Ameliorating effect of 2'-Fucosyllactose and 6'-Sialyllactose on lipopolysaccharide-induced intestinal inflammation.

Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL co-treatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pre-treatment HMO mixture in vitro; thus, this ratio was selected and used for low, middle, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as body weight loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggested that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.

Joule spectroscopy of hybrid superconductor-semiconductor nanodevices.

Hybrid superconductor-semiconductor devices offer highly tunable platforms, potentially suitable for quantum technology applications, that have been intensively studied in the past decade. Here we establish that measurements of the superconductor-to-normal transition originating from Joule heating provide a powerful spectroscopical tool to characterize such hybrid devices. Concretely, we apply this technique to junctions in full-shell Al-InAs nanowires in the Little-Parks regime and obtain detailed information of each lead independently and in a single measurement, including differences in the superconducting coherence lengths of the leads, inhomogeneous covering of the epitaxial shell, and the inverse superconducting proximity effect; all-in-all constituting a unique fingerprint of each device with applications in the interpretation of low-bias data, the optimization of device geometries, and the uncovering of disorder in these systems. Besides the practical uses, our work also underscores the importance of heating in hybrid devices, an effect that is often overlooked.

Structural, magnetic, and magnetocaloric properties of R2NiMnO6 (R = Eu, Gd, Tb).

The crystal structure, cryogenic magnetic properties, and magnetocaloric performance of double perovskite Eu2NiMnO6 (ENMO), Gd2NiMnO6 (GNMO), and Tb2NiMnO6 (TNMO) ceramic powder samples synthesized by solid-state method have been investigated. X-ray diffraction structural investigation reveal that all compounds crystallize in the monoclinic structure with a P21/n space group. A ferromagnetic to paramagnetic (FM-PM) second-order phase transition occurred in ENMO, GNMO, and TNMO at 143, 130, and 112 K, respectively. Maximum magnetic entropy changes and relative cooling power with a 5 T applied magnetic field are determined to be 3.2, 3.8, 3.5 J/kgK and 150, 182, 176 J/kg for the investigated samples, respectively. The change in structural, magnetic, and magnetocaloric effect attributed to the superexchange mechanism of Ni2+-O-Mn3+ and Ni2+-O-Mn4+. The various atomic sizes of Eu, Gd, and Tb affect the ratio of Mn4+/Mn3+, which is responsible for the considerable change in properties of double perovskite.

Perinatal exposure to di-(2-ethylhexyl) phthalate induces hepatic lipid accumulation mediated by diacylglycerol acyltransferase 1.

INTRODUCTION: Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer in consumer products and medical devices. It is also suspected to exacerbate the development of fatty liver. However, the mechanisms underlying excessive lipid synthesis and its deposition in the liver are yet to be identified. This study was aimed to evaluate the molecular mechanisms of hepatic lipid accumulation in adult male offspring after perinatal exposure to DEHP. METHOD: Corn oil and DEHP (0.75 mg/kg/day) were administered once per day to dam from gestation day 6 to postnatal day (PND) 21 by oral gavage. After the weaning period, DEHP treated male pups were categorized into early life stage- and lifelong period group. Male rats both control and early life stage group administered corn oil, and lifelong period group administered DEHP from PND 22 to 70. Histological examination and triglyceride (TG) levels in the liver were analyzed. Expressions of transcription factors associated with lipid accumulation in the liver were analyzed. RESULTS: Both early life stage- and lifelong period group, hepatic TG levels, and mRNA and protein expression of diacylglycerol acyltransferase 1 (DGAT1) were significantly higher than control (TG: all p < 0.05, mRNA & protein: p < 0.05 and p < 0.001, respectively). The average body weight from PND 35 to 63, and mRNA and protein expression of sterol regulatory element binding protein 1c in lifelong period group were significantly lower than control (all p < 0.05); however, alanine transaminase were significantly higher than control (p < 0.01). CONCLUSION: Perinatal exposure to DEHP may induce the hepatic lipid accumulation through up-regulation of DGAT1 expression.

Analysis of expression profiling data suggests explanation for difficulties in finding biomarkers for nasal polyps.

