The number of studies concerning Submarine Groundwater Discharge (SGD) grew quickly as we entered the 21st century. Many hydrological and oceanographic processes that drive and influence SGD were ...identified and characterized during this period. These processes included tidal effects on SGD, water and solute fluxes, biogeochemical transformations through the subterranean estuary, and material transport via SGD from land to sea. Here we compile and summarize the significant progress in SGD assessment methodologies, considering both the terrestrial and marine driving forces, and local as well as global evaluations of groundwater discharge with an emphasis on investigations published over the past decade. Our treatment presents the state-of-the-art progress of SGD studies from geophysical, geochemical, bio-ecological, economic, and cultural perspectives. We identify and summarize remaining research questions, make recommendations for future research directions, and discuss potential future challenges, including impacts of climate change on SGD and improved estimates of the global magnitude of SGD.
We recently demonstrated that marrow stromal cells (MSCs) augment collateral remodeling through release of several cytokines such as VEGF and bFGF rather than via cell incorporation into new or ...remodeling vessels. The present study was designed to characterize the full spectrum of cytokine genes expressed by MSCs and to further examine the role of paracrine mechanisms that underpin their therapeutic potential. Normal human MSCs were cultured under normoxic or hypoxic conditions for 72 hours. The gene expression profile of the cells was determined using Affymetrix GeneChips representing 12 000 genes. A wide array of arteriogenic cytokine genes were expressed at baseline, and several were induced >1.5-fold by hypoxic stress. The gene array data were confirmed using ELISA assays and immunoblotting of the MSC conditioned media (MSC(CM)). MSC(CM) promoted in vitro proliferation and migration of endothelial cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partially attenuated these effects. Similarly, MSC(CM) promoted smooth muscle cell proliferation and migration in a dose-dependent manner. Using a murine hindlimb ischemia model, murine MSC(CM) enhanced collateral flow recovery and remodeling, improved limb function, reduced the incidence of autoamputation, and attenuated muscle atrophy compared with control media. These data indicate that paracrine signaling is an important mediator of bone marrow cell therapy in tissue ischemia, and that cell incorporation into vessels is not a prerequisite for their effects.
Bone Health During the Menopause Transition and Beyond Karlamangla, Arun S; Burnett-Bowie, Sherri-Ann M; Crandall, Carolyn J
Obstetrics and gynecology clinics of North America,
12/2018, Volume:
45, Issue:
4
Journal Article
Peer reviewed
Open access
The menopause transition is a critical period for bone health, with rapid losses in bone mass and strength occurring in a 3-year window bracketing the date of the final menstrual period. Declines in ...bone mass are accompanied by deleterious changes in bone macrostructure and microarchitecture, which may be captured by changes in composite strength indices and indices of trabecular thickness and connectivity. The onset of the rapid bone loss phase is preceded by changes in sex steroid hormones and increases in markers of bone resorption, measurements of which may be clinically useful in predicting the onset of the rapid loss phase and in identifying the women who will lose the most bone strength over the menopause transition.
FGF‐23 is a novel regulator of phosphate metabolism. We studied the regulation of FGF‐23 by dietary phosphate in 66 men and women using two assays. Dietary phosphate restriction decreased FGF‐23 and ...loading increased FGF‐23 significantly. An assay that measured intact FGF‐23 showed the effects of dietary phosphate much more clearly than an assay that also measures presumed biologically inactive fragments. Dietary phosphate is a key regulator of circulating FGF‐23; choice of assay is critical when studying FGF‐23 physiology.
Introduction: Fibroblast growth factor 23 (FGF‐23) is a novel phosphaturic factor discovered through genetic studies of patients with renal phosphate wasting disorders. Ablation of the FGF‐23 gene in mice reduces renal phosphate excretion and increases serum phosphate, suggesting that FGF‐23 is critical for normal phosphate homeostasis. We examined the role of dietary phosphate in the regulation of FGF‐23 in humans.
Materials and Methods: Sixty‐six healthy males and females were randomized to either phosphate‐depleted or ‐loaded diets for 5 days, after a 4‐day run‐in diet. FGF‐23 was measured using an “intact” assay that only detects intact FGF‐23 peptide and with a “C‐terminal” assay that measures both intact FGF‐23 peptide and presumed biologically inactive carboxyl terminal fragments. The main outcome was the within group change in FGF‐23 with either phosphate depletion or loading.
Results: Using the intact FGF‐23 assay, mean FGF‐23 area under the curve (AUC) decreased by 9 ± 16% with phosphate depletion (p = 0.0041) and increased by 35 ± 29% with loading (p < 0.0001). Using the C‐terminal FGF‐23 assay, mean FGF‐23 AUC decreased by 8 ± 12% with phosphate depletion (p = 0.0003) and increased by 13 ± 20% with loading (p = 0.0016). Increases in FGF‐23 with phosphate loading were greater with the intact assay than with the C‐terminal assay (p = 0.0003). Using the intact assay only, FGF‐23 was significantly associated with serum phosphate (r = 0.39, p < 0.01), 24‐h urinary phosphate (r = 0.47, p < 0.01), fractional excretion of phosphate (r = 0.29, p < 0.01), and 1,25‐dihydroxyvitamin D (r = −0.30, p < 0.01). The association between the assays was weak (r = 0.26, p < 0.01).
Conclusions: Dietary phosphate is a key regulator of circulating FGF‐23 levels in humans. Additionally, choice of assay is critical when performing physiologic investigations of FGF‐23.
