Effect of postbiotic Lactiplantibacillus plantarum LRCC5314 supplemented in powdered milk on type 2 diabetes in mice.

Type 2 diabetes (T2D) is a chronic multifactorial disease characterized by a combination of insulin resistance and impaired glucose regulation. The alleviative effects of probiotics on T2D have been widely studied. However, studies on the effects of postbiotics, known as inactivated probiotics, on dairy products are limited. This study aimed to evaluate the effectiveness of postbiotic Lactiplantibacillus plantarum LRCC5314 in milk powder (MP-LRCC5314) in a stress-T2D mouse model. Compared with probiotic MP-LRCC5314, postbiotic MP-LRCC5314 significantly influenced stress-T2D-related factors. The administration of heat-killed MP-LRCC5314 reduced corticosterone levels, increased short-chain fatty acid production by modulating gut microbiota, and regulated immune response, glucose metabolism, stress-T2D-related biomarkers in the brain, gut, and adipose tissues, as well as glucose and insulin sensitivity. Additionally, heat-killed MP-LRCC5314 treatment led to a decrease in pro-inflammatory cytokine levels and an increase in anti-inflammatory cytokine levels. Overall, these findings suggest that adding postbiotic MP-LRCC5314 to milk powder could serve as a potential supplement for stress-T2D mitigation.

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial.

BACKGROUND: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. PATIENTS AND METHODS: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis. RESULTS: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ≥1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. CONCLUSION: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01905657.

Surgeon volume and prognosis of patients with advanced papillary thyroid cancer and lateral nodal metastasis.

BACKGROUND: Surgery is the most important treatment modality for papillary thyroid cancer (PTC). However, the relationship between surgeon volume and long-term oncological outcomes has not been explored. METHODS: Patients diagnosed with N1b PTC after initial thyroid surgery between 1 July 1994 and 31 December 2011 were eligible for inclusion in the study. Surgeons were categorized into high (at least 100 operations per year) and low (fewer than 100 operations per year) volume groups. Kaplan-Meier survival analysis according to surgeon volume was performed, and Cox proportional hazard modelling was used to estimate hazard ratios (HRs) with 95 per cent confidence intervals according to patient, tumour and surgeon factors. RESULTS: A total of 1103 patients with a median follow-up of 81 (i.q.r. 62-108) months were included in the study. During follow-up, 200 patients (18·1 per cent) developed structural recurrence. A high surgeon volume was associated with low structural recurrence (P = 0·006). After adjustment for age, sex and conventional risk factors for recurrence (histology, tumour size, gross extrathyroidal extension, margin status, more than 5 positive lymph nodes, radioactive iodine therapy), the adjusted HR for structural recurrence for low-volume surgeons was 1·46 (95 per cent c.i. 1·08 to 1·96), compared with high-volume surgeons. Distant metastasis (P = 0·242) and disease-specific mortality (P = 0·288) were not affected by surgeon volume. CONCLUSION: Surgeon volume is associated with structural recurrence, but not distant metastasis or cancer-specific death in patients with N1b PTC. Surgeon volume is important in initial surgery for advanced PTC with extensive nodal metastasis in order to ensure curative outcome and reduce treatment-related morbidity.

Prognostic significance of gross extrathyroidal extension invading only strap muscles in differentiated thyroid carcinoma.

