Gut microbiome predicts cognitive function and depressive symptoms in late life.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

Excited-State Half-Lives in

The known I^{π}=8_{1}^{+}, E_{x}=2129-keV isomer in the semimagic nucleus ^{130}Cd_{82} was populated in the projectile fission of a ^{238}U beam at the Radioactive Isotope Beam Factory at RIKEN. The high counting statistics of the accumulated data allowed us to determine the excitation energy, E_{x}=2001.2(7) keV, and half-life, T_{1/2}=57(3) ns, of the I^{π}=6_{1}^{+} state based on γγ coincidence information. Furthermore, the half-life of the 8_{1}^{+} state, T_{1/2}=224(4) ns, was remeasured with high precision. The new experimental information, combined with available data for ^{134}Sn and large-scale shell model calculations, allowed us to extract proton and neutron effective charges for ^{132}Sn, a doubly magic nucleus far-off stability. A comparison to analogous information for ^{100}Sn provides first reliable information regarding the isospin dependence of the isoscalar and isovector effective charges in heavy nuclei.

Effect of pneumatic leg compression on post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy: a double-blind randomised controlled trial.

Post-induction hypotension is common and associated with postoperative complications. We hypothesised that pneumatic leg compression reduces post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy. In this double-blind randomised study, patients were allocated randomly to the pneumatic leg compression group (n = 50) or control (n = 50). In the intervention group, pneumatic leg compression was initiated before induction of anaesthesia. In the control group, pneumatic leg compression was initiated 20 min after anaesthesia induction. The primary outcome was the incidence of post-induction hypotension in these groups. Post-induction hypotension was defined as systolic blood pressure < 90 mmHg during the first 20 min after induction. Haemodynamic variables and area under the curve of post-induction systolic blood pressure over time were assessed. Complications associated with pneumatic leg compression were recorded, including: peripheral neuropathy; compartment syndrome; extensive bullae beneath the leg sleeves; and pulmonary thromboembolism. The incidence of post-induction hypotension decreased in the pneumatic leg compression group compared with that in the control group; 5 (10%) vs. 29 (58%), respectively, p < 0.001. In the pneumatic leg compression group, the lowest systolic, diastolic and mean blood pressures 20 min after induction of anaesthesia were significantly greater than the control group. Pneumatic leg compression resulted in an increased area under the curve of systolic blood pressure in the first 20 min after induction, p = 0.001. There were no pneumatic leg compression-related complications. Pneumatic leg compression reduced post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy, suggesting that it is an effective and safe intervention to prevent post-induction hypotension among elderly patients undergoing general anaesthesia.

Differentiable Preisach Modeling for Characterization and Optimization of Particle Accelerator Systems with Hysteresis.

Future improvements in particle accelerator performance are predicated on increasingly accurate online modeling of accelerators. Hysteresis effects in magnetic, mechanical, and material components of accelerators are often neglected in online accelerator models used to inform control algorithms, even though reproducibility errors from systems exhibiting hysteresis are not negligible in high precision accelerators. In this Letter, we combine the classical Preisach model of hysteresis with machine learning techniques to efficiently create nonparametric, high-fidelity models of arbitrary systems exhibiting hysteresis. We experimentally demonstrate how these methods can be used in situ, where a hysteresis model of an accelerator magnet is combined with a Bayesian statistical model of the beam response, allowing characterization of magnetic hysteresis solely from beam-based measurements. Finally, we explore how using these joint hysteresis-Bayesian statistical models allows us to overcome optimization performance limitations that arise when hysteresis effects are ignored.

Incidence and Distribution of the Pathogens Causing Central Nervous System Infections at the University Hospital of Korea.

