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Hiking is a common recreational activity that provides numerous health benefits, such as reduced risk of heart disease, reduced blood pressure, and improved cardiorespiratory fitness. The use of specifically designed trekking poles has become popular among participants seeking to alleviate sore knees and increase balance and stability while walking. This review provides an overview of physiologic and biomechanical responses elicited when trekking poles are used during outdoor activities, such as hiking or Nordic walking, and discusses the clinical implications of the use of trekking poles. Google Scholar, PubMed, and ScienceDirect databases, as well as university library catalogues, were searched for literature published between 1980 and 2019. The keywords used to search the literature were hiking poles, trekking poles, and Nordic walking and their combination with physiological responses, ground reaction forces, joint forces, spatiotemporal parameters, kinematics, electromyography, and/or balance. The related topics included the academic disciplines of biomechanics, sports science, and wilderness medicine. Reference lists of located studies were also reviewed for additional sources. During free, unloaded walking, users should compare the cost and benefit of using poles: Trekking poles decrease lower extremity loading and forces but increase cardiovascular demand. When carrying a large external load, trekking poles may offer benefit by decreasing lower extremity muscle activity and increasing balance and stability.

BACKGROUND Natural killer (NK) cell impairment is a feature of pulmonary arterial hypertension (PAH) and contributes to disease development in mouse models of NK cell deficiency (Ormiston et al, Circulation, 2012; Ratsep et al, AJP Lung, 2018). PAH is also strongly associated with mutations in BMPR2, the gene encoding the type-II bone morphogenetic protein receptor. Genetic and experimental evidence point to a loss of BMPR2 in the pulmonary endothelium as a critical contributor to disease development. However, the impact of endothelial BMPR2 loss on NK cell impairment in PAH remains unknown. METHODS AND RESULTS SiRNA-mediated silencing of BMPR2 in human pulmonary artery endothelial cells (HPAEC) significantly reduced the surface presentation and secretion of the α-type receptor for interleukin-15 (IL-15Rα), a major regulator of NK cell survival, proliferation and activity. Assessment of IL-15Rα transcriptional variants by RNA-Seq and glycosylation by immunoblotting demonstrated that this reduction was not due to changes in receptor transcription or processing. Treatment of HPAECs with the matrix metalloproteinase inhibitor Batimastat also ruled out a role for altered IL-15Rα cleavage with BMPR2 silencing. Instead, confocal microscopy identified impaired trafficking of IL-15Rα through the trans-Golgi-network (TGN) in BMPR2-silenced cells. To evaluate the effects of impaired IL-15 mediated signaling and NK cell loss on PAH development, NK cell-deficient Il15-/- rats and immune-competent Il15+/+ littermates were exposed to either the monocrotaline (MCT) or SUGEN/hypoxia models of experimental pulmonary hypertension. While both male and female Il15-/- rats developed more severe disease than their wildtype counterparts in the SUGEN/Hypoxia model, only male Il15-/- rats demonstrated this enhanced severity in the MCT model, which is the only one of the two models to reproduce the sex-based difference in disease severity that is observed in human PAH patients. Assessment of genes associated with sex hormone signaling and metabolism identified a potential increase in pulmonary Cyp1b1 expression (n=5-7, p=0.08) in male MCT-challenged Il15-/- rats relative to Il15+/+ controls. CONCLUSION We have identified the loss of IL-15 signaling as a novel BMPR2-dependent contributor to NK cell impairment and pulmonary arterial hypertension pathogenesis. Ongoing work includes assessing the contribution of sex hormones to immune-mediated disease processes in PAH.