BACKGROUND: In the eighth edition of the AJCC staging system for differentiated thyroid carcinoma (DTC), minimal extrathyroidal extension (ETE) is no longer a determinant of T3 category. Instead, gross ETE invading only strap muscles has been designated as a new T3b category. The long-term prognosis of patients with DTC and gross ETE invading only strap muscles was investigated. METHODS: This was a retrospective analysis of patients who underwent thyroidectomy between 1996 and 2005. Differences in cancer-specific and recurrence-free survival according to extent of ETE were assessed. RESULTS: A total of 3174 patients with DTC were included. No significant differences were observed in 10-year cancer-specific survival among patients with no ETE (98·6 per cent), microscopic ETE (98·3 per cent) and gross ETE invading only strap muscles (98·9 per cent) (P = 0·375). The 10-year recurrence-free survival rate for patients with gross ETE invading only strap muscles (89·2 per cent) was shorter than that for patients with no ETE (93·7 per cent; P = 0·016), but similar to that of patients with microscopic ETE (90·3 per cent). In univariable analysis, patients with gross ETE invading only strap muscles had a significantly higher risk of recurrence than those with no ETE (hazard ratio (HR) 1·67, 95 per cent c.i. 1·10 to 2·55; P = 0·017). In multivariable analysis, gross ETE invading only strap muscles was not an independent predictor of recurrence (HR 1·09, 0·71 to 1·69; P = 0·685). CONCLUSION: Although gross ETE invading only strap muscles may provide prognostic information about long-term recurrence, it does not affect mortality. The actual impact of gross ETE invading only strap muscles will be important in revising the staging system in the future.

Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior.

Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1f/f; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1f/f; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.

Proliferation of prostate epithelia induced by IL-6 from stroma reacted with Trichomonas vaginalis.

Benign prostatic hyperplasia (BPH) is characterized by the proliferation of stromal and epithelial cell types in the prostate, and interactions between the two types of cells. We demonstrated previously that proliferation of prostate stromal cells was induced by BPH epithelial cells in response to Trichomonas vaginalis (Tv) infection via crosstalk with mast cells. In this study, we investigated whether IL-6 released by the proliferating stromal cells in turn induce the BPH epithelial cells to multiply. When culture supernatants of the proliferating prostate stromal cells were added to BPH epithelial cells, the latter multiplied, and expression of cyclin D1, FGF2 and Bcl-2 increased. Blocking the IL-6 signalling pathway with anti-IL-6R antibody or JAK1/2 inhibitor inhibited the proliferation of the BPH epithelial cells and reduced the expression of IL-6, IL-6R and STAT3. Also, epithelial-mesenchymal transition was detected in the proliferating BPH epithelial cells. In conclusion, IL-6 released from proliferating prostate stromal cells induced by BPH epithelial cells infected with Tv in turn induces multiplication of the BPH epithelial cells. This result provides first evidence that the inflammatory microenvironment of prostate stromal cells resulting from Tv infection induces the proliferation of prostate epithelial cells by stromal-epithelial interaction.

A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer.

BACKGROUND: Eribulin is a microtubule dynamics inhibitor with a novel mechanism of action. This phase 3 study aimed to compare overall survival (OS) in patients with heavily pretreated non-small cell lung cancer (NSCLC) receiving eribulin to treatment of physician's choice (TPC). PATIENTS AND METHODS: Patients with advanced NSCLC who had received ≥2 prior therapies, including platinum-based doublet and epidermal growth factor receptor tyrosine kinase inhibitor, were randomly assigned to receive eribulin or TPC (gemcitabine, pemetrexed, vinorelbine, docetaxel). The primary endpoint was OS. Secondary endpoints were progression-free survival and objective response rate. RESULTS: Five hundred and forty patients were randomized to either eribulin (n = 270) or TPC (n = 270). Median OS for eribulin and TPC was the same: 9.5 months [hazard ratio (HR): 1.16; 95% confidence interval: 0.95-1.41; P = 0.13]. Progression-free survival for eribulin and TPC was 3.0 and 2.8 months, respectively (HR: 1.09; 95% confidence interval: 0.90-1.32; P = 0.39). The objective response rate was 12% for eribulin and 15% for TPC. Clinical benefit rate (eribulin, 57%; TPC, 55%) and disease control rate (eribulin, 63%; TPC, 58%) were similar between treatment arms. The most common adverse event was neutropenia, which occurred in 57% of eribulin patients and 49% of TPC patients at all grades. Other non-hematologic side-effects were manageable and similar in both groups except for peripheral sensory neuropathy (all grades; eribulin, 16%; TPC, 9%). CONCLUSION: This phase 3 study did not demonstrate superiority of eribulin over TPC with regard to overall survival. However, eribulin does show activity in the third-line setting for NSCLC. TRIAL REGISTRATION ID: www.ClinicalTrials.gov; NCT01454934.