BACKGROUND: The pathogens involved in central nervous system (CNS) infections are various, such as viruses, bacteria, and fungi, so a syndromic approach can be required. In addition, since their rapid and accurate detection is very crucial, molecular diagnostics using cerebrospinal fluid is becoming the emerging standard method. METHODS: The study was conducted retrospectively to identify the incidence and distribution patterns of the pathogens according to gender, age, season, and month and to analyze their codetection from August 2017 to July 2020. It was also conducted to investigate turn-around times (TATs) according to the detection method. The detection methods were FilmArray® Meningitis/Encephalitis (M/E) method (FilmArray), Cepheid® Xpert EV assay (Xpert), and Multiplex PCR method for five species of bacteria. RESULTS: The overall incidence for at least one pathogen was 13.9% (346/2,496). The highest incidence was shown in age group 4 (3 - 6 years), with 27.4%. The detection rates by FilmArray, Xpert, and Multiplex PCR method were 39.8%, 41.7%, and 0.4%, respectively. Enterovirus (EV) showed the highest incidence rate, which accounted for 37.0%. The distribution of the pathogens according to the age groups were the highest in age group 4, with 47.5% (168/354), followed by 27.4% (97/354) in age group 5. Of the ten cases in which bacteria were detected, S. agalactiae accounted for 60.0% (6/10), most of which occurred in age group 1. E. coli K1, L. monocytogenes, and N. meningitidis were not detected. In the viral distribution, EV accounted for the highest proportion in all age groups. The overall proportion of EV accounted for 87.6% (310/354), followed by human parechovirus with 2.8% (10/354). The most commonly detected season was summer, comprising 75.1%. A total of eight cases of co-detection with two pathogens accounted for 1.6% (8/507) in FilmArray. In FilmArray, all TATs were found to be shorter than Xpert. CONCLUSIONS: The information on the incidence and distribution patterns of the pathogens causing CNS infections and their rapid detection are critically important to clinicians in the management of immunocompromised patients, elderly, and children. The expeditious molecular diagnostics for these pathogens would be valuable in medical decisions by clinicians.

Prenylflavonoids isolated from Macaranga tanarius stimulate odontoblast differentiation of human dental pulp stem cells and tooth root formation via the mitogen-activated protein kinase and protein kinase B pathways.

AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'-geranyl-naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analysed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student's t-test. The data were considered to have statistical significance when the P-value was less than 0.05. RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.

Comparison of the diagnostic performance of the 2017 and 2018 versions of LI-RADS for hepatocellular carcinoma on gadoxetic acid enhanced MRI.

AIM: To compare the diagnostic performance of the 2017 (v2017) and 2018 versions (v2018) of the Liver Imaging-Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) using gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) and to evaluate the effect in v2018. MATERIALS AND METHODS: Treatment-naive patients at high-risk for HCC who underwent Gd-EOB-MRI were included. The LI-RADS categories were assigned according to v2017 and v2018. The diagnostic performances were compared between v2017 and v2018 according to the size and combination of imaging features. RESULTS: A total of 117 patients with 137 observations were identified, including 89 HCCs; 76.2% (64/84) of observations with threshold growth were re-classified as subthreshold growth when using v2018 instead of v2017. The final categories changed in nine (14%) cases. For the combination of LR-5/LR-5V, there were no significant differences in sensitivity and specificity between the two versions (sensitivity, 64% versus 58.4%; specificity, 87.5% versus 85.4%; all p>0.05). For the combination of LR-4 and LR-5/5V, the diagnostic performance of v2018 was inferior to that of v2017 when considering only major features (accuracy, 86.1% versus 80.3%, respectively; p=0.013), particularly in observations measuring 10-20 mm, but was comparable after adding the ancillary features (accuracy, 86.9% versus 86.1%, respectively; p=1.00). CONCLUSION: In LI-RADS v2018, although a considerable number of observations re-classified subthreshold growth, changes in the assigned categories were insignificant; overall diagnostic performance was comparable to that of v2017, but v2018 might emphasise the value of ancillary features in combination with major features for determining the probability of HCC.

Targetoid hepatic observations on gadoxetic acid-enhanced MRI using LI-RADS version 2018: emphasis on hepatocellular carcinomas assigned to the LR-M category.

AIM: To determine useful imaging features for differentiating hepatocellular carcinoma (HCC) categorised as LR-M from non-HCC malignancies in using the Liver Imaging-Reporting and Data System (LI-RADS) version 2018 on gadoxetic acid-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Patients at high-risk for HCC with surgically confirmed HCCs (n=131) and non-HCC malignancies (n=90) and who had undergone gadoxetic acid-enhanced MRI were included. LI-RADS categories were assigned to identify hepatic observations defined as LR-M by two radiologists. Major and ancillary imaging features of hepatic observation with targetoid appearance including intratumoural septa were compared between HCCs and non-HCC malignancies. A classification tree analysis (CTA) was applied to differentiate high-risk HCCs from non-HCC malignancies in the LR-M category. RESULTS: A total of 36 HCCs (27.5%) and 70 non-HCC malignancies (77.8%) were assigned as LR-M. An enhancing capsule (p=0.0293), blood products in the mass (p=0.0393), non-targetoid restriction (p=0.018), and a septum (p=0.0053) were significantly predictive of HCC. On CTA, the presence of a septum was an initial predictor for a high probability of HCC followed by non-targetoid restriction. The CTA model has a sensitivity of 63.9%, specificity of 90%, and accuracy of 81.1% for differentiating HCC assigned LR-M from non-HCC malignancy. CONCLUSION: A considerable proportion of HCCs could have been categorised as LR-M as they had a targetoid appearance on gadoxetic acid-enhanced MRI. An intratumoural septum and non-targetoid restriction as well as enhancing capsule and blood products in the mass may be useful for differentiating HCC assigned to LR-M from non-HCC malignancy on gadoxetic acid-enhanced MRI.

