Perchloroethylene-contaminated drinking water and the risk of breast cancer: additional results from Cape Cod, Massachusetts, USA.

In 1998 we published the results of a study suggesting an association between breast cancer and perchloroethylene (PCE; also called tetrachloroethylene) exposure from public drinking water. The present case-control study was undertaken to evaluate this association further. The cases were composed of female residents of eight towns in the Cape Cod region of Massachusetts who had been diagnosed with breast cancer from 1987 through 1993 (n = 672). Controls were composed of demographically similar women from the same towns (n = 616). Women were exposed to PCE when it leached from the vinyl lining of water distribution pipes from the late 1960s through the early 1980s. A relative delivered dose of PCE that entered a home was estimated using an algorithm that took into account residential history, water flow, and pipe characteristics. Small to moderate elevations in risk were seen among women whose exposure levels were above the 75th and 90th percentiles when 0-15 years of latency were considered (adjusted odds ratios, 1.5-1.9 for > 75th percentile, 1.3-2.8 for > 90th percentile). When data from the present and prior studies were combined, small to moderate increases in risk were also seen among women whose exposure levels were above the 75th and 90th percentiles when 0-15 years of latency were considered (adjusted odds ratios, 1.6-1.9 for > 75th percentile, 1.3-1.9 for > 90th percentile). The results of the present study confirm those of the previous one and suggest that women with the highest PCE exposure levels have a small to moderate increased risk of breast cancer

A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages

Increasing evidence suggests that the cytokine transforming growth factor-β (TGF-β) inhibits the development of atherosclerosis. The lipoprotein lipase (LPL) enzyme expressed by macrophages has been implicated in the pathogenesis of atherosclerosis by stimulating the uptake of lipoprotein particles. Unfortunately, the action of TGF-β on the expression of LPL in macrophages remains largely unclear. We show that TGF-β inhibits LPL gene expression at the transcriptional level. Transient transfection assays reveal that the −31/+187 sequence contains the minimal TGF-β-responsive elements. Electrophoretic mobility shift assays show that Sp1 and Sp3 interact with two regions in the −31/+187 sequence. Mutations of these Sp1/Sp3 sites abolish the TGF-β-mediated suppression whereas multimers of the sequence impart the response to a heterologous promoter. TGF-β has no effect on the binding or steady-state polypeptide levels of Sp1 and Sp3. These results, therefore, suggest a novel mechanism for the TGF-β-mediated repression of LPL gene transcription that involves regulation of the action of Sp1 and Sp3

The Young Lady\u27s Guide

Contents Papers for thoughtful girls, by Sarah Tytler. A woman’s thoughts about women, by the author of John Halifax, gentleman . Fashion, from Mrs. Sydney Cox’s Friendly counsel for girls . Novel-reading, from the Greyson letters, by Henry Rogers. From Daughters and Women of England, by Sarah S. Ellis. From Hannah More.--From The young ladies’ mentor , by a lady. The social position and culture due to woman, by W. R. Williams.--Education of the heart, woman’s best, by Sarah S. Ellis. From The young woman’s friend , by J. A. James

Energy-dense snacks can have the same expected satiation as sugar-containing beverages

AbstractSugar-sweetened beverages (SSBs) are thought to be problematic for weight management because energy delivered in liquid form may be less effective at suppressing appetite than solid foods. However, little is known about the relative ‘expected satiation’ (anticipated fullness) of SSBs and solid foods. This is relevant because expected satiation is an important determinant of portion selection and energy intake. Here, we used a method of constant stimuli to assess the expected satiation of test meals that were presented in combination with different caloric and non-caloric beverages (500 ml) (Experiment 1 and 2), as well as with high-energy solid snack foods (Experiment 2). All energy-containing beverages and snack foods were presented in 210 kcal portions. Both experiments found that expected satiation was greater for meals containing caloric versus non-caloric beverages (201.3 ± 17.3 vs. 185.4 ± 14.1 kcal in Experiment 2; p < 0.05). Further, Experiment 2 showed that this difference was greater in participants who were familiar with our test beverages, indicating a role for learning. Notably, we failed to observe a significant difference in expected satiation between any of the caloric beverages and snack foods in Experiment 2 (range: 192.5–205.2 kcal; p = 0.87). This finding suggests that it may be more appropriate to consider beverages and solid foods on the same continuum, recognizing that the expected satiation of some solid foods is as weak as some beverages

Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development

Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P&lt;0.001) and at age 4 years (r = 0.16, P = 0.02). In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02). This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04). We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fa

Structural determinants for EB1-mediated recruitment of APC and spectraplakins to the microtubule plus end