Metabolomic analysis identifies potential diagnostic biomarkers for aspirin-exacerbated respiratory disease.

BACKGROUND: To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To investigate potential diagnostic biomarkers for AERD using metabolomic analysis. METHODS: An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/Q-ToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA. RESULTS: A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE4 and LTE4 /PGF2 α ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE4 and LTE4 /PGF2 α ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE4 levels were significantly correlated with the fall in FEV1 % after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463). CONCLUSIONS AND CLINICAL RELEVANCE: Serum metabolite level of LTE4 and LTE4 /PGF2 α ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/Q-ToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.

Patterns, predictive factors and prognostic impact of multilevel metastasis in N1b papillary thyroid carcinoma.

BACKGROUND: The patterns, predictive factors and prognostic impact of multilevel metastasis in patients with N1b papillary thyroid carcinoma (PTC) were investigated. METHODS: A retrospective review of patients with N1b PTC from a tertiary referral centre in Korea who underwent unilateral modified radical neck dissection was undertaken. RESULTS: Of 658 patients, multilevel metastasis was found in 73·9 per cent; the most common type was metastasis in two levels. Tumour size per 0·1-cm increment (adjusted odds ratio (OR) 1·33, 95 per cent c.i. 1·08 to 1·64), microscopic extrathyroidal extension (adjusted OR 1·72, 1·10 to 2·71), gross extrathyroidal extension (adjusted OR 2·35, 1·24 to 4·46), unilateral central lymph node metastasis (adjusted OR 2·45, 1·53 to 3·92) and bilateral central lymph node metastasis (adjusted OR 4·06, 2·29 to 7·18) were independent predictors of multilevel metastasis. Only four-level metastasis significantly increased the risk of overall locoregional recurrence (LRR) (adjusted hazard ratio (HR) 7·41, 95 per cent c.i. 2·20 to 24·53) and lateral neck LRR (adjusted HR 7·22, 1·82 to 28·65), compared with one-level metastasis. Two subgroup analyses were conducted, showing that only three-level metastasis including metastasis in level V significantly increased the risk of overall LRR (adjusted HR 5·66, 1·20 to 26·75). In addition, having level V metastasis was an independent predictor of both overall (adjusted HR 3·26, 1·72 to 6·18; P < 0·001) and lateral neck (adjusted HR 3·28, 1·50 to 7·16; P = 0·003) LRR. CONCLUSION: Level V metastasis rather than multilevel metastasis itself is associated with an increased risk of LRR. Patients with N1b PTC and level V metastasis require risk restratification and meticulous follow-up.

Bone mineral density among Korean females aged 20-50 years: influence of age at menarche (The Korea National Health and Nutrition Examination Survey 2008-2011).

To evaluate a possible correlation between bone mineral density (BMD) and age at menarche, the present study used the BMD dataset of the Korea National Health and Nutrition Examination Survey IV-V (KNHANES IV-V). Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. INTRODUCTION: To investigate any correlation between bone mineral density (BMD) and age at menarche in Korean females using data from the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-V; 2008-2011). METHODS: In total, 37,753 individuals participated in health examination surveys between 2008 and 2011. A total of 5032 premenopausal females aged 20-50 years were eligible. Age, height, weight, and age at menarche were assessed. RESULTS: Results from the univariate linear regression and analysis of covariance (ANCOVA) indicated that age (per 1 year), height (per 1 cm), weight (per 1 kg), exercise (per 1 day/week), familial osteoporosis history (yes), parity (n = 0 to ≥4), and menarche age distribution were associated with BMD of the total femur, femur neck, and lumbar spine. After stratifying the bone area and adjusting for age, parity, alcohol intake, smoking, exercise, and familial osteoporosis history, no effect was seen for the total femur or femur neck. Age at menarche 16~17 and ≥18 years groups were associated with BMD of the lumbar spine only. CONCLUSIONS: Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. Females with late menarche may achieve lower peak bone mass at some skeletal sites, which may put them at greater risk for osteoporosis in later life.