Improved Value for the Gamow-Teller Strength of the

A record number of ^{100}Sn nuclei was detected and new isotopic species toward the proton dripline were discovered at the RIKEN Nishina Center. Decay spectroscopy was performed with the high-efficiency detector arrays WAS3ABi and EURICA. Both the half-life and the ß-decay end point energy of ^{100}Sn were measured more precisely than the literature values. The value and the uncertainty of the resulting strength for the pure 0^{+}→1^{+} Gamow-Teller decay was improved to B_{GT}=4.4_{-0.7}^{+0.9}. A discrimination between different model calculations was possible for the first time, and the level scheme of ^{100}In is investigated further.

Proton Shell Evolution below

The ß-delayed γ-ray spectroscopy of neutron-rich ^{123,125}Ag isotopes is investigated at the Radioactive Isotope Beam Factory of RIKEN, and the long-predicted 1/2^{-} ß-emitting isomers in ^{123,125}Ag are identified for the first time. With the new experimental results, the systematic trend of energy spacing between the lowest 9/2^{+} and 1/2^{-} levels is extended in Ag isotopes up to N=78, providing a clear signal for the reduction of the Z=40 subshell gap in Ag towards N=82. Shell-model calculations with the state-of-the-art V_{MU} plus M3Y spin-orbit interaction give a satisfactory description of the low-lying states in ^{123,125}Ag. The tensor force is found to play a crucial role in the evolution of the size of the Z=40 subshell gap. The observed inversion of the single-particle levels around ^{123}Ag can be well interpreted in terms of the monopole shift of the π1g_{9/2} orbitals mainly caused by the increasing occupation of ν1h_{11/2} orbitals.

Cognitive decline in association with hyposmia in idiopathic rapid eye movement sleep behavior disorder: a prospective 2-year follow-up study.

BACKGROUND AND PURPOSE: The aim was to analyze the characteristics and progression of cognitive dysfunction in non-demented idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with baseline olfactory function. METHODS: From a prospective polysomnography-confirmed iRBD cohort, 25 patients (16 patients in 2-year follow-up) and 13 normal controls were included. Initial and 2-year follow-up cognitive functions were analyzed with olfactory function and 18 F-fluorinated-N-3-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)-nortropane (18 F-FP-CIT) uptake in deep nuclei initially. RESULTS: Idiopathic RBD patients had impaired attention, memory and executive function compared to controls. Baseline cognitive tests were comparable between the iRBD subgroups with and without hyposmia. 18 F-FP-CIT uptake tended to be lower in the hyposmic group than in the normosmic group. The olfactory test score was positively correlated with amygdala uptake in iRBD patients (P = 0.027). After 2 years, visuospatial and verbal memory dysfunction worsened more in hyposmics than in normosmics. Lower initial olfactory test score was associated with more severe declines in verbal memory function. CONCLUSIONS: Hyposmia may be a predictive sign of cognitive decline in iRBD patients.

Estimation of thermal comfort felt by human exposed to extreme heat wave in a complex urban area using a WRF-MENEX model.

