Association of invasion-promoting tenascin-C additional domains with breast cancers in young women

Introduction: Tenascin-C (TNC) is a large extracellular matrix glycoprotein that shows prominent stromal expression in many solid tumours. The profile of isoforms expressed differs between cancers and normal breast, with the two additional domains AD1 and AD2 considered to be tumour associated. The aim of the present study was to investigate expression of AD1 and AD2 in normal, benign and malignant breast tissue to determine their relationship with tumour characteristics and to perform in vitro functional assays to investigate the role of AD1 in tumour cell invasion and growth. Methods: Expression of AD1 and AD2 was related to hypoxanthine phosphoribosyltransferase 1 as a housekeeping gene in breast tissue using quantitative RT-PCR, and the results were related to clinicopathological features of the tumours. Constructs overexpressing an AD1-containing isoform (TNC-14/AD1/16) were transiently transfected into breast carcinoma cell lines (MCF-7, T-47 D, ZR-75-1, MDA-MB-231 and GI-101) to assess the effect in vitro on invasion and growth. Statistical analysis was performed using a nonparametric Mann-Whitney test for comparison of clinicopathological features with levels of TNC expression and using Jonckheere-Terpstra trend analysis for association of expression with tumour grade. Results: Quantitative RT-PCR detected AD1 and AD2 mRNA expression in 34.9% and 23.1% of 134 invasive breast carcinomas, respectively. AD1 mRNA was localised by in situ hybridisation to tumour epithelial cells, and more predominantly to myoepithelium around associated normal breast ducts. Although not tumour specific, AD1 and AD2 expression was significantly more frequent in carcinomas in younger women (age ≤40 years; P < 0.001) and AD1 expression was also associated with oestrogen receptor-negative and grade 3 tumours (P < 0.05). AD1 was found to be incorporated into a tumour-specific isoform, not detected in normal tissues. Overexpression of the TNC-14/AD1/16 isoform significantly enhanced tumour cell invasion (P < 0.01) and growth (P < 0.01) over base levels. Conclusions: Together these data suggest a highly significant association between AD-containing TNC isoforms and breast cancers in younger women (age ≤40 years), which may have important functional significance in vivo

Plant communities affect arbuscular mycorrhizal fungal diversity and community composition in grassland microcosms

The diversity of arbuscular mycorrhizal (AM) fungi was investigated in an unfertilized limestone grassland soil supporting different synthesized vascular plant assemblages that had developed for 3 yr. The experimental treatments comprised: bare soil; monocultures of the nonmycotrophic sedge Carex flacca; monocultures of the mycotrophic grass Festuca ovina; and a species-rich mixture of four forbs, four grasses and four sedges. The diversity of AM fungi was analysed in roots of Plantago lanceolata bioassay seedlings using terminal-restriction fragment length polymorphism (T-RFLP). The extent of AM colonization, shoot biomass and nitrogen and phosphorus concentrations were also measured. The AM diversity was affected significantly by the floristic composition of the microcosms and shoot phosphorus concentration was positively correlated with AM diversity. The diversity of AM fungi in P. lanceolata decreased in the order: bare soil > C. flacca > 12 species > F. ovina. The unexpectedly high diversity in the bare soil and sedge monoculture likely reflects differences in the modes of colonization and sources of inoculum in these treatments compared with the assemblages containing established AM-compatible plants

Interest in healthy living outweighs presumed cultural norms for obesity for Ghanaian women

BACKGROUND: Cultural norms indicate that obesity reflects increased wealth and prosperity. Yet obesity is linked to serious medical illnesses. The purpose of this study was to determine if Ghanaian women would change their body image if it meant a healthier life. METHODS: A questionnaire was administered to 305 Ghanaian women waiting for clinic appointments at Korle Bu Teaching Hospital, Accra Ghana. This survey included questions on current health, selection of figural stimuli, decision making on health and social determinants and 5 questions on self-perception of health from SF-36. Anthropometric measures were taken and body mass index calculated. Women were also provided with health related information at the conclusion of the interview. RESULTS: The majority of all women surveyed would reduce their current body image if it meant that they would have an overall healthier life and reduce the risks of obesity-linked illnesses and complications. Currently obese women were significantly more likely than non-obese women to reduce their body image to reduce the risk of hypertension (OR 2.03 [1.64 – 2.51],<0.001); cardiovascular accident (OR 1.96 [1.61 – 2.38],<0.001); diabetes (OR 2.00 [1.63 – 2.44],<0.001); myocardial infarction (OR 2.27 [1.80 – 2.86],<0.001); if requested by a spouse(OR 2.64 [1.98 – 3.52],<0.001); and to improve overall health (OR 1.95 [1.60 – 2.37], <0.001). There was no association with current body image and responses to SF-36. The decision to select a new body image was not influenced by education, income, marital status or parity. Age 50 years old and less was significantly associated with the body image size reduction to reduce the risk of hypertension, diabetes, and a cardiovascular accident. CONCLUSION: The Ghanaian women interviewed in this study are interested in living a healthy life and are willing to reduce their body size to reduce the risk of obesity-linked illnesses. The target group for any interventional studies and measures to reduce obesity appears to be women age 50 and younger

The Iowa Homemaker vol.37, no.2

They Say it’s Love, Ann Baur, page 4 Marry in a College Chapel, Merna Borror, page 6 Learned by Heart, Beth Cummings Paschal, page 7 I’d Like to Know, Sandy Newman, page 8 Blueprint for Packing, Carolyn McIntyre, page 10 The Honeymoon, Reverie to Reality, Jackie Andre, page 11 Present Picker, Marilyn Jensen Nadler, page 12 An Electric Dinner, Ann Walters, page 14 Say Yes… To Entertaining, Rosemary McBride and Roma Walker, page 15 ABC’s of Money Management, Linda Nelson and Marie Budolfson, page 16 What’s in a Wedding Custom, Janice Furman, page 18 Plain Clothes Man? Ha!, Norma Scholes, page 22 Why All This Fuss Over Sex, Gail A. McClure, page 2

