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Glioblastoma is inherently resistant to radiation and drug treatments. This is mediated by the most common forms of cell death are often actively inhibited. Identifying and exploiting alternative cell death pathways are essential to overcoming or bypassing drug resistance. Ferroptosis, a newly described, morphologically and biochemically distinct, cell death mechanism is characterized by iron-dependent cellular accumulation of reactive oxygen species. The combination of siramesine, a lysosome disruptor, and lapatinib, a dual tyrosine kinase inhibitor (TKI), synergistically induced death in glioma cancer cells. This cell death had characteristics of ferroptosis: it was blocked by the ferroptosis inhibitor ferrostatin-1 and the iron chelator deferoxamine. In addition, the amount of ROS and lipid peroxidation were increased in glioma cells. Iron transport protein remained unchanged but reactive iron levels increased. One target for kinase inhibitors is protein bisulfate isomerase (PDI). Knockdown of PDI in combination with siramesine increased cell death that was blocked by ferrostatin-1. Taken together, drug combinations that alter reactive iron and ROS levels might induce ferroptosis and overcome drug resistance in glioma cells.
The ability to use serving size information on food labels is important for managing age-related chronic conditions such as diabetes, obesity and cancer. Past research suggests that older adults are at risk for failing to accurately use this portion of the food label due to numeracy skills. However, the extent to which older adults pay attention to serving size information on packages is unclear. We compared the effects of numeracy and attention on age differences in accurate use of serving size information while individuals evaluated product healthfulness.
Accuracy and attention were assessed across two tasks in which participants compared nutrition labels of two products to determine which was more healthful if they were to consume the entire package. Participants’ eye movements were monitored as a measure of attention while they compared two products presented side-by-side on a computer screen. Numeracy as well as food label habits and nutrition knowledge were assessed using questionnaires.
Sacramento area, California, USA, 2013–2014.
Stratified sample of 358 adults, aged 20–78 years.
Accuracy declined with age among those older adults who paid less attention to serving size information. Although numeracy, nutrition knowledge and self-reported food label use supported accuracy, these factors did not influence age differences in accuracy.
The data suggest that older adults are less accurate than younger adults in their use of serving size information. Age differences appear to be more related to lack of attention to serving size information than to numeracy skills.
In April and May of 2014, the Court of Justice of the European Union (CJEU), sitting as a Grand Chamber, issued two preliminary rulings with dramatic implications for internet privacy—a topic of increasing global concern following Edward Snowden’s leaks on the data surveillance programs run by the U.S. National Security Agency (NSA) and its allies. The first case, Digital Rights Ireland Ltd. v. Minister for Communications, Marine and Natural Resources and others joined with Kärtner Landesregierung and others, found an unacceptable interference in the rights to privacy and data protection in a European Union directive that required private telecom and internet companies to retain records of user activity and to make those records available for use by law enforcement. The second case, Google Spain SL, Google Inc. v. Agencia Española de Protección de Datos and Mario Costeja González, recognized that there are situations where an internet search engine, such as Google, could be ordered to erase links from search results to protect individual privacy. While these two cases have dramatically different policy implications, both demonstrate Europe’s efforts to apply human rights to modern technology and to reconcile security, freedom of information, and privacy.
The current study examined the influence of phonological structure and language experience on the nonword repetition performance of bilingual children. Twenty-six Spanish-dominant and 26 English-dominant Spanish–English bilingual five-year-old children were matched on current exposure to the dominant language and year of first exposure to English. Participants repeated non-wordlike nonwords in English and Spanish. The Spanish-dominant group performed better than the English-dominant group for both Spanish and English nonwords. In addition, there was a main effect for test language, where Spanish nonwords were produced more accurately than English nonwords overall. The Spanish-dominant group advantage for nonwords is interpreted as emerging from the extra practice the dominant Spanish speakers had producing multisyllabic words.
A girl aged 6 presented with haematuria and her sister (aged 5) presented with haematuria and proteinuria. Family history showed multiple individuals suffering from end stage renal failure from the paternal side of the pedigree. Following kidney biopsy in the father and paternal grandmother, the pathological diagnosis was of focal segmental glomerulosclerosis (FSGS). Exome sequencing was undertaken in the proband's sister and grandmother. Genetic variants shared by both affected individuals were interrogated to identify the genetic cause of disease. Candidate variants were then sequenced in all the family members to determine segregation with the disease. A mutation of COL4A5 known to cause Alport syndrome segregated with disease from the paternal side of the pedigree and a variant in NPHS1 was present in both paediatric cases and inherited from their mother. This study highlights the advantages of exome sequencing over single gene testing; disease presentation can be heterogeneous with several genes representing plausible candidates; candidate gene(s) may be unavailable as a diagnostic test; consecutive, single gene testing typically concludes once a single causal mutation is identified. In this family, we were able to confirm a diagnosis of Alport syndrome, which will facilitate testing in other family members.