Thermal comfort could indicate human thermal sensation when exposed to a local meteorological condition. Because humans can suffer illness when exposed to heat or even die, it is essential to assess human comfort levels to increased temperature and to provide this information to the public. This study aims to estimate thermal comfort using the human heat balance model combined with a numerical meteorological model in Seoul mega city during the heat wave periods experienced during 2016. The gridded thermal comfort index of physiological subjective temperature (PST) was calculated based on the Man-Environment Heat Exchange (MENEX) model, which used as inputs the meteorological parameters, clothing insulations, and metabolic rates. High-resolution meteorological parameters were obtained by coupling Weather Research and Forecasting (WRF) model with Building Effect Parameterization (BEP) + Building Energy Model (BEM) using detailed urban classification. The modeling results showed that the PST distribution has a clearly heterogeneous spatial distribution during the heat wave period. The high PST values were largely found in the residential area during the day, due to the high temperature and low wind speed associated with high-density buildings, and the daily maximum PST reached a very hot level (44.1-54.0 °C). Our study suggested that the human heat balance model combined with the numerical meteorological model could be used to provide more reliable information about thermal comfort to groups that may be vulnerable to the effects of heat waves in complex urban environments.

Adipochemokines induced by ultraviolet irradiation contribute to impaired fat metabolism in subcutaneous fat cells.

BACKGROUND: Adipose tissue is now appreciated as the pivotal regulator of metabolic and endocrine functions. Subcutaneous (SC) fat, in contrast to visceral fat, may protect against metabolic syndrome and systemic inflammation. We demonstrated that chronic as well as acute ultraviolet (UV) irradiation to the skin induces loss of underlying SC fat. UV-irradiated SC fat may produce chemokines or cytokines that modulate lipid homeostasis and secretion of adipokines. OBJECTIVES: To elucidate UV-induced specific adipochemokines implicated in UV-induced modulation of SC fat. METHODS: Primary cultured adipocytes were treated with conditioned medium from UV- or sham-irradiated skin cells. Young and older healthy participants provided SC fat from sun-exposed and sun-protected skin. Sun-protected skin from other participants was irradiated with UV. Differentially expressed adipochemokines were screened by cytokine array, and confirmed in vitro and in vivo. The functions of select adipochemokines involved in lipid metabolism were examined via short interfering RNA-mediated knockdown of cognate receptors. RESULTS: Specific adipochemokines, including C-X-C motif chemokine (CXCL) family members such as CXCL5/ENA-78, and C-C motif chemokine (CCL) family members such as CCL20/MIP-3α and CCL5/RANTES, were greatly induced in SC fat by UV exposure. They could impair triglyceride synthesis via downregulation of lipogenic enzymes and sterol regulatory element-binding protein-1 through their respective cognate receptors, CXC chemokine receptor type (CXC-R)2, C-C chemokine receptor type (CCR)-6, and CCR-5. In addition, UV irradiation induced infiltration of adipose tissue macrophages responsible for the secretion of several chemokines into SC fat. CONCLUSIONS: These UV-induced adipochemokines may be implicated in the reduction of lipogenesis in SC fat, leading to impairment of fat homeostasis and associated comorbidities such as obesity.

Compliance and persistence with hydroxychloroquine in South Korean patients with systemic lupus erythematosus.

We aimed to analyze compliance and persistence with hydroxychloroquine (HCQ) in real practice and identify risk factors for poor adherence in South Korean patients with systemic lupus erythematosus (SLE). This retrospective longitudinal study evaluated 235 SLE patients in whom oral HCQ was newly started from 2002 to 2016 at a tertiary hospital in South Korea. Compliance was assessed using one-year medication possession ratio (MPR) and non-compliance was defined as a one-year MPR < 0.8. Persistence was determined as the time from HCQ treatment initiation to discontinuation without interruption for ≥56 days. The mean one-year MPR of HCQ was 0.88 and the frequency of non-compliance was 19.9%. During the study period, 115 (48.9%) patients discontinued HCQ and forgetfulness and/or carelessness (73%) were the most common reason for HCQ non-persistence, followed by adverse events (10.4%), unknown factors (10.4%), and pregnancy (6.1%). Median duration until HCQ discontinuation was 55.1 months and the one-year persistence rate to HCQ was 0.8. SLE Disease Activity Index 2000 (SLEDAI-2K) < 6 was a significant risk factor for non-compliance (OR = 2.98, p = 0.001) and non-persistence (HR = 1.55, p = 0.046) with HCQ after adjusting confounding factors. However, HCQ adherence was not associated with the dose of HCQ or concomitant immunosuppressive medications. Our data showed that overall adherence to HCQ in SLE patients was suboptimal in real practice and SLEDAI-2K score < 6 was a risk factor for poor adherence, suggesting the need to improve adherence with HCQ treatment in SLE patients, especially in those with low disease activity.

18F-NaF PET/CT for the evaluation of temporomandibular joint disorder.

