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1.
Rhinology ; 61(1): 47-53, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36306524

ABSTRACT

BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.


Subject(s)
Disorders of Excessive Somnolence , Nasal Obstruction , Nose Diseases , Humans , Nose Diseases/complications , Nose Diseases/surgery , Nose Diseases/diagnosis , Quality of Life , Sleepiness , Nasal Obstruction/etiology , Nasal Obstruction/surgery , Nasal Obstruction/psychology , Syndrome , Nose
2.
Eur Rev Med Pharmacol Sci ; 26(8): 2794-2801, 2022 04.
Article in English | MEDLINE | ID: mdl-35503624

ABSTRACT

OBJECTIVE: The nitric oxide (NO) metabolite nitrite has been shown to attenuate hyperglycemia via its increase in insulin sensitivity and glucose uptake. However, the oral use of nitrite is limited due to its potential formation of the carcinogenic N-nitrosamines via reaction of acidic nitrite and the secondary amines. We investigated the anti-diabetic effect of sodium nitrite (SN) combined with glutathione (GSH) in streptozotocin (STZ)-induced diabetic mice for potential use of GSH as a protective agent in future nitrite therapy. MATERIALS AND METHODS: STZ-induced diabetic mice were orally treated for 5 weeks with vehicle, SN, GSH or SN + GSH. Oral glucose tolerance test and the measurement of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were carried out to evaluate anti-diabetic effects of SN and SN + GSH. Plasma levels of total NO metabolites (NOx) were measured to confirm nitrite absorption. RESULTS: SN and SN + GSH significantly improved the glucose tolerance (p < 0.05), but GSH alone did not. The efficacy of combination treatment with SN and GSH in improving the glucose tolerance was higher than that of SN alone. Oral treatment with SN or SN + GSH significant reduced FBG and HbA1c levels (p < 0.05). Interestingly, daily oral administration of SN + GSH was more effective in reducing FBG and HbA1c levels than that of SN alone. Administration of SN or SN + GSH significantly increased plasma NOx levels (p < 0.05), and combination treatment with SN + GSH was more effective in increasing plasma NOx levels than that with SN alone. CONCLUSIONS: Combination treatment with SN and GSH is more effective in controlling hyperglycemia and increasing the plasma NOx levels in an experimental mouse model of diabetes. Since oral administration of GSH has been shown to be non-toxic in humans, the combination of SN and GSH may be important in potential future nitrite therapy.


Subject(s)
Diabetes Mellitus, Experimental , Glutathione , Hyperglycemia , Sodium Nitrite , Animals , Antioxidants/administration & dosage , Antioxidants/metabolism , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/metabolism , Glucose/metabolism , Glutathione/administration & dosage , Glycated Hemoglobin/metabolism , Hyperglycemia/drug therapy , Mice , Nitric Oxide/metabolism , Sodium Nitrite/administration & dosage , Streptozocin
3.
Int J Oral Maxillofac Surg ; 51(11): 1394-1400, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35249786

ABSTRACT

The aim of this study was to identify the risk factors associated with developing oral squamous cell carcinoma (OSCC) from surgically excised oral leukoplakia (OL) in patients with previous oral cavity cancer. Clinicopathological data of 84 patients who were treated for OL between July 2002 and July 2020 and who had previously received treatment for OSCC were reviewed retrospectively. The follow-up time ranged from 0.69 to 17.99 years (mean 6.78 ± 4.25 years). The overall cumulative malignant transformation rate was 25% and the annual transformation rate was 5.73%. Kaplan-Meier survival analysis and the log-rank test showed that Candida infection (P = 0.010) was a risk factor associated with malignant transformation. In the multivariate Cox regression analysis, tongue and floor of the mouth as the location of the leukoplakia (P = 0.039), multifocal lesions of OL (P = 0.047), and Candida infection (P = 0.018) were the three independent prognostic factors related to the development of OSCC from the treated OL. A cautious approach to OL of the tongue with Candida infection or multifocal disease in this group of patients would be appropriate.


Subject(s)
Candidiasis , Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Mouth Neoplasms/surgery , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck , Retrospective Studies , Leukoplakia, Oral , Cell Transformation, Neoplastic/pathology , Risk Assessment
4.
AJNR Am J Neuroradiol ; 41(10): 1897-1904, 2020 10.
Article in English | MEDLINE | ID: mdl-32943420

ABSTRACT

BACKGROUND AND PURPOSE: Human papillomavirus is a prognostic marker for oropharyngeal squamous cell carcinoma. We aimed to determine the value of CT-based radiomics for predicting the human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: Eighty-six patients with oropharyngeal squamous cell carcinoma were retrospectively collected and grouped into training (n = 61) and test (n = 25) sets. For human papillomavirus status and overall survival prediction, radiomics features were selected via a random forest-based algorithm and Cox regression analysis, respectively. Relevant features were used to build multivariate Cox regression models and calculate the radiomics score. Human papillomavirus status and overall survival prediction were assessed via the area under the curve and concordance index, respectively. The models were validated in the test and The Cancer Imaging Archive cohorts (n = 78). RESULTS: For prediction of human papillomavirus status, radiomics features yielded areas under the curve of 0.865, 0.747, and 0.834 in the training, test, and validation sets, respectively. In the univariate Cox regression, the human papillomavirus status (positive: hazard ratio, 0.257; 95% CI, 0.09-0.7; P = .008), T-stage (≥III: hazard ratio, 3.66; 95% CI, 1.34-9.99; P = .011), and radiomics score (high-risk: hazard ratio, 3.72; 95% CI, 1.21-11.46; P = .022) were associated with overall survival. The addition of the radiomics score to the clinical Cox model increased the concordance index from 0.702 to 0.733 (P = .01). Validation yielded concordance indices of 0.866 and 0.720. CONCLUSIONS: CT-based radiomics may be useful in predicting human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma.


Subject(s)
Oropharyngeal Neoplasms/virology , Papillomavirus Infections/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/virology , Tomography, X-Ray Computed/methods , Aged , Algorithms , Alphapapillomavirus , Female , Humans , Image Interpretation, Computer-Assisted/methods , Male , Middle Aged , Oropharyngeal Neoplasms/diagnostic imaging , Oropharyngeal Neoplasms/mortality , Proportional Hazards Models , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/mortality
5.
Eur J Neurol ; 27(1): 210-212, 2020 01.
Article in English | MEDLINE | ID: mdl-31444924

ABSTRACT

BACKGROUND AND PURPOSE: The brain's cholinergic network has various interconnections with the cortical and subcortical structures. Disruption of cholinergic pathways by white matter hyperintensities (WMH) may cause pathologic changes within brain regions. Thus, WMH may represent an important pathological contributor to subcortical vascular cognitive impairment (scVCI). We aimed to investigate associations between the magnitude of WMH and volumetric changes in cortical and subcortical regions innervated by cholinergic neurons in patients with scVCI. METHODS: We enrolled patients with scVCI, defined as moderate to severe WMH or multiple (>2) lacunar infarcts outside the brainstem. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were used to quantify the magnitude of cholinergic pathway disruptions by WMH. We measured cortical thickness and subcortical volumes of 11 brain regions innervated by cholinergic neurons. Partial correlation of brain region volumes with total CHIPS scores was obtained using multiple linear regression. RESULTS: In total, 80 patients were enrolled. The mean age was 78.4 ± 6.5 years, median Mini-Mental State Examination score was 17 (interquartile range, 13-20) and median CHIPS score was 11 (interquartile range, 7-17). CHIPS scores were positively correlated with subcortical volumes of the putamen (r' = 0.46, P = 0.002) and pallidum (r' = 0.45, P = 0.002), and were negatively associated with inferior temporal (r' = -0.35, P = 0.002) and medial orbitofrontal (r' = -0.32, P = 0.002) cortical thickness. CONCLUSION: Our study suggested that WMH in cholinergic pathways may contribute to volumetric structural changes in cortical and subcortical structures innervated by cholinergic neurons.


Subject(s)
Cerebral Cortex/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/psychology , Dementia, Vascular/diagnostic imaging , Dementia, Vascular/psychology , Neural Pathways/physiopathology , Parasympathetic Nervous System/physiopathology , Aged , Aged, 80 and over , Cognitive Dysfunction/pathology , Dementia, Vascular/pathology , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Mental Status and Dementia Tests , Neuropsychological Tests , Parasympathetic Nervous System/pathology , Stroke, Lacunar/diagnostic imaging , Stroke, Lacunar/pathology , White Matter/diagnostic imaging , White Matter/pathology
6.
Eur J Neurol ; 26(5): 747-753, 2019 05.
Article in English | MEDLINE | ID: mdl-30565350