Association between shortened telomere length and systemic lupus erythematosus: a meta-analysis.

Objective We aimed to evaluate the relationship between telomere length and systemic lupus erythematosus (SLE). Methods PUBMED and EMBASE databases were searched; meta-analyses were performed comparing telomere length in SLE patients and healthy controls, and on SLE patients in subgroups based on ethnicity, sample type, assay method and data type. Results Eight studies including 472 SLE patients and 365 controls were ultimately selected which showed that telomere length was significantly shorter in the SLE group than in the control group (standardized mean difference (SMD) = -0.835, 95% confidence interval (CI) = -1.291 to -0.380, p = 3.3 × 10-4). Stratification by ethnicity showed significantly shortened telomere length in the SLE group in Caucasian, Asian and mixed populations (SMD = -0.455, 95% CI = -0.763 to -0.147, p = 0.004; SMD = -0.887, 95% CI = -1.261 to -0.513, p = 3.4 × 10-4; SMD = -0.535, 95% CI = -0.923 to -0.147, p = 0.007; respectively). Furthermore, telomere length was significantly shorter in the SLE group than in the control group in whole blood and peripheral blood mononuclear cell groups (SMD = -0.361, 95% CI = -0.553 to -0.169, p = 2.3 × 10-4; SMD = -1.546, 95% CI = -2.583 to -0.510, p = 0.003; respectively); a similar trend was observed in leukocyte groups (SMD = -0.699, 95% CI = -1.511 to -0.114, p = 0.092). Meta-analyses based on assay method or data type revealed similar associations. Conclusions Our meta-analysis demonstrated that telomere length was significantly shorter in patients with SLE, regardless of ethnicity, sample type or assay method evaluated.

Deep gray matter atrophy in neuromyelitis optica spectrum disorder and multiple sclerosis.

BACKGROUND AND PURPOSE: We investigated changes in deep gray matter (DGM) volume and its relationship to cognition and clinical factors in a large cohort of patients with neuromyelitis optica spectrum disorder (NMOSD) and compared them with results from multiple sclerosis (MS). METHODS: Brain magnetic resonance imaging (3 Tesla) and clinical data from 91 patients with NMOSD, 52 patients with MS and 44 healthy controls (HCs) were prospectively evaluated. Differences in DGM volumes were compared among groups. The relationships between DGM atrophy and clinical variables were also analysed. RESULTS: Patients with NMOSD exhibited significantly reduced thalamic volumes compared with HCs (P = 0.029), although this atrophy was less severe than that seen in patients with MS (P < 0.001). DGM atrophy was restricted to the thalamus in NMOSD, but it was broadly distributed in MS. Patients with NMOSD with cognitive impairment (CI) exhibited more severe thalamic atrophy than those with cognitive preservation (P = 0.017) and HCs (P = 0.003), whereas patients with MS with CI revealed DGM atrophy across the entire structure, with the exception of the bilateral pallidum, left hippocampus and amygdala, relative to HCs. The Expanded Disability Status Scale score was correlated with thalamic atrophy in both NMOSD and MS. Patients with NMOSD with brain lesions demonstrated more severe thalamic atrophy than did those without brain lesions and HCs (P < 0.001). CONCLUSIONS: The DGM atrophy was less severe and more selectively distributed in NMOSD than in MS. Thalamic atrophy was associated with clinical disability, including CI, in both NMOSD and MS.