In this article, we explore the potential role of social media in helping movements expand and/or strengthen themselves internally, processes we refer to as scaling up. Drawing on a case study of ...Black Lives Matter (BLM) that includes both analysis of public social media accounts and interviews with BLM groups, we highlight possibilities created by social media for building connections, mobilizing participants and tangible resources, coalition building, and amplifying alternative narratives. We also discuss challenges and risks associated with using social media as a platform for scaling up. Our analysis suggests that while benefits of social media use outweigh its risks, careful management of online media platforms is necessary to mitigate concrete, physical risks that social media can create for activists.
Bone marrow cell therapy is reported to contribute to collateral formation through cell incorporation into new or remodeling vessels. However, the possible role of a paracrine contribution to this ...effect is less well characterized.
Murine marrow-derived stromal cells (MSCs) were purified by magnetic bead separation of cultured bone marrow. The release of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and monocyte chemoattractant protein-1 (MCP-1) was demonstrated by analysis of MSC conditioned media (MSC-CM). MSC-CM enhanced proliferation of endothelial cells and smooth muscle cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partly attenuated these effects. Balb/C mice (n=10) underwent distal femoral artery ligation, followed by adductor muscle injection of 1x10(6) MSCs 24 hours later. Compared with controls injected with media (n=10) or mature endothelial cells (n=8), distal limb perfusion improved, and mid-thigh conductance vessels increased in number and total cross-sectional area. MSC injection improved limb function and appearance, reduced the incidence of auto-amputation, and attenuated muscle atrophy and fibrosis. After injection, labeled MSCs were seen dispersed between muscle fibers but were not seen incorporated into mature collaterals. Injection of MSCs increased adductor muscle levels of bFGF and VEGF protein compared with controls. Finally, colocalization of VEGF and transplanted MSCs within adductor tissue was demonstrated.
MSCs secrete a wide array of arteriogenic cytokines. MSCs can contribute to collateral remodeling through paracrine mechanisms.
Current approaches to diagnosing testosterone deficiency do not consider the physiological consequences of various testosterone levels or whether deficiencies of testosterone, estradiol, or both ...account for clinical manifestations.
We provided 198 healthy men 20 to 50 years of age with goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assigned them to receive a placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel daily for 16 weeks. Another 202 healthy men received goserelin acetate, placebo gel or testosterone gel, and anastrozole (to suppress the conversion of testosterone to estradiol). Changes in the percentage of body fat and in lean mass were the primary outcomes. Subcutaneous- and intraabdominal-fat areas, thigh-muscle area and strength, and sexual function were also assessed.
The percentage of body fat increased in groups receiving placebo or 1.25 g or 2.5 g of testosterone daily without anastrozole (mean testosterone level, 44±13 ng per deciliter, 191±78 ng per deciliter, and 337±173 ng per deciliter, respectively). Lean mass and thigh-muscle area decreased in men receiving placebo and in those receiving 1.25 g of testosterone daily without anastrozole. Leg-press strength fell only with placebo administration. In general, sexual desire declined as the testosterone dose was reduced.
The amount of testosterone required to maintain lean mass, fat mass, strength, and sexual function varied widely in men. Androgen deficiency accounted for decreases in lean mass, muscle size, and strength; estrogen deficiency primarily accounted for increases in body fat; and both contributed to the decline in sexual function. Our findings support changes in the approach to evaluation and management of hypogonadism in men. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00114114.).
The Politics of Potholes Burnett, Craig M.; Kogan, Vladimir
The Journal of politics,
01/2017, Volume:
79, Issue:
1
Journal Article
Peer reviewed
By conditioning their support for political incumbents on observed performance outcomes, voters can motivate elected officials to represent their interests faithfully while in office. Whether ...elections serve this function in subnational US government remains unclear, however, because much of the existing research on retrospective voting in these contexts focuses on outcomes that are not obviously salient to voters or over which the relevant government officials have limited influence. In this study, we examine one outcome—the quality of local roads—that is both salient and unquestionably under the control of city government. Our analysis leverages within-city variation in the number of pothole complaints in one of America’s largest cities and shows that such variation can explain neighborhood-level differences in support for incumbents in two political offices—mayor and city council—across several electoral cycles.
Context:
In postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy.
Objective:
The objective of the study was to ...determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength.
Design:
This was an open-label, randomized controlled trial.
Participants and Methods:
We performed high-resolution peripheral quantitative computed tomography at the distal tibia and radius in 94 postmenopausal osteoporotic women randomized to 2 years of teriparatide 20 μg sc daily, denosumab 60 mg sc every 6 months, or both.
Results:
Total volumetric bone mineral density (vBMD) at the radius and tibia, trabecular vBMD at the radius, and cortical vBMD at the tibia all increased more in the combination group than both monotherapy groups (P < .002 for all comparisons with combination). Cortical thickness at the tibia also increased more in the combination group (8.1% ± 4.3%) than both other groups (P < .001). Cortical porosity at both the radius and tibia increased progressively over the 24-month treatment period in the teriparatide group but was stable in both other groups (P < .001 teriparatide vs both other groups). Trabecular vBMD at the tibia increased similarly in all groups, whereas radius trabecular vBMD increased more in the combination group than the other groups (P < .01 for both comparisons). Finite element analysis-estimated strength improved or was maintained by all treatments at both the radius and tibia.
Conclusions:
Two years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments, particularly in cortical bone. These findings suggest that this regimen may be beneficial in postmenopausal osteoporosis.
As assessed by HR-pQCT, two years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments, particularly in cortical bone.
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