| 1. |
- Lacalle, Estibaliz, et al.
(author)
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Bicarbonate-Triggered In Vitro Capacitation of Boar Spermatozoa Conveys an Increased Relative Abundance of the Canonical Transient Receptor Potential Cation (TRPC) Channels 3, 4, 6 and 7 and of CatSper-gamma Subunit mRNA Transcripts
- 2022
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In: Animals. - : MDPI. - 2076-2615. ; 12:8
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Journal article (peer-reviewed)abstract
- Simple Summary The detection of sub-fertile boars has been a difficult task, and despite their prevalence being low, its impact is very significant because it implies economic drawbacks for artificial insemination (AI) centers and farms. Unfortunately, some crucial reproductive processes fall beyond the routine analysis performed in the porcine model, such as sperm capacitation, which is a necessary event for fertilization. A synergistic action of bicarbonate (HCO3-) with calcium (Ca2+) is needed to achieve capacitation. The transport of Ca2+ is mediated by CatSper channels and Canonical Transient Potential Channels (TRPC). We quantified mRNA transcripts of different subunits of CatSper (beta, gamma and delta) and TRPC (1, 3, 4, 6 and 7) before and after in vitro capacitation by HCO3- ions. Our results showed that in vitro capacitation using HCO3- increases the relative abundance of mRNA transcripts of almost all subunits of Ca2+ channels, except CatSper-delta and TRPC1, which were significantly reduced. More studies are needed to elucidate the specific roles of the TRPC channels at a physiological and functional level. Sperm capacitation is a stepwise complex biochemical process towards fertilization. It includes a crucial early calcium (Ca2+) transport mediated by CatSper channels and Canonical Transient Potential Channels (TRPC). We studied the relative abundance of mRNA transcripts changes of the CatSper beta, gamma and delta subunits and TRPC-channels 1, 3, 4, 6 and 7 in pig spermatozoa, after triggering in vitro capacitation by bicarbonate ions at levels present in vivo at the fertilization site. For this purpose, we analyzedfive5 ejaculate pools (from three fertile adult boars) before (control-fresh samples) and after in vitro exposure to capacitation conditions (37 mM NaHCO3, 2.25 mM CaCl2, 2 mM caffeine, 0.5% bovine serum albumin and 310 mM lactose) at 38 degrees C, 5% CO2 for 30 min. In vitro capacitation using bicarbonate elicits an increase in the relative abundance of mRNA transcripts of almost all studied Ca2+ channels, except CatSper-delta and TRPC1 (significantly reduced). These findings open new avenues of research to identify the specific role of each channel in boar sperm capacitation and elucidate the physiological meaning of the changes on sperm mRNA cargo.
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| 2. |
- Nguyen, Thanh N, et al.
(author)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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In: Neurology. - 1526-632X. ; 100:4
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Journal article (peer-reviewed)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 3. |
- Agredano Torres, Manuel, et al.
(author)
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Coils and power supplies design for the SMART tokamak
- 2021
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In: Fusion engineering and design. - : Elsevier BV. - 0920-3796 .- 1873-7196. ; 168, s. 112683-112683
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Journal article (peer-reviewed)abstract
- A new spherical tokamak, the SMall Aspect Ratio Tokamak (SMART), is currently being designed at the University of Seville. The goal of the machine is to achieve a toroidal field of 1 T, a plasma current of 500 kA and a pulse length of 500 ms for a plasma with a major radius of 0.4 m and minor radius of 0.25 m. This contribution presents the design of the coils and power supplies of the machine. The design foresees a central solenoid, 12 toroidal field coils and 8 poloidal field coils. Taking the current waveforms for these set of coils as starting point, each of them has been designed to withstand the Joule heating during the tokamak operation time. An analytical thermal model is employed to obtain the cross sections of each coil and, finally, their dimensions and parameters. The design of flexible and modular power supplies, based on IGBTs and supercapacitors, is presented. The topologies and control strategy of the power supplies are explained, together with a model in MATLAB Simulink to simulate the power supplies performance, proving their feasibility before the construction of the system.
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| 4. |
- Collantes, Edward Ryan A., et al.