ABSTRACT

BACKGROUND AND PURPOSE: The purpose was to evaluate the association between the left ventricular ejection fraction (LVEF) and cerebral small vessel disease (cSVD) in ischaemic stroke patients. METHODS: Consecutive first-ever ischaemic stroke patients between 2010 and 2013 were included. White matter hyperintensity (WMH) volumes were rated using both the Fazekas score and quantitative methods on fluid-attenuated inversion recovery images. As spectra of cSVD, lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVSs) were also evaluated. To assess the dose-response relationship between LVEF and cSVD, the burdens of each radiological marker and the total cSVD score were rated. RESULTS: A total of 841 patients were included [median WMH volume 2.98 (1.22-10.50) ml; the frequencies of lacunes, CMBs and moderate to severe EPVSs were 38%, 31% and 35%, respectively]. In the multivariate analysis about predictors of WMH volumes, the LVEF (B = -0.052, P < 0.001) remained significant after adjusting for confounders. LVEF was also a predictor of lacunes [adjusted odds ratio (aOR) 0.978, P = 0.012], CMBs (aOR = 0.96, P < 0.001) and moderate to severe EPVSs (aOR = 0.94, P < 0.001) after adjusting for their confounders. The LVEF values were negatively correlated with the burdens of lacunes (P = 0.026), CMBs (P < 0.001) and EPVSs (P = 0.002). The total cSVD score also showed a negative association with LVEF in a dose-response manner (P < 0.001). CONCLUSIONS: The burden of cSVD is negatively correlated with the LVEF in a dose-response manner. Our results suggest clues for further studies about determining the pathophysiology of cSVD.


Subject(s)
Brain Ischemia/physiopathology , Cerebral Small Vessel Diseases/physiopathology , Stroke Volume , Stroke/physiopathology , Aged , Brain Ischemia/complications , Brain Ischemia/diagnostic imaging , Cerebral Small Vessel Diseases/complications , Cerebral Small Vessel Diseases/diagnostic imaging , Echocardiography, Doppler , Female , Humans , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging , Stroke/complications , Stroke/diagnostic imaging , Ventricular Function, Left , White Matter/diagnostic imaging
8.
Eye (Lond) ; 32(1): 104-112, 2018 01.
Article in English | MEDLINE | ID: mdl-28776594

ABSTRACT

PurposeTo investigate the microstructural differences of the inner retina in the peripapillary and macular areas in children with or without retinopathy of prematurity (ROP).MethodsThis prospective cohort study included school-age children with a history of ROP and age-matched healthy, full-term children. The macular ganglion cell complex (mGCC), peripapillary retinal nerve fiber layer (RNFL), refractive status, and ocular biometry were measured. The metrics of the mGCC and associated anatomical changes were the primary outcomes. Mann-Whitney U tests and chi-squared tests were used to compare variables between the two groups.ResultsA total of 41 eyes from 21 preterm children with ROP and 34 eyes from 17 full-term children were enrolled. ROP eyes had significantly thicker mGCC (P<0.001) with uneven distribution compared with full-term eyes. The RNFLs of ROP eyes were thicker in the temporal quadrants but thinner in the nasal quadrants (P=0.01 and.04, respectively). In addition, the ROP eyes had shallower anterior chamber depths (ACDs), thicker lenses, and higher degrees of refractive errors (all P<0.05) but similar axial lengths (ALs) (P=0.58) compared with full-term eyes.ConclusionsThe mGCC was thicker in children with ROP, and their inner retinal structures had a different distribution pattern than those in full-term children. The myopia of children with ROP was associated with the abnormal development of the anterior segment rather than long ALs. These alterations in inner retinal anatomy and optic components emphasize the importance of careful examinations to monitor the development of glaucoma or visual decline in children with ROP.


Subject(s)
Infant, Premature , Retinal Pigment Epithelium/diagnostic imaging , Retinopathy of Prematurity/diagnosis , Tomography, Optical Coherence/methods , Female , Follow-Up Studies , Gestational Age , Humans , Infant, Newborn , Male , Nerve Fibers/pathology , Prospective Studies , Refraction, Ocular , Retinopathy of Prematurity/physiopathology , Visual Acuity
9.
Bioorg Med Chem ; 25(21): 5975-5980, 2017 11 01.
Article in English | MEDLINE | ID: mdl-28964629

