‘He’s Got Growth’: Coaches Understanding and Management of the Growth Spurt in Male Academy Football

The majority of studies investigating maturation in football have focused on the impact of maturity status or timing upon athletic performance. There is comparatively little research investigating the impact of the adolescent growth spurt, and few research articles that have focussed on injury incidence and burden rather than performance. The aim of this study was to explore and better understand how the adolescent growth spurt impacts youth football players within professional academies. This longitudinal mixed-methods study aimed to understand youth football coaches’ perceptions, experiences, and management of male adolescent football players. Players’ maturity status, growth velocities, and match performance were measured and interviews with coaches were conducted in parallel. The qualitative and quantitative data were combined to generate a deeper contextualised understanding. This study revealed that academy football coaches describe adolescent growth as a ‘condition’; players are diagnosed with growth through perceived signs and symptoms, which coaches must manage and treat. Growth was also seen to impact coaches’ perceptions and therefore had implications for selection and release decisions. The findings from this study emphasise the complexities of experiencing and managing adolescent growth and maturation in the context of elite youth football

Activation of the LH receptor up regulates the type 2 adiponectin receptor in human granulosa cells

PURPOSE: Adiponectin is a predominantly adipocyte-derived hormone which influences insulin sensitivity and energy homeostasis through at least two receptors, AdipoR1 and AdipoR2. In animal models, adiponectin may regulate ovarian steroidogenesis, folliculogenesis, and ovulation. The receptors AdipoR1 and AdipoR2 are present in the human ovary, but their regulation is unknown. In these studies, we determined the effects of LH receptor activation on the expression and function of the two adiponectin receptors in human granulosa cells. METHODS: Granulosa cells were obtained at the time of oocyte retrieval in women undergoing in vitro fertilization (IVF). Cells were isolated and cultured for 48 h in DMEM/F12 medium with 5 % FBS and 50 ug/ml gentamicin. Medium was changed to low serum for 12 h and cells were treated with hCG (100 ng/ml), forskolin (30 μMol/L), or FSH (1 IU/ml) for 24 h for mRNA experiments. mRNA was isolated and RT PCR was performed using Taqman assays and quantification with the delta delta CT method. For immunocytochemistry, cells were grown on chamber slides and treated with hCG for 1 to 24 h and fixed with acetone. ICC was performed with polyclonal rabbit primary antibodies followed by alexa fluor goat anti-rabbit antibody and imaging with a fluorescence microscope and Zeiss software analysis. 3β-hydroxysteroid dehydrogenase (3βHSD) enzyme activity was determined by measuring the progesterone produced when cells were provided with an excess of 22-hydroxy-cholesterol as substrate following an incubation with hCG (1 IU/ml) and/or adiponectin (10 ng/ml). Progesterone content in the media was determined by ELISA. RESULTS: Messenger RNA for the two Adiponectin receptors is differentially regulated by activation of LHR with hCG treatment. AdipoR2 was increased nearly 4-fold (p < 0.05), whereas AdipoR1 expression was not changed by hCG treatment. Treatment with either FSH or forskolin (an activator of cAMP) had similar effects. Basal AdipoR2 protein was fairly low in granulosa cells in culture however treatment of cells with hCG resulted in a discernible increase in immunodetectable cytoplasmic protein as early as 6 h after treatment and was maintained for at least 24 h. The number of cells positive for AdipoR2 at 6 h increased from a basal of 20 % to almost 60 % (p < 0.05). Adiponectin treatment of hCG-primed cells resulted in increased 3βHSD activity by approximately 60 % over hCG alone and more than 3-fold over basal levels. CONCLUSIONS: AdipoR2 is regulated by the LH receptor function via a cAMP dependant mechanism. Increased expression of adipoR2 prior to and following ovulation may contribute to enhanced 3βHSD activity and increased progesterone secretion by the corpus luteum of the ovary. Dysregulation of adiponectin that may occur with PCOS may impair normal progesterone production

Oxidative stress and cardiovascular risk in type 1 diabetes mellitus: Insights from the DCCT/EDIC study

Background--Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results--A random subcohort of 349 participants was selected from the DCCT/EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT, and 1 to 2 years post-DCCT (EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F2α isoprostanes, and its metabolite, 2,3 dinor-8 iso prostaglandin F2α. Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor-8 iso prostaglandin F2α, an oxidative marker, were significantly associated with lower risk of cardiovascular disease (-4.5% risk for 10% higher paraoxonase, P \u3c 0.003; -5.3% risk for 10% higher 2,3 dinor-8 iso prostaglandin F2α, P=0.0092). In contrast, the oxidative markers myeloperoxidase and F2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Conclusions--Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. © 2018 The Authors