(author)
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EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma
- 2022
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In: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:2, s. 240-252
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Journal article (peer-reviewed)abstract
- Juvenile open-angle glaucoma (JOAG) is a severe type of glaucoma with onset before age 40 and dominant inheritance. Using exome sequencing we identified 3 independent families from the Philippines with novel EFEMP1 variants (c.238A>T, p.Asn80Tyr; c.1480T>C, p.Ter494Glnext*29; and c.1429C>T, p.Arg477Cys) co-segregating with disease. Affected variant carriers (N = 34) exhibited severe disease with average age of onset of 16 years and with 76% developing blindness. To investigate functional effects, we transfected COS7 cells with vectors expressing the three novel EFEMP1 variants and showed that all three variants found in JOAG patients caused significant intracellular protein aggregation and retention compared to wild type and also compared to EFEMP1 variants associated with other ocular phenotypes including an early-onset form of macular degeneration, Malattia Leventinese/Doyne's Honeycomb retinal dystrophy. These results suggest that rare EFEMP1 coding variants can cause JOAG through a mechanism involving protein aggregation and retention, and that the extent of intracellular retention correlates with disease phenotype. This is the first report of EFEMP1 variants causing JOAG, expanding the EFEMP1 disease spectrum. Our results suggest that EFEMP1 mutations appear to be a relatively common cause of JOAG in Filipino families, an ethnically diverse population.
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| 5. |
- Karametsidis, Georgios, et al.
(author)
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The trade-off between condition and growth shapes juveniles' survival of harvested demersal fish of the Mediterranean sea
- 2023
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In: Marine Environmental Research. - : Elsevier. - 0141-1136 .- 1879-0291. ; 184
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Journal article (peer-reviewed)abstract
- Fish body condition and growth are two interrelated traits closely associated with species life history and fitness, whose trade-off can ultimately impact population dynamics albeit seldom empirically demonstrated. They can intricately affect survival rates, which are particularly relevant for species under exploitation. Using individual spatiotemporal information in Northwestern Mediterranean, we document for the first time the existence of a trade-off between condition and growth in regulating survival dynamics in two important fish species for the Mediterranean fisheries that are characterized by contrasting life histories. For the European hake (Merluccius merluccius), a benthopelagic species, juveniles' body condition was detected to be positively linked to survival and negatively associated with the growth of this age group. For the red mullet (Mullus barbatus), the same pattern was observed for young adults. We also show that the observed patterns on a regional level have a clear spatial dependence as we found that observed body condition over a local scale had a broad effect on the population dynamics of the whole region, with the Ebro delta area emerging as the demographic engine of the two species. We discuss our results in the context of fisheries management and underline the importance of improving current stock assessment models and spatially based fishery management towards incorporating body condition and growth due to their influence on important parameters such as survival.
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| 6. |
- Li, Jing, et al.
(author)
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CYP3A phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors
- 2006
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 98:23, s. 1714-1723
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Journal article (peer-reviewed)abstract
- Background: Gefitinib is an orally active inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) with activity in non-small-cell lung cancer. The response to gefitinib is variable, possibly because of interindividual variation in the activity of cytochrome P450 3A (CYP3A), the principal enzyme that metabolizes gefitinib. We prospectively assessed the influence of CYP3A activity on gefitinib disposition and toxicity. Methods: Twenty-seven patients with advanced cancer were treated with daily oral gefitinib at 250 mg (n = 13) or 500 mg (n = 14) for 28 days. Concentration-time profiles of midazolam and geftinib were constructed based on measurement of their concentration in serial blood samples using high-performance liquid chromatography and mass spectroscopy. CYP3A activity was determined at baseline by assessment of midazolam apparent oral clearance. Pharmacokinetic studies were performed for a period of 28 days, and population modeling was performed using NONMEM software. A structural pharmacokinetic model was developed to describe the concentration-time profiles of unbound and total gefitinib plasma concentrations, and patient-specific covariates were added to the model to account for unexplained interindividual variability in pharmacokinetic parameters. Statistical tests were two-sided. Results: Gefitinib pharmacokinetics exhibited wide interindividual variability (interindividual variability on total and unbound gefitinib apparent oral clearance was 79% and 74%, respectively). Midazolam clearance (mean = 40 L/h, range = 10-111) was highly correlated with that of total and unbound gefitinib (R2 = .60 and R2 = .68, respectively) and with steady-state plasma through concentrations of gefitinib (R2 = .58 and R2 = .60, respectively), and it accounted for approximately 40% of interindividual variability in gefitinib clearance in the pharmacokinetic model. Both total and unbound gefitinib steady-state plasma trough concentrations were associated with the development of diarrhea (P <.05), but not skin rash. At a dose of 250 mg gefitinib, 11 of 13 patients achieved steady-state plasma trough concentrations above the IC 50 for inhibition of mutant EGFR in vitro (0.015 μM), but only one achieved a steady-state plasma trough concentration above the IC 50 for inhibition of wild-type EGFR (0.1 μM). Conclusions: As an in vivo phenotypic probe of CYP3A, midazolam oral clearance may have utility for prediction of gefitinib exposure and dose selection. A pharmacokinetic model incorporating this indicator of CYP3A activity has potential for optimization of treatment with gefitinib and other TK inhibitors that are metabolized in a similar manner.