Comparison of the characteristics of Mycobacterium tuberculosis isolates from sputum and lung lesions in chronic tuberculosis patients.

Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB. We studied the resected lungs of nine surgery patients with chronic TB. The isolates isolated from the sputum and different lung lesions of each patient were tested for phenotypic DST and genotyped using restriction fragment length polymorphism (RFLP) typing method. Genetic analysis to resistance to first and second line drugs was also performed. Five of nine patients were MDR-TB and three XDR-TB. DST results for ten anti-TB drugs were in accordance among different lung lesions in eight patients. However, only three of these eight patients showed the concordance of DST with sputum. Even though the isolates were heteroresistant, genotyping them by RFLP showed the clonal population in each individual patient. Six of eight followed-up patients achieved successful cure. In conclusion, the heteroresistance between sputum and lung lesions and a clonal population without mixed infection might provide useful information in establishing treatment regimen and surgery decision for MDR- and XDR-TB.

Revisiting the diagnostic criteria of clinical chorioamnionitis in preterm birth.

OBJECTIVE: To re-evaluate the utility of the conventional criteria for clinical chorioamnionitis in the prediction of early-onset neonatal sepsis (EONS) in preterm birth. DESIGN: Retrospective cohort study. SETTING: Seoul, Republic of Korea. SAMPLE: A total of 1468 singleton births between 24 and 34 weeks due to preterm labour (n = 713) or preterm prelabour rupture of membranes (n = 755). METHOD: We evaluated three diagnostic categories of clinical chorioamnionitis: Criteria 1, conventional criteria; Criteria 2, combination of any three conventional parameters without prerequisite fever; Criteria 3, Criteria 1 plus positive maternal C-reactive protein and neutrophil left-shift into minor criteria. EONS included proven or suspected sepsis within 7 days following birth. Neonatal morbidity and mortality of EONS were also reviewed. MAIN OUTCOME MEASURES: Diagnostic performance of three combinations. RESULTS: The prevalence of EONS was 13.8%. Among 203 cases of EONS, maternal manifestation of clinical chorioamnionitis by criteria 1 was evident in only one out of seven, indicating 15.3% sensitivity for EONS prediction. However, with application of criteria 2, sensitivity significantly increased to 34.0%, while compromising specificity from 92.3% to 78.7%. Criteria 3 showed similar diagnostic performance compared with criteria 1 (sensitivity 16.7%, specificity 91.6%). Overall, neonatal mortality and neonatal composite morbidity in EONS were 14.9% and 67.8%, respectively, and there was no difference in neonatal morbidity and mortality between neonates whose mothers showed fever as a sign of clinical chorioamnionitis and those whose mothers did not. CONCLUSION: The renouncement of fever as a prerequisite for the criteria of clinical chorioamnionitis could increase sensitivity for the identification of EONS, a serious outcome of preterm birth. TWEETABLE ABSTRACT: The renouncement of fever as an essential can increase sensitivity for prediction of neonatal sepsis.

The sphingosine-1-phosphate receptor 1 binding molecule FTY720 inhibits osteoclast formation in rats with ligature-induced periodontitis.