BACKGROUND: Identification of clinically useful biomarkers for Nasal Polyposis in chronic rhinosinusitis (CRSwNP) has proven dif-ficult. We analyzed gene expression profiling data to find explanations for this. METHODS: We analyzed mRNA expression profiling data, GSE36830, of six uncinate tissues from healthy controls and six NP from CRSwNP patients. We performed Ingenuity Pathway Analysis (IPA) of differentially expressed genes to identify pathways and predicted upstream regulators. RESULTS: We identified 1,608 differentially expressed genes and 177 significant pathways, of which Th1 and Th2 activation pathway and leukocyte extravasation signaling were most significant. We identified 75 upstream regulators whose activity was predicted to be upregulated. These included regulators of known pathogenic and therapeutic relevance, like IL-4. However, only seven of the 75 regulators were actually differentially expressed in NP, namely CSF1, TYROBP, CCL2, CCL11, SELP, ADORA3, ICAM1. Interes-tingly, these did not include IL-4, and four of the seven were receptors. This suggested a potential explanation for the discrepancy between the predicted and observed expression levels of the regulators, namely that the receptors, and not their ligands, were upregulated. Indeed, we found that 10 receptors of key predicted upstream regulators were upregulated, including IL4R. CONCLUSION: Our findings indicate that the difficulties in finding specific biomarkers for CRSwNP depend on the complex underly-ing mechanisms, which include multiple pathways and regulators, each of which may be subdivided into multiple components such as ligands, soluble and membrane-bound receptors. This suggests that combinations of biomarkers may be needed for CRSwNP diagnostics.

Correction to: CD4 T cell count is positively associated with lumbar spine bone mass in HIV-infected men under the age of 50 years.

Two sentences in the Discussion section were incorrect.

Charge localization and reentrant superconductivity in a quasi-ballistic InAs nanowire coupled to superconductors.

A semiconductor nanowire with strong spin-orbit coupling in proximity to a superconductor is predicted to display Majorana edge states emerging under a properly oriented magnetic field. The experimental investigation of these exotic states requires assessing the one-dimensional (1D) character of the nanowire and understanding the superconducting proximity effect in the presence of a magnetic field. Here, we explore the quasi-ballistic 1D transport regime of an InAs nanowire with Ta contacts. Fine-tuned by means of local gates, the observed plateaus of approximately quantized conductance hide the presence of a localized electron, giving rise to a lurking Coulomb blockade effect and Kondo physics. When Ta becomes superconducting, this local charge causes an unusual, reentrant magnetic field dependence of the supercurrent, which we ascribe to a 0 - π transition. Our results underline the relevant role of unintentional charge localization in the few-channel regime where helical subbands and Majorana quasi-particles are expected to arise.

CD4 T cell count is inversely associated with lumbar spine bone mass in HIV-infected men under the age of 50 years.

HIV-infected men under the age of 50 years had a lower bone mass compared to that of HIV-uninfected men. Lower CD4 T cell counts, independent of whether antiretroviral therapy (ART) was used, were associated with lower BMD. HIV-infected patients with low CD4 T cell counts may need follow-up and intervention regarding bone health, including younger patients. INTRODUCTION: HIV-infected patients have a low bone mineral density (BMD) owing to multifactorial interaction between common osteoporosis risk factors and HIV-related factors, including chronic inflammation and ART. Although HIV infection and ART might affect bone metabolism, little data is available for patients aged under 50 years. We aimed to investigate the association of HIV infection-induced low CD4 T cell counts and ART with BMD in men aged under 50 years. METHODS: We performed an age- and body mass index-matched case-control study. BMD values of HIV-infected and HIV-uninfected men (< 50 years) were compared, and HIV-infected men were stratified by CD4 T cell counts and ART use. RESULTS: After adjusting confounders, HIV-infected men with CD4 T cell counts ≥ 500 cells/µL (n = 28) and < 500 cells/µL (n = 139) had lower BMD at the femoral neck (FN, p < 0.001) and total hip (TH, p < 0.001) than HIV-uninfected men (n = 167). HIV-infected men with CD4 T cell counts < 500/µL had lower BMD at the lumbar spine (LS, p = 0.034) than those with counts of ≥ 500 cells/µL, but not at FN and TH. The CD4 T cell count (γ = 0.169, p = 0.031) was positively correlated with BMD at LS. There was no significant difference in the BMD (p = 0.499-> 0.999) between the ART-naïve (n = 75) and ART-user group (n = 92). CONCLUSIONS: Despite their relatively younger age, HIV-infected men had a lower BMD than HIV-uninfected men. Lower CD4 T cell counts, irrespective of ART, might result in lower bone mass.

