Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer

Objective To quantitatively assess and compare the quality of life (QoL) of women with a self-reported diagnosis of lower limb lymphedema (LLL), to women with lower limb swelling (LLS), and to women without LLL or LLS following treatment for endometrial cancer. Methods 1399 participants in the Australian National Endometrial Cancer Study were sent a follow-up questionnaire 3–5 years after diagnosis. Women were asked if they had experienced swelling in the lower limbs and, if so, whether they had received a diagnosis of lymphedema by a health professional. The 639 women who responded were categorised as: Women with LLL (n = 68), women with LLS (n = 177) and women without LLL or LLS (n = 394). Multivariable-adjusted generalized linear models were used to compare women’s physical and mental QoL by LLL status. Results On average, women were 65 years of age and 4 years after diagnosis. Women with LLL had clinically lower physical QoL (M= 41.8, SE= 1.4) than women without LLL or LLS (M= 45.1, SE= 0.8, p = .07), however, their mental QoL was within the normative range (M= 49.6; SE= 1.1 p = 1.0). Women with LLS had significantly lower physical (M= 41.0, SE= 1.0, p = .003) and mental QoL (M= 46.8; SE= 0.8, p < .0001) than women without LLL or LLS (Mental QoL: M= 50.6, SE= 0.8). Conclusion Although LLL was associated with reductions in physical QoL, LLS was related to reductions in both physical and mental QoL 3-5 years after cancer treatment. Early referral to evidence-based lymphedema programs may prevent long-term impairments to women’s QoL.

Nedd4-2functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells

Constitutive albumin uptake by the proximal tubule is achieved by a receptor-mediated process in which the Cl– channel, ClC-5, plays an obligate role. Here we investigated the functional interaction between ClC-5 and ubiquitin ligases Nedd4 and Nedd4-2 and their role in albumin uptake in opossum kidney proximal tubule (OK) cells. In vivo immunoprecipitation using an anti-HECT antibody demonstrated that ClC-5 bound to ubiquitin ligases, whereas glutathione S-transferase pull-downs confirmed that the C terminus of ClC-5 bound both Nedd4 and Nedd4-2. Nedd4-2 alone was able to alter ClC-5 currents in Xenopus oocytes by decreasing cell surface expression of ClC-5. In OK cells, a physiological concentration of albumin (10 μg/ml) rapidly increased cell surface expression of ClC-5, which was also accompanied by the ubiquitination of ClC-5. Albumin uptake was reduced by inhibiting either the lysosome or proteasome. Total levels of Nedd4-2 and proteasome activity also increased rapidly in response to albumin. Overexpression of ligase defective Nedd4-2 or knockdown of endogenous Nedd4-2 with small interfering RNA resulted in significant decreases in albumin uptake. In contrast, pathophysiological concentrations of albumin (100 and 1000 μg/ml) reduced the levels of ClC-5 and Nedd4-2 and the activity of the proteasome to the levels seen in the absence of albumin. These data demonstrate that normal constitutive uptake of albumin by the proximal tubule requires Nedd4-2, which may act via ubiquitination to shunt ClC-5 into the endocytic pathway.

Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart

G protein-coupled receptors (GPCRs) are critical for cardiovascular physiology. Cardiac cells express >100 nonchemosensory GPCRs, indicating that important physiological and potential therapeutic targets remain to be discovered. Moreover, there is a growing appreciation that members of the large, distinct taste and odorant GPCR families have specific functions in tissues beyond the oronasal cavity, including in the brain, gastrointestinal tract and respiratory system. To date, these chemosensory GPCRs have not been systematically studied in the heart. We performed RT-qPCR taste receptor screens in rodent and human heart tissues that revealed discrete subsets of type 2 taste receptors (TAS2/Tas2) as well as Tas1r1 and Tas1r3 (comprising the umami receptor) are expressed. These taste GPCRs are present in cultured cardiac myocytes and fibroblasts, and are enriched in myocytes, which we corroborated using in situ hybridization. Tas1r1 gene-targeted mice (Tas1r1Cre/Rosa26tdRFP) strikingly recapitulated these data. In vivo taste receptor expression levels were developmentally regulated in the postnatal period. Intriguingly, several Tas2rs were upregulated in cultured rat myocytes and in mouse heart in vivo following starvation. The discovery of taste GPCRs in the heart opens an exciting new field of cardiac research. We predict that these taste receptors may function as nutrient sensors in the heart.

The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis

Heparan sulfate (HS) sugar chains attached to core proteoglycans (PGs) termed HSPGs mediate an extensive range of cell-extracellular matrix (ECM) and growth factor interactions based upon their sulfation patterns. When compared with non-osteogenic (maintenance media) culture conditions, under established osteogenic culture conditions, MC3T3-E1 cells characteristically increase their osteogenic gene expression profile and switch their dominant fibroblast growth factor receptor (FGFR) from FGFR1 (0.5-fold decrease) to FGFR3 (1.5-fold increase). The change in FGFR expression profile of the osteogenic-committed cultures was reflected by their inability to sustain an FGF-2 stimulus, but respond to BMP-2 at day 14 of culture. The osteogenic cultures decreased their chondroitin and dermatan sulfate PGs (biglycan, decorin, and versican), but increased levels of the HS core protein gene expression, in particular glypican-3. Commitment and progress through osteogenesis is accompanied by changes in FGFR expression, decreased GAG initiation but increased N- and O-sulfation and reduced remodeling of the ECM (decreased heparanase expression) resulting in the production of homogenous (21 kDa) HS chain. With the HSPG glypican-3 expression strongly upregulated in these processes, siRNA was used to knockdown this gene to examine the effect on osteogenic commitment. Reduced glypican-3 abrogated the expression of Runx2, and thus differentiation. The reintroduction of this HSPG into Runx2-null cells allowed osteogenesis to proceed. These results demonstrate the dependence of osteogenesis on specific HS chains, in particular those associated with glypican-3.

Osteogenic differentiation of murine embryonic stem cells is mediated by fibroblast growth factor receptors

The mechanisms involved in the control of embryonic stem (ES) cell differentiation are yet to be fully elucidated. However, it has become clear that the family of fibroblast growth factors (FGFs) are centrally involved. In this study we examined the role of the FGF receptors (FGFRs 1-4) during osteogenesis in murine ES cells. Single cells were obtained after the formation of embryoid bodies, cultured on gelatin-coated plates, and coaxed to differentiate along the osteogenic lineage. Upregulation of genes was analyzed at both the transcript and protein levels using gene array, relative-quantitative PCR (RQ-PCR), and Western blotting. Deposition of a mineralized matrix was evaluated with Alizarin Red staining. An FGFR1-specific antibody was generated and used to block FGFR1 activity in mES cells during osteogenic differentiation. Upon induction of osteogenic differentiation in mES cells, all four FGFRs were clearly upregulated at both the transcript and protein levels with a number of genes known to be involved in osteogenic differentiation including bone morphogenetic proteins (BMPs), collagen I, and Runx2. Cells were also capable of depositing a mineralized matrix, confirming the commitment of these cells to the osteogenic lineage. When FGFR1 activity was blocked, a reduction in cell proliferation and a coincident upregulation of Runx2 with enhanced mineralization of cultures was observed. These results indicate that FGFRs play critical roles in cell recruitment and differentiation during the process of osteogenesis in mES cells. In particular, the data indicate that FGFR1 plays a pivotal role in osteoblast lineage determination.