BACKGROUND AND OBJECTIVE: Osteoclast precursors (OPs) re-migrate from the bone surface into blood vessels through sphingosine-1-phosphate receptor 1 (S1PR1) expression. T cells also express S1PR1, mediating their migration from the lymph nodes into blood vessels. OP and T-cell migration are one of the sequential steps related to osteoclast formation. To characterize the role of S1PR1 in osteoclast formation induced by periodontitis, we investigated the effect of S1PR1-binding molecule FTY720 (FTY) on the number of OPs and T cells in periodontal tissue and peripheral blood of rats with ligature-induced periodontitis. MATERIAL AND METHODS: Rats were divided into four groups; control (Con), FTY, periodontitis (Peri), and periodontitis+FTY (Peri+FTY) groups. Ligatures were placed around the first molars in the left and right mandibles. The rats were intraperitoneally injected with vehicle or 3 mg/kg FTY daily until they were killed. The number of osteoclasts and cluster of differentiation (CD)11b, CD3 and receptor activator of NF-κB ligand (RANKL)-positive cells in first molar furcation were counted by tartrate-resistant acid phosphatase or immunohistochemistry staining. The number of CD11b- and CD3-positive cells in peripheral blood was estimated by flow cytometry. RESULTS: The number of osteoclasts in the Peri group was higher than Con, Peri+FTY and FTY groups (p < 0.05) and CD11b, CD3 and RANKL-positive cells were also higher in the Peri group than other groups in furcation (p < 0.05). While CD11b-positive cells in furcation of the Peri+FTY group were lower than the Peri group (p < 0.05), they were higher in peripheral blood (p < 0.05). Dissimilar to CD11b-positive cells, CD3-positive cells in the Peri+FTY group were lower in peripheral blood as well as furcation than the Peri group (p < 0.05). RANKL-positive cells in furcation of the Peri+FTY group were also lower than Peri group (p < 0.05). CONCLUSION: These results indicate that FTY may facilitate re-migration of OPs from the alveolar bone surface into blood vessels, blocking T-cell migration from the lymph nodes into blood vessels and subsequently reducing osteoclast formation induced by periodontitis. This suggests that S1PR1-S1P binding may play a role in osteoclast formation of periodontitis by modulating OP and T-cell migration.

Impact of RRAM Read Fluctuations on the Program-Verify Approach.

The stochastic nature of the conductive filaments in oxide-based resistive memory (RRAM) represents a sizeable impediment to commercialization. As such, program-verify methodologies are highly alluring. However, it was recently shown that program-verify methods are unworkable due to strong resistance state relaxation after SET/RESET programming. In this paper, we demonstrate that resistance state relaxation is not the main culprit. Instead, it is fluctuation-induced false-reading (triggering) that defeats the program-verify method, producing a large distribution tail immediately after programming. The fluctuation impact on the verify mechanism has serious implications on the overall write/erase speed of RRAM.

Intratumoural heterogeneity measured using FDG PET and MRI is associated with tumour-stroma ratio and clinical outcome in head and neck squamous cell carcinoma.

AIM: To evaluate the association between the tumour-stroma ratio and intratumoural heterogeneity measured using 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) and magnetic resonance imaging (MRI), and further investigate the prognostic significance of imaging biomarkers in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Textural-based imaging parameters of the primary tumour were extracted in 44 patients. In addition, the difference between the minimum and maximum apparent diffusion coefficient (ADC) values (ADCdiff) was calculated on MRI. The relationships between the tumour-stroma ratio and imaging parameters were evaluated. The associations between imaging parameters and recurrence-free survival (RFS) were assessed using Cox proportional hazard regression models. RESULTS: Coarseness (r=-0.382) on PET and ADCdiff (r=0.534) on MRI were significantly correlated with the proportion of stroma. The best imaging biomarkers for the 2-year RFS prediction were coarseness (AUC=0.741) and ADCdiff (AUC=0.779). Multivariate analysis showed that coarseness (hazard ratio=10.549, 95% confidence interval=2.544-43.748, p=0.001) was an independent prognostic factor for RFS. CONCLUSION: Heterogeneity imaging parameters are significantly associated with the tumour-stroma ratio. These imaging biomarkers may help to facilitate the risk stratification for tumour recurrence in HNSCC.

Adalimumab-induced pulmonary sarcoidosis not progressing upon treatment with etanercept.