Effects of Monobutyl and Di(n-butyl) Phthalate in Vitro on Steroidogenesis and Leydig Cell Aggregation in Fetal Testis Explants from the Rat: Comparison with Effects in Vivo in the Fetal Rat and Neonatal Marmoset and in Vitro in the Human

BACKGROUND: Certain phthalates can impair Leydig cell distribution and steroidogenesis in the fetal rat in utero, but it is unknown whether similar effects might occur in the human. OBJECTIVES: Our aim in this study was to investigate the effects of di(n-butyl) phthalate (DBP), or its metabolite monobutyl phthalate (MBP), on testosterone production and Leydig cell aggregation (LCA) in fetal testis explants from the rat and human, and to compare the results with in vivo findings for DBP-exposed rats. We also wanted to determine if DBP/MBP affects testosterone production in vivo in the neonatal male marmoset. METHODS: Fetal testis explants obtained from the rat [gestation day (GD)19.5] and from the human (15–19 weeks of gestation) were cultured for 24–48 hr with or without human chorionic gonadotropin (hCG) or 22R-hydroxycholesterol (22R-OH), and with or without DBP/MBP. Pregnant rats and neonatal male marmosets were dosed with 500 mg/kg/day DBP or MBP. RESULTS: Exposure of rats in utero to DBP (500 mg/kg/day) for 48 hr before GD21.5 induced major suppression of intratesticular testosterone levels and cytochrome P450 side chain cleavage enzyme (P450scc) expression; this short-term treatment induced LCA, but was less marked than longer term (GD13.5–20.5) DBP treatment. In vitro, MBP (10(−3) M) did not affect basal or 22R-OH-stimulated testosterone production by fetal rat testis explants but slightly attenuated hCG-stimulated steroidogenesis; MBP induced minor LCA in vitro. None of these parameters were affected in human fetal testis explants cultured with 10(−3) M MBP for up to 48 hr. Because the in vivo effects of DBP/MBP were not reproduced in vitro in the rat, the absence of MBP effects in vitro on fetal human testes is inconclusive. In newborn (Day 2–7) marmosets, administration of a single dose of 500 mg/kg MBP significantly (p = 0.019) suppressed blood testosterone levels 5 hr later. Similar treatment of newborn co-twin male marmosets for 14 days resulted in increased Leydig cell volume per testis (p = 0.011), compared with co-twin controls; this is consistent with MBP-induced inhibition of steroidogenesis followed by compensatory Leydig cell hyperplasia/hypertrophy. CONCLUSIONS: These findings suggest that MBP/DBP suppresses steroidogenesis by fetal-type Leydig cells in primates as in rodents, but this cannot be studied in vitro

The complexities of breast cancer desmoplasia

The stromal, or 'desmoplastic', responses seen histologically in primary breast carcinomas can vary from being predominantly cellular (fibroblasts/myofibroblasts) with little collagen to being a dense acellular tissue. The mechanisms underlying the stromal response are complex; paracrine activation of myofibroblasts by growth factors is important but the contribution of cytokines/chemokines should not be ignored. A recent xenograft study has proposed that platelet-derived growth factor (PDGF) is the initiator of the desmoplastic response, but this has not been confirmed by (limited) analyses in vivo. Further studies are required to elaborate the mechanisms of the desmoplastic response, to determine its role in breast cancer progression and whether it is the same for all carcinomas

Middle managers’ role in implementing evidence-based practices in healthcare: a systematic review

Abstract Background Middle managers are in a unique position to promote the implementation of evidence-based practices (EBPs) in healthcare organizations, yet knowledge of middle managers’ role in implementation and determinants (e.g., individual-, organizational-, and system-level factors) which influence their role remains fractured, spanning decades and disciplines. To synthesize understanding, we undertook a systematic review of studies of middle managers’ role in healthcare EBP implementation and determinants of that role. Methods We searched MEDLINE/PubMed and Business Source Complete (Ebsco) for literature on middle managers’ role in healthcare EBP implementation and its determinants. We abstracted data from records that met inclusion criteria (i.e., written in English, peer-reviewed, and reporting either a protocol or results of an empirical study) into a matrix for analysis. We summarized categorical variables using descriptive statistics. To analyze qualitative data, we used a priori codes and then allowed additional themes to emerge. Results One hundred five records, spanning across several countries and healthcare settings and relating to a range of EBPs, met our inclusion criteria. Studies of middle managers’ role in healthcare EBP implementation and its determinants substantially increased from 1996 to 2015. Results from included studies suggest that middle managers shape implementation climate in addition to fulfilling the four roles hypothesized in extant theory of middle managers’ role in implementation. However, extant studies offered little understanding of determinants of middle managers’ role. Conclusions Our findings suggest that middle managers may play an important role in facilitating EBP implementation. Included studies offered little understanding regarding the relative importance of various roles, potential moderators of the relationship between middle managers’ roles and EBP implementation, or determinants of middle managers’ role in EBP implementation. Future studies should seek to understand determinants and moderators of middle managers’ role. Clearer understanding may facilitate the translation of evidence into practice

Scalable Preparation and Differential Pharmacologic and Toxicologic Profiles of Primaquine Enantiomers

Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (−)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (−)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (−)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (−)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (−)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (−)-(R)-PQ may have a better safety margin than the racemate in human

Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility

Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here we performed RNA-sequencing on 4 brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery