Synthesis and Oligonuclear Structures of Strontium and Barium Complexes with Protonated and Deprotonated N-Mesityl-P,P-diphenylphosphinic Amide Ligands.

Metalation of N-mesityl-P,P-diphenylphosphinic amide Ph2P(O)-NHMes (HL, I) with MgBu2 and Ae{N(SiMe3)2}2 (Ae = Ca, Sr, and Ba) yields alkaline-earth metal complexes with the compositions of [(thf)nAe(L·HL)2] [Ae/n = Mg/0 (II), Ca/2 (III)] as well as of [Sr2L3(L·HL)(HL)] (1), [Ba2L3(L·HL)(HL)] (2), [Ba3L6] (3), and [(thf)2Ba3L6] (4). In III, 1, 2, and 3, the alkaline-earth metal atoms are in severely distorted octahedral environments, and the structural distortions are partially caused by the small O-Ae-N bite angles of the chelating Ph2P(O)-NMes anions. The substructures (L·HL) contain N-H···N hydrogen bridges, stabilizing the arrangement of the ligands in complexes II, III, 1, and 2. In the trinuclear barium complex [Ba(µ-L)3Ba(µ-L)3Ba] (3), a rigid adjustment of the anionic L bases leads to a C3-symmetric molecule in the crystalline state with bridging oxygen atoms. Due to the small O-Ba-N bite angles of the chelating anions, vacant coordination sites are available at the outer barium centers. Coordination of thf bases in these gaps yields the complex [(thf)Ba(µ-L)3Ba(µ-L)3Ba(thf)] (4). However, THF is unable to deaggregate the trinuclear complexes into smaller barium-containing moieties. Increasing the radius of the alkaline-earth metals and increasing the nuclearity of these compounds lead to decreasing solubility in common organic solvents. NMR studies verify that the molecular structures of these alkaline-earth metal complexes are maintained in ethereal solvents and toluene.

Probabilistic Material Flow Analysis of Seven Commodity Plastics in Europe.

The omnipresence of plastics in our lives and their ever-increasing application range continuously raise the requirements for the monitoring of environmental and health impacts related to both plastics and their additives. We present a static probabilistic material flow analysis of seven polymers through the European and Swiss anthropospheres to provide a strong basis for exposure assessments of polymer-related impacts, which necessitates that the plastic flows from production to use and finally to waste management are well-understood. We consider seven different polymers, chosen for their popularity and application variety: low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP), polystyrene (PS), expanded polystyrene (EPS), polyvinyl chloride (PVC), and polyethylene terephthalate (PET). We include synthetic textile products and consider trade flows at various stages of the life cycle, thus achieving a complete overview of the consumption for these polymers. In Europe, the order of consumption is PP > LDPE > PET > HDPE > PVC > PS > EPS. Textile products account for 42 ± 3% of the consumption of PET and 22 ± 4% of PP. Incineration is the major waste management method for HDPE, PS, and EPS. No significant difference between landfilling and incineration for the remaining polymers is found. The highest recycling share is found for PVC. These results can serve as a basis for a detailed assessment of exposure pathways of plastics or their additives in the environment or exposure of additives on human health.

Merkel cell carcinoma in East Yorkshire: A case series and literature review of current management.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumour of the skin. The incidence is rising and it is associated with sun exposure and immunosuppression. Our aim was to perform a 10-year retrospective review of MCC treated in East Yorkshire and to examine disease progression, surgical and adjuvant management, and outcomes. METHODS: A 10-year retrospective review was undertaken of patients identified through the histopathology database. Case notes and digital patient records were examined for patient demographics, disease characteristics, management and outcome. Disease stage was calculated using the 2010 AJCC TNM classification. RESULTS: Thirty-seven patients with complete records were included. Twenty-one patients were male and 16 female, with mean age 76.7 years at presentation. Pre-malignant or malignant skin changes were documented in 15 patients, and immunosuppression in 15 patients. Mean duration of lesion was 17.5 weeks. Following diagnosis 22/37 patients underwent further surgery with 11 patients undergoing sentinel lymph node (LN) biopsy. LN disease was palpable at presentation in 8 patients. Three year survival is 40%. CONCLUSIONS: There is no standardised management of MCC and randomised trials are challenging due to relatively small numbers. There has been little progress made in terms of improving survival. Development of a national database for patients with this condition would allow prospective data collection and more accurate assessment of current treatment protocols and their efficacy. LEVEL OF EVIDENCE: IV.

Combining GPS, GIS, and accelerometry to explore the physical activity and environment relationship in children and young people - a review.

The environment has long been associated with physical activity engagement, and recent developments in technology have resulted in the ability to objectively quantify activity behaviours and activity context. This paper reviews studies that have combined Global Positioning Systems (GPS), Geographic Information Systems (GIS) and accelerometry to investigate the PA-environment relationship in children and young people (5-18 years old). Literature searches of the following bibliographic databases were undertaken: Sportdiscus, Medline, Embase, CINAHL, Psychinfo and Applied Social Sciences Index and Abstracts (ASSIA). Fourteen studies met the inclusion criteria, and covered topics including greenspace use, general land use, active travel, and the built environment. Studies were largely cross-sectional and took place across developed countries (UK, USA, Canada, New Zealand, and Australia). Findings suggest that roads and streets, school grounds, and the home location are important locations for total PA, and moderate to vigorous PA (MVPA). The relationship between greenspace was positive, however, multiple definitions and outcome measures add complexity to the results. MVPA was more likely in those exposed to higher levels of greenspace compared to sedentary individuals. Total MVPA time in greenspace is low, but when framed as a proportion of the total can be quite high. Domestic gardens may be an important area for higher intensity activity.

Risk factors for complications following breast reduction: results from a randomized control trial.

Reduction mammoplasty has been shown to benefit physical, physiological, and psycho-social health. However, there are some recognized complications. It would be beneficial if one could identify and modify the factors which increase the rate of complications. To determine the effects of resection weight, BMI, age, and smoking on complication rates following reduction mammoplasty. Data were gathered as a part of randomized control trial (RCT) examining psycho-social & QOL benefits of reduction mammoplasty. Sixty-seven consecutive female patients referred to either the Hull Breast Unit or Hull Plastic and Reconstructive Surgery Unit and underwent Inferior pedicle reduction mammoplasty were recruited. Complications were recorded prospectively. Data gathered included resection weight, BMI, age, and smoking status. Smoking status was categorized into current; ex; and never. Prospective records of all complications were noted. SPSS was used for purposes of statistical analysis. Of the 67 patients, 16 (23.9%) had complications. Higher resection weight, increased BMI, and older age are associated with high rate of complications with significance reaching p-values of p < 0.001, p = 0.034, and p = 0.004, respectively. Among the 67 women who had surgery, nine (13.4%) were current smokers, 20 (29.9%) were ex-smokers, and 38 (56.7%) never smoked. The incidence of complications was highest among current smokers and lowest among those who had never smoked. When comparing the current smokers with those who are not currently smoking, there is a 37% difference in the occurrence of complication. The chi-squared test shows that this is a significant difference (p < 0.01) at the 99% confidence interval. Higher resection weight, increased BMI, older age, and smoking are risk factors for complications. Patients should be adequately counseled about losing weight and stopping smoking.

The 'Butter Test' to guide effective tissue cleansing after high-pressure injection injury.

A case of high-pressure fingertip injury with an unknown paint primer injectate, and the use of a simple test to determine whether it is water- or solvent-based in order to guide subsequent optimal debridement, is presented. The favourable outcome achieved was felt to have resulted, in part, from the effective single debridement thus achieved.

Is there increased risk of local and in-transit recurrence following sentinel lymph node biopsy?

Recent publications have suggested that sentinel lymph node biopsy (SLNB) and completion lymphadenectomy (CLND) increase the rate of local and in-transit disease up to 23% in sentinel node positive group of patients with cutaneous melanoma. This retrospective study combined the data from two national centres on local and in-transit disease in 972 melanoma patients who underwent SLNB procedure over 6.5 years period. In total, 77 patients (7.9%) developed loco-regional recurrence: 41 (4.2%) local recurrence only and 36 patients (3.7%) in-transit metastases during a mean follow-up of 42 months. Patients with positive sentinel lymph node were three times more likely to develop loco-regional metastases than those with no nodal disease (17 vs. 5.6%). Over one third of all recurrences developed following excision of thick (Breslow thickness over 4mm) primary tumours. In both centres age and Breslow thickness were found to be significantly higher in the recurrence group (p<0.001 for both). This study revealed a strong association between increased risk of loco-regional metastases and aggressive tumour biology and adverse patients factors. No conclusive evidence was found to support an increased incidence in patients undergoing SLNB and CLND compared to that published for patients undergoing wide local excision alone.

Fibroma of a tendon sheath at the wrist: a rare cause of compression of the median nerve.

We report a case of fibroma of a tendon sheath, a rare benign tumour, which presented as a painless swelling at the wrist and caused symptoms of median nerve compression. We have also reviewed similar cases.

E1A-mediated paclitaxel sensitization in HER-2/neu-overexpressing ovarian cancer SKOV3.ip1 through apoptosis involving the caspase-3 pathway.

HER-2/neu-overexpressing breast cancer cells are more resistant to the chemotherapeutic agent paclitaxel (Taxol) than low-HER-2/neu-expressing breast cancer cells, and the adenoviral type 5 EIA can down-regulate HER-2/neu overexpression. Therefore, in this study, we asked (a) whether EIA might sensitize response to paclitaxel in human HER-2/neu-overexpressing ovarian cancer cells, and, if so, what is the mechanism responsible; and (b) whether this enhanced chemosensitivity would translate into a therapeutic effect in an ovarian cancer xenograft model. Consequently, we demonstrated that: (a) adenovirus type 5 E1A could enhance the sensitivity of paclitaxel in paclitaxel-resistant HER-2/neu-overexpressing human ovarian cancer cells in vitro by inducing apoptosis, (b) this induction was heavily dependent on activation of the caspase-3 pathway, and (c) nude mice bearing i.p. HER-2/neu-overexpressing human ovarian cancer cells and treated with both paclitaxel and E1A gene therapy survived significantly longer than did mice treated only with paclitaxel or E1A gene therapy. Thus, we concluded that the E1A gene enhanced both the in vitro and in vivo sensitivity of paclitaxel in paclitaxel-resistant HER-2/ neu-overexpressing ovarian cancer SKOV3.ipl cells. Because a Phase I clinical trial using E1A gene targeted to HER-2/neu down-regulation has recently been completed, the current study also provided a scientific basis to further develop a novel therapy that combines paclitaxel and E1A gene therapy and its testing in a Phase II trial.

Dendritic cells augment granulocyte-macrophage colony-stimulating factor (GM-CSF)/herpes simplex virus thymidine kinase-mediated gene therapy of lung cancer.

Lung cancer, the leading cause of cancer death in the United States, is resistant to most currently available therapies. To evaluate a multicomponent gene therapy approach that replaces tumor-bearing host immune deficits, we genetically modified Line 1 (L1C2), a weakly immunogenic alveolar cell carcinoma cell line. L1C2 was transduced ex vivo with a retroviral construct that contained two components: a cytokine gene (granulocyte-macrophage colony-stimulating factor) and a drug sensitivity gene (herpes simplex virus thymidine kinase). The third component of this therapy, in vitro-activated syngeneic bone marrow-derived dendritic cells, was included to augment antigen presentation. The addition of ganciclovir (GCV) caused the lysis of transduced tumor cells, resulting in the release of potential tumor antigens. Ex vivo-transduced tumor cells regressed in vivo following GCV therapy but were not effective in the treatment of established parental tumors. To treat established tumors, dendritic cells were administered in combination with transduced tumor cells and GCV. A total of 50% of these mice rejected the 5-day-old established tumors and were immune to rechallenge with parental L1C2 cells. Thus, this multicomponent gene therapy system leads to both the regression of established tumors and enhanced immunogenicity in this weakly immunogenic murine lung cancer model.