Systematic review and meta-analysis of iron therapy in anaemic adults without chronic kidney disease: updated and abridged Cochrane review

AIMS: Anaemia is increasingly recognized as having an independent impact upon patient outcomes in cardiac disease. The role of novel iron therapies to treat anaemia is increasing. This systematic review and meta-analysis assesses the efficacy and safety of iron therapies for the treatment of adults with anaemia. METHODS AND RESULTS: Electronic databases and search engines were searched as per Cochrane methodology. Randomized controlled trials (RCTs) of iron vs. inactive control or placebo, as well as alternative formulations, doses, and routes in anaemic adults without chronic kidney disease or in the peri-partum period were eligible. The primary outcome of interest was mortality at 1 year. Secondary outcomes were blood transfusion, haemoglobin levels, quality of life, serious adverse events, and length of hospital stay. A total of 64 RCTs (including five studies of heart failure patients) comprising 9004 participants were included. None of the studies was at a low risk of bias. There were no statistically significant differences in mortality between iron and inactive control. Both oral and parenteral iron significantly reduced the proportion of patients requiring blood transfusion compared with inactive control [risk ratio (RR) 0.66, 95% confidence interval (CI) 0.48-0.90; and RR 0.84, 95% CI 0.73-0.97, respectively]. Haemoglobin was increased more by both oral and parenteral iron compared with inactive control [mean difference (MD) 0.91 g/dL, 95% CI 0.48 to 1.35; and MD 1.04, 95% CI 0.52 to 1.57, respectively], and parenteral iron demonstrated a greater increase when compared with oral iron (MD 0.53 g/dL, 95% CI 0.31-0.75). In all comparisons, there were no differences in the results comparing patients with and without heart failure. CONCLUSION: Both oral and parenteral iron are shown to decrease the proportion of people who require blood transfusion and increase haemoglobin levels, without any benefit on mortality. Further trials at a low risk of bias, powered to measure clinically significant endpoints, are still required

The Distribution Of Chlorine And Iodine In Soil In The Vicinity Of Lead Mining And Smelting Operations, Bixby Area, S.E. Missouri, U.S.A.

Iodine and Cl are enriched in soils in the vicinity of the Magmont and Buick lead mines near Bixby, southeastern Missouri. The enrichments, up to 5.6 ppm I and 305 ppm Cl, are against regional background of 1.26 ppm I and 41 ppm Cl. The area of highest I and Cl is thought to reflect a zone of base metal sulphide mineralization occurring about 400 m below the surface. Iodine and Cl are also enriched in soils immediately adjacent to a tailings pond, hence these elements would appear to be leached from this source. A zone of enhanced I values (up to 2.65 ppm I) to the north of a lead smelter is superimposed on a much larger zone of lead enrichment (up to 12,000 ppm Pb) and is thought to represent I released from sulphide ores on smelting. © 1988

Development of Cut-points for Determining Activity Intensity From a Wrist-worn ActiGraph Accelerometer in Free-living Adults

Despite recent popularity of wrist-worn accelerometers for assessing free-living physical behaviours, there is a lack of user-friendly methods to characterize physical activity from a wrist-worn ActiGraph accelerometer. Participants in this study completed a laboratory protocol and/or 3–8 hours of directly observed free-living (criterion measure of activity intensity) while wearing ActiGraph GT9X Link accel- erometers on the right hip and non-dominant wrist. All laboratory data (n = 36) and 11 participants’ free- living data were used to develop vector magnitude count cut-points (counts/min) for activity intensity for the wrist-worn accelerometer, and 12 participants’ free-living data were used to cross-validate cut-point accuracy. The cut-points were: \u3c2,860 counts/min (sedentary); 2,860–3,940 counts/min (light); and ≥3,941counts/min (moderate-to-vigorous (MVPA)). These cut-points had an accuracy of 70.8% for asses- sing free-living activity intensity, whereas Sasaki/Freedson cut-points for the hip accelerometer had an accuracy of 77.1%, and Hildebrand Euclidean Norm Minus One (ENMO) cut-points for the wrist accel- erometer had an accuracy of 75.2%. While accuracy was higher for a hip-worn accelerometer and for ENMO wrist cut-points, the high wear compliance of wrist accelerometers shown in past work and the ease of use of count-based analysis methods may justify use of these developed cut-points until more accurate, equally usable methods can be developed

Nuclear localization and function of polypeptide ligands and their receptors: a new paradigm for hormone specificity within the mammary gland?

The specific effects triggered by polypeptide hormone/growth factor stimulation of mammary cells were considered mediated solely by receptor-associated signaling networks. A compelling body of new data, however, clearly indicates that polypeptide ligands and/or their receptors are transported into the nucleus, where they function directly to regulate the expression of specific transcription factors and gene loci. The intranuclear function of these complexes may contribute to the explicit functions associated with a given ligand, and may serve as new targets for pharmacologic intervention

The deal.II Library, Version 9.1

This paper provides an overview of the new features of the finite element library deal.II, version 9.1

A Humanized Pattern of Aromatase Expression is Associated with Mammary Hyperplasia in Mice

Aromatase is essential for estrogen production and is the target of aromatase inhibitors, the most effective endocrine treatment for postmenopausal breast cancer. Peripheral tissues in women, including the breast, express aromatase via alternative promoters. Female mice lack the promoters that drive aromatase expression in peripheral tissues; thus, we generated a transgenic humanized aromatase (Arom(hum)) mouse line containing a single copy of the human aromatase gene to study the link between aromatase expression in mammary adipose tissue and breast pathology. Arom(hum) mice expressed human aromatase, driven by the proximal human promoters II and I.3 and the distal promoter I.4, in breast adipose fibroblasts and myoepithelial cells. Estrogen levels in the breast tissue of Arom(hum) mice were higher than in wild-type mice, whereas circulating levels were similar. Arom(hum) mice exhibited accelerated mammary duct elongation at puberty and an increased incidence of lobuloalveolar breast hyperplasia associated with increased signal transducer and activator of transcription-5 phosphorylation at 24 and 64 wk. Hyperplastic epithelial cells showed remarkably increased proliferative activity. Thus, we demonstrated that the human aromatase gene can be expressed via its native promoters in a wide variety of mouse tissues and in a distribution pattern nearly identical to that of humans. Locally increased tissue levels, but not circulating levels, of estrogen appeared to exert hyperplastic effects on the mammary gland. This novel mouse model will be valuable for developing tissue-specific aromatase inhibition strategies

Lead Speciation in the Dusts Emitted from Non-Ferrous Metallurgy Processes

The paper presents results for the speciation analysis of lead in dusts derived from dedusting of technological gasses from metallurgical processes of non-ferrous metals with different elementary content, made in accordance with two equal sequential extractions. Analytical procedure A provided possibilities for determination of fraction of Pb2+, metallic lead and fraction containing mainly lead sulfides. The second procedure (procedure B) was sequential extraction in accordance with Tessier. The results obtained in accordance with procedure A indicate that, regardless of the dust origin, the dominant group of Pb compounds is composed of lead salts which are soluble under alkaline conditions or lead compounds that form plumbites in the reaction with NaOH

Prolactin receptor is a negative prognostic factor in patients with squamous cell carcinoma of the head and neck

Background: The influence of human prolactin (hPRL) on the development of breast and other types of cancer is well established. Little information, however, exists on the effects of hPRL on squamous cell carcinomas of the head and neck (SCCHNs). Methods: In this study, we evaluated prolactin receptor (PRLR) expression in SCCHN cell lines and assessed by immunohistochemistry the expression in 89 patients with SCCHNs. The PRLR expression was correlated with clinicopathological characteristics as well as clinical outcome. The effect of hPRL treatment on tumour cell growth was evaluated in vitro. Results: Immunoreactivity for PRLR was observed in 85 out of 89 (95%) tumours. Multivariate COX regression analysis confirmed high levels of PRLR expression (>25% of tumour cells) to be an independent prognostic factor with respect to overall survival (HR=3.70, 95% CI: 1.14–12.01; P=0.029) and disease-free survival (P=0.017). Growth of PRLR-positive cancer cells increased in response to hPRL treatment. Conclusion: Our data indicate that hPRL is an important growth factor for SCCHN. Because of PRLR expression in a vast majority of tumour specimens and its negative impact on overall survival, the receptor represents a novel prognosticator and a promising drug target for patients with SCCHNs

Context-dependent effects on spatial variation in deer-vehicle collisions

Identifying factors that contribute to the risk of wildlife‐vehicle collisions (WVCs) has been a key focus of wildlife managers, transportation safety planners and road ecologists for over three decades. Despite these efforts, few generalities have emerged which can help predict the occurrence of WVCs, heightening the uncertainty under which conservation, wildlife and transportation management decisions are made. Undermining this general understanding is the use of study area boundaries that are incongruent with major biophysical gradients, inconsistent data collection protocols among study areas and species‐specific interactions with roads. We tested the extent to which factors predicting the occurrence of deer‐vehicle collisions (DVCs) were general among five study areas distributed over a 11,400‐km2 region in the Canadian Rocky Mountains. In spite of our system‐wide focus on the same genus (i.e., Odocoileus hemionus and O. virginianus), study area delineation along major biophysical gradients, and use of consistent data collection protocols, we found that large‐scale biophysical processes influence the effect of localized factors. At the local scale, factors predicting WVC occurrence varied greatly between individual study areas. Distance to water was an important predictor of WVCs in three of the five study areas, while other variables had modest importance in only two of the five study areas. Thus, lack of generality in factors predicting WVCs may have less to do with methodological or taxonomic differences among study areas than the large‐scale, biophysical context within which the data were collected. These results highlight the critical need to develop a conceptual framework in road ecology that can unify the disparate results emerging from field studies on WVC occurrence

Mechanisms underlying the diminished sensitivity to prolactin negative feedback during lactation: Reduced STAT5 signaling and up-regulation of cytokine-inducible SH2 domain-containing protein (CIS) expression in tuberoinfundibular dopaminergic neurons

Hyperprolactinaemia during lactation is a consequence of the sucking stimulus and in part due to reduced prolactin (PRL) negative feedback. To date, the mechanisms involved in this diminished sensitivity to PRL feedback are unknown but may involve changes in PRL signal transduction within tuberoinfundibular dopaminergic (TIDA) neurons. Therefore, we investigated signal transducers and activators of transcription (STAT) 5 signaling in the TIDA neurons of lactating rats. Dual-label confocal immunofluorescence studies were used to determine the intracellular distribution of STAT5 within TIDA neurons in the dorsomedial arcuate nucleus. In lactating rats with pups removed for 16 h, injection of ovine PRL significantly (P < 0.05) increased the STAT5 nuclear/cytoplasmic ratio compared with vehicle-treated mothers. In contrast, ovine PRL injection did not increase the STAT5 nuclear/cytoplasmic ratio in lactating mothers with pups, demonstrating that PRL signal transduction through STAT5 is reduced in TIDA neurons in the presence of pups. To investigate possible mechanisms involved in reduced PRL signaling, we examined the expression of suppressors of cytokine signaling (SOCS) proteins. Northern analysis on whole hypothalamus showed that CIS (cytokine-inducible SH2 domain-containing protein), but not SOCS1 or SOCS3, mRNA expression was significantly (P < 0.01) up-regulated in suckled lactating rats. Semiquantitative RT-PCR on arcuate nucleus micropunches also showed up-regulation of CIS transcripts. Immunofluorescence studies demonstrated that CIS is expressed in all TIDA neurons in the dorsomedial arcuate nucleus, and the intensity of CIS staining in these neurons is significantly (P < 0.05) increased in lactating rats with sucking pups. Together, these results support the hypothesis that loss of sensitivity to PRL-negative feedback during lactation is a result of increased CIS expression in TIDA neurons