Summary
This study was performed to examine whether capsaicin, the main pungent ingredient of red peppers, exerts protective effects against testicular injuries induced by transient scrotal ...hyperthermia. Capsaicin (0.33 mg kg−1) was administered subcutaneously to mice one hour before heat stress (HS) in a 43°C water bath for 20 min. After 7 days, mice exposed to HS showed low testicular weight, severe vacuolisation of seminiferous tubules followed by loss of spermatogenic cells, and appearance of multinucleated giant cells and remarkable TUNEL‐positive apoptotic cells, as well as weak immunoreactivity of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in spermatogenic cells. Levels of lipid peroxidation and heat shock 70‐kDa protein 1 (Hsp72) and BCL2‐associated X protein (Bax) mRNA were greatly increased, but PHGPx, manganese superoxide dismutase (MnSOD), and B‐cell lymphoma‐extra large (Bcl‐xL) mRNAs were significantly diminished in the testes by HS. However, capsaicin pre‐treatment significantly suppressed the spermatogenic cell death, oxidative stress (levels of MDA, PHGPx immunoreactivity, and Hsp72, PHGPx, and MnSOD mRNA) and apoptosis (levels of TUNEL‐positive cells, and Bcl‐xL and Bax mRNA) in testes by HS. These suggest that capsaicin has a protective effect against spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti‐apoptotic activities.
Health care workers who had received a dose of ChAdOx1 nCoV-19 were offered a choice of receiving either ChAdOx1 nCoV-19 or mRNA-1273 9 to 12 weeks after the initial dose. Levels of S-specific and ...RBD-specific IgG increased by a factor of 5 after a ChAdOx1 nCoV-19 boost and by a factor of 115 to 125 after an mRNA-1273 boost.
The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality ...of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients.
A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated i.e. very-short (1 month) or short (3 months) with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%, major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation.
In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen.
PROSPERO registration number CRD42021284004.
We investigate the photophysical and amplified spontaneous emission properties of a series of monodisperse solution-processable oligofluorenes functionalized with hexyl chains at the C9 position of ...each fluorene unit. Thin films of these oligofluorenes are then used in organic field-effect transistors and their charge transport properties are examined. We have particularly focused our attention on the influence of oligofluorene length on the absorption and steady-state fluorescence spectra, on the HOMO/LUMO energy levels, on the photoluminescence lifetime and quantum yield as well as on the amplified spontaneous emission properties and the charge carrier mobilities. Differential scanning calorimetry and X-ray diffraction measurements demonstrate that, among all oligofluorene derivatives used in this study, only the structure and morphology of the pentafluorene film is significantly modified by a thermal treatment above the glass transition temperature, resulting in a 9 nm blue-shift of the fluorescence spectrum without significant changes in the photoluminescence quantum yield and in the amplified spontaneous emission threshold. In parallel, hole field-effect mobility is significantly increased from 8.6 × 10(-7) to 3.8 × 10(-5) cm(2) V(-1) s(-1) upon thermal treatment, due to an increase of crystallinity. This study provides useful insights into the morphological control of oligofluorene thin films and how it affects their photophysical and charge transport properties. Moreover, we provide evidence that, because of the low threshold, the tunability of the amplified spontaneous emission and the photostability of the films, these oligofluorenes are promising candidates for organic solid-state laser applications.
Here, we present precise phase-connected pulse timing solutions for 16 γ-ray-selected pulsars recently discovered using the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope plus one ...very faint radio pulsar (PSR J1124–5916) that is more effectively timed with the LAT. We describe the analysis techniques including a maximum likelihood method for determining pulse times of arrival from unbinned photon data. A major result of this work is improved position determinations, which are crucial for multiwavelength follow-up. For most of the pulsars, we overlay the timing localizations on X-ray images from Swift and describe the status of X-ray counterpart associations. We report glitches measured in PSRs J0007+7303, J1124–5916, and J1813–1246. We analyze a new 20 ks Chandra ACIS observation of PSR J0633+0632 that reveals an arcminute-scale X-ray nebula extending to the south of the pulsar. We were also able to precisely localize the X-ray point source counterpart to the pulsar and find a spectrum that can be described by an absorbed blackbody or neutron star atmosphere with a hard power-law component. Another Chandra ACIS image of PSR J1732–3131 reveals a faint X-ray point source at a location consistent with the timing position of the pulsar. Finally, we present a compilation of new and archival searches for radio pulsations from each of the γ-ray-selected pulsars as well as a new Parkes radio observation of PSR J1124–5916 to establish the γ-ray to radio phase offset.