ABSTRACT

In this report we describe the development of an alternative approach to arylstannane chemistry for radiolabeling antibodies with radioiodine or astatine based on aryliodonium salts precursors. Bifunctional aryliodonium salts were designed and tested for the synthesis of 125I and 211At labeled prosthetic groups for bioconjugation. The nature of the electron rich aryl group was varied and its impact on the regioselectivity of radiohalogenation was evaluated. Unexpectedly, whereas the 2-thienyl group provided the best regioselectivity towards the radioiodination of the aryl moiety of interest (98:2), it was less selective for astatination (87:13); the anisyl group providing the best regioselectivity of astatination (94:6). Under optimized conditions, both radioiodination and astatination could be performed very efficiently in mild conditions (radiochemical yields>85%). The ionic nature of the precursors was exploited to develop an efficient purification approach: the HPLC step that is usually necessary in conventionnal approaches to optimize removal of organotin toxic precursors and side products was replaced by a filtration through a silica cartridge with a significantly reduced loss of radiolabeled product. The purified radioiodinated and astatinated prosthetic groups were then conjugated efficiently to an anti-CD138 monoclonal antibody (75-80% conjugation yield). By using this novel and simple radiohalogenation procedure, higher overall radiochemical yields of astatination were obtained in comparison with the use of an arylstannane precursor and procedures of the litterature for labeling the same antibody. Overall, due to their simplicity of use and high robustness, these new precursors should simplify the labeling of proteins of interest with iodine and astatine radioisotopes for imaging and therapeutic applications.


Subject(s)
Antibodies, Monoclonal/chemistry , Astatine/chemistry , Hydrocarbons, Iodinated/chemistry , Hydrocarbons, Iodinated/chemical synthesis , Iodine Radioisotopes , Molecular Structure , Salts/chemical synthesis , Salts/chemistry , Temperature
11.
Eur J Neurol ; 24(11): 1348-1354, 2017 11.
Article in English | MEDLINE | ID: mdl-28833961

ABSTRACT

BACKGROUND AND PURPOSE: Previous studies have revealed that the predictors of short- and long-term stroke recurrence are different. We designed a comprehensive stroke recurrence (CSR) model, composed of demographic, clinical and radiological findings, to predict long-term ischaemic stroke recurrences. METHODS: We retrospectively collected the derivation cohort from consecutive patients with first-ever ischaemic stroke within 7 days of symptom onset. Univariate and multivariable Cox regression analysis were used to evaluate the association between 2-year recurrence and demographic, clinical and neuroradiological factors. The CSR score was calculated by adding the integer value of independent predictors that was derived from the ß-coefficient in the multivariable analysis. To qualify the model, we analyzed the receiver operating characteristics curve. We assessed internal validation with bootstrap methods and assessed external validation with another independent cohort. RESULTS: A total of 958 patients were enrolled, and 63 patients had recurrent strokes during the follow-up periods. The rate of stroke recurrence was 7.0% at 2 years. In the multivariable analysis, multiple stage lesions, isolated cortical lesions on diffusion-weighted imaging, severe white matter hyperintensities, multiple lacunar infarctions and relevant arterial stenosis were independently associated with stroke recurrence. The CSR model showed good discrimination [area under the curve (AUC), 0.81 (0.74-0.88)], which was consistent with internal [AUC, 0.75 (0.66-0.85)] and external [AUC, 0.80 (0.69-0.90)] validation. CONCLUSIONS: Abnormal neuroimaging findings, rather than cardiovascular risk factors, are predictive of long-term ischaemic stroke recurrence. Causative mechanism of stroke and underlying hostile brain milieu seem to be associated with long-term stroke recurrence.


Subject(s)
Brain Ischemia/diagnostic imaging , Brain/diagnostic imaging , Neuroimaging , Stroke/diagnostic imaging , Aged , Brain/pathology , Brain Ischemia/pathology , Cohort Studies , Diffusion Magnetic Resonance Imaging , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Stroke/pathology
12.
Oncogene ; 36(50): 6884-6894, 2017 12 14.
Article in English | MEDLINE | ID: mdl-28846108

ABSTRACT

The restriction (R)-point decision is fundamental to normal differentiation and the G1-S transition, and the decision-making machinery is perturbed in nearly all cancer cells. The mechanisms underlying the cellular context-dependent R-point decision remain poorly understood. We found that the R-point was dysregulated in Runx3-/-mouse embryonic fibroblasts (MEFs), which formed tumors in nude mice. Ectopic expression of Runx3 restored the R-point and abolished the tumorigenicity of Runx3-/-MEFs and K-Ras-activated Runx3-/-MEFs (Runx3-/-;K-RasG12D/+). During the R-point, Runx3 transiently formed a complex with pRb and Brd2 and induced Cdkn1a (p21Waf1/Cip1/Sdi1; p21), a key regulator of the R-point transition. Cyclin D-CDK4/6 promoted dissociation of the pRb-Runx3-Brd2 complex, thus turning off p21 expression. However, cells harboring oncogenic K-Ras maintained the pRb-Runx3-Brd2 complex and p21 expression even after introduction of Cyclin D1. Thus, Runx3 plays a critical role in R-point regulation and defense against cellular transformation.