AIM: To investigate the usefulness of a quantitative parameter (maximum standardised uptake value [SUVmax]) of 18F-sodium fluoride (NaF) positron-emission tomography (PET)/computed tomography (CT) for the evaluation of temporomandibular joint (TMJ) disorder (TMD). MATERIALS AND METHODS: Seventy-six TMD patients (male: female=14:62, age=40.3±17.1 years, bilateral: unilateral=40:36) with 152 TMJs were enrolled. The 18F-NaF PET/CT parameter (SUVmax) was compared with the presence of TMJ arthralgia (arthralgic=86, non-arthralgic=66) and clinical subtypes based on the Research Diagnostic Criteria for TMD Axis I (TMD osteoarthritis=49, non-TMD osteoarthritis=67, and asymptomatic TMJ=36). Splint therapy was applied to 48 patients for 6 months without considering 18F-NaF PET/CT findings. Post-splint therapy 18F-NaF PET/CT was performed in 32 patients and clinical responses to the therapy were classified into improvement (n=33), no change (n=10), or aggravation (n=7) for 50 TMJs excluding asymptomatic TMJs (n=14). RESULTS: SUVmax was significantly greater in arthralgic TMJs than in non-arthralgic TMJs (6.62±3.56 versus 4.32±1.53, p<0.0001). SUVmax was also significantly greater in TMD osteoarthritis (6.75±3.85) than in non-TMD osteoarthritis (5.21±2.70) and asymptomatic TMJs (4.86±1.99; p=0.0386). After splint therapy, SUVmax was significantly increased in aggravated TMJs (from 7.80±3.72 to 11.00±5.74, p=0.0156), whereas no significant change in SUVmax was observed in improved (from 6.16±2.68 to 6.09±2.60, p=0.4915) and unchanged (from 6.46±4.19 to 6.77±4.32, p=0.3223) TMJs. CONCLUSIONS: 18F-NaF PET/CT is a useful imaging tool for TMD evaluation because SUVmax showed a fair diagnostic performance for arthralgic TMJ and TMD osteoarthritis, and a correlation with the therapeutic response.

Prediction and clinical implications of portal vein/superior mesenteric vein invasion in patients with resected pancreatic head cancer: the significance of preoperative CT parameters.

AIM: To determine the preoperative computed tomography (CT) parameters that predict portal vein/superior mesenteric vein (PV-SMV) invasion in patients with pancreatic head cancer, and to assess whether PV-SMV invasion affects patient survival. MATERIALS AND METHODS: Sixty patients with PV-SMV invasion, and 60 randomly selected patients without it, who had undergone preoperative CT and subsequent surgery for pancreatic head cancer were enrolled. The following CT parameters were evaluated using multivariate logistic regression and receiver operating characteristic analyses to predict vessel invasion (tumour size and margin, length of involved vessel, distance from the tumour to the vessel, vessel irregularity, the teardrop sign, and tumour-vein interface [TVI]). The Cox proportional hazard model was used to evaluate the effects of PV-SMV invasion on survival. RESULTS: In multivariate analysis, tumour size (odds ratio [OR]=1.99) and TVI (OR=3.79 [≤90°], 20.66 [>90°, ≤180°], and 47.24 [>180°]) were independent CT predictors of PV-SMV invasion (p<0.05); they achieved a sensitivity of 87%, a specificity of 75%, and an accuracy of 81%; however, PV-SMV invasion did not affect patient survival after surgery (p=0.374). CONCLUSION: In patients with pancreatic head cancer, preoperative CT parameters can predict PV-SMV invasion with high accuracy. PV-SMV invasion did not affect treatment outcome after surgery.

Enhanced superconductivity in surface-electron-doped iron pnictide Ba(Fe1.94Co0.06)2As2.

The superconducting transition temperature (TC) in a FeSe monolayer on SrTiO3 is enhanced up to 100 K (refs ,,,). High TC is also found in bulk iron chalcogenides with similar electronic structure to that of monolayer FeSe, which suggests that higher TC may be achieved through electron doping, pushing the Fermi surface (FS) topology towards leaving only electron pockets. Such an observation, however, has been limited to chalcogenides, and is in contrast to the iron pnictides, for which the maximum TC is achieved with both hole and electron pockets forming considerable FS nesting instability. Here, we report angle-resolved photoemission characterization revealing a monotonic increase of TC from 24 to 41.5 K upon surface doping on optimally doped Ba(Fe1-xCox)2As2. The doping changes the overall FS topology towards that of chalcogenides through a rigid downward band shift. Our findings suggest that higher electron doping and concomitant changes in FS topology are favourable conditions for the superconductivity, not only for iron chalcogenides, but also for iron pnictides.

agr functionality affects clinical outcomes in patients with persistent methicillin-resistant Staphylococcus aureus bacteraemia.

Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) often persists despite appropriate antibiotic therapy. It is unclear what microbiological factors contribute to poor clinical outcomes in persistent MRSAB (pMRSAB). We aimed to identify clinical and microbiological risk factors for in-hospital mortality in pMRSAB. We analysed MRSAB cases prospectively collected between 2009 and 2016 at 11 hospitals in Korea, defining cases of pMRSAB as MRSAB lasting ≥5 days despite administration of effective antibiotics. The first blood isolates from the pMRSAB cases were tested for staphylococcal cassette chromosome mec type, staphylococcal protein A type, accessary gene regulator (agr) type, genes for Panton-Valentine leukocidin and phenol-soluble modulin-mec, vancomycin minimum inhibitory concentration, vancomycin heteroresistance, and agr functionality. We also collected clinical information for each case. Of 960 MRSAB cases, 152 pMRSAB were finally eligible. Univariable analysis revealed that in-hospital mortality was significantly associated with Charlson's comorbidity-weighted index (CCWI) score, Pitt bacteremia score, sequential organ failure assessment score, presentation with septic shock, pneumonia, agr dysfunction, and vancomycin heteroresistance. Bone and joint infections were negatively associated with in-hospital mortality. Multivariable analysis revealed the following independent risk factors for in-hospital mortality: CCWI score [adjusted odds ratio (aOR), per one point, 1.25; 95% confidence interval (CI), 1.08-1.44; P = 0.003), Pitt bacteremia score (aOR, per one point, 1.33; 95% CI, 1.09-1.62; P = 0.005), non-eradicated foci of infection (aOR, 3.12; 95% CI, 1.18-8.27; P = 0.022), and agr dysfunction (aOR, 2.48; 95% CI, 1.12-5.47; P = 0.025). agr dysfunction is an independent risk factor for in-hospital mortality in pMRSAB.

Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort.

Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum effect (CIE). However, data on the characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 µg/ml with a high inoculum (∼5 × 107 CFU/ml). The blaZ gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10-7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76-12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62-7.80) and erythromycin (OR 5.00, 95 % CI, 2.50-9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.

Value of unenhanced MRI with diffusion-weighted imaging for detection of primary small (≤20 mm) solid pancreatic tumours and prediction of pancreatic ductal adenocarcinoma.

AIM: To determine the diagnostic performance of unenhanced magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI; NonMRI) for the detection of primary small (≤20 mm) pancreatic solid tumours and prediction of pancreatic ductal adenocarcinoma (PDAC) in comparison with pancreatic computed tomography (CT; PanCT) and pancreatic MRI with magnetic resonance cholangiopancreatography (PanMRI). METHODS AND MATERIALS: The institutional review board approved this retrospective study and waived the requirement for informed consent. A total of 126 patients who underwent PanCT and PanMRI, including 94 small (≤20 mm) pancreatic tumours (51 PDACs, 34 neuroendocrine tumours [NETs], nine solid pseudopapillary tumours [SPTs]), and 32 patients with a normal pancreas, comprised the study population. Two observers assessed three sets of images: PanCT, PanMRI and NonMRI (T1- and T2-weighted images and DWI). Receiver operating characteristic curve analysis and diagnostic accuracy using the area under the receiver operating characteristic curve (Az) were used for statistical analysis. RESULTS: On NonMRI and PanMRI, all of tumours except one NET were detected, but eight tumours (six NETs, one PDAC, one SPT) were not detected on PanCT (p<0.01). For prediction of PDAC, the Az value of the NonMRI (0.884 for observer 1; 0.930 for observer 2) was comparable with PanCT (0.922; 0.924; p>0.05), and inferior to PanMRI (0.930; 0.977; p<0.05), but all of 51 PDACs were considered as probable or definite PDAC on NonMRI by both observers. CONCLUSION: NonMRI showed better performance than PanCT, and competitive performance to PanMRI for the detection of primary small solid pancreatic tumours, and showed reasonable sensitivity for prediction of PDACs compared with PanCT and PanMRI.