that (1) PBDE concentrations in the computer laboratory were higher with computers on compared with the computers off, (2) indoor concentrations at an electronics recycling facility were as high as 650 000 pg/m3 for decabromodiphenyl ether (PBDE 209), and (3) PBDE 209 concentrations were up to 1900 pg/m3 at the downwind fenceline at an automotive shredding/metal recycling facility. The inhalation exposure estimates for all the sites were typically below 110 pg/kg/day with the exception of the indoor air samples adjacent to the electronics shredding equipment, which gave exposure estimates upward of 40 000 pg/kg/day. Although there were elevated inhalation exposures at the three source sites, the exposure was not expected to cause adverse health effects based on the lowest reference dose (RfD) currently in the Integrated Risk Information System (IRIS), although these RfD values are currently being re-evaluated by the U.S. Environmental Protection Agency. More research is needed on the potential health effects of PBDEs.
We examined predictors of organochlorine concentrations in serum specimens from women who were pregnant in the 1960s and participated in the Child Health and Development Study in the San Francisco ...Bay Area of California. That study enrolled pregnant women at the Kaiser-Permanente Medical Facilities, conducted interviews, and drew blood specimens; these specimens were centrifuged and the resulting serum specimens were frozen and placed in long-term storage. For the current investigation, organochlorines were measured by dual-column GC-electron capture detection in specimens collected in 1963-1967 from 399 pregnant women during the second and third trimesters. Using multiple linear regression models adjusted for serum lipids, we evaluated factors predicting concentrations of 11 polychlorinated biphenyl (PCB) congeners, their sum, and several pesticides and metabolites. Variables evaluated were age, race, place of birth, date of blood draw, body mass index, occupation, past residence on a farm, parity, and duration of pregnancy at blood draw. Concentrations of highly chlorinated PCBs and the sum of the PCBs increased with age. Concentrations of certain PCB congeners, as well as the sum, were significantly higher among nonwhites and increased with calendar date of blood draw. p,p′-DDT and p,p′-DDE concentrations were about 50% higher for nonwhites compared with whites and for those born in California or the southeastern United States versus elsewhere in the United States. Higher body mass index was associated with lower concentrations of several PCBs and p,p′-DDE but with higher heptachlor epoxide and DDT levels. The increase in use of PCBs during the 1960s is apparently detectable as increasing concentrations in maternal sera between 1963 and 1967. Marked racial and regional differences in serum pesticide levels were likely caused by geographic variation in previous agricultural and vector-control uses. The relationship to body mass index appears to be complex.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Introduction
Tuberculosis (TB) is a problem in South Africa. Initial loss to follow up (LTFU) among TB patients is high varying between 14.9 and 18%. Some of the reasons for this are: lack ...of proper communication between patient and staff on next steps after testing, not aware that results are ready; and other competing priorities. Receiving reminder messages that result is ready is an intervention that can be explored to reduce initial LTFU. This can be through either receiving a note from the Ward-Based Outreach Teams (WBOTs) or via short message service (SMS) advising the patient to collect test result at the facility. This proposal aims to assess the effectiveness of WBOTs or SMS technology in reducing TB initial LTFU.
Methods
This will be a mixed methods approach. In depth interviews with WBOT Managers and TB Program Managers will be conducted. Focus group discussions with WBOT members will also be conducted. Two interventions (enhanced WBOTs/SMS technology) will be tested using a 3 arm randomized controlled trial (standard of care, SMS technology or enhanced WBOTs). The WBOTs will deliver paper note reminders while SMS intervention will entail sending reminder SMS messages to patients as soon as TB results are ready.
Integrins are involved in the binding and internalization of both enveloped and nonenveloped viruses. By using 3 distinct cell systems--CHO cells lacking expression of α₅β₁-integrin, HeLa cells ...treated with siRNA to α₅-integrin, and mouse β₁-integrin knockout fibroblasts, we show that α₅β₁-integrin is required for efficient infection by pseudovirions bearing the ebolavirus glycoprotein (GP). These integrins are necessary for viral entry but not for binding or internalization. Given the need for endosomal cathepsins B and L (CatB and CatL) to prime GPs for fusion, we investigated the status of CatB and CatL in integrin-positive and integrin-negative cell lines. α₅β₁-Integrin-deficient cells lacked the double-chain (DC) forms of CatB and CatL, and this correlated with decreased CatL activity in integrin-negative CHO cells. These data indicate that α₅β₁-integrin-negative cells may be refractory to infection by GP pseudovirions because they lack the necessary priming machinery (the double-chain forms of CatB and CatL). In support of this model, we show that GP pseudovirions that have been preprimed in vitro to generate the 19-kDa form of GP overcome the requirement for α₅β₁-integrin for infection. These results provide further support for the requirement for endosomal cathepsins for ebolavirus infection, identify the DC forms of these cathepsins as previously unrecognized factors that contribute to cell tropism of this virus, and reveal a previously undescribed role for integrins during viral entry as regulators of endosomal cathepsins, which are required to prime the entry proteins of ebolavirus and other pathogenic viruses.
Transplantation of a single hematopoietic stem cell is an important method for its functional characterization, but the standard transplantation protocol relies on cell homing to the bone marrow ...after intravenous injection. Here, we present a method to transplant single cells directly into the bone marrow of live mice. We developed an optical platform that integrates a multiphoton microscope with a laser ablation unit for microsurgery and an optical tweezer for cell micromanipulation. These tools allow image-guided single cell transplantation with high spatial control. The platform was used to deliver single hematopoietic stem cells. The engraftment of transplants was tracked over time, illustrating that the technique can be useful for studying both normal and malignant stem cells in vivo.
