The effects of an increase in intensity during tapering on 1,500m running performance

We examined the effect of completing the final interval training session during a taper at either: i) race pace; or ii) faster than race pace, on 1,500 m running performance and neuromuscular performance. Ten trained runners (age 21.7 ± 3.0 years, height 182.9 ± 7.0 cm, body mass 73.4 ± 6.8 kg, personal best 1,500 m time 4:17.5 ± 0:26.9 min) completed two conditions, consisting of 7-d of regular training and a 7-d taper, separated by three weeks of training. In one condition, the taper was prescribed using prediction models based on the practices of elite British middle-distance runners, with the intensity of the final interval session being equal to 1,500 m race pace (RP). The taper was repeated in the HI condition, except the final interval session was completed at 115% of 1,500 m race pace. A 1,500 m treadmill time trial, measures of maximum voluntary isometric strength (MVC) and rate of force development (RFD) were completed before and after regular training and tapering. Performance was most likely improved after RP (mean ± 90% confidence limits, 10.1 ± 1.6 s), and possibly beneficial after HI (4.2 ± 12.0 s). Both MVC force (p = 0.002) and RFD (p = 0.02) were improved after tapering, without differences between conditions. A race-pace taper based on the practices of elite middle-distance runners is recommended to improve performance in young, sub-elite runners. The effect of this strategy with an increase in interval intensity is highly variable and should be implemented with caution

Mapping Groundwater Dependent Ecosystems in California

BACKGROUND: Most groundwater conservation and management efforts focus on protecting groundwater for drinking water and for other human uses with little understanding or focus on the ecosystems that depend on groundwater. However, groundwater plays an integral role in sustaining certain types of aquatic, terrestrial and coastal ecosystems, and their associated landscapes. Our aim was to illuminate the connection between groundwater and surface ecosystems by identifying and mapping the distribution of groundwater dependent ecosystems (GDEs) in California. METHODOLOGY/PRINCIPAL FINDINGS: To locate where groundwater flow sustains ecosystems we identified and mapped groundwater dependent ecosystems using a GIS. We developed an index of groundwater dependency by analyzing geospatial data for three ecosystem types that depend on groundwater: (1) springs and seeps; (2) wetlands and associated vegetation alliances; and (3) stream discharge from groundwater sources (baseflow index). Each variable was summarized at the scale of a small watershed (Hydrologic Unit Code-12; mean size = 9,570 ha; n = 4,621), and then stratified and summarized to 10 regions of relative homogeneity in terms of hydrologic, ecologic and climatic conditions. We found that groundwater dependent ecosystems are widely, although unevenly, distributed across California. Although different types of GDEs are clustered more densely in certain areas of the state, watersheds with multiple types of GDEs are found in both humid (e.g. coastal) and more arid regions. Springs are most densely concentrated in the North Coast and North Lahontan, whereas groundwater dependent wetlands and associated vegetation alliances are concentrated in the North and South Lahontan and Sacramento River hydrologic regions. The percentage of land area where stream discharge is most dependent on groundwater is found in the North Coast, Sacramento River and Tulare Lake regions. GDE clusters are located at the highest percentage in the North Coast (an area of the highest annual rainfall totals), North Lahontan (an arid, high desert climate with low annual rainfall), and Sacramento River hydrologic regions. That GDEs occur in such distinct climatic and hydrologic settings reveals the widespread distribution of these ecosystems. CONCLUSIONS/SIGNIFICANCE: Protection and management of groundwater-dependent ecosystems are hindered by lack of information on their diversity, abundance and location. By developing a methodology that uses existing datasets to locate GDEs, this assessment addresses that knowledge gap. We report here on the application of this method across California, but believe the method can be expanded to regions where spatial data exist

Promoting Physical Activity with Hard-to-Reach Women: An Iterative and Participatory Research Study

Approximately half of all UK women are insufficiently physically active, with the lowest activity rates among ‘Hard-to-Reach’ or unreached women. In this article, Kathryn Brook, Dr Andy Pringle FRSPH, Dr Jackie Hargreaves and Dr Nicky Kime of Leeds Beckett University outline their research into developing methods to assess and meet the needs of ‘Hard-to-Reach’ women in needs-led and person-centred interventions