Key

Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the ß^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.

Diagnostic utility of skin autofluorescence when patch test results are doubtful.

BACKGROUND: The standard diagnostic test for allergic contact dermatitis is the patch test, which can also be used to identify irritant contact dermatitis. Doubtful reactions (?+) can be often clinically relevant to individuals and can require additional tests. OBJECTIVES: The purpose of this study was to examine whether autofluorescence (AF) measurements in patients with doubtful reactions are helpful in diagnosing contact dermatitis. METHODS: Patients with a history of contact dermatitis were patch tested on the upper back for 48-hours of occlusion using aqueous solutions of 5% sodium lauryl sulfate. Reaction intensity was scored, and AF was measured on reactive lesions and non-lesions. Three dermatologists classified the results as positive or negative using the fluorescence photographs of patients with a doubtful reaction. RESULTS: Among doubtful reactions, the R/G% values were significantly higher in the AF- based positive group than in the negative group (P = .0086). On the other hand, the heterogeneity values of R, G, and B (HR, HG, HB) were significantly lower in the AF-based positive group (P = .0026, .0046, .0004 respectively). CONCLUSIONS: Measuring AF along with the clinical readings can help confirm doubtful patch test reactions.

Mirage Andreev Spectra Generated by Mesoscopic Leads in Nanowire Quantum Dots.

We study transport mediated by Andreev bound states formed in InSb nanowire quantum dots. Two kinds of superconducting source and drain contacts are used: epitaxial Al/InSb devices exhibit a doubling of tunneling resonances, while, in NbTiN/InSb devices, Andreev spectra of the dot appear to be replicated multiple times at increasing source-drain bias voltages. In both devices, a mirage of a crowded spectrum is created. To describe the observations a model is developed that combines the effects of a soft induced gap and of additional Andreev bound states both in the quantum dot and in the finite regions of the nanowire adjacent to the quantum dot. Understanding of Andreev spectroscopy is important for the correct interpretation of Majorana experiments done on the same structures.

High tuberculosis transmission rate in children with nursery exposure to undetected pulmonary tuberculosis.

SETTING: Nursery for newborns in Busan, Republic of Korea. OBJECTIVE: To evaluate tuberculosis (TB) transmission from a health care worker with active pulmonary TB to neonatal contacts. DESIGN: For the first investigation, infants who had been in the nursery 3 months before the index patient was diagnosed with pulmonary TB were enrolled. After a child who had stayed in the nursery 10 months before the diagnosis of the index patient was diagnosed with tuberculous meningitis, a second contact investigation was conducted. RESULTS: Respectively 315 and 1334 children participated in the first and second investigations. The mean age of the contacts was 66.3 days; the rate of latent tuberculous infection (LTBI) at the first investigation was 42.5% (134/315). Only one infant had an abnormal chest X-ray, and was thought to have pulmonary TB. In the second investigation, the mean age of the participants was 17.6 months. The proportion of children with LTBI was 18.7% (249/1334). CONCLUSIONS: The LTBI rate in the present study was much higher than that estimated from other contact investigations. To minimise the risk of nosocomial TB transmission to neonates, screening and management of TB in health care workers should be strengthened.

Erythrocyte sedimentation rate measured using microhemagglutination is not elevated in monoclonal gammopathy compared with other diseases.

BACKGROUND: The erythrocyte sedimentation rate (ESR) as measured using the Westergren method is extremely elevated in patients with monoclonal gammopathy (MG) owing to the abundance of positively charged paraproteins. However, it has not been determined if the ESR is likewise high in patients with MG when measured using alternate ESR methods. METHODS: The ESR was measured using both the modified Westergren and microhemagglutination method (TEST1) in 36 patients with MG and in 159 individuals with other diseases. RESULTS: Erythrocyte sedimentation rates measured by the Westergren vs microhemagglutination methods showed substantial, but not remarkably high correlation. ESR measured using the Westergren method was higher in MG than in non-MG patients; however, ESR measured using microhemagglutination was not different in the 2 groups, resulting in a larger ΔESR (microhemagglutination ESR-Westergren ESR) in MG patients. When considered as continuous variables, none of the tested interfering plasma proteins (C-reactive protein, globulin, or fibrinogen) showed substantial correlations with Westergren or microhemagglutination ESRs. MG and low hematocrit were the only factors independently associated with ΔESR on multivariate analysis. CONCLUSION: We demonstrated, for the first time, that the ESR as measured by microhemagglutination is not elevated in patients with MG compared with those without. The ESR does not correlate with a particular plasma protein, showing that its measurement is multifactorial. The presence of MG is an independent factor for ΔESR.