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| 7. |
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| 8. |
- Mancini, A., et al.
(author)
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Mechanical and electromagnetic design of the vacuum vessel of the SMART tokamak
- 2021
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In: Fusion engineering and design. - : Elsevier BV. - 0920-3796 .- 1873-7196. ; 171
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Journal article (peer-reviewed)abstract
- The SMall Aspect Ratio Tokamak (SMART) is a new spherical device that is currently being designed at the University of Seville. SMART is a compact machine with a plasma major radius () greater than 0.4 m, plasma minor radius () greater than 0.2 m, an aspect ratio () over than 1.7 and an elongation () of more than 2. It will be equipped with 4 poloidal field coils, 4 divertor field coils, 12 toroidal field coils and a central solenoid. The heating system comprises of a Neutral Beam Injector (NBI) of 600 kW and an Electron Cyclotron Resonance Heating (ECRH) of 6 kW for pre-ionization. SMART has been designed for a plasma current () of 500 kA, a toroidal magnetic field () of 1 T and a pulse length of 500 ms preserving the compactness of the machine. The free boundary equilibrium solver code FIESTA [1] coupled to the linear time independent, rigid plasma model RZIP [2] has been used to calculate the target equilibria taking into account the physics goals, the required plasma parameters, vacuum vessel structures and power supply requirements. We present here the final design of the SMART vacuum vessel together with the Finite Element Model (FEM) analysis carried out to ensure that the tokamak vessel provides high quality vacuum and plasma performance withstanding the electromagnetic loads caused by the interaction between the eddy currents induced in the vessel itself and the surrounding magnetic fields. A parametric model has been set up for the topological optimization of the vessel where the thickness of the wall has been locally adapted to the expected forces. An overview of the new machine is presented here.
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| 9. |
- Miguel-Jimenez, Sara, et al.
(author)
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In vitro assessment of egg yolk-, soya bean lecithin- and liposome-based extenders for cryopreservation of dairy bull semen
- 2020
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In: Animal Reproduction Science. - : Elsevier. - 0378-4320 .- 1873-2232. ; 215
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Journal article (peer-reviewed)abstract
- The study was conducted to compare the effect of four commercially available extenders (Triladyl®- egg yolk-based; Andromed® and Bioxcell®-plant based and Optixcell®-liposome-based) on post-thaw sperm quality and functionality variables evaluated using computer-assisted sperm analysis and flow cytometry. A total of 30 ejaculates from five bulls were analysed. With use of Triladyl®, sperm had a greater post-thaw total motility than with use of Bioxell® and Optixcell® but there was no difference as compared with use of Andromed® with the greatest (P < 0.05) percentage of progressively motile cells. With use of Optixcell®, there was a greater (P < 0.05) percentage of sperm with an intact membrane than with use of Triladyl® and Bioxcell®, but values were similar with use of Andromed®. Acrosome damage in semen preserved with use of Optixcell® was less than with use of Bioxcell® and Andromed®. With use of Optixcell®, there was a greater percentage of viable spermatozoa with a lesser lipid disruption (P < 0.05) when compared with the other extenders. Production of peroxides was greater for sperm cryopreserved with use of Triladyl® and Optixcell® while less superoxide was produced in the samples cryopreserved with the egg yolk-based extender. Optixcell® appears to be a promising alternative to replace traditional egg yolk extenders. With use of Optixcell®, however, there were greater peroxide concentrations after thawing. With use of Andromed®, there were similar results as with use of Optixcell®, therefore, it could be an effective substitute for egg-yolk based media due to the greater proportion of highly and progressively motile spermatozoa at thawing.
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| 10. |
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