Separating structure and electrons in VO2Above 341 kelvin—not far from room temperature—bulk vanadium dioxide (VO2) is a metal. But as soon as the material is cooled below 341 kelvin, VO2 turns into ...an insulator and, at the same time, changes its crystal structure from rutile to monoclinic. Lee et al. studied the peculiar behavior of a heterostructure consisting of a layer of VO2 placed underneath a layer of the same material that has a bit less oxygen. In the VO2 layer, the structural transition occurred at a higher temperature than the metal-insulator transition. In between those two temperatures, VO2 was a metal with a monoclinic structure—a combination that does not occur in the absence of the adjoining oxygen-poor layer.Science, this issue p. 1037The metal-insulator transition in correlated materials is usually coupled to a symmetry-lowering structural phase transition. This coupling not only complicates the understanding of the basic mechanism of this phenomenon but also limits the speed and endurance of prospective electronic devices. We demonstrate an isostructural, purely electronically driven metal-insulator transition in epitaxial heterostructures of an archetypal correlated material, vanadium dioxide. A combination of thin-film synthesis, structural and electrical characterizations, and theoretical modeling reveals that an interface interaction suppresses the electronic correlations without changing the crystal structure in this otherwise correlated insulator. This interaction stabilizes a nonequilibrium metallic phase and leads to an isostructural metal-insulator transition. This discovery will provide insights into phase transitions of correlated materials and may aid the design of device functionalities.
The Reactor Experiment for Neutrino Oscillation (RENO) has been taking electron antineutrino (ν¯e) data from the reactors in Yonggwang, Korea, using two identical detectors since August 2011. Using ...roughly 500 live days of data through January 2013 we observe 290 775 (31 514) reactor ν¯e candidate events with 2.8% (4.9%) background in the near (far) detector. The observed visible positron spectra from the reactor ν¯e events in both detectors show a discrepancy around 5 MeV with regard to the prediction from the current reactor ν¯e model. Based on a far-to-near ratio measurement using the spectral and rate information, we have obtained sin22θ13=0.082±0.009(stat.)±0.006(syst.) and |Δmee2|=2.62−0.23+0.21(stat.)−0.13+0.12(syst.)×10−3 eV2.
The RENO experiment has analyzed about 500 live days of data to observe an energy dependent disappearance of reactor νover ¯_{e} by comparing their prompt signal spectra measured in two identical ...near and far detectors. In the period between August of 2011 and January of 2013, the far (near) detector observed 31 541 (290 775) electron antineutrino candidate events with a background fraction of 4.9% (2.8%). The measured prompt spectra show an excess of reactor νover ¯_{e} around 5 MeV relative to the prediction from a most commonly used model. A clear energy and baseline dependent disappearance of reactor νover ¯_{e} is observed in the deficit of the observed number of νover ¯_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.082±0.009(stat)±0.006(syst) and |Δm_{ee}^{2}|=2.62_{-0.23}^{+0.21}(stat)_{-0.13}^{+0.12}(syst)×10^{-3} eV^{2}.
Summary
Background
Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated.
Objectives
We compared ...autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non‐severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs).
Methods
Peripheral blood neutrophils from patients with SA (n = 30) and NSA (n = 38) were treated with interleukin (IL)‐8 (100 ng/mL). Autophagy (light chain 3‐II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin‐1, and IL‐8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil‐derived neurotoxin (EDN).
Results
Untreated and IL‐8‐treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P < 0.01). IL‐8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P < 0.001). IL‐8‐induced NET production levels negatively were correlated with FEV1/FVC (r = −0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin‐1, and IL‐8 production from AECs. Higher levels of NET‐induced ECP and EDN were released from PBEs in SA compared with NSA groups.
Conclusions and Clinical Relevance
Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.
Nail melanoma (NM) is an important differential diagnosis in patients with longitudinal melanonychia. However, diagnosis is often challenging as it is difficult to differentiate from other pigmented ...nail disorders. The main challenge for diagnosis is obtaining adequate nail matrix biopsy specimens for histopathological assessment. Furthermore, the histopathological changes in the early stages of NM are subtle and contribute to a delay in diagnosis and care. Therefore, the integration of clinical and histopathological analyses is essential. Clinical and dermoscopic features, such as a broadened width of asymmetric bands in an irregular pattern, with multicolour pigmentation, periungual pigmentation, and continuous growth, are features that support the diagnosis of NM. The essential histological features that must be assessed are cellular morphology, architectural features, melanocyte density, and inflammatory changes. The reported mutations in NMs were BRAF (0–43%), NRAS (0–31%), KIT (0–50%), NF1 (0–50%), and GNAQ (0–25%). Surgery is the primary treatment for NM. The recommended treatment for in situ or minimally invasive NM is functional surgery, but cases with suspected bone invasion should be treated with amputation. Targeted therapy and immunotherapy are indicated for advanced stages of NM. This review summarizes the updated guidelines for the diagnosis and treatment of NM.