Glial Progenitor-Like Phenotype in Low-Grade Glioma and Enhanced CD133-Expression and Neuronal Lineage Differentiation Potential in High-Grade Glioma

Background: While neurosphere-as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem/progenitor cells as well as the prognostic value of stem/progenitor cell marker expression in glioma are poorly clarified. Methodology/Principal Findings: Viable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade glioma specimens were flow-cytometrically analyzed for markers characteristics of stem cells (CD133); glial progenitors (PDGFR alpha, A2B5, O4, and CD44); and late oligodendrocyte progenitors (O1). In parallel, the expression of glial fibrillary acidic protein (GFAP), synaptophysin and neuron-specific enolase (NSE) was immunohistochemically analyzed in fixed tissue specimens. Irrespective of the grade and morphological diagnosis of gliomas, glioma cells concomitantly expressed PDGFRa, A2B5, O4, CD44 and GFAP. In contrast, O1 was weakly expressed in all low-grade and the majority of high-grade glioma specimens analyzed. Co-expression of neuronal markers was observed in all high-grade, but not low-grade, glioma specimens analyzed. The rare CD133 expressing cells in low-grade glioma specimens typically co-expressed vessel endothelial marker CD31. In contrast, distinct CD133 expression profiles in up to 90% of CD45-negative glioma cells were observed in 12 of the 17 high-grade glioma specimens and the majority of these CD133 expressing cells were CD31 negative. The CD133 expression correlates inversely with length of patient survival. Surprisingly, cytogenetic analysis showed that gliomas contained normal and abnormal cell karyotypes with hitherto indistinguishable phenotype. Conclusions/Significance: This study constitutes an important step towards clarification of lineage commitment and differentiation blockage of glioma cells. Our data suggest that glioma cells may resemble expansion of glial lineage progenitor cells with compromised differentiation capacity downstream of A2B5 and O4 expression. The concurrent expression of neuronal markers demonstrates that high-grade glioma cells are endowed with multi-lineage differentiation potential in vivo. Importantly, enhanced CD133 expression marks a poor prognosis in gliomas

Changes in elderly women's health-related quality of life following discontinuation of hormone replacement therapy

BACKGROUND: Many women have discontinued hormone replacement therapy (HRT) in view of recent findings. The goal of this study was to determine if HRT discontinuation is associated with changes in health-related quality of life (HRQOL) in elderly women. METHODS: We studied women enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) program, linking prescription claims with data from a longitudinal mail survey. HRQOL measures included the number of days out of the last 30 that physical health was not good and analogous measures for mental health, pain, and interference with activities, as well as a composite "healthy days" measure developed by CDC. Longitudinal analyses focused on 2,357 women who completed surveys in both 2002 and 2003, and who used HRT at baseline (mean age = 75.5, range = 65–102). Propensity scores were used to match HRT continuers and discontinuers according to HRT type, demographics, and baseline HRQOL. Analysis of covariance was used to compare HRQOL change in continuers and discontinuers. RESULTS: Between 2002 and 2003, 43% of HRT users discontinued therapy. Analysis of covariance to examine HRQOL change revealed complex interactions with age. Discontinuers aged 65–74 reported greater increases in days in which mental health was not good (p < .05), fewer "healthy days" (p < .05), more days in which health interfered with activities (p < .01), and more days with pain (p < .01). Among women aged 75–84, HRT discontinuers reported more days in which physical health was not good (p < .01); no other significant effects were observed in this group. Relative to HRT continuers, discontinuers aged 85 and older experienced apparent HRQOL improvements following cessation, with fewer days in which physical health was not good (p < .01), fewer days of poor mental health (p < .05), and more "healthy days" (p < .01). CONCLUSIONS: These results suggest that there are substantial age differences in response to HRT discontinuation. While women aged 65–74 experienced apparent declines in HRQOL following HRT cessation, women aged 85 and older experienced relative improvements. The HRQOL declines observed among younger women underscore the importance of communication between clinicians and patients throughout the discontinuation process. These results also demonstrate the value of HRQOL surveillance as a component of health program administration

Total Intermittent Pringle Maneuver during Liver Resection Can Induce Intestinal Epithelial Cell Damage and Endotoxemia