The Palaeoproterozoic Yerrida, Bryah and Padbury Group sedimentary rocks are located on the northern margin of the Archaean Yilgarn Craton and are host to epigenetic gold (Peak Hill, Fortnum and Horseshoe), volcanic-hosted massive sulphide (VHMS; Horseshoe Lights, Red Bore and DeGrussa) and epithermal copper deposits (Thaduna). The DeGrussa Cu–Au–Ag VHMS deposit (12.4 Mt @ 4.7% Cu and 1.8 g/t Au) comprises four lenses and is hosted in turbiditic sedimentary rocks and basalts of the DeGrussa host sediments/Karalundi Formation, the lowest mafic volcano-sedimentary unit of the Bryah Group and crosscut by intrusive dolerite of Narracoota Formation age. Immediate wall rocks to the ore lenses are commonly altered to chlorite and talc-carbonate. A number of geochronological techniques were employed to date mineralisation in the DeGrussa deposit. These include rhenium–osmium (Re–Os) of molybdenite, Pb isotopes of galena and pyrite, and U–Pb on zircon. Re–Os geochronology of molybdenite resulted in ages of 2027 ± 7 Ma and 2011 ± 7 Ma and 2013 ± 7 Ma for mineralisation, similar to Pb–Pb model ages for galena of 2060 ± 50 Ma and 2075 ± 50 Ma. U–Pb for magmatic zircons from intrusive dolerite within the mine sequence provided ages of 1991 ± 7 Ma, 1999 ± 7 Ma and 2003 ± 7 Ma with granodiorite rocks providing ages of 2014 ± 7 Ma and 2018 ± 9 Ma. Remobilisation of DeGrussa sulphides occurred at approximately 1980 Ma given Re–Os ages of pyrrhotite (1982 ± 7 Ma and 1984 ± 8 Ma) and Pb–Pb pyrite ages of 1980 ± 30 Ma. Re-examination of the Pb isotopic evolution models for this area and the Capricorn Orogen suggests that the model of Stacey and Kramers (1975) is more appropriate than Cumming and Richards (1975) ; using the former model leads to revised model ages as follows: Horseshoe Lights VHMS 2000 ± 35 Ma; Nathans 1820 ± 30 Ma, Peak Hill (Main pit: 1610 Ma, 1620 Ma, 1705 Ma, and 2070 ± 30 Ma; Fiveways: 1955 Ma; Mt. Pleasant: 1770 Ma), Horseshoe/Cassidy 1940 ± 30 Ma, Mikhaburra 1915 ± 30 Ma, and Labouchere 1800 ± 30 Ma. These new ages coincide with major regional orogenic events – the Glenburgh from 2005 to 1960 Ma, the Capricorn from 1830 to 1780 Ma, the Mangaroon from 1690 to 1620 Ma, and the Edmundian from 920 to 850 Ma. Although orogenic events are compressional, the Yerrida/Bryah Group sedimentary rocks, along with mineralisation at the DeGrussa and Horseshoe Lights deposits, were formed in an extensional basin setting during the Glenburgh Orogeny. These new ages assist in constraining stratigraphic and mineralising events of the Palaeoproterozoic Yerrida, Bryah and Padbury Group with regional orogenic events and may provide guidance for exploration for significant gold and base metal mineralisation, not only in the Bryah, but also throughout the larger Capricorn Orogen.

Atauro is a key to understanding the late stage volcanic and subduction history of the Banda Arc to the north of Timor. A volcanic history of bi-modal subaqueous volcanism has been established and new whole rock and trace element geochemical data show two compositional groups, basaltic andesite and dacite–rhyolite. 40Ar/39Ar geochronology of hornblende from rhyo-dacitic lavas confirms that volcanism continued until 3.3 Ma. Following the cessation of volcanism, coral reef marine terraces have been uplifted to elevations of 700 m above sea level. Continuity of the terraces at constant elevations around the island reflects regional-scale uplift most likely linked to sublithospheric processes such as slab detachment. Local scale landscape features of the eastern parts of Atauro are strongly controlled by normal faults. The continuation of arc-related volcanism on Atauro until at least 3.3 Ma suggests that subduction of Australian lithosphere continued until near this time. This data is consistent with findings from the earthquake record where the extent of the Wetar seismic gap to a depth of 350 km suggests slab breakoff, as a result of collision, commenced at ∼4 Ma, leading to subsequent regional uplift recorded in elevated terraces on Atauro and neighbouring islands.