No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia.
A prospective observational ...cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics.
Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group.
Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.
Summary
Background
A multidrug regimen including isoniazid, rifampicin, pyrazinamide and ethambutol is commonly used as first‐line treatment for tuberculosis. However, this regimen can occasionally ...result in severe adverse drug reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and drug‐induced liver injury. The culprit drug and mechanistic basis for the hypersensitive reaction are unknown.
Objectives
To investigate drug‐specific T‐cell responses in patients with antituberculosis drug (ATD)‐induced cutaneous hypersensitivity and its underlying mechanism.
Methods
We enrolled eight patients with ATD‐induced maculopapular exanthema and DRESS and performed a lymphocyte transformation test. Subsequently, drug‐specific T‐cell clones were generated from four of the patients who showed proliferation in response to ATDs. We measured the drug‐specific proliferative responses and counted the drug‐specific interferon (IFN)‐γ/granzyme B‐producing cells after drug stimulation. Antihuman leukocyte antigen (HLA) class I and class II blocking antibodies were used to analyse human leukocyte antigen‐restricted T‐cell responses.
Results
Positive proliferative responses to ATDs were mostly found in patients with cutaneous hypersensitivity. Furthermore, we isolated isoniazid/rifampicin‐specific T cells from patients, which consisted primarily of CD4+ T cells. Drug‐specific CD4+ T cells proliferated and secreted IFN‐γ/granzyme B when stimulated with isoniazid or rifampicin, respectively. Isoniazid‐responsive T‐cell clones did not proliferate in the presence of rifampicin and vice versa. Drug‐specific T‐cell responses were blocked in the presence of anti‐HLA class II antibodies.
Conclusions
This study identifies the presence of isoniazid/rifampicin‐specific T cells in patients with ATD‐induced maculopapular exanthema and DRESS. Furthermore, it highlights the important role of drug‐specific T‐cell immune responses in the pathogenesis of these reactions.
What's already known about this topic?
Antituberculosis drug (ATD) treatment often induces severe adverse drug reactions including hepatotoxicity, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and maculopapular exanthema.
What does this study add?
This study identified an isoniazid/rifampicin‐specific T‐cell response in patients with ATD‐induced maculopapular exanthema and DRESS.
This study describes the nature of isoniazid/rifampicin‐specific CD4+ T cells and the mechanism of drug‐specific T‐cell activation in ATD‐induced maculopapular exanthema and DRESS syndrome.
What is the translational message?
As the first‐line treatment for tuberculosis is a combination regimen, the culprit drug is frequently not identified.
A lymphocyte transformation test for ATDs would be beneficial to assess the risk of drug hypersensitivity reaction.
Linked Comment: Pavlos et al. Br J Dermatol 2017; 176:292–293.
Objective
To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature.
Design
A multicentre, randomised, open‐label, ...equivalence trial and a meta‐analysis.
Setting
Tertiary referral hospitals in South Korea.
Population
Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm).
Methods
Eligible women were screened and randomised at 16‒22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α‐hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237).
Main outcome measure
Preterm birth (PTB) before 37 weeks of gestation.
Results
A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention‐to‐treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI −7.6 to 13.8%), which was within the equivalence margin of 15%. The meta‐analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments.
Conclusion
Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length.
Tweetable
Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.
Tweetable
Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.
Abstract Background Urinary tract infections (UTIs) are the most common infectious complication in kidney transplant recipients (KTRs). The aim of this study to investigate the risk factors for and ...causative organisms of UTI as well as to evaluate the impact these diseases on allograft function in KTRs. Methods We analyzed patients who underwent kidney transplantation (KT) between January 2000 and December 2010. Among a total of 344 KTRs, 50 (14.5%) patients experienced 106 UTI episodes during a mean follow-up of 35.9 ± 26.0 months. Twenty three patients experiencing recurrent UTI were compared with 27 nonrecurrent UTI patients and with 50 non-UTI patients matched for age, gender, and transplantation date. Results The number of patients with renal calculi, diabetes, or prior dialysis was significantly greater among the UTI group compared with control subjects. In addition, the number of patients with renal calculi was significantly higher among the recurrent compared with the nonrecurrent cohort (43.5 vs 7.4%; P = .003). The most common causative organism was Escherichia coli (64.1%), followed by Enterococcus species (20.5%). Higher rates of antibiotic resistance, especially Extended Spectrum Beta-Lactamasc (ESBL) production, were observed among the recurrent compared with the nonrecurrent group (53.1 vs 0%; P = .013). The rate of decline of estimated glomerular filtration rate was significantly faster in the UTI than the non-UTI group, whereas it did not differ between the recurrent and nonrecurrent group. Conclusions Adequate treatment of an initial UTI to prevent as recurrent infection and prolong graft longevity is especially reasonable for KTRs with renal calculi or in cases of antibiotic-resistant microorganisms.