Osteoid cell-derived chemokines drive bone-metastatic prostate cancer.

One of the greatest challenges in improving prostate cancer (PCa) survival is in designing new therapies to effectively target bone metastases. PCa regulation of the bone environment has been well characterized; however, bone-targeted therapies have little impact on patient survival, demonstrating a need for understanding the complexities of the tumor-bone environment. Many factors contribute to creating a favorable microenvironment for prostate tumors in bone, including cell signaling proteins produced by osteoid cells. Specifically, there has been extensive evidence from both past and recent studies that emphasize the importance of chemokine signaling in promoting PCa progression in the bone environment. Chemokine-focused strategies present promising therapeutic options for treating bone metastasis. These signaling pathways are complex, with many being produced by (and exerting effects on) a plethora of different cell types, including stromal and tumor cells of the prostate tumor-bone microenvironment. ​This review highlights an underappreciated molecular family that should be interrogated for treatment of bone metastatic prostate cancer (BM-PCa).

Harnessing the Plasma Proteome to Mirror Current and Predict Future Cardiac Remodeling After Myocardial Infarction.

To identify plasma proteins that mirror current and predict future remodeling after myocardial infarction (MI), we retrospectively interrogated plasma proteomes of day (D)0 control (n = 16) and D3 MI (n = 15) from C57BL/6 J mice (20 ± 1 months). A total of 165 unique proteins were correlated with cardiac physiology variables. We prospectively tested the hypothesis that candidates identified retrospectively would predict cardiac physiology at an extended timepoint (D7 MI) in a second cohort of mice (n = 4 ± 1 months). We also examined human plasma from healthy controls (n = 18) and patients 48 h after presentation for MI (n = 41). Retrospectively, we identified 5 strong reflectors of remodeling (all r ≥ 0.60 and p < 0.05). Prospectively, ApoA1, IgA, IL-17E, and TIMP-1 mirrored current and predicted future remodeling. In humans, cytokine-cytokine receptor signaling was the top enriched KEGG pathway for all candidates. In summary, we identified plasma proteins that serve as useful prognostic indicators of adverse remodeling and progression to heart failure.

Embolization of cranial dural arteriovenous fistulas in the liquid embolic era: A Sydney experience.

Endovascular management of dural arteriovenous fistulas has become a mainstay of treatment. In particular, modern techniques have allowed greater fistula penetration and likelihood of complete obliteration. However, the efficacy of newer agents has not been quantified outside of predominantly small case reports and case series. Furthermore, the Australian experience with fistula embolization has yet to be reported in the literature. To this aim, we performed a retrospective review of our endovascular management of a large cohort of cranial dural arteriovenous fistulas in the liquid embolic era. This retrospective case series included ninety-six consecutive patients of any Cognard grade, treated between 2005 and 2016. Liquid embolic agents were used exclusively in eighty-three cases. The overall complete obliteration rate was 89.6% with a residual fistula rate of 2%, and complication rate of 8.3%. This Sydney, Australia cohort demonstrates excellent treatment effect and safety outcomes and thus supports the primary treatment of this condition by endovascular means.

Effects of herbicides on Behr's metalmark butterfly, a surrogate species for the endangered butterfly, Lange's metalmark.

Lange's metalmark butterfly, Apodemia mormo langei Comstock, is in danger of extinction due to loss of habitat caused by invasive exotic plants which are eliminating its food, naked stem buckwheat. Herbicides are being used to remove invasive weeds from the dunes; however, little is known about the potential effects of herbicides on butterflies. To address this concern we evaluated potential toxic effects of three herbicides on Behr's metalmark, a close relative of Lange's metalmark. First instars were exposed to recommended field rates of triclopyr, sethoxydim, and imazapyr. Life history parameters were recorded after exposure. These herbicides reduced the number of adults that emerged from pupation (24-36%). Each herbicide has a different mode of action. Therefore, we speculate that effects are due to inert ingredients or indirect effects on food plant quality. If these herbicides act the same in A. mormo langei, they may contribute to the decline of this species.

Does synergized pyrethrin applied over wetlands for mosquito control affect Daphnia magna zooplankton or Callibaetis californicus mayflies?