Subject(s)
Cell Transformation, Neoplastic , Core Binding Factor Alpha 3 Subunit/physiology , Animals , Carcinogenesis , Cyclin-Dependent Kinase Inhibitor p21/genetics , Genes, ras , HEK293 Cells , Humans , Mice , Protein Serine-Threonine Kinases/physiology , Retinoblastoma Protein/physiology , Transcription Factors
13.
Oncogene ; 36(49): 6793-6804, 2017 12 07.
Article in English | MEDLINE | ID: mdl-28846112

ABSTRACT

RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes). Emerging diverse roles of Pol III genes suggest that individual Pol III genes are exquisitely regulated by transcription and epigenetic factors. Here we report global Pol III expression/methylation profiles and molecular mechanisms of Pol III regulation that have not been as extensively studied, using nc886 as a representative Pol III gene. In a human mammary epithelial cell system that recapitulates early breast tumorigenesis, the fraction of actively transcribed Pol III genes increases reaching a plateau during immortalization. Hyper-methylation of Pol III genes inhibits Pol III binding to DNA via inducing repressed chromatin and is a determinant for the Pol III repertoire. When Pol III genes are hypo-methylated, MYC amplifies their transcription, regardless of its recognition DNA motif. Thus, Pol III expression during tumorigenesis is delineated by methylation and magnified by MYC.


Subject(s)
Breast/metabolism , Cell Transformation, Neoplastic/genetics , Epigenesis, Genetic , RNA Polymerase III/metabolism , Transcription, Genetic , Breast/cytology , Cells, Cultured , Chromatin/genetics , Chromatin/metabolism , DNA/genetics , DNA/metabolism , DNA Methylation , Epithelial Cells/metabolism , Humans , Protein Binding , Proto-Oncogene Proteins c-myc/genetics , RNA, Untranslated/genetics
14.
Aliment Pharmacol Ther ; 45(12): 1493-1505, 2017 06.
Article in English | MEDLINE | ID: mdl-28436552

ABSTRACT

BACKGROUND: Preventing mother to child transmission of chronic hepatitis B infection in the setting of a high maternal viral load is challenging. The idea has emerged from antepartum tenofovir treatment with combination immunoprophylaxis. AIMS: To demonstrate the efficacy and safety of tenofovir to prevent mother to child transmission of hepatitis B virus. METHODS: PubMed, EMBASE, and Cochrane databases were searched through August 16, 2016. Comparative trials of second or third trimester tenofovir administration vs. controls for patients with chronic hepatitis B infection and non-comparative case series assessing mother to child transmission rates and evaluating maternal and foetal safety outcomes were included. RESULTS: Ten studies (one randomised controlled trial, four non-randomised controlled trials and five case series) that enrolled 733 women were included. The pooled results from comparative trials (599 pregnancies) showed that tenofovir significantly reduced the risk of infant hepatitis B surface antigen seropositivity by 77% (odds ratio=0.23, 95% confidence intervals=0.10-0.52, P=.0004) without heterogeneity (I2 =0%). In the case series analysis (134 pregnancies), only two cases (1.5%) of mother to child transmission with extremely high maternal viral load and non-compliance to treatment were identified. Maternal and foetal safety parameters including congenital malformation and foetal death were re-assuring. CONCLUSIONS: For pregnant women with high hepatitis B virus DNA levels, tenofovir administration in the second or third trimester can prevent mother to child transmission when combined with hepatitis B immunoglobulin and the hepatitis B vaccine. Tenofovir is safe and tolerable for both the mother and foetus.


