Dapsone is an important medication for the treatment of leprosy, but a life-threatening drug hypersensitivity syndrome develops in some patients. In this report from China, an
HLA-B
locus is ...identified as a strong genetic risk factor for the syndrome.
Dapsone (4-4′-sulfonyldianiline), which was first synthesized in 1908,
1
is both an antibiotic and an antiinflammatory agent. Dapsone alone or in combination with other drugs has been used for the prevention and treatment of infectious diseases (e.g., leprosy, malaria, and actinomycetoma, as well as
Pneumocystis jirovecii
pneumonia in persons with human immunodeficiency virus HIV infection) and chronic inflammatory diseases characterized by the infiltration of neutrophils or eosinophils (e.g., dermatitis herpetiformis, linear IgA dermatosis, subcorneal pustular dermatosis, and erythema elevatum diutinum).
2
,
3
About 0.5 to 3.6% of persons treated with dapsone have a drug hypersensitivity syndrome,
3
–
5
which was first described by . . .
Traumatic brain injury (TBI) is a principal cause of death and disability worldwide. Melatonin, a hormone made by the pineal gland, is known to have anti-inflammatory and antioxidant properties. In ...this study, using a weight-drop model of TBI, we investigated the protective effects of ramelteon, a melatonin MT1/MT2 receptor agonist, and its underlying mechanisms of action. Administration of ramelteon (10 mg/kg) daily at 10:00 a.m. alleviated TBI-induced early brain damage on day 3 and long-term neurobehavioral deficits on day 28 in C57BL/6 mice. Ramelteon also increased the protein levels of interleukin (IL)-10, IL-4, superoxide dismutase (SOD), glutathione, and glutathione peroxidase and reduced the protein levels of IL-1β, tumor necrosis factor, and malondialdehyde in brain tissue and serum on days 1, 3, and 7 post-TBI. Similarly, ramelteon attenuated microglial and astrocyte activation in the perilesional cortex on day 3. Furthermore, ramelteon decreased Keap 1 expression, promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation, and increased levels of downstream proteins, including SOD-1, heme oxygenase-1, and NQO1 on day 3 post-TBI. However, in Nrf2 knockout mice with TBI, ramelteon did not decrease the lesion volume, neuronal degeneration, or myelin loss on day 3; nor did it mitigate depression-like behavior or most motor behavior deficits on day 28. Thus, timed ramelteon treatment appears to prevent inflammation and oxidative stress via the Nrf2-antioxidant response element pathway and might represent a potential chronotherapeutic strategy for treating TBI.
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•Ramelteon provided marked neuroprotection after TBI.•Ramelteon activated the Nrf2-ARE pathway in the brain after TBI.•The protection by ramelteon was partially lost in Nrf2-/- mice with TBI.
Surface modified-LiV3O8 cathode materials with Al2O3 are successfully synthesized via a facile thermolysis process. The 0.5 wt.% Al2O3-coated LiV3O8 exhibits an enhanced cyclic stability at various ...charge-discharge current densities. At a current density of 100 mA ga1, it delivers an initial specific discharge capacity of 283.1 mAh ga1 between 2.0 and 4.0 V. Moreover, high capacities of 139.4 and 118.5 mAh ga1 are obtained at the 100th cycle at current densities of 2000 and 3000 mA ga1, respectively. The improved electrochemical performance is attributed to the Al2O3 coating, which can hinder the irreversible phase transformation and act as a protective layer to prevent the active material from direct contact with electrolyte. Furthermore, the formation of a LiaVaAlaO solid solution at the LiV3O8/Al2O3 interface provides a fast Li+ diffusion path which is of benefit to the electrochemical behaviors.
IMPORTANCE: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of ...relapse and death are needed. OBJECTIVE: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. INTERVENTIONS: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. RESULTS: Among 443 women who were randomized, 434 were included in the full analysis set (mean SD age, 46 9.9 years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio HR for risk of recurrence or death, 0.64 95% CI, 0.42-0.95; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 95% CI, 0.38-0.92; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 95% CI, 0.47-1.19; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 95% CI, 0.46-1.13; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. CONCLUSIONS AND RELEVANCE: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01112826
In the quest to build general-purpose photonic quantum computers, fusion-based quantum computation has risen to prominence as a promising strategy. This model allows a ballistic construction of large ...cluster states which are universal for quantum computation, in a scalable and loss-tolerant way without feed forward, by fusing many small n-photon entangled resource states. However, a key obstacle to this architecture lies in efficiently generating the required essential resource states on photonic chips. One such critical seed state that has not yet been achieved is the heralded three-photon Greenberger-Horne-Zeilinger (3-GHZ) state. Here, we address this elementary resource gap, by reporting the first experimental realization of a heralded 3-GHZ state. Our implementation employs a low-loss and fully programmable photonic chip that manipulates six indistinguishable single photons of wavelengths in the telecommunication regime. Conditional on the heralding detection, we obtain the desired 3-GHZ state with a fidelity 0.573±0.024. Our Letter marks an important step for the future fault-tolerant photonic quantum computing, leading to the acceleration of building a large-scale optical quantum computer.