The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors.
To identify gene-environment ...interaction effects on childhood asthma using genome-wide single-nucleotide polymorphism (SNP) data and air pollution exposure. Identified loci were further analyzed at epigenetic and transcriptomic levels.
We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO
levels) at the birth address and performed a genome-wide interaction study for doctors' diagnoses of asthma up to 8 years in three European birth cohorts (n = 1,534) with look-up for interaction in two separate North American cohorts, CHS (Children's Health Study) and CAPPS/SAGE (Canadian Asthma Primary Prevention Study/Study of Asthma, Genetics and Environment) (n = 1,602 and 186 subjects, respectively). We assessed expression quantitative trait locus effects in human lung specimens and blood, as well as associations among air pollution exposure, methylation, and transcriptomic patterns.
In the European cohorts, 186 SNPs had an interaction P < 1 × 10
and a look-up evaluation of these disclosed 8 SNPs in 4 loci, with an interaction P < 0.05 in the large CHS study, but not in CAPPS/SAGE. Three SNPs within adenylate cyclase 2 (ADCY2) showed the same direction of the interaction effect and were found to influence ADCY2 gene expression in peripheral blood (P = 4.50 × 10
). One other SNP with P < 0.05 for interaction in CHS, rs686237, strongly influenced UDP-Gal:betaGlcNAc β-1,4-galactosyltransferase, polypeptide 5 (B4GALT5) expression in lung tissue (P = 1.18 × 10
). Air pollution exposure was associated with differential discs, large homolog 2 (DLG2) methylation and expression.
Our results indicated that gene-environment interactions are important for asthma development and provided supportive evidence for interaction with air pollution for ADCY2, B4GALT5, and DLG2.
To compare and describe the quality of life (QOL) of women allocated to tamoxifen or exemestane within the Intergroup Exemestane Study (IES).
Postmenopausal women with primary breast cancer who were ...disease free after 2 to 3 years were randomly assigned to switch from tamoxifen to exemestane or continue with tamoxifen until 5 years of treatment were completed. A subset of IES centers participated in a QOL substudy. The Functional Assessment of Cancer Therapy-Breast (FACT-B) and endocrine subscale (ES) were administered before random assignment and at predefined follow-up times. The primary end point was the FACT-B composite Trial Outcome Index (TOI). Secondary end points included total FACT-B+ES score, total ES score, and severity of individual endocrine symptoms. This analysis reports QOL up to 24 months.
Five hundred eighty-two patients from eight countries were enrolled onto the substudy. Completion and return of questionnaires was excellent, with 85% available for analysis. QOL was generally good and stable over 2 years, with no clinically meaningful differences found between groups in TOI or ES. Prevalence of severe endocrine symptoms at trial entry was high for vasomotor complaints and sexual problems, which persisted for both groups during the study. No significant differences between groups were seen for any endocrine symptoms apart from vaginal discharge, which was more pronounced with tamoxifen (P < .001).
The switch from tamoxifen to exemestane neither increased nor decreased endocrine symptoms present after 2 to 3 years of tamoxifen; the switch also did not initiate significant reports of new symptoms. Results indicate that the clinical benefits of exemestane over tamoxifen are achieved without significant detrimental effect on QOL.
Mapping the characteristics of Africa's smallholder-dominated croplands, including the sizes and numbers of fields, can provide critical insights into food security and a range of other socioeconomic ...and environmental concerns. However, accurately mapping these systems is difficult because there is 1) a spatial and temporal mismatch between satellite sensors and smallholder fields, and 2) a lack of high-quality labels needed to train and assess machine learning classifiers. We developed an approach designed to address these two problems, and used it to map Ghana's croplands. To overcome the spatio-temporal mismatch, we converted daily, high resolution imagery into two cloud-free composites (the primary growing season and subsequent dry season) covering the 2018 agricultural year, providing a seasonal contrast that helps to improve classification accuracy. To address the problem of label availability, we created a platform that rigorously assesses and minimizes label error, and used it to iteratively train a Random Forests classifier with active learning, which identifies the most informative training sample based on prediction uncertainty. Minimizing label errors improved model F1 scores by up to 25%. Active learning increased F1 scores by an average of 9.1% between first and last training iterations, and 2.3% more than models trained with randomly selected labels. We used the resulting 3.7 m map of cropland probabilities within a segmentation algorithm to delineate crop field boundaries. Using an independent map reference sample (
= 1,207), we found that the cropland probability and field boundary maps had respective overall accuracies of 88 and 86.7%, user's accuracies for the cropland class of 61.2 and 78.9%, and producer's accuracies of 67.3 and 58.2%. An unbiased area estimate calculated from the map reference sample indicates that cropland covers 17.1% (15.4-18.9%) of Ghana. Using the most accurate validation labels to correct for biases in the segmented field boundaries map, we estimated that the average size and total number of field in Ghana are 1.73 ha and 1,662,281, respectively. Our results demonstrate an adaptable and transferable approach for developing annual, country-scale maps of crop field boundaries, with several features that effectively mitigate the errors inherent in remote sensing of smallholder-dominated agriculture.
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