Subject(s)
Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/transmission , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/drug therapy , Tenofovir/therapeutic use , Combined Modality Therapy , Female , Hepatitis B Vaccines/therapeutic use , Hepatitis B virus/drug effects , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/therapy , Humans , Infant , Infectious Disease Transmission, Vertical/statistics & numerical data , Mothers/statistics & numerical data , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/therapy , Tenofovir/adverse effects , Treatment Outcome , Viral Load/drug effects , Viral Load/genetics
15.
Dalton Trans ; 46(14): 4749-4758, 2017 Apr 05.
Article in English | MEDLINE | ID: mdl-28338136

ABSTRACT

Three hydroxypyridinone (HOPO) positional isomers - 1,2-HOPO (L1H) and its water soluble analogue (L1'H), 3,2-HOPO (L2H) and 3,4-HOPO (L3H) have been investigated for the complexation of Zr(iv). Potentiometric and UV-Vis spectrometric studies show a higher thermodynamic stability for the formation of Zr(L1')4 in comparison with Zr(L2)4 and Zr(L3)4 as well as a higher kinetic inertness in competition studies with EDTA or Fe3+ at a radiotracer concentration with 89Zr. Besides the low pKa of L1H or L1'H (pKa = 5.01) in comparison with L2H and L3H (pKa = 8.83 and 9.55, respectively), the higher stability of Zr(L1')4 can be attributed in part to the presence of the amide group next to the chelating oxygen that induces intramolecular H-bond and amide/π interactions that were observed by X-ray crystallography and confirmed by quantum chemical calculations. The data presented here indicate that the 1,2-HOPO L1' exhibits the best characteristics for Zr(iv) complexation. However, 3,2-HOPO and 3,4-HOPO patterns, if appropriately tuned, for instance with the addition of an amide group as in the 1,2-HOPO ligand, may also become interesting alternatives for the design of Zr(iv) chelators with improved characteristics for applications in nuclear imaging with 89Zr.

16.
Eur J Neurol ; 24(4): 617-623, 2017 04.
Article in English | MEDLINE | ID: mdl-28224695

ABSTRACT

BACKGROUND AND PURPOSE: The aim was to evaluate the relationship between distal hyperintense vessel sign (HVS) and early neurological deterioration (END) in acute ischaemic stroke with large vessel steno-occlusion. METHODS: Acute ischaemic stroke patients with symptomatic severe steno-occlusion in the middle cerebral artery or internal carotid artery were recruited within 24 h from symptom onset. Stroke outcomes were evaluated using the National Institutes of Health Stroke Scale (NIHSS) score at the time of admission and at 72 h and 7 days. END was defined as an increment of ≥1 in the motor NIHSS score or ≥2 in the total NIHSS score. Distal HVS was defined as hyperintensity on fluid-attenuated inversion recovery image, located distal to the Sylvian fissure. The extent of distal HVS was divided into absent, subtle and prominent. RESULTS: Amongst a total of 325 participants, END was found in 103 (32%) patients. END was associated with age, atrial fibrillation, initial NIHSS score, initial infarct volume, severe leukoaraiosis, hemorrhagic infarction and distal HVS. In multivariate analysis, distal HVS remained an independent predictor of END [adjusted odds ratio (aOR) 2.86, 95% confidence interval (CI) 1.65-4.97, P < 0.001]. Initial infarct volume (aOR = 1.01, 95% CI 1.01-1.02, P < 0.001) and severe leukoaraiosis (aOR = 3.16, 95% CI 1.77-5.65, P < 0.001) were also associated with END, independently of distal HVS. In the analysis of the burden of distal HVS and stroke outcomes, prominent distal HVS was associated with stroke severity and infarct volume in a dose-response manner. CONCLUSIONS: Distal HVS is associated with END in acute ischaemic stroke patients with large vessel steno-occlusion.


Subject(s)
Atrial Fibrillation/diagnostic imaging , Brain Ischemia/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Leukoaraiosis/diagnostic imaging , Middle Cerebral Artery/diagnostic imaging , Stroke/diagnostic imaging , Age Factors , Aged , Aged, 80 and over , Atrial Fibrillation/complications , Brain Ischemia/complications , Carotid Artery, Internal/diagnostic imaging , Female , Humans , Leukoaraiosis/complications , Magnetic Resonance Imaging , Male , Middle Aged , Prognosis , Severity of Illness Index , Stroke/complications
17.
Mucosal Immunol ; 10(1): 104-116, 2017 01.
Article in English | MEDLINE | ID: mdl-27118489