Dicam promotes proliferation and maturation of chondrocyte through Indian hedgehog signaling in primary cilia.

OBJECTIVES: Primary cilium is required for mechano-biological signal transduction in chondrocytes, and its interaction with extracellular matrix is critical for cartilage homeostasis. However, the role of cilia-associated proteins that affect the function of cilia remains to be elucidated. Here, we show that Dicam has a novel function as a modulator of primary cilia-mediated Indian hedgehog (Ihh) signaling in chondrocytes. METHODS: Cartilage-specific Dicam transgenic mouse was constructed and the phenotype of growth plates at embryonic day 15.5 and 18.5 was analyzed. Primary chondrocytes and tibiae isolated from embryonic day 15.5 mice were used in vitro study. RESULTS: Dicam was mainly expressed in resting and proliferating chondrocytes of the growth plate and was increased by PTHrP and BMP2 in primary chondrocytes. Cartilage-specific Dicam gain-of-function demonstrated increased length of growth plate in long bones. Dicam enhanced both proliferation and maturation of growth plate chondrocytes in vivo and in vitro, and it was accompanied by enhanced Ihh and PTHrP signaling. Dicam was localized to primary cilia of chondrocytes, and increased the number of primary cilia and their assembly molecule, IFT88/Polaris as well. Dicam successfully rescued the knock-down phenotype of IFT88/Polaris and it was accompanied by increased number of cilia in tibia organ culture. CONCLUSION: These findings suggest that Dicam positively regulates primary cilia and Ihh signaling resulting in elongation of long bone.

Comparison of robotic and coblation tongue base resection for obstructive sleep apnoea.

OBJECTIVES: To compare the efficacy and safety of transoral robotic surgery (TORS) with endoscope-guided coblation tongue base resection. DESIGN: Retrospective case-control study. SETTING: University-based tertiary care medical center. PARTICIPANTS: Patients with obstructive sleep apnoea (OSA) who underwent endoscope-guided tongue base coblation resection or transoral robotic surgery (TORS) in combination with lateral pharyngoplasty at a single institution in South Korea between April 2013 and December 2016 were investigated. Forty-five patients who had moderate-to-severe OSA with tongue base collapse and a minimum follow-up period of 6 months with postoperative polysomnography (PSG) were enrolled in this study. MAIN OUTCOME MEASURES: All patients underwent pre- and postoperative (at least 4 months after surgery) overnight PSG. Available information on results of the PSG, Epworth sleepiness scale and complications of the TORS and coblation groups were compared. RESULTS: Postoperative PSG studies showed improved sleep quality for most patients. The mean postoperative apnoea-hypopnea index (AHI) was reduced significantly from 45.0 to 17.0 events/h (P < .0001) in the TORS group and from 45.6 to 16.2 events/h (P < .0001) in the coblation group. The mean rates of improvement (AHI reduction > 50%) were 75.0% in TORS patients and 62.1% in coblation patients and the difference was not significant. Less frequent postoperative morbidity, including bleeding, taste dysfunction and foreign body sensation, was recorded in TORS patients. CONCLUSIONS: Both the coblation and TORS groups showed similar surgical outcomes, TORS achieved PSG results non-inferior to and complication rates comparable to coblation.

Effect of oregano oil and tannic acid combinations on the quality and sensory characteristics of cooked chicken meat.