Detection of Magnesium-Rich Ejecta in the Middle-Aged Supernova Remnant N49B

The middle-aged supernova remnant (SNR) N49B in the Large Magellanic Cloud has been observed with the {\it Chandra X-Ray Observatory}. The superb angular resolution of {\it Chandra} resolves the complex structure of X-ray emitting filaments across the SNR. All observed features are soft ($E <$ 3 keV) and we find no evidence for either point-like or extended hard emission within the SNR. Spectral lines from O, Ne, Mg, Si, S, and Fe are present. Equivalent width images for the detected elemental species and spatially-resolved spectral analysis reveal the presence of Mg-rich ejecta within the SNR. We find no such enrichment in O or Ne, which may reflect details of the nucleosynthesis process or the heating and cooling of the ejecta as it evolved. The bright circumferential filaments are emission from the shocked dense interstellar medium (ISM). We detect faint diffuse X-ray emission that extends beyond the X-ray bright filaments toward the west and southeast. These features appear to be the blast wave shock front expanding into lower density portions of the ISM seen in projection. We set an upper limit of $\sim$$2\times 10^{33}$ ergs s$^{-1}$ on the 0.5 $-$ 5 keV band X-ray luminosity of any embedded compact object.Comment: 3 text pages (ApJ emulator style), 3 figures, 1 table, Accepted for the publication in Ap J Letter

A method for exposing rodents to resuspended particles using whole-body plethysmography

BACKGROUND: Epidemiological studies have reported increased risks of cardiopulmonary-related hospitalization and death in association with exposure to elevated levels of particulate matter (PM) across a wide range of urban areas. In response to these findings, researchers have conducted animal inhalation exposures aimed at reproducing the observed toxicologic effects. However, it is technically difficult to quantitate the actual amount of PM delivered to the lung in such studies, and dose is frequently estimated using default respiration parameters. Consequently, the interpretation of PM-induced effects in rodents exposed via whole-body inhalation is often compromised by the inability to determine deposited dose. To address this problem, we have developed an exposure system that merges the generation of dry, aerosolized particles with whole-body plethysmography (WBP), thus permitting inhalation exposures in the unrestrained rat while simultaneously obtaining data on pulmonary function. RESULTS: This system was validated using an oil combustion-derived particle (HP12) at three nominal concentrations (3, 12, and 13 mg/m(3)) for four consecutive exposure days (6 hr/day); a single 6-hour exposure to 13 mg/m(3 )of HP12 was also conducted. These results demonstrated that the system was both reliable and consistent over these exposure protocols, achieving average concentrations that were within 10% of the targeted concentration. In-line filters located on the exhaust outlets of individual WBP chambers showed relative agreement in HP12 mass for each day and were not statistically different when compared to one another (p = 0.16). Temperatures and relative humidities were also similar between chambers during PM and air exposures. Finally, detailed composition analyses of both HP12 filter and bulk samples showed that grinding and aerosolization did not change particle chemistry. CONCLUSION: The results of this study demonstrate that it is possible to expose rodents to resuspended, dry PM via whole-body inhalation while these animals are maintained in WBP chambers. This new methodology should significantly improve the ability to assess dosimetry under minimally stressful exposure conditions

Metal Abundances in the Magellanic Stream

We report on the first metallicity determination for gas in the Magellanic Stream, using archival HST GHRS data for the background targets Fairall 9, III Zw 2, and NGC 7469. For Fairall 9, using two subsequent HST revisits and new Parkes Multibeam Narrowband observations, we have unequivocally detected the MSI HI component of the Stream (near its head) in SII1250,1253 yielding a metallicity of [SII/H]=-0.55+/-0.06(r)+/-0.2(s), consistent with either an SMC or LMC origin and with the earlier upper limit set by Lu et al. (1994). We also detect the saturated SiII1260 line, but set only a lower limit of [SiII/H]>-1.5. We present serendipitous detections of the Stream, seen in MgII2796,2803 absorption with column densities of (0.5-1)x10^13 cm^-2 toward the Seyfert galaxies III Zw 2 and NGC 7469. These latter sightlines probe gas near the tip of the Stream (80 deg down-Stream of Fairall 9). For III Zw 2, the lack of an accurate HI column density and the uncertain MgIII ionization correction limits the degree to which we can constrain [Mg/H]; a lower limit of [MgII/HI]>-1.3 was found. For NGC 7469, an accurate HI column density determination exists, but the extant FOS spectrum limits the quality of the MgII column density determination, and we conclude that [MgII/HI]>-1.5. Ionization corrections associated with MgIII and HII suggest that the corresponding [Mg/H] may range lower by 0.3-1.0 dex. However, an upward revision of 0.5-1.0 dex would be expected under the assumption that the Stream exhibits a dust depletion pattern similar to that seen in the Magellanic Clouds. Remaining uncertainties do not allow us to differentiate between an LMC versus SMC origin to the Stream gas.Comment: 30 pages, 8 figures, LaTeX (aaspp4), also available at http://casa.colorado.edu/~bgibson/publications.html, accepted for publication in The Astronomical Journa