ABSTRACT

In humans, the composition of gut commensal bacteria is closely correlated with obesity. The bacteria modulate metabolites and influence host immunity. In this study, we attempted to determine whether there is a direct correlation between specific commensal bacteria and host metabolism. As mice aged, we found significantly reduced body weight and fat mass in Atg7ΔCD11c mice when compared with Atg7f/f mice. When mice shared commensal bacteria by co-housing or feces transfer experiments, body weight and fat mass were similar in both mouse groups. By pyrosequencing analysis, Bacteroides acidifaciens (BA) was significantly increased in feces of Atg7ΔCD11c mice compared with those of control Atg7f/f mice. Wild-type C57BL/6 (B6) mice fed with BA were significantly more likely to gain less weight and fat mass than mice fed with PBS. Of note, the expression level of peroxisome proliferator-activated receptor alpha (PPARα) was consistently increased in the adipose tissues of Atg7ΔCD11c mice, B6 mice transferred with fecal microbiota of Atg7ΔCD11c mice, and BA-fed B6 mice. Furthermore, B6 mice fed with BA showed elevated insulin levels in serum, accompanied by increased serum glucagon-like peptide-1 and decreased intestinal dipeptidyl peptidase-4. These finding suggest that BA may have potential for treatment of metabolic diseases such as diabetes and obesity.


Subject(s)
Adipose Tissue/physiology , Bacteroides/immunology , Gastrointestinal Microbiome/immunology , Insulin Resistance/immunology , Intestines/physiology , Obesity/microbiology , Adipose Tissue/microbiology , Animals , Autophagy-Related Protein 7/genetics , Cells, Cultured , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Feces/microbiology , Gene Expression Regulation , Glucagon-Like Peptide 1/blood , Humans , Insulin/blood , Intestines/microbiology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Obesity/immunology , PPAR alpha/genetics , PPAR alpha/metabolism , Symbiosis
18.
Oncogene ; 36(7): 999-1011, 2017 02 16.
Article in English | MEDLINE | ID: mdl-27425596

ABSTRACT

The tumor-suppressor RUNX3 has a critical role in a lineage determination, cell cycle arrest and apoptosis. Lozenge (Lz), a Drosophila homolog of mammalian RUNX family members, has integral roles in these processes and specifically in eye cell fate determination. To elucidate the genetic modifiers of Lz/RUNX3, we performed a large-scale functional screen in a fly mutant library. The screen revealed genetic interactions between the Lz, Rac and Hippo pathways. Analysis of interactions among these genes revealed that the defective phenotype resulting from activation of Yki, an end point effector of the Hippo pathway, was suppressed by Lz and enhanced by Rac-Trio. Molecular biological analysis using mammalian homologs reveled that LATS1/2-mediated YAP phosphorylation-facilitated dissociation of the YAP-TEAD4 complex and association of the YAP-RUNX3 complex. When cells were stimulated to proliferate, activated RAC-TRIO signaling inhibited LATS1/2-mediated YAP phosphorylation; consequently, YAP dissociated from RUNX3 and associated with TEAD, thereby replacing the YAP-RUNX3 complex with YAP-TEAD. RUNX3 contributed to both association and dissociation of YAP-TEAD complex, most likely through the formation of the YAP-TEAD-RUNX3 ternary complex. Ectopic expression of RUNX3 in MKN28 gastric cancer cells reduced tumorigenicity, and the tumor-suppressive activity of RUNX3 was associated with its ability to interact with YAP. These results identify a novel regulatory mechanism, mediated by the Hippo and RAC-TRIO pathways, that changes the binding partner of YAP.


Subject(s)
Core Binding Factor Alpha 3 Subunit/metabolism , DNA-Binding Proteins/metabolism , Drosophila Proteins/metabolism , Drosophila/genetics , Muscle Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/pathology , Transcription Factors/metabolism , Tumor Suppressor Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Apoptosis , Biomarkers, Tumor , Cell Nucleus/genetics , Cell Nucleus/metabolism , Cell Proliferation , Core Binding Factor Alpha 3 Subunit/genetics , DNA-Binding Proteins/genetics , Drosophila/growth & development , Drosophila/metabolism , Drosophila Proteins/genetics , Gene Expression Regulation, Neoplastic , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , Humans , Male , Mice , Mice, Nude , Muscle Proteins/genetics , Phosphoproteins/genetics , Phosphoproteins/metabolism , Phosphorylation , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , TEA Domain Transcription Factors , Trans-Activators , Transcription Factors/genetics , Tumor Cells, Cultured , Tumor Suppressor Proteins/genetics , Xenograft Model Antitumor Assays , YAP-Signaling Proteins
19.
Eur J Neurol ; 23(11): 1658-1665, 2016 11.
Article in English | MEDLINE | ID: mdl-27444813