The hypocholesterolemic activity for novel ureido fibrate analogues was found to be over 100-fold greater than for any “second-generation” fibrate in cholesterol-fed rats. A comparison of 12 related analogues revealed that the optimal configuration for a urea-bridging region located between two aromatic rings consisted of a trisubstituted nitrogen, optimally substituted with a C7 alkyl chain and linked by dimethylene to a phenoxyisobutyrate moiety found in most fibrate analogues. The hypocholesterolemic potency of these compounds was found to correlate with their increased intrinsic fibrate activity as determined by the ability to induce omega-hydroxylase activity either in rat hepatocyte cultures or in vivo, and not with their 10-fold increased ACAT inhibitory potency when compared to other fibrates. The most active compound, 2-(4-(2-(N'-(2,4- difluorophenyl)-N-heptylureido)ethyl)phenoxy)-2-methylpropionic acid, referred to as (2), was found to induce omega-hydroxylase activity in hepatocytes at concentrations between 5 and 100 nM compared to 1-20 microM concentrations for bezafibrate, and lower serum VLDL+LDL cholesterol in rats at doses between 0.1 and 0.5 mg/kg per day compared to doses of 25-100 mg/kg per day for bezafibrate. Single-dose pharmacokinetic studies with 2 indicated that total drug exposure will be much lower at hypocholesterolemic doses due to the enhanced intrinsic activity, and may result in an improved safety profile for these novel trisubstituted ureido fibrate analogues in rats and humans compared to other fibrates.

The hypothesis that mitochondrial sterol 27-hydroxylase plays a role in the sterol-mediated down-regulation of LDL receptor activity was evaluated in HepG2 cells. 27-Hydroxycholesterol was found to be more potent at suppressing LDL receptor activity than cholesterol (IC50 values of 8 mu M and 142 mu M for 27-hydroxycholesterol and cholesterol, respectively) when the sterols were delivered to cells from 2-hydroxypropyl-beta-cyclodextrin (beta-CD)-solubilized solutions. Cyclosporin, an immunosuppressant which has been shown to inhibit the 27-hydroxylation of sterols, was used to assess whether the formation of endogenous 27-hydroxycholesterol was required for the cholesterol-induced suppression of LDL receptor activity. Cyclosporin dose-dependently inhibited the 27-hydroxylation of cholesterol by HepG2 mitochondria (Ki = 0.25 mu M) and HepG2 cell cultures (IC50 = 1 mu M). At 1 mu M, cyclosporin had no effect on LDL receptor activity, and did not prevent the suppression of LDL receptor activity caused by: 1) the addition of beta-CD-solubilized cholesterol, 2) the receptor-mediated uptake of beta-VLDL, or 3) the inhibition of cholesterol esterification. In contrast, 10 mu M cyclosporin was found to inhibit the esterification of cholesterol and to increase the cellular level of free cholesterol resulting in suppression of LDL receptor activity. These results suggest that if mitochondrial sterol 27-hydroxylase plays a role in the regulation of LDL receptor activity, it is not through the formation of potent regulatory oxysterols, but through its effects on the availability and/or size of the free cholesterol pool regulating LDL receptor activity.

We investigated the effect of electroporation on the motility of sperm from chinook salmon, Oncorhynchus tshawytscha , the ability of the electroporated sperm to fertilize ova, and to transfer exogenous DNA into chinook salmon eggs. Sperm were electroporated in the presence of pRSV-lacZ DNA over a range of field strengths, from 250 V/cm to 1150 V/cm, with pulse lengths of 7.7, 18.6 and 27.4 ms. The motility of the sperm was found to decrease with increasing field strength. The ability of the electroporated sperm to fertilize salmon ova was comparable to the control sperm. The rates of development of the control and treated embryos were similar. Successful transfer of DNA was indicated by Southern analysis. Depending on the electroporation conditions, 1 out of 20 fry in one experiment, and 2 out of 20 fry in a second experiment showed hybridization to pRSV-lacZ DNA. Whether the plasmid DNA detected in these fry was integrated or not is not clear, but three bands were detected in all the positive fry.