926 research outputs found

    The importance of the urologist in male oncology fertility preservation.

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    To demonstrate that surgical sperm retrieval (SSR) and spermatogonial stem cell retrieval (SSCR) in an oncological context are safe and successful. This a retrospective study in a tertiary hospital in the UK. Patients requiring fertility preservation from December 2017 to January 2020 were included. Data were analysed with Microsoft Excel 2016 and the Statistical Package for the Social Sciences (version 20). Among 1264 patients referred to the Reproductive Medical Unit at the University College of London Hospitals for cryopreservation prior to gonadotoxic treatment, 39 chose to go forward with SSR/SSCR because they presented as azoo-/cryptozoospermic or an inability to masturbate/ejaculate. Interventions were testicular sperm extraction (23 patients) or aspiration (one), electroejaculation (one), and testicular wedge biopsy for SSCR (14). The median (range) age was 15.0 (10-65) years and the median testosterone level was 4.4 nmoL/L. Primary diagnoses were sarcoma in 11 patients, leukaemia in nine, lymphoma in eight, testicular tumour in five, other oncological haematological entities in two, other solid cancers in two, while two patients had non-oncological haematological diseases. SSR/SSCR could be offered within 7.5 days on average. Chemotherapy could follow within 2 days from SSR/SSCR, and bone marrow transplant occurred within 19.5 days (all expressed as medians). The success rate for SSR was 68.0% (at least one vial/straw collected). The mean (SD) Johnsen score of testicular biopsies was 5.23 (2.25) with a trend towards positive correlation with SSR success (P = 0.07). However, age, hormonal profile and type of cancer did not predict SSR outcome. We show that SSR and SSCR in an oncological context are valid treatment options with a high success rate for patients in which sperm cryopreservation from semen is impossible. By providing an effective pathway, fertility preservation is possible with minimal delay to oncological treatment

    MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation

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    <p>Rationale: Dedifferentiation of vascular smooth muscle cells (VSMC) leading to a proliferative cell phenotype significantly contributes to the development of atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of proteins including connexin 43 (Cx43) has been associated with VSMC proliferation in atherosclerosis.</p> <p>Objective: To investigate whether MAPK phosphorylation of Cx43 is directly involved in VSMC proliferation.</p> <p>Methods and Results: We show in vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of apolipoprotein-E receptor null (ApoE−/−) mice and in C57Bl/6 mice treated with platelet-derived growth factor–BB (PDGF). We tested the involvement of Cx43 MAPK phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43 C-terminus (Cx43CT) and produced null phosphorylation Ser>Ala (Cx43MK4A/Cx43CTMK4A) and phospho-mimetic Ser>Asp (Cx43MK4D/Cx43CTMK4D) mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild-type (Cx43+/+) and Cx43 null (Cx43−/−) mice and analytic size exclusion studies of purified proteins identify that interactions between cyclin E and Cx43 requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that interactions between Cx43 and cyclin E are lost and VSMC proliferation does not occur after treatment of carotids with PDGF and that neointima formation is significantly reduced in carotids after injury.</p> <p>Conclusions: We identify MAPK-phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show that this interaction is critical for VSMC proliferation. This novel interaction may be important in the development of atherosclerotic lesions.</p&gt

    Relativistic deformed mean-field calculation of binding energy differences of mirror nuclei

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    Binding energy differences of mirror nuclei for A=15, 17, 27, 29, 31, 33, 39 and 41 are calculated in the framework of relativistic deformed mean-field theory. The spatial components of the vector meson fields and the photon are fully taken into account in a self-consistent manner. The calculated binding energy differences are systematically smaller than the experimental values and lend support to the existency of the Okamoto--Nolen-Schiffer anomaly found decades ago in nonrelativistic calculations. For the majority of the nuclei studied, however, the results are such that the anomaly is significantly smaller than the one obtained within state-of-the-art nonrelativistic calculations.Comment: 13 pages, REVTeX, no figure

    Boost Invariance and Multiplicity Dependence of the Charge Balance Functionin π+p\pi^{+}p and K+pK^{+}p Collisions at s=22\sqrt s= 22 GeV/c

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    Boost invariance and multiplicity dependence of the charge balance function are studied in \pi^{+}\rp and \rK^{+}\rp collisions at 250 GeV/cc incident beam momentum. Charge balance, as well as charge fluctuations, are found to be boost invariant over the whole rapidity region, but both depend on the size of the rapidity window. It is also found that the balance function becomes narrower with increasing multiplicity, consistent with the narrowing of the balance function when centrality and/or system size increase, as observed in current relativistic heavy ion experiments.Comment: 4 pages, 5 figures, Revte

    The Exact Correspondence between Phase Times and Dwell Times in a Symmetrical Quantum Tunneling Configuration

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    The general and explicit relation between the phase time and the dwell time for quantum tunneling or scattering is investigated. Considering a symmetrical collision of two identical wave packets with an one-dimensional barrier, here we demonstrate that these two distinct transit time definitions give connected results where, however, the phase time (group delay) accurately describes the exact position of the scattered particles. The analytical difficulties that arise when the stationary phase method is employed for obtaining phase (traversal) times are all overcome. Multiple wave packet decomposition allows us to recover the exact position of the reflected and transmitted waves in terms of the phase time, which, in addition to the exact relation between the phase time and the dwell time, leads to right interpretation for both of them.Comment: 11 pages, 2 figure