In paediatric pulmonary embolism, cardiac findings and thromboembolic outcomes are poorly defined. We conducted a mixed retrospective-prospective cohort study of paediatric pulmonary embolism at the Children's Hospital Colorado between March, 2006 and January, 2011. A total of 58 consecutive children – age less than or equal to 21 years – with acute pulmonary embolism were enrolled. Data collection included clinical and laboratory characteristics, treatments, serial echocardiographic and electrocardiographic findings, and outcomes of pulmonary embolism non-resolution and recurrence. The median age was 16.5 years ranging from 0 to 21 years. The most prevalent clinical risk factors were oral contraceptive pill use (52% of female patients), presence of a non-infectious inflammatory condition (21%), and trauma (21%). Thrombophilias included heterozygous factor V Leiden in 21%; antiphospholipid antibody syndrome was established in 31% overall. Proximal pulmonary artery involvement was present in 34%. At presentation, nearly half of the patients had hypoxaemia and 37% had tachycardia. The classic electrocardiographic finding of S1Q3T3 was present in 12% acutely; tricuspid regurgitation greater than 3 metres per second, septal flattening, and right ventricular dilation were each present on acute echocardiogram in 25%. Nearly all patients received therapeutic anticoagulation, with initial systemic tissue plasminogen activator administered in 16% for occlusive iliofemoral deep venous thrombosis and/or massive pulmonary embolism. Pulmonary embolism resolution was observed in 82% by 6 months. Recurrent pulmonary embolism occurred in 9%. There were no pulmonary embolism-related deaths. Right ventricular dysfunction was rare in follow-up. These data indicate that acute heart strain is common, but chronic cardiac dysfunction is rare, following aggressive management of acute pulmonary embolism in children.
Self-help therapies, such as bibliotherapy, are becoming increasingly more available to the general population as a treatment for psychological disorders, such as depression and anxiety. However, relatively few of these self-help books are properly evaluated to test their treatment efficacy. Two studies aimed to test a new self-help book to treat fears, phobias and anxiety in order to see if symptoms of anxiety and associated symptoms, such as functioning and coping, were improved compared to baseline scores and a waiting-list control group. Study 1 adopted a minimal guided approach (experimental group: n = 25; waiting-list control group: n = 29) whereas Study 2 adopted a non-guided approach (experimental group: n = 17; waiting-list control group: n = 16). In both studies, functioning and coping were improved and the current state of phobic symptoms was reduced. The main phobia improved only when adopting a guided approach and general psychological distress only reduced when adopting a non-guided approach. These studies provide preliminary support for a modest effect in a subclinical population. The results could have good implications for the treatment of anxiety and the use of self-help methods as an additional treatment aid or as a preventative treatment.
Weed species respond to the cumulative effect of multiple practices employed within weed management systems. However, this response is rarely studied at the system level, and the relationships between weed communities and management systems in crops are not well understood. We used multivariate analyses to assess relationships among tomato management systems and weed species identified through on-farm sampling of 59 fields. Giant foxtail, common lambsquarters, prickly sida, and carpetweed were common in all systems. Eastern black nightshade was common in the conventional processing and mixed fresh-market systems but largely absent from the organic system. Barnyardgrass and goosegrass were common in the organic fresh-market system but not in the other systems. Canonical correspondence analysis identified distinct associations between specific species and the management systems. Common purslane was strongly associated with the rain-fed, mixed fresh-market system, and barnyardgrass, goosegrass, yellow nutsedge, and green foxtail were associated with the irrigated, organic fresh-market system. Indicator species analysis identified five species that were significant indicators of the organic, fresh-market system and one species that was a significant indicator of the rain-fed, mixed fresh-market system. Weed populations persist or increase when a set of species-specific environmental conditions are met. The association of weed species in this study with particular systems supports the hypothesis that weed communities are strongly affected by management systems.
The influence of management practices at a system level is rarely studied in weed science, even though weed communities respond to the cumulative effect of farm management systems. On-farm visits and detailed grower surveys were used to objectively classify 59 Indiana tomato fields into management systems. Fields were chosen to represent a range of practices used to grow conventional and organic tomatoes. Multivariate statistical analyses identified five distinct management systems based primarily on differences in hours spent hand-weeding, use of plastic mulch, irrigation, row spacing, and whether tomatoes were staked. Farmers generally reported many more hours of hand-weeding for organically managed fields than for fields in the other groups. This finding may reflect a trade-off between the use of herbicides and the need for hand-weeding. However, some organically managed fields were grouped with conventional fresh market fields, suggesting that management practices besides herbicide inputs can be used to reduce hand-weeding. Although some fresh market fields used to produce organic or conventional tomatoes had similar management systems, there was little overlap between fields in fresh market or processing tomato production. Further research is needed to determine underlying relationships among management systems and weed control in Indiana tomato production.
A point-prevalence survey performed among residents of eight nursing homes in Melbourne, Australia, found a rate of fecal VRE colonization of 3.1% (9/292; 95% confidence interval, 1.1-5.1), all vanB Enterococcusfaecium. This is a higher rate than in the general community (3.1% vs 0.2%). Many residents (16%) had been inpatients in acute-care hospitals in the previous 3 months.
Fieldwork east of Oakham, Rutland has located evidence of prehistoric settlement, land use patterns, and ceremonial monuments. Part of this included the excavation of a cropmark site which has revealed an unusual sequence of Neolithic/Early Bronze Age pit circles and a burial area. This is complemented by a fieldwalking survey of the surrounding areas, allowing consideration of the relationship of juxtaposed flint scatters and the excavated ceremonial area.
In Christoph Wetzel's 1988 painting, An Everyday Story, the divided canvas proudly depicts women's accomplishments in the German Democratic Republic (Figure 1). On one side, a woman operates a large piece of heavy machinery in a rolling mill, cool and competent behind the enormous mass of metal and gears. On the other side, the same woman helps her two children prepare for school in the morning. In the act of combing her daughter's hair, she looks out directly at the viewer, her expression asking: “And what are you surprised at?” This painting, displayed as part of a 1995 exposition on art commissioned by government agencies in the GDR, graphically displays that government's ideological commitment to women's paid labor, especially in jobs that, in capitalist societies, are often thought to be inappropriate for women.
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