Lung function decline in non-tuberculous mycobacterial pulmonary disease according to disease severity.

BACKGROUND: The severity of non-tuberculous mycobacterial pulmonary disease (NTM-PD) can be classified based on an assessment of the patient´s body mass index, age, presence of cavity, erythrocyte sediment rate and sex (BACES). In this study, changes in lung function according to disease severity were analysed.METHODS: Patients with NTM-PD who underwent at least two lung function tests between 1 January 2011 and 31 December 2021, were classified according to their BACES score into mild (0-1), moderate (2-3) and severe (4-5) groups, and changes in lung function were assessed using BACES scores.RESULTS: A total of 354 patients were divided into three groups: mild (n = 108), moderate (n = 216) and severe (n = 30). As disease severity increased, the decrease in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) was greater: respectively 26.4 mL/year, 31.3 mL/year and 35.7 mL/year in case of FEV1 (P for trend = 0.002); 18.9 mL/year, 25.5 mL/year and 48.9 mL/year in case of FVC (P for trend = 0.002); and 0.7%/year, 1.3%/year and 2.5%/year for DLCO (P for trend = 0.023) in the mild, moderate and severe groups.CONCLUSION: The decrease in lung function in NTM-PD was correlated with disease severity.

Changes of Neurotransmitters in Youth with Internet and Smartphone Addiction: A Comparison with Healthy Controls and Changes after Cognitive Behavioral Therapy.

BACKGROUND AND PURPOSE: Neurotransmitter changes in youth addicted to the Internet and smartphone were compared with normal controls and in subjects after cognitive behavioral therapy. In addition, the correlations between neurotransmitters and affective factors were investigated. MATERIALS AND METHODS: Nineteen young people with Internet and smartphone addiction and 19 sex- and age-matched healthy controls (male/female ratio, 9:10; mean age, 15.47 ± 3.06 years) were included. Twelve teenagers with Internet and smartphone addiction (male/female ratio, 8:4; mean age, 14.99 ± 1.95 years) participated in 9 weeks of cognitive behavioral therapy. Meshcher-Garwood point-resolved spectroscopy was used to measure γ-aminobutyric acid and Glx levels in the anterior cingulate cortex. The γ-aminobutyric acid and Glx levels in the addicted group were compared with those in controls and after cognitive behavioral therapy. The γ-aminobutyric acid and Glx levels correlated with clinical scales of Internet and smartphone addiction, impulsiveness, depression, anxiety, insomnia, and sleep quality. RESULTS: Brain parenchymal and gray matter volume-adjusted γ-aminobutyric acid-to-creatine ratios were higher in subjects with Internet and smartphone addiction (P = .028 and .016). After therapy, brain parenchymal- and gray matter volume-adjusted γ-aminobutyric acid-to-creatine ratios were decreased (P = .034 and .026). The Glx level was not statistically significant in subjects with Internet and smartphone addiction compared with controls and posttherapy status. Brain parenchymal- and gray matter volume-adjusted γ-aminobutyric acid-to-creatine ratios correlated with clinical scales of Internet and smartphone addictions, depression, and anxiety. Glx/Cr was negatively correlated with insomnia and sleep quality scales. CONCLUSIONS: The high γ-aminobutyric acid levels and disrupted balance of γ-aminobutyric acid-to-Glx including glutamate in the anterior cingulate cortex may contribute to understanding the pathophysiology and treatment of Internet and smartphone addiction and associated comorbidities.