    Small Corrections to the Tunneling Phase Time Formulation

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    After reexamining the above barrier diffusion problem where we notice that the wave packet collision implies the existence of {\em multiple} reflected and transmitted wave packets, we analyze the way of obtaining phase times for tunneling/reflecting particles in a particular colliding configuration where the idea of multiple peak decomposition is recovered. To partially overcome the analytical incongruities which frequently rise up when the stationary phase method is adopted for computing the (tunneling) phase time expressions, we present a theoretical exercise involving a symmetrical collision between two identical wave packets and a unidimensional squared potential barrier where the scattered wave packets can be recomposed by summing the amplitudes of simultaneously reflected and transmitted wave components so that the conditions for applying the stationary phase principle are totally recovered. Lessons concerning the use of the stationary phase method are drawn.Comment: 14 pages, 3 figure

    Tri-meson-mixing of π\pi-η\eta-η\eta' and ρ\rho-ω\omega-ϕ\phi in the light-cone quark model

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    The radiative transition form factors of the pseudoscalar mesons {π\pi, η\eta, η\eta'} and the vector mesons {ρ\rho, ω\omega, ϕ\phi} are restudied with π\pi-η\eta-η\eta' and ρ\rho-ω\omega-ϕ\phi in tri-meson-mixing pattern, which is described by tri-mixing matrices in the light-cone constituent quark model. The experimental transition decay widths are better reproduced with tri-meson-mixing than previous results in a two-mixing-angle scenario of only two-meson η\eta-η\eta' mixing and ω\omega-ϕ\phi mixing.Comment: 8 pages, 6 figures, final version to appear in EPJ

    Glucose self-monitoring in non-insulin-treated patients with type 2 diabetes in primary care settings: A randomized trial

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    IMPORTANCE The value of self-monitoring of blood glucose (SMBG) levels in patients with non-insulin-treated type 2 diabetes has been debated. OBJECTIVE To compare 3 approaches of SMBG for effects on hemoglobin A1c levels and health-related quality of life (HRQOL) among people with non-insulin-treated type 2 diabetes in primary care practice. DESIGN, SETTING, AND PARTICIPANTS The Monitor Trial studywas a pragmatic, open-label randomized trial conducted in 15 primary care practices in central North Carolina. Participants were randomized between January 2014 and July 2015. Eligible patients with type 2 non-insulin-treated diabetes were: older than 30 years, established with a primary care physician at a participating practice, had glycemic control (hemoglobin A1c) levels higher than 6.5%but lower than 9.5%within the 6 months preceding screening, as obtained from the electronic medical record, and willing to comply with the results of random assignment into a study group. Of the 1032 assessed for eligibility, 450 were randomized. INTERVENTIONS No SMBG, once-daily SMBG, and once-daily SMBG with enhanced patient feedback including automatic tailored messages delivered via the meter. MAIN OUTCOMES AND MEASURES Coprimary outcomes included hemoglobin A1c levels and HRQOL at 52 weeks. RESULTS A total of 450 patients were randomized and 418 (92.9%) completed the final visit. There were no significant differences in hemoglobin A1c levels across all 3 groups (P = .74; estimated adjusted mean hemoglobin A1c difference, SMBG with messaging vs no SMBG, -0.09%; 95%CI, -0.31% to 0.14%; SMBG vs no SMBG, -0.05%; 95%CI, -0.27%to 0.17%). There were also no significant differences found in HRQOL. There were no notable differences in key adverse events including hypoglycemia frequency, health care utilization, or insulin initiation. CONCLUSIONS AND RELEVANCE In patients with non-insulin-treated type 2 diabetes, we observed no clinically or statistically significant differences at 1 year in glycemic control or HRQOL between patients who performed SMBG compared with those who did not perform SMBG. The addition of this type of tailored feedback provided through messaging via ameter did not provide any advantage in glycemic control

    Health literacy, glycemic control, and physician-advised glucose self-monitoring use in type 2 diabetes

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    Objective: To measure the association between health literacy and both patient-reported and clinical outcomes in patients with non-insulin-treated type 2 diabetes. Research Design and Methods: We surveyed patients with non-insulin-treated type 2 diabetes (n = 448) from 15 primary care practices. The association between health literacy and patient-reported and clinical outcomes, including numeracy of self-monitoring of blood glucose (SMBG) use, how often physicians advised patients to conduct SMBG testing, and glycemic control (as measured by A1C), was investigated. Results: Study participants included 448 patients with non-insulin-treated type 2 diabetes located within central North Carolina. Participants with limited health literacy had poorer glycemic control (A1C 7.7 ± 1.1% vs. 7.5 ± 1.0%, P = 0.016) despite using SMBG testing more frequently (daily SMBG testing 49.3 vs. 30.7%, P = 0.001) compared to individuals with adequate health literacy. The difference in how often physicians advised patients to conduct SMBG testing between limited and adequate health literacy groups was not significant (P = 0.68). Conclusion: Limited health literacy was associated with poorer glyce-mic control and an increased frequency of SMBG testing in patients with non-insulin-treated type 2 diabetes. There was no significant difference in how often physicians advised patients to conduct SMBG testing between patients with limited and adequate health literacy
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