EB1 is a member of a conserved protein family that localizes to growing microtubule plus ends. EB1 proteins also recruit cell polarity and signaling molecules to microtubule tips. However, the mechanism by which EB1 recognizes cargo is unknown. Here, we have defined a repeat sequence in adenomatous polyposis coli (APC) that binds to EB1's COOH-terminal domain and identified a similar sequence in members of the microtubule actin cross-linking factor (MACF) family of spectraplakins. We show that MACFs directly bind EB1 and exhibit EB1-dependent plus end tracking in vivo. To understand how EB1 recognizes APC and MACFs, we solved the crystal structure of the EB1 COOH-terminal domain. The structure reveals a novel homodimeric fold comprised of a coiled coil and four-helix bundle motif. Mutational analysis reveals that the cargo binding site for MACFs maps to a cluster of conserved residues at the junction between the coiled coil and four-helix bundle. These results provide a structural understanding of how EB1 binds two regulators of microtubule-based cell polarity

A survey to evaluate the association of COVID-19 restrictions on perceived mood and coping in Australian community level athletes

Australian community level athletes faced unprecedented changes to their training andcompetition options as the global COVID-19 pandemic took a stronghold. This disruptionwas predicted to have a negative impact on emotional well-being as communitiesbraced through periods of social isolation and physical distancing requirements. Thisstudy provides an Australian perspective on the emotional well-being of communitylevel athletes and the extent to which they coped during the COVID-19 pandemic.Emotional well-being and coping were measured using the Brief Emotional ExperienceScale and the 28-item Brief Cope Scale. Both instruments were administered alongwith other questions pertaining to participant demographics and training status via anonline survey between April and June 2020. The survey was disseminated to communityathletes through word-of-mouth and social media platforms. No significant differencesin emotional well-being were observed between athlete groups as a result of COVID-19and its associated restrictions. Coping scores also appeared to be preserved in Australiancommunity athletes, which contrasts the impact expected asa result of the COVID-19pandemic. While tentative, the observed preservation in coping may have bufferedpotential declines in emotional well-being, which has beendocumented in professionaland semi-professional athletes and the general population. These unexpected findingsand tentative suppositions warrant further investigationand highlight the importance ofconducting a country- or region-specific approach to examining the impact of COVID-19on community athletes, as responses to COVID-19 are undoubtedly not consistentthroughout the world

Structure and characterisation of hydroxyethylcellulose–silica nanoparticles

Functionalising nanoparticles with polymers has gained much interest in recent years, as it aids colloidal stability and manipulation of surface properties. Here, polymer-coated thiolated silica nanoparticles were synthesised by self-condensation of 3-mercaptopropyltrimethoxysilane in the presence of hydroxyethylcellulose. These nanoparticles were characterised by dynamic light scattering, small angle neutron scattering, Nanoparticle Tracking Analysis, Raman spectroscopy, FT-IR spectroscopy, thermogravimetric analysis, Ellman's assay, transmission electron microscopy and cryo-transmission electron microscopy. It was found that increasing the amount of hydroxyethylcellulose in the reaction mixture increased the nanoparticle size and reduced the number of thiol groups on their surface. Additionally, by utilising small angle neutron scattering and dynamic light scattering, it was demonstrated that higher concentrations of polymer in the reaction mixture (0.5–2% w/v) resulted in the formation of aggregates, whereby several silica nanoparticles are bridged together with macromolecules of hydroxyethylcellulose. A correlation was identified between the aggregate size and number of particles per aggregate based on size discrepancies observed between DLS and SANS measurements. This information makes it possible to control the size of aggregates during a simple one-pot synthesis; a prospect highly desirable in the design of potential drug delivery systems

General practitioners' views on reattribution for patients with medically unexplained symptoms: a questionnaire and qualitative study

Background: The successful introduction of new methods for managing medically unexplained symptoms in primary care is dependent to a large degree on the attitudes, experiences and expectations of practitioners. As part of an exploratory randomised controlled trial of reattribution training, we sought the views of participating practitioners on patients with medically unexplained symptoms, and on the value of and barriers to the implementation of reattribution in practice. Methods: A nested attitudinal survey and qualitative study in sixteen primary care teams in north-west England. All practitioners participating in the trial (n = 74) were invited to complete a structured survey. Semi-structured interviews were undertaken with a purposive sub-sample of survey respondents, using a structured topic guide. Interview transcripts were used to identify key issues, concepts and themes, which were grouped to construct a conceptual framework: this framework was applied systematically to the data. Results: Seventy (95%) of study participants responded to the survey. Survey respondents often found it stressful to work with patients with medically unexplained symptoms, though those who had received reattribution training were more optimistic about their ability to help them. Interview participants trained in reattribution (n = 12) reported that reattribution increased their confidence to practice in a difficult area, with heightened awareness, altered perceptions of these patients, improved opportunities for team-building and transferable skills. However general practitioners also reported potential barriers to the implementation of reattribution in routine clinical practice, at the level of the patient, the doctor, the consultation, diagnosis and the healthcare context. Conclusion: Reattribution training increases practitioners' sense of competence in managing patients with medically unexplained symptoms. However, barriers to its implementation are considerable, and frequently lie outside the control of a group of practitioners generally sympathetic to patients with medically unexplained symptoms and the purpose of reattribution. These findings add further to the evidence of the difficulty of implementing reattribution in routine general practice