The effectiveness of an intervention in reducing risk of dioxin exposure in Da Nang : changes in community knowledge, attitudes and prevention practices after 2.5 years

Introduction Environmental and biological samples taken around Da Nang Air Base have shown elevated levels of dioxin over many years [1-3]. A pre-intervention knowledge, attitudes and practices (KAP) survey (2009), a risk reduction program (2010) and a post intervention KAP survey (2011) were undertaken in four wards surrounding Danang Airbase. A follow-up evaluation was undertaken in 2013. Methods A KAP survey was implemented among 400 randomly selected food handlers. Eleven indepth interviews and four focus group discussions were also undertaken. Results The knowledge of respondents remained positive and/or improved at 2.5 years follow-up. There were no significant differences in attitudes toward preventing dioxin exposure across surveys; most respondents were positive in all three surveys. An increase in households (69.5%) undertaking measures to prevent exposure was observed, which was higher than in the pre-intervention survey (39.6%) and post- intervention survey (60.4%) (χ2 = 95.6; p < 0.001). The proportion of respondents practicing appropriate preventive measures was also significantly improved. Conclusions Despite most of the intervention program’s activities ceasing in 2010, the risk reduction program has resulted in positive outcomes over the longer-term, with many knowledge and attitude measures remaining stable or imporving. Some KAP indicators decreased, but these KAP indicators were still significantly higher than the pre-intervention levels.

The molecular structure of the phosphate mineral beraunite Fe2+Fe⅗+(PO4)4(OH)5⋅4H2O– A vibrational spectroscopic study

The mineral beraunite from Boca Rica pegmatite in Minas Gerais with theoretical formula Fe2+Fe5 3+(PO4)4(OH)5⋅4H2O has been studied using a combination of electron microscopy with EDX and vibrational spectroscopic techniques. Raman spectroscopy identifies an intense band at 990 cm-1 and 1011 cm-1. These bands are attributed to the PO4 3- v, symmetric stretching mode. The m3 antisymmetric stretching modes are observed by a large number of Raman bands. The Raman bands at 1034, 1051, 1058, 1069 and 1084 together with the Raman bands at 1098, 1116, 1133, 1155 and 1174 cm-1 are assigned to the m3 antisymmetric stretching vibrations of PO4 3- and the HOPO3 2- units. The observation of these multiple Raman bands in the symmetric and antisymmetric stretching region gives credence to the concept that both phosphate and hydrogen phosphate units exist in the structure of beraunite. The series of Raman bands at 567, 582,601, 644, 661, 673, and 687 cm-1 are assigned to the PO4 3- v2 bending modes. The series of Raman bands at 437, 468, 478, 491, 503 cm-1 are attributed to the PO4 3- and OPO3 2- v4 bending modes. No Raman bands of beraunite which could be attributed to the hydroxyl stretching unit were observed. Infrared bands at 3511 and 3359 cm-1 are ascribed to the OH stretching vibration of the OH units. Very broad bands at 3022 and 3299 cm-1 are attributed to the OH stretching vibrations of water. Vibrational spectroscopy offers insights into the molecular structure of the phosphate mineral beraunite.

Solid-state structure of some substituted hexahydro-1,4:5,8-diepoxy­naphthalenes

The structure of several carboxy-substituted hexahydro-1,4:5,8-diepoxynaphthalenes have been solved with X-ray crystallography, in some cases confirming previously contentious structures. The compounds of interest are constructed in efficient one-step 2 × [4+2] cycloaddition reactions from furan and acetylene carboxylate derivatives.

Nanostructured high strength Mg-5%Al-x%Nd alloys prepared by mechanical alloying

Nanostructured high strength Mg-5%Al-x%Nd alloys were prepared by mechanical alloying. Microstructural characterization reveled average crystalline size to be about 30 nm after mechanical alloying while it increased to about 90 nm after sintering and extrusion. Mechanical properties showed increase in 0.2% yield stress, ultimate tensile strength was attributed to reduction in gain size as well as to the enhanced diffusion after mechanical activation. Although ultra high yield stress was observed from the specimen with 5% Nd, its ductility was reduced to about 1.6%.

Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

This study reports that treatment of osseous defects with different growth factors initiates distinct rates of repair. We developed a new method for monitoring the progression of repair, based upon measuring the in vivo mechanical properties of healing bone. Two different members of the bone morphogenetic protein (BMP) family were chosen to initiate defect healing: BMP-2 to induce osteogenesis, and growth-and-differentiation factor (GDF)-5 to induce chondrogenesis. To evaluate bone healing, BMPs were implanted into stabilised 5 mm bone defects in rat femurs and compared to controls. During the first two weeks, in vivo biomechanical measurements showed similar values regardless of the treatment used. However, 2 weeks after surgery, the rhBMP-2 group had a substantial increase in stiffness, which was supported by the imaging modalities. Although the rhGDF-5 group showed comparable mechanical properties at 6 weeks as the rhBMP-2 group, the temporal development of regenerating tissues appeared different with rhGDF-5, resulting in a smaller callus and delayed tissue mineralisation. Moreover, histology showed the presence of cartilage in the rhGDF-5 group whereas the rhBMP-2 group had no cartilaginous tissue. Therefore, this study shows that rhBMP-2 and rhGDF-5 treated defects, under the same conditions, use distinct rates of bone healing as shown by the tissue mechanical properties. Furthermore, results showed that in vivo biomechanical method is capable of detecting differences in healing rate by means of change in callus stiffness due to tissue mineralisation.

4-Methoxyanilinium 2-carboxy-4,5-dichlorobenzoate

In the structure of the title salt C7H10NO+ C8H3Cl2O4- the benzene planes of the cation and anion are essentially parallel [inter-ring dihedral angle 4.8(2)deg]. In the anion the carboxylic acid and carboxylate groups make dihedral angles of 19.0(2) and 79.5(2)\%, respectively, with the benzene ring. Aminium N-H...O, carboxylic acid O-H...O and weak aromatic C-H...O hydrogen-bonding associations with carboxyl O-atom acceptors together with cation-anion pi-pi ring interactions [minimum ring centroid separation = 3.734(3)Ang] give a two-dimensional sheet structure which lies parallel to (001).

Poly-[μ-aqua-μ5-[(2,3,6-trichlorophenyl)acetato)-caesium]

In the structure of the title complex [Cs(C8H4Cl3O2)(H2O)]n, the Cs salt of the commercial herbicide fenac [(2,3,6-trichlorophenyl)acetic acid], the irregular eight-coordination about Cs+ comprises a bidentate chelate (O:Cl) interaction involving a carboxyl O-atom and an ortho-related ring substituted Cl atom which is also bridging, a triple-bridging carboxyl O-atom and a bridging water molecule. A two-dimensional sheet polymer is generated, lying parallel to (100), within which there are water O---H...O(carboxyl) hydrogen-bonding interactions.

Poly[μ-aqua-aqua-μ5-(4-nitrobenzoato)-caesium]

In the structure of the title complex [Cs(C7H4N2O2)(H2O)2]n, the Cs salt of 4-nitrobenzoic acid, the irregular CsO9 coordination sphere comprises three bridging nitro O-donors, a bidentate carboxyl (O,O')-chelate interaction, a triple-bridging water molecule and a monodentate water molecule. A three-dimensional framework polymer is generated, within which there are water O-H...Ocarboxyl and water O-H...O(water) hydrogen-bonding interactions.

Poly[μ-aqua-bis(μ5-2,4-dichlorobenzoato)dipotassium

In the title compound, [K2(C7H3Cl2O2)2(H2O)]n, the potassium salt of 2,4-dichlorobenzoic acid, the repeating unit in the polymeric structure consists of two identical irregular KO6Cl complex units related by twofold rotational symmetry, linked by a bridging water molecule lying on the twofold axis. The coordination polyhedron about each K+ comprises a carboxyl O-atom and a Cl-atom donor from a bidentate chelate ligand interaction, four O-atom donors from a doubly bridging bidentate carboxyl (O,O')-chelate interaction and the water molecule. A two-dimensional layered coordination polymer structure lying parallel to (100) is generated through a series of conjoined cyclic bridges between K centres and is stabilized by water O-H...O(carboxyl) hydrogen-bonding interactions.