Soil microbial communities and degradation of pesticides in greenhouse effluent through a woodchip bioreactor.

Pesticides, including insecticides and fungicides, are major contaminants in the effluent from intensive agricultural systems, such as greenhouses. Because of their constant use and persistence, some pesticides can accumulate in soil and/or run off into adjacent waterways. Microbial communities in soil can degrade some pesticides, and bioreactors with enhanced microbial communities have the potential to facilitate decontamination before the effluent is released into the environment. In this study, we sampled the soil along a gradient from immediately below greenhouses, into, through and below a bioreactor. Multi-analyte pesticide screening was undertaken along with shotgun metagenomic sequencing, to assess microbial community taxonomic profiles and metabolic pathway responses for functional analysis. Two insecticides (imidacloprid and fipronil) and nine fungicides were identified in the soil samples, with a general decrease in most pesticides with increasing distance from the greenhouses. Diversity indexes of taxonomic profiles show changes in the microbial community along the gradient. In particular, microbial communities were significantly different in the bioreactor, with lower Shannon diversity compared to immediately below the greenhouses, in the channels leading into the bioreactor and further downstream. Metabolic pathway analysis revealed significant changes in a wide range of core housekeeping genes such as protein/amino acid synthesis and lipid/fatty acid biosynthesis among the sampling sites. The result demonstrates that the composition and potential functional pathways of the microbial community shifted towards an increased tendency for phytol and contaminant degradation in the bioreactor, facilitated by high organic matter content. This highlights the potential to use enhanced microbial communities within bioreactors to reduce contamination by some pesticides in sediment receiving run-off from greenhouses.

Denosumab Prevents Bone Loss and Microarchitectural Deterioration in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression Therapy: A Randomized Controlled Trial.

PURPOSE: Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)-positive early-stage breast cancer but accelerates bone loss. We therefore hypothesized that suppressing bone remodeling using denosumab (DMAB) would prevent bone loss in these women. METHODS: In a 12-month double-blind randomized trial, 68 women with ER-positive early-stage breast cancer commencing ovarian function suppression and AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n = 34) once every 6 months (at 0 and 6 months). Volumetric bone mineral density (BMD), microarchitecture, and estimated bone strength of the distal tibia and distal radius were measured using high-resolution peripheral quantitative computed tomography, and spine and hip BMD were measured using dual-energy X-ray absorptiometry at 0, 6, and 12 months. The primary end point and treatment effect was the mean adjusted between group difference (MAD; [95% CI]) in distal tibial total volumetric BMD over 12 months, with a single P value tested over all time points. The study is registered with the Australian New Zealand Clinical Trials Registry (anzctr.org.au; identifier: ACTRN12616001051437). RESULTS: Intention-to-treat analysis included all 68 randomly assigned women. Over 12 months, compared with PBO, DMAB prevented the decrease in distal tibial total BMD (MAD, 20.8 mg HA/cm3 [95% CI, 17.3 to 24.2]), cortical BMD (42.9 mg HA/cm3 [95% CI, 32.1 to 53.9]), trabecular BMD (3.32 mg HA/cm3 [95% CI, 1.45 to 5.20], P = .004), estimated stiffness (11.6 kN/m [95% CI, 7.6 to 15.6]), and failure load (563 N [95% CI, 388 to 736]). Findings were similar at the distal radius. Decreases in BMD at the lumbar spine (MAD, 0.13 g/cm2 [95% CI, 0.11 to 0.15]), total hip (0.08 g/cm2 [95% CI, 0.07 to 0.09], and femoral neck (0.06 g/cm2 [95% CI, 0.05 to 0.07]) were also prevented. All P < .001 unless otherwise noted. CONCLUSION: Treatment with DMAB at commencement of estradiol suppression therapy preserves BMD, bone microarchitecture, and estimated strength, and is likely to increase fracture-free survival.

Cardiometabolic Effects of Denosumab in Premenopausal Women with Breast Cancer Receiving Estradiol Suppression: RCT.

CONTEXT: Menopause is associated with changes in musculoskeletal, body composition, and metabolic parameters that may be amplified in premenopausal women receiving estradiol suppression for breast cancer. Denosumab offsets deleterious skeletal effects of estradiol suppression and has been reported to have effects on body composition and metabolic parameters in pre-clinical and observational studies, though evidence from double-blind randomized controlled trials is limited. OBJECTIVE: To assess the effect of denosumab on body composition and metabolic parameters. METHODS: In a pre-specified secondary analysis of a 12-month randomized, double-blind, placebo-controlled trial, 68 premenopausal women with breast cancer initiating ovarian function suppression and aromatase inhibition were randomized to denosumab 60-mg or placebo administered at baseline and 6 months. Outcome measures were total and regional fat and lean mass (DXA), body mass index (BMI), waist and hip circumference, fasting glucose, HOMA-IR, and lipid profile. Using a mixed model, between-group mean adjusted differences, MAD, [95% confidence interval], over time are reported. RESULTS: Over 12 months, relative to placebo, android and gynoid fat mass decreased in the denosumab group (-266 g [95%CI -453 to -79], P = 0.02, and -452 g [95%CI -783 to -122], P = 0.03, respectively). Total fat mass and waist circumference were lower in the denosumab group but not significantly so (-1792g [95% CI -3346 to -240], P = 0.08 and (- 3.77 cm [95% CI -6.76 to -0.79], P = 0.06, respectively). No significant treatment effects were detected in lean mass, BMI, hip circumference, fasting glucose, HOMA-IR, or lipid profile. CONCLUSIONS: In premenopausal women receiving estradiol suppression, denosumab decreases some measures of fat mass with no detectable effects on other measures of body composition or metabolic parameters.