BackgroundThe current SARS-CoV-2 pandemic has highlighted a need for easy and safe blood sampling in combination with accurate serological methodology. Venipuncture for testing is usually performed ...by trained staff at healthcare centres. Long travel distances to healthcare centres in rural regions may introduce a bias of testing towards relatively large communities with closer access. Rural regions are therefore often not represented in population-based data.AimThe aim of this retrospective cohort study was to develop and implement a strategy for at-home testing in a rural region of Sweden during spring 2021, and to evaluate its role to provide equal health care for its inhabitants.MethodsWe developed a sensitive method to measure antibodies to the S-protein of SARS-CoV-2 and optimised this assay for clinical use together with a strategy of at-home capillary blood sampling.ResultsWe demonstrated that our ELISA gave comparable results after analysis of capillary blood or serum from SARS-CoV-2-experienced individuals. We demonstrated stability of the assay under conditions that reflected temperature and humidity during winter or summer. By assessment of capillary blood samples from 4,122 individuals, we could show both feasibility of the strategy and that implementation shifted the geographical spread of testing in favour of rural areas.ConclusionImplementation of at-home sampling enabled citizens living in remote rural areas access to centralised and sensitive laboratory antibody tests. The strategy for testing used here could therefore enable disease control authorities to get rapid access to information concerning immunity to infectious diseases, even across vast geographical distance.
We searched for radio pulsars in 25 of the non-variable, unassociated sources in the Fermi LAT Bright Source List with the Green Bank Telescope at 820 MHz. We report the discovery of three radio and ...Delta *g-ray millisecond pulsars (MSPs) from a high Galactic latitude subset of these sources. All of the pulsars are in binary systems, which would have made them virtually impossible to detect in blind Delta *g-ray pulsation searches. They seem to be relatively normal, nearby (<=2 kpc) MSPs. These observations, in combination with the Fermi detection of Delta *g-rays from other known radio MSPs, imply that most, if not all, radio MSPs are efficient Delta *g-ray producers. The Delta *g-ray spectra of the pulsars are power law in nature with exponential cutoffs at a few GeV, as has been found with most other pulsars. The MSPs have all been detected as X-ray point sources. Their soft X-ray luminosities of ~1030-1031 erg s--1 are typical of the rare radio MSPs seen in X-rays.
In order to extract neutrino oscillation parameters, long-baseline neutrino oscillation experiments rely on detailed models of neutrino interactions with nuclei. These models constitute an important ...source of systematic uncertainty, partially because detectors to date have been blind to final state neutrons. Three-dimensional projection scintillator trackers comprise components of the near detectors of the next generation long-baseline neutrino experiments. Due to the good timing resolution and fine granularity, this technology is capable of measuring neutron kinetic energy in neutrino interactions on an event-by-event basis and will provide valuable data for refining neutrino interaction models and ways to reconstruct neutrino energy. Two prototypes have been exposed to the neutron beamline at Los Alamos National Laboratory (LANL) in both 2019 and 2020, with neutron energies between 0 and 800 MeV. In order to demonstrate the capability of neutron detection, the total neutron-scintillator cross section as a function of neutron energy is measured and compared to external measurements. The measured total neutron cross section in scintillator between 98 and 688 MeV is 0.36 ± 0.05 barn.
The PI3K/AKT/mTOR pathway is frequently activated in various squamous cell carcinomas (SCCs). Although mTOR inhibitors are suggested as effective treatments in immunosuppressed patients with ...metastatic SCC, they are still not proven to be favorable in treating skin SCC patients not undergoing immunosuppressive therapy. Moreover, the exact mechanism of the mTOR signaling pathway in SCC has not yet been identified. In this study, we aimed to determine the genes associated with mTOR inhibitors in skin SCC.
The identification of cell viability according to concentration of everolimus and Western blot was done. To analyze the global gene expression profiles, A431 and HSC-1 cells were treated with dimethyl sulfoxide (DMSO) or 100 nM of everolimus for 72 hours. Furthermore, differentially expressed genes (DEGs) were identified using Affymetrix analysis. To identify the gene network associated with everolimus resistance in SCC cells, pathway analysis was performed using the Ingenuity Pathway Analysis (IPA) tool.
The effects of cell death with respect to the mTOR inhibitor concentration were observed in the HSC-1 cell line; however, the mTOR inhibitor did not show effective cytotoxic activity in the A431 cell line. p-mTOR concentration also diminished with respect to everolimus concentrations in the HSC-1 cell line. Moreover, the microarray results showed that the
genes were related to mTOR inhibitor resistance. However, CCND1 gene overexpression was most closely related to mTOR inhibitor resistance.
We identified mTOR inhibitor resistance genes, and our findings may help select therapeutic targets in skin SCC.
For 20 years, dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and a platelet P2Y
receptor inhibitor, has been the gold standard of antithrombotic pharmacology after ...percutaneous coronary intervention (PCI). In the past 5 years, several investigations have challenged this paradigm by testing the efficacy and safety of P2Y
inhibitor monotherapy (that is, without aspirin) following a short course of DAPT. Collectively, these studies suggested a reduction in the risk of major bleeding and no significant increase in thrombotic or ischaemic events compared with guideline-recommended DAPT. Current recommendations are evolving to inform clinical practice on the ideal candidates for P2Y
inhibitor monotherapy after PCI. Generalizing the results of studies of P2Y
inhibitor monotherapy requires a thorough understanding of their design, populations, interventions, comparators and results. In this Review, we provide an up-to-date overview on the use of P2Y
inhibitor monotherapy after PCI, including supporting pharmacodynamic and clinical evidence, practical recommendations and future directions.
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