LiVO3 is synthesized via a ball-milling route followed by a solid-state reaction at different temperatures. As cathode materials for lithium ion batteries, the electrochemical performances of LiVO3 ...are investigated by galvanostatic charge–discharge test and electrochemical impedance spectroscopy (EIS). The LiVO3 compound synthesized at 350 °C possesses the optimal performance, delivering an initial discharge capacity of 302.5 mAh g−1 between 1.0 V and 3.5 V at a current density of 50 mA g−1, and exhibiting a good cycling stability. Li-ion diffusion coefficient of 10−9.5–10−8 cm2 s−1 in the LiVO3 electrode is calculated by galvanostatic intermittent titration technique (GITT). The good performances can be attributed to its relatively low crystallization and small particle size.
► LiVO3 is synthesized by a ball-milling route followed by a solid-state reaction. ► The LiVO3 compound synthesized at 350 °C possesses the optimal performance. ► It delivers an initial discharge capacity of 302.5 mAh g−1. ► Li-ion diffusion coefficient of 10−9.5–10−8 cm2 s−1 is calculated by GITT.
A resonant optical tunneling effect (ROTE) is a special phenomenon that bridges the wave optics and the quantum physics, and has attracted continuous research efforts for many years. This paper aims ...to summarize the latest progress of the ROTE in theoretical modeling and application studies. As the background, the analogies of photon tunneling and electron tunneling are first discussed using different optical structures and their corresponding quantum configurations. Then, two theoretical models are presented based on the optics interpretation and the quantum interpretation, respectively. Next, the applications of the ROTE are explored for optical switches and refractive index sensors. Finally, brief discussions are presented to distinguish the ROTE from some other similar phenomena.
We perform molecular dynamic simulations to investigate the effects of orientation and grain boundary (GB) on shock response of graphene, including shock-induced slip and spall. For compression under ...different loading orientations, the critical resolved shear stress for slip is constant along a given growth direction (armchair or zigzag) in single-crystal graphene, and spall initiates in elastically deformed graphene via tension-induced debonding. For bicrystal graphene, the locations of compression-induced slip and initial spall are influenced by preexisting stress field at GB and the interactions between GB and shock waves, respectively. Both of these two factors are related to GB structure, including the density of pentagon-heptagon pairs at GB. However, bicrystals show negligible anisotropy in shock-compression response. For polycrystalline graphene at high shock strength, slips initiate at GBs and triple junctions under shock compression, develop along GBs or toward grain interior, and serve as nucleation sites for spall damage.
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In this work, the influences of chemical composition and annealing processing on the phase morphology, structural evolution and associated magnetocaloric effect have been investigated in ...off-stoichiometric La1+xFe13−ySiy (x = 0.2–1.2 and y = 1.1–1.8) alloys. A peculiar microstructure, constituting of the facet-like La(Fe,Si)13 phase grains and surrounding La5Si3 secondary phase, is present in the composition range x = 0.7–1.2. A large magnetic entropy change of 16 J/kg K at 2 T is obtained in these La-rich bulk samples subjected to a relatively short annealing time of 3 days. The phase formation mechanism is studied by means of the diffusion couple technique. The transition phase La1Fe1Si1 that appears as the lamellar morphology in La-rich alloys plays the key role in accelerating the inter-diffusion with α-Fe, thus eventually forms the La(Fe,Si)13 functional phase at fast rate. Our finding indicates that off-stoichiometric La-Fe-Si composition alloys can be a promising magnetic refrigerant suitable for time- and energy-saving mass production.
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Scrub typhus, caused by mite-borne Orientia tsutsugamushi (O. tsutsugamushi), is a major febrile disease in the Asia-Pacific region. The DNA load of O. tsutsugamushi in the blood was previously found ...to be significantly higher in patients with fatal disease than those with non-fatal disease and correlated with the duration of illness, presence of eschar, and hepatic enzyme levels. In this prospective observation study, we analyzed the association of bacterial DNA load with clinical features, disease severity, and genotype using real-time PCR targeting the 56 kDa TSA gene of O. tsutsugamushi in the blood samples of 117 surviving patients with scrub typhus who had not received appropriate antibiotic treatment. The median O. tsutsugamushi DNA load was 3.11×103 copies/mL (range, 44 to 3.3×106 copies/mL). The severity of patients was categorized as mild, moderate, and severe based on the number of dysfunctional organs, and no significant difference in O. tsutsugamushi DNA load was found among these groups. Patients infected with the Karp group showed a significantly higher O. tsutsugamushi DNA load than those in the Gilliam (P < 0.05) and TA763 (P < 0.01) groups. Patients belonging to the Li ethnic group showed a significantly higher DNA load than those in the Han ethnic groups. The blood bacterial DNA load of patients showed no significant difference between groups divided by gender, age, with or without eschar, or the season of disease onset. The highest body temperature recorded during fever onset was positively correlated with O. tsutsugamushi DNA load (ρ = 0.272, P = 0.022). Correlation analyses indicated that the serum total bilirubin level was positively correlated with O. tsutsugamushi DNA load. In conclusion, the findings in this study demonstrated the association of DNA load of O. tsutsugamushi with the severity and genotype in patients with scrub typhus in Hainan, China.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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