Laparo-endoscopic single-site (LESS) radical nephrectomy with renal vein thrombectomy: initial report

Abstract Background By combining trocar sites and extraction incision, Laparo-endoscopic Single-site Surgery (LESS) may provide less morbidity than traditional laparoscopy. Concerns continue about LESS for locally advanced tumors. We present our experience with LESS-radical nephrectomy with renal vein thrombectomy (LESS-RN-RVT) Case Presentation Between 5-6/2009, 2 patients underwent LESS-RN-RVT (1 right-/1 left-side). Standard steps of multi-site laparoscopic radical nephrectomy were performed, including stapled renal vein thrombectomy and intact specimen extraction. Both cases were successfully completed by LESS without complications. Mean tumor size was 7.8 cm, incision size 4.5 cm, operative time 152 min, EBL 100 ml, and hospital stay 2.5 days. Both patients had negative margins, and are alive at time of last follow-up. One did not require postoperative opiates. Conclusions LESS-RN-RVT is safe and feasible in selected patients with renal vein thrombi. Further accumulation of data and comparison to multiport laparoscopic technique are requisite

Evaluation of an epigenetic assay for predicting repeat prostate biopsy outcome in African American men

OBJECTIVE: To evaluate an epigenetic assay performed on tissue from negative prostate biopsies in a group of African American (AA) men undergoing repeat biopsy, and to compare accuracy for predicting repeat biopsy outcome to prior studies conducted in predominantly Caucasian populations. MATERIALS AND METHODS: The study population consisted of 211 AA men from 7 urology centers across the United States; all of whom were undergoing 12-core transrectal ultrasound-guided repeat biopsy within 30 months from a negative index biopsy. All biopsy cores from the negative index biopsy were profiled for the epigenetic biomarkers GSTP1, APC, and RASSF1 using ConfirmMDx for Prostate Cancer (MDxHealth, Irvine, CA). RESULTS: Upon repeat biopsy, 130 of 211 subjects (62%) had no prostate cancer (PCa) detected and 81 of 211 (38%) were diagnosed with PCa. Of the subjects with PCa, 54 (67%) were diagnosed with Gleason score (GS) = 7 disease. For detection of PCa at repeat biopsy, ConfirmMDx sensitivity was 74.1% and specificity was 60.0%, equivalent to prior studies (P = .235 and .697, respectively). For detection of GS >= 7 PCa, sensitivity was 78% and specificity was 53%. The negative predictive values for detection of all PCa and GS >= 7 PCa were 78.8% and 94.2%, respectively. CONCLUSION: In this group of AA men, we successfully validated an epigenetic assay to assess the need for repeat biopsy. Results were consistent with previous studies from predominantly Caucasian populations. Therefore, the ConfirmMDx assay is a useful tool for risk stratification of AA men who had an initial negative biopsy

Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure

Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2

SUMMARY To maintain lifelong production of blood cells, hematopoietic stem cells (HSC) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSC (LT-HSC) reside in several, perhaps overlapping, niches that produce regulatory molecules/signals necessary for homeostasis and increased output following stress/injury 1–5. Despite significant advances in specific cellular or molecular mechanisms governing HSC/niche interactions, little is understood about regulatory function within the intact mammalian hematopoietic niche. Recently, we and others described a positive regulatory role for Prostaglandin E2 (PGE2) on HSC function ex vivo 6,7. While exploring the role of endogenous PGE2 we unexpectedly observed hematopoietic egress after nonsteroidal anti-inflammatory drug (NSAID) treatment. Surprisingly, this was independent of the SDF-1/CXCR4 axis. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin (OPN). Hematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in higher species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced EP4 receptor signaling. These results not only uncover unique regulatory roles for EP4 signaling in HSC retention in the niche but also define a rapidly translatable strategy to therapeutically enhance transplantation

Effect of vitamin D on bone mineral density of elderly patients with osteoporosis responding poorly to bisphosphonates

BACKGROUND: Bisphosphonates are indicated in the prevention and treatment of osteoporosis. However, bone mineral density (BMD) continues to decline in up to 15% of bisphosphonate users. While randomized trials have evaluated the efficacy of concurrent bisphosphonates and vitamin D, the incremental benefit of vitamin D remains uncertain. METHODS: Using data from the Canadian Database of Osteoporosis and Osteopenia (CANDOO), we performed a 2-year observational cohort study. At baseline, all patients were prescribed a bisphosphonate and counseled on vitamin D supplementation. After one year, patients were divided into two groups based on their response to bisphosphonate treatment. Non-responders were prescribed vitamin D 1000 IU daily. Responders continued to receive counseling on vitamin D. RESULTS: Of 449 patients identified, 159 were non-responders to bisphosphonates. 94% of patients were women. The mean age of the entire cohort was 74.6 years (standard deviation = 5.6 years). In the cohort of non-responders, BMD at the lumbar spine increased 2.19% (p < 0.001) the year after vitamin D was prescribed compared to a decrease of 0.55% (p = 0.36) the year before. In the cohort of responders, lumbar spine BMD improved 1.45% (p = 0.014) the first year and 1.11% (p = 0.60) the second year. The difference between the two groups was statistically significant the first year (p < 0.001) but not the second (p = 0.60). Similar results were observed at the femoral neck but were not statistically significant. CONCLUSION: In elderly patients with osteoporosis not responding to bisphosphonates, vitamin D 1000 IU daily may improve BMD at the lumbar spine

Mapping of the Disease Locus and Identification of ADAMTS10 As a Candidate Gene in a Canine Model of Primary Open Angle Glaucoma

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure, but the specific mechanisms are unknown. In this study, we used genome-wide SNP arrays to map the disease gene in a colony of Beagle dogs with inherited POAG to within a single 4 Mb locus on canine chromosome 20. The Beagle POAG locus is syntenic to a previously mapped human quantitative trait locus for intraocular pressure on human chromosome 19. Sequence capture and next-generation sequencing of the entire canine POAG locus revealed a total of 2,692 SNPs segregating with disease. Of the disease-segregating SNPs, 54 were within exons, 8 of which result in amino acid substitutions. The strongest candidate variant causes a glycine to arginine substitution in a highly conserved region of the metalloproteinase ADAMTS10. Western blotting revealed ADAMTS10 protein is preferentially expressed in the trabecular meshwork, supporting an effect of the variant specific to aqueous humor outflow. The Gly661Arg variant in ADAMTS10 found in the POAG Beagles suggests that altered processing of extracellular matrix and/or defects in microfibril structure or function may be involved in raising intraocular pressure, offering specific biochemical targets for future research and treatment strategies

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

Termite sensitivity to temperature affects global wood decay rates.

Deadwood is a large global carbon store with its store size partially determined by biotic decay. Microbial wood decay rates are known to respond to changing temperature and precipitation. Termites are also important decomposers in the tropics but are less well studied. An understanding of their climate sensitivities is needed to estimate climate change effects on wood carbon pools. Using data from 133 sites spanning six continents, we found that termite wood discovery and consumption were highly sensitive to temperature (with decay increasing >6.8 times per 10°C increase in temperature)-even more so than microbes. Termite decay effects were greatest in tropical seasonal forests, tropical savannas, and subtropical deserts. With tropicalization (i.e., warming shifts to tropical climates), termite wood decay will likely increase as termites access more of Earth's surface

Long-term survival of participants in the prostate cancer prevention trial

The Prostate Cancer Prevention Trial (PCPT) is a seminal study in the field of urology. More than 10 years after its initial publication, updated data from this trial continue to shape our understanding of prostate cancer. Among the major findings from the PCPT has been the demonstration that prostate cancer is common in men with prostate-specific antigen (PSA) once thought to be in the normal range, [1] finasteride prevents the development of benign prostatic hypertrophy, [2] it increases the sensitivity of PSA [3] and digital rectal examination. [4] Furthermore the PCPT helped to establish the link between erectile dysfunction and cardiovascular disease, [5] and perhaps most importantly finasteride demonstrated a 25% relative risk reduction in the diagnosis of prostate cancer compared with placebo. [6