ABSTRACT

BACKGROUND AND PURPOSE: We investigated the effect of stress hyperglycemia on the functional outcomes of non-diabetic hemorrhagic stroke. In addition, we investigated the usefulness of intensive rehabilitation for improving functional outcomes in patients with stress hyperglycemia. METHODS: Non-diabetic hemorrhagic stroke patients were recruited and divided into two groups: intracerebral hemorrhage (ICH) (n = 165) and subarachnoid hemorrhage (SAH) (n = 156). Each group was divided into non-diabetics with or without stress hyperglycemia. Functional assessments were performed at 7 days and 3, 6 and 12 months after stroke onset. The non-diabetic with stress hyperglycemia groups were again divided into two groups who either received or did not receive intensive rehabilitation treatment. Serial functional outcome was compared between groups. RESULTS: For the ICH group, patients with stress hyperglycemia had worse modified Rankin Scale, National Institutes of Health Stroke Scale, Functional Ambulatory Category and Korean Mini-Mental State Examination scores than patients without stress hyperglycemia. For the SAH group, patients with stress hyperglycemia had worse scores on all functional assessments than patients without stress hyperglycemia at all time-points. After intensive rehabilitation treatment of patients with stress hyperglycemia, the ICH group had better scores on Functional Ambulatory Category and the SAH group had better scores on all functional assessments than patients without intensive rehabilitation treatment. CONCLUSIONS: Stress hyperglycemia affects the long-term prognosis of non-diabetic hemorrhagic stroke patients. Among stress hyperglycemia patients, intensive rehabilitation can enhance functional improvement after stroke.


Subject(s)
Hyperglycemia/complications , Intracranial Hemorrhages/rehabilitation , Stroke Rehabilitation , Stroke/complications , Subarachnoid Hemorrhage/rehabilitation , Aged , Cohort Studies , Female , Humans , Hyperglycemia/blood , Intracranial Hemorrhages/blood , Intracranial Hemorrhages/complications , Male , Middle Aged , Prognosis , Stroke/blood , Subarachnoid Hemorrhage/blood , Subarachnoid Hemorrhage/complications , Treatment Outcome
20.
Diabet Med ; 33(9): 1275-82, 2016 09.
Article in English | MEDLINE | ID: mdl-26871458

ABSTRACT

AIM: Diabetes is a known risk factor for hearing impairment. No study regarding the association of insulin resistance (IR), ß-cell dysfunction and impaired fasting glucose (IFG) with hearing impairment has been reported in the population without diabetes. We examined these associations using a representative sample of the Korean population. METHODS: Participants included 1589 males and 2496 females, who were ≥ 20 years of age and without diabetes from the Korea National Health and Nutritional Examination Surveys of the Korean population (2010). Audiometric tests and laboratory examinations were performed. Homeostasis model assessments of IR and ß-cell function (HOMA-IR and HOMA-ß) were calculated. RESULTS: The prevalence of both high- and low-/mid-frequency hearing impairment among subjects with IFG was higher compared with those with normal glycaemia (42.2% vs. 24.5%, 14.7% vs. 7.8%, respectively). After adjustment for age, HOMA-IR and HOMA-ß showed significant association with high-frequency hearing impairment in males. In the multiple logistic regression analyses adjusting for confounding variables, the presence of IFG, higher HOMA-IR and lower HOMA-ß remained as independent risk factors for high-frequency mild hearing impairment in males < 70 years [odds ratio (OR) 1.441, 95% confidence interval (95% CI), 1.056 to 1.967; OR, 1.448, 95% CI, 1.039 to 2.101; and OR, 0.447, 95% CI, 0.274 to 0.729, P < 0.05, respectively). CONCLUSIONS: IR, ß-cell dysfunction and IFG are associated with high-frequency mild hearing impairment in the male population < 70 years before the onset of diabetes.


Subject(s)
Hearing Loss, High-Frequency/epidemiology , Hearing Loss, Sensorineural/epidemiology , Insulin Resistance , Insulin-Secreting Cells/metabolism , Prediabetic State/epidemiology , Adult , Audiometry, Pure-Tone , Blood Glucose/metabolism , Cross-Sectional Studies , Diabetes Mellitus, Type 2 , Fasting/metabolism , Female , Humans , Logistic Models , Male , Middle Aged , Nutrition Surveys , Prediabetic State/metabolism , Republic of Korea/epidemiology , Sex Factors
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