The antioxidant effects of oregano essential oil and tannic acid combinations on ground chicken breast and thigh meats were studied. Six treatments, including: 1) control (none added), 2) 100 ppm oregano essential oil + 5 ppm tannic acid, 3) 100 ppm oregano essential oil + 10 ppm tannic acid, 4) 200 ppm oregano essential oil + 5 ppm tannic acid, 5) 200 ppm oregano essential oil + 10 ppm tannic acid, and 6) 5 ppm butylated hydroxyanisole (BHA) for breast or 14 ppm for thigh meat, were prepared. Cooked meat samples were individually vacuum-packaged in oxygen-impermeable vacuum bags and then cooked in-bag to an internal temperature of 75°C. After cooling to room temperature, the cooked meat was re-packaged in new oxygen-permeable bags and stored at 4°C for 7 days. Cooked ground chicken meats were analyzed for lipid and protein oxidation and volatiles at 0, 3, and 7 d of storage. The significant differences among the treatments were very clear in cooked meat samples: Thigh meat patties showed higher 2-thiobarbituric acid reactive substances (TBARS), total carbonyl, and volatiles content compared to the breast meat during storage. A combination of 200 ppm oregano oil with 10 ppm tannic acid showed the most significant effects (P < 0.05) on TBARS, total carbonyl, and off-odor volatile formation for both breast and thigh meats. Oregano oil (200 ppm) and 10 ppm tannic acid combination also showed positive effects on the sensory scores of chicken thigh meat. In conclusion, the combination of 200 ppm oregano oil and 10 ppm tannic acid could be a good replacement for the synthetic antioxidants in ground cooked chicken meat.

Fungal-derived cues promote ocular autoimmunity through a Dectin-2/Card9-mediated mechanism.

Uveitis (intraocular inflammation) is a leading cause of loss of vision. Although its aetiology is largely speculative, it is thought to arise from complex genetic-environmental interactions that break immune tolerance to generate eye-specific autoreactive T cells. Experimental autoimmune uveitis (EAU), induced by immunization with the ocular antigen, interphotoreceptor retinoid binding protein (IRBP), in combination with mycobacteria-containing complete Freund's adjuvant (CFA), has many clinical and histopathological features of human posterior uveitis. Studies in EAU have focused on defining pathogenic CD4+ T cell effector responses, such as those of T helper type 17 (Th17) cells, but the innate receptor pathways precipitating development of autoreactive, eye-specific T cells remain poorly defined. In this study, we found that fungal-derived antigens possess autoimmune uveitis-promoting function akin to CFA in conventional EAU. The capacity of commensal fungi such as Candida albicans or Saccharomyces cerevisae to promote IRBP-triggered EAU was mediated by Card9. Because Card9 is an essential signalling molecule of a subgroup of C-type lectin receptors (CLRs) important in host defence, we evaluated further the proximal Card9-activating CLRs. Using single receptor-deficient mice we identified Dectin-2, but not Mincle or Dectin-1, as a predominant mediator of fungal-promoted uveitis. Conversely, Dectin-2 activation by α-mannan reproduced the uveitic phenotype of EAU sufficiently, in a process mediated by the Card9-coupled signalling axis and interleukin (IL)-17 production. Taken together, this report relates the potential of the Dectin-2/Card9-coupled pathway in ocular autoimmunity. Not only does it contribute to understanding of how innate immune receptors orchestrate T cell-mediated autoimmunity, it also reveals a previously unappreciated ability of fungal-derived signals to promote autoimmunity.

Hardly water-soluble drug-loaded gelatin nanoparticles sustaining a slow release: preparation by novel single-step O/W/O emulsion accompanying solvent diffusion.

Paclitaxel (PTX)-loaded gelatin nanoparticles (NPs) were prepared, for the first time, by novel O/W/O emulsion with a single-step emulsion process accompanying solvent diffusion, in contrast to the conventional double-step emulsion processes. Linoleic acid was chosen among the natural fatty acids as the exterior medium for the single-step emulsion process accompanying solvent diffusion. The size mean and zeta potential of the PTX-loaded gelatin NPs in their suspension were 164.95 nm (±6.43 nm) distributed with a polydispersity of 0.074 (±0.046) and -23.85 mV (±12.66 mV), respectively. The size of the PTX-loaded gelatin NPs prepared in this study was the smallest among the reported sizes of PTX-loaded gelatin NPs, which would contribute to the enhanced permeability and retention (EPR). In addition, TEM showed that the loaded PTX was located mostly inside the gelatin NPs unlike previous investigations. Accordingly, the conceptual model of the designed PTX-loaded gelatin nanoparticle was introduced. Sustaining a slow PTX release on a day-time scale without an initial burst release into a release medium was observed along with a delay of more than 2 days (i.e., 50 h) before a bursting PTX release from 50 to 70 h despite the addition of a protein degrading enzyme. The observed PTX-loading efficiency was 54.5%. This loading efficiency was greater than that of previous study using gelatin of bloom 75-100 of Lu et al. to prepare PTX-loaded gelatin NPs using a desolvation method.