Contains fulltext : 110009.pdf (publisher's version ) (Open Access)OBJECTIVES: The intermittent Pringle maneuver (IPM) is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepato)splanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage) with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP) in patients undergoing liver resection with IPM. METHODS: Patients who underwent liver surgery received total IPM (total-IPM) or selective IPM (sel-IPM). A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM). Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day. RESULTS: 24 patients (13 males) were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005). In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed. CONCLUSION: Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099475

Multisite Phosphorylation of the Guanine Nucleotide Exchange Factor Cdc24 during Yeast Cell Polarization

BACKGROUND:Cell polarization is essential for processes such as cell migration and asymmetric cell division. A common regulator of cell polarization in most eukaryotic cells is the conserved Rho GTPase, Cdc42. In budding yeast, Cdc42 is activated by a single guanine nucleotide exchange factor, Cdc24. The mechanistic details of Cdc24 activation at the onset of yeast cell polarization are unclear. Previous studies have suggested an important role for phosphorylation of Cdc24, which may regulate activity or function of the protein, representing a key step in the symmetry breaking process. METHODOLOGY/PRINCIPAL FINDINGS:Here, we directly ask whether multisite phosphorylation of Cdc24 plays a role in its regulation. We identify through mass spectrometry analysis over thirty putative in vivo phosphorylation sites. We first focus on sites matching consensus sequences for cyclin-dependent and p21-activated kinases, two kinase families that have been previously shown to phosphorylate Cdc24. Through site-directed mutagenesis, yeast genetics, and light and fluorescence microscopy, we show that nonphosphorylatable mutations of these consensus sites do not lead to any detectable consequences on growth rate, morphology, kinetics of polarization, or localization of the mutant protein. We do, however, observe a change in the mobility shift of mutant Cdc24 proteins on SDS-PAGE, suggesting that we have indeed perturbed its phosphorylation. Finally, we show that mutation of all identified phosphorylation sites does not cause observable defects in growth rate or morphology. CONCLUSIONS/SIGNIFICANCE:We conclude that lack of phosphorylation on Cdc24 has no overt functional consequences in budding yeast. Yeast cell polarization may be more tightly regulated by inactivation of Cdc42 by GTPase activating proteins or by alternative methods of Cdc24 regulation, such as conformational changes or oligomerization

Multiple receptor tyrosine kinases are expressed in adult rat retinal ganglion cells as revealed by single-cell degenerate primer polymerase chain reaction

BACKGROUND: To achieve a better understanding of the repertoire of receptor tyrosine kinases (RTKs) in adult retinal ganglion cells (RGCs) we performed polymerase chain reaction (PCR), using degenerate primers directed towards conserved sequences in the tyrosine kinase domain, on cDNA from isolated single RGCs univocally identified by retrograde tracing from the superior colliculi.RESULTS: All the PCR-amplified fragments of the expected sizes were sequenced, and 25% of them contained a tyrosine kinase domain. These were: Axl, Csf-1R, Eph A4, Pdgfrbeta, Ptk7, Ret, Ros, Sky, TrkB, TrkC, Vegfr-2, and Vegfr-3. Non-RTK sequences were Jak1 and 2. Retinal expression of Axl, Csf-1R, Pdgfrbeta, Ret, Sky, TrkB, TrkC, Vegfr-2, and Vegfr-3, as well as Jak1 and 2, was confirmed by PCR on total retina cDNA. Immunodetection of Csf-1R, Pdgfralpha/beta, Ret, Sky, TrkB, and Vegfr-2 on retrogradely traced retinas demonstrated that they were expressed by RGCs. Co-localization of Vegfr-2 and Csf-1R, of Vegfr-2 and TrkB, and of Csf-1R and Ret in retrogradely labelled RGCs was shown. The effect of optic nerve transection on the mRNA level of Pdgfrbeta, Csf-1R, Vegfr-2, Sky, and Axl, and of the Axl ligands Gas6 and ProteinS, was analysed. These analyses show transection-induced changes in Axl and ProteinS mRNA levels.CONCLUSIONS: The repertoire of RTKs expressed by RGCs is more extensive than previously anticipated. Several of the receptors found in this study, including Pdgfrbeta, Csf-1R, Vegfr-2, Sky, and Axl, and their ligands, have not previously been primarily associated with retinal ganglion cells