Haptoglobin Genotype and the Rate of Renal Function Decline in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Many patients with type 1 diabetes develop renal disease despite moderately good metabolic control, suggesting other risk factors may play a role. Recent evidence suggests that the haptoglobin (HP) 2-2 genotype, which codes for a protein with reduced antioxidant activity, may predict renal function decline in type 1 diabetes. We examined this hypothesis in 1,303 Caucasian participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. HP genotype was determined by polyacrylamide gel electrophoresis. Glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and albumin excretion based on timed urine samples. Participants were followed up for a mean of 22 years. HP genotype was significantly associated with the development of sustained estimated glomerular filtration rate (GFR) \u3c60 mL/min/1.73 m2and with end-stage renal disease (ESRD), with HP 2-2 having greater risk than HP 2-1 and 1-1. No association was seen with albuminuria. Although there was no treatment group interaction, the associations were only significant in the conventional treatment group, where events rates were much higher. We conclude that the HP genotype is significantly associated with the development of reduced GFR and ESRD in the DCCT/EDIC study

Consistent Pulmonary and Systemic Responses from Inhalation of Fine Concentrated Ambient Particles: Roles of Rat Strains Used and Physicochemical Properties

Several studies have reported health effects of concentrated ambient particles (CAP) in rodents and humans; however, toxicity end points in rodents have provided inconsistent results. In 2000 we conducted six 1-day exposure studies where spontaneously hypertensive (SH) rats were exposed to filtered air or CAPs (≤ 2.5 μm, 1,138–1,765 μg/m(3)) for 4 hr (analyzed 1–3 hr afterward). In seven 2-day exposure studies in 2001, SH and Wistar Kyoto (WKY) rats were exposed to filtered air or CAP (≤ 2.5 μm, 144–2,758 μg/m(3)) for 4 hr/day × 2 days (analyzed 1 day afterward). Despite consistent and high CAP concentrations in the 1-day exposure studies, no biologic effects were noted. The exposure concentrations varied among the seven 2-day exposure studies. Except in the first study when CAP concentration was highest, lavageable total cells and macrophages decreased and neutrophils increased in WKY rats. SH rats demonstrated a consistent increase of lavage fluid γ -glutamyltransferase activity and plasma fibrinogen. Inspiratory and expiratory times increased in SH but not in WKY rats. Significant correlations were found between CAP mass (microgram per cubic meter) and sulfate, organic carbon, or zinc. No biologic effects correlated with CAP mass. Despite low chamber mass in the last six of seven 2-day exposure studies, the levels of zinc, copper, and aluminum were enriched severalfold, and organic carbon was increased to some extent when expressed per milligram of CAP. Biologic effects were evident in those six studies. These studies demonstrate a pattern of rat strain–specific pulmonary and systemic effects that are not linked to high mass but appear to be dependent on CAP chemical composition

Development of novel methods for non-canonical myeloma protein analysis with an innovative adaptation of immunofixation electrophoresis, native top-down mass spectrometry, and middle-down de novo sequencing

OBJECTIVES: Multiple myeloma (MM) is a malignant plasma cell neoplasm, requiring the integration of clinical examination, laboratory and radiological investigations for diagnosis. Detection and isotypic identification of the monoclonal protein(s) and measurement of other relevant biomarkers in serum and urine are pivotal analyses. However, occasionally this approach fails to characterize complex protein signatures. Here we describe the development and application of next generation mass spectrometry (MS) techniques, and a novel adaptation of immunofixation, to interrogate non-canonical monoclonal immunoproteins. METHODS: Immunoprecipitation immunofixation (IP-IFE) was performed on a Sebia Hydrasys Scan2. Middle-down de novo sequencing and native MS were performed with multiple instruments (21T FT-ICR, Q Exactive HF, Orbitrap Fusion Lumos, and Orbitrap Eclipse). Post-acquisition data analysis was performed using Xcalibur Qual Browser, ProSight Lite, and TDValidator. RESULTS: We adapted a novel variation of immunofixation electrophoresis (IFE) with an antibody-specific immunosubtraction step, providing insight into the clonal signature of gamma-zone monoclonal immunoglobulin (M-protein) species. We developed and applied advanced mass spectrometric techniques such as middle-down de novo sequencing to attain in-depth characterization of the primary sequence of an M-protein. Quaternary structures of M-proteins were elucidated by native MS, revealing a previously unprecedented non-covalently associated hetero-tetrameric immunoglobulin. CONCLUSIONS: Next generation proteomic solutions offer great potential for characterizing complex protein structures and may eventually replace current electrophoretic approaches for the identification and quantification of M-proteins. They can also contribute to greater understanding of MM pathogenesis, enabling classification of patients into new subtypes, improved risk stratification and the potential to inform decisions on future personalized treatment modalities