Tumor necrosis factor alpha (TNF-α) inhibitors effectively treat sarcoidosis, but can, paradoxically, induce sarcoidosis. The TNF-α inhibitor etanercept is most commonly associated with paradoxical sarcoidosis, which has previously been reported to be resolved by adalimumab. However, we describe the case of a patient with ankylosing spondylitis and adalimumab-induced sarcoidosis not aggravated by switching to etanercept, thus indicating that etanercept could be a treatment option for patients who develop paradoxical sarcoid-like reactions after treatment with other TNF-α inhibitors.

Associations between SLC2A9 polymorphisms and gout susceptibility : A meta-analysis.

OBJECTIVE: The aim of this study was to determine whether polymorphisms in solute carrier family 2 and facilitated glucose transporter member 9 (SLC2A9) are associated with susceptibility to gout. METHODS: A meta-analysis was conducted on associations between the rs12510549, rs16890979, and rs1014290 polymorphisms of SLC2A9 and gout susceptibility using fixed and random effects models. RESULTS: Eleven comparative studies comprising 1,472 patients and 3,269 controls from Caucasian and Asian populations were included in this meta-analysis. The meta-analysis identified a significant negative association between gout and allele 2 (minor) of the rs12510549 polymorphism in the overall population (OR = 0.641, 95 % CI = 0.540-0.761, P = 4.1 × 10-7). Stratification by ethnicity identified a significant negative association between this polymorphism and gout in Caucasians (OR = 0.647, 95 % CI = 0.542-0.771, P = 1.2 × 10-6) but not in Asians (OR = 0.515, 95 % CI = 0.214-1.236, P = 0.137). The meta-analysis showed a significant negative association between gout and allele 2 of the rs16890979 polymorphism in all study subjects (OR = 0.229, 95 % CI = 0.084-0.628, P = 0.004). Stratification by ethnicity identified a significant negative association between this polymorphism and gout in Caucasians (OR = 0.469, 95 % CI = 0.317-0.695, P = 1.6 × 10-6) and in Asians (OR = 0.192, 95 % CI = 0.072-0.513, P = 0.001). A significant negative association was found between allele 2 of the rs1014290 polymorphism and gout susceptibility in Asians (OR = 0.597, 95 % CI = 0.478-0.746, P = 5.4 × 10-6) but not in Caucasians (OR = 0.778, 95 % CI = 0.595-1.043, P = 0.095). CONCLUSIONS: This meta-analysis shows that the rs12510549, rs16890979, and rs1014290 polymorphisms of SLC2A9 protect against the development of gout in Caucasians and/or Asians.

Body mass index and oral health status in Korean adults: the Fifth Korea National Health and Nutrition Examination Survey.

OBJECTIVES: The objective of this study was to examine the relationship between body mass index (BMI) and oral health status in Korean adults. METHODS: We used the Fifth Korea National Health and Nutrition Examination Survey to investigate the association between BMI and oral health status. Subjects who were measured for weight and height and had an oral examination in 2010 and 2012 were included (n = 11 466). Using multiple logistic regression analyses adjusted for gender, age, educational level, household income, smoking, frequency of tooth brushing and history of diabetes mellitus, the risk of dental caries and periodontitis was estimated in association with BMI. RESULTS: In the study population, 90.4% had more than one decayed, missing and filled tooth (DMFT) for permanent tooth, and 23.4% had a community periodontal index score (CPI) of 3 or 4. Distribution of underweight, normal weight, overweight and obese was 4.8, 40.5, 22.4 and 32.2%, respectively. Decayed, missing and filled tooth was highest in the normal weight group, and CPI was significantly highest in the obese group. In the overweight and obese groups, the odds ratios for periodontitis (CPI ≥ 3) were 1.18 [95% confidence interval (CI), 1.01-1.37] before and 1.27 (95% CI, 1.10-1.48) after adjustment for confounding factors. However, the risk for dental caries (DMFT ≥ 1) was not significantly associated with BMI. CONCLUSIONS: Body mass index was related to periodontitis, but not to dental caries, suggesting that obesity is a risk factor for periodontitis.