BACKGROUND: Public health agencies may apply aerosolized synergized pyrethrin over wetlands repeatedly to control mosquitoes. This concerns wildlife managers because studies have shown the accumulation of pyrethroids, which are chemically similar to pyrethrin, in sediments in amounts that can be toxic to invertebrates. The authors tested whether repeated applications of synergized pyrethrin over wetlands caused mortality of two aquatic invertebrates: the zooplankton Daphnia magna Straus and a mayfly, Callibaetis californicus Banks. Fifteen wetland mesocosms were either exposed to repeated pyrethrin sprays or were protected by lids. Invertebrates in screened cages were placed in mesocosms before the fifth and eleventh spray, and directly into wetlands before spray 11. Six mesocosms were exposed to spray deposition. Caged adult mosquitoes were used to verify that sprays drifted over mesocosms. Sediments were analyzed for insecticide residues. RESULTS: There were no detectable effects of synergized pyrethrin on 36 h survival of Daphnia or mayflies, but most exposed adult mosquitoes died. Some exposed sediments yielded pyrethrin (< or =34.5 ng g(-1)); most showed piperonyl butoxide (PBO) (< or =14.9 ng g(-1)). CONCLUSIONS: Deposition of aerosolized 25% pyrethrin + 5% PBO may contaminate wetlands, but its application at rates used for mosquito control did not produce detectable effects on indicator species.

Influence of phosphate and copper on reductive dechlorination of thiobencarb in California rice field soils.

The potential for reductive dechlorination of the herbicide thiobencarb (TB) by microbes and its prevention in saturated anaerobic rice field soils was examined in laboratory microcosms. TB is effective in controlling both annual grasses and broadleaf weeds. In anoxic microcosms, TB was effectively degraded within 30 days to its dechlorinated product, deschlorothiobencarb (DTB), in two Sacramento Valley rice field soils. TB dechlorination, and subsequent degradation, followed pseudo-zero- (lag phase) and first-order (degradation phase) kinetics. Logistic regression analysis (r2 > 0.841) produced a half-life (t(1/2)) in nonsterile soils ranging from 10 to 15 days, which was also observed when microcosms were amended with low concentrations (<3 mg L(-1)) of copper (Cu2+; as the fungicides Cu(OH)2 and CuSO4.5H2O). High Cu2+ concentrations (>40 mg L(-1)) were added to the microcosms to determine if copper toxicity to dechlorinating microbes is concentration dependent within the range used. After 30 days, the low-copper-amended soils closely resembled the nonsterile experiments to which no Cu2+ was added while the high-copper-amended microcosms were similar to the sterile experiment. Microcosms were also separately amended with 5.7 g L(-1) phosphate (PO4(2-); as KH2PO4), a nutrient regularly applied to rice fields. Phosphate-amended experiments also showed TB degradation, but no DTB formation, indicating the phosphate played a role, possibly as a microbial inhibitor or an alternative electron acceptor, in limiting the dechlorination of TB. In summary, TB dechlorination was inhibited at high Cu(OH)2, CuSO4.5H2O, and KH2PO4 concentrations.

Influence of water temperature on acetylcholinesterase activity in the Pacific tree frog (Hyla regilla).

This investigation evaluated whether acetylcholinesterase (AChE) in Pacific tree frogs (Hyla regilla) from different geographical locations was influenced by different temperatures during early aquatic life stages, independent of pesticide exposure. Tadpoles were collected from both a California coastal pond and a Sierra Nevada mountain range pond, USA. Groups of frogs from each location were raised in temperatures representative of either the Sierra Nevada (8 degrees C) or the coastal (19 degrees C) location. Metamorphs from both locations raised as tadpoles at 19 degrees C had AChE activities of 42.3 and 38.7 nm/min/mg protein, while those raised as tadpoles at 8 degrees C had activities of 26.9 and 28.2 nm/min/mg protein. A two-way analysis of variance revealed temperature to be the significant factor in determining AChE activity (F = 22.3, p < 0.001), although origin was not important (F = 0.09, p = 0.75). Interpretations regarding the influence of pesticides upon AChE activity in Pacific tree frogs must consider the influence of environmental temperature to enable cross-population comparisons.

Influence of organic carbon on reductive dechlorination of thiobencarb in California rice field soils.

The herbicide thiobencarb is suspected of causing delayed phytotoxicity syndrome (DPS) in rice plants. While the ultimate agent appears to be its dechlorinated product (deschlorothiobencarb), the influence of organic carbon on the formation of deschlorothiobencarb in California rice field soils has not been investigated. Thus, two different soils were compared for their ability to reductively dechlorinate thiobencarb with carbon augmentation: one from the eastern Sacramento Valley, which has historically displayed DPS, and one from the western Sacramento Valley, which has not. Rice straw was homogenized into samples of each soil to produce 0, 0.33 or 2% organic carbon augmentation. During 90-days of anoxic incubation, substantial deschlorothiobencarb production was measured in both soil types. However, only the thiobencarb degradation rate in the eastern valley soil was positively correlated with carbon content. Thus, other characteristics of DPS-resistant soils may limit deschlorothiobencarb formation.