101 Dothideomycetes genomes: A test case for predicting lifestyles and emergence of pathogens.

Dothideomycetes is the largest class of kingdom Fungi and comprises an incredible diversity of lifestyles, many of which have evolved multiple times. Plant pathogens represent a major ecological niche of the class Dothideomycetes and they are known to infect most major food crops and feedstocks for biomass and biofuel production. Studying the ecology and evolution of Dothideomycetes has significant implications for our fundamental understanding of fungal evolution, their adaptation to stress and host specificity, and practical implications with regard to the effects of climate change and on the food, feed, and livestock elements of the agro-economy. In this study, we present the first large-scale, whole-genome comparison of 101 Dothideomycetes introducing 55 newly sequenced species. The availability of whole-genome data produced a high-confidence phylogeny leading to reclassification of 25 organisms, provided a clearer picture of the relationships among the various families, and indicated that pathogenicity evolved multiple times within this class. We also identified gene family expansions and contractions across the Dothideomycetes phylogeny linked to ecological niches providing insights into genome evolution and adaptation across this group. Using machine-learning methods we classified fungi into lifestyle classes with >95 % accuracy and identified a small number of gene families that positively correlated with these distinctions. This can become a valuable tool for genome-based prediction of species lifestyle, especially for rarely seen and poorly studied species.

Correction: ESRP1 is overexpressed in ovarian cancer and promotes switching from mesenchymal to epithelial phenotype in ovarian cancer cells.

Since publication of the original article, the authors have noticed that there were errors in the labelling of Figures 6D and 6E. The correct figure and its legend are reproduced here. The authors wish to apologise for any inconvenience caused.

Repeated measurement of fractional exhaled nitric oxide is not essential for asthma screening

Background: Older guidelines recommend that fractional exhaled nitric oxide (FeNO) should be checked more than twice during the same session to confirm an asthma diagnosis. Recent studies show the excellent reproducibility of FeNO measurements. Objective: We aimed to determine whether repeated FeNO measurements during the same session are necessary for asthma screening. Methods: We retrospectively reviewed the electronic medical records of adult outpatients who visited the respiratory medicine department for diagnosis of asthma and assessed FeNO measurements obtained from June 2016 to July 2017. Results: Of the 132 patients enrolled, 79 (59.8%) were diagnosed with asthma. Repeated FeNO measurements taken during the same session showed high reproducibility (intraclass correlation coefficient >0.9; P<.001) and a strong correlation (Pearson coefficient >0.9; P<.001), although reproducibility and correlation were slightly weaker in patients with low FeNO values. The value of repeated measurement was not significant; however, the second FeNO measurement was significantly higher than the first measurement in patients with the worst and best lung function. The predictive power of the first measurement of FeNO (sensitivity, 80.5%; specificity, 85.1%) was not inferior to the second (sensitivity, 76.6%; specificity 85.1%). The same was true of the geometric mean of the two. Conclusion: Repeated FeNO measurement during the same session is not essential for asthma screening in cases where the first acceptable FeNO measurement is performed using the proper method

Introducción: Aunque las guías más antiguas recomiendan que el óxido nítrico exhalado (FeNO) se determine más de dos veces en la misma sesión para el diagnóstico de asma, algunos estudios recientes han demostrado la excelente reproducibilidad de las mediciones de FeNO. Objetivo: Nuestro objetivo fue determinar si las mediciones repetidas de FeNO durante la misma sesión son necesarias para el cribado del asma. Métodos: Revisamos retrospectivamente los registros médicos electrónicos de pacientes adultos ambulatorios que visitaron el departamento de neumología para confirmar un diagnóstico de asma durante los meses de junio de 2016 a julio de 2017, y se evaluaron las mediciones de FeNO obtenidas. Resultados: De un total de 132 pacientes estudiados, 79 pacientes (59,8%) fueron diagnosticados con asma. Las mediciones repetidas de FeNO tomadas durante la misma sesión mostraron una alta reproducibilidad (coeficiente de correlación intraclase> 0,9; p <0,001) y una fuerte correlación (coeficiente de Pearson> 0,9; p <0,001); sin embargo, la reproducibilidad y la correlación fueron ligeramente más débiles en sujetos con valores bajos de FeNO. El valor de la medición repetida no fue significativamente diferente entre sí en general; sin embargo, la segunda medición de FeNO fue significativamente más alta que la primera medición en sujetos con valores de la función pulmonar más bajos y más altos. El poder predictivo de FeNO para el diagnóstico de asma medido la primera vez (sensibilidad, 80,5%; especificidad, 85,1%) no fue inferior al medido la segunda vez (sensibilidad, 76,6%; especificidad 85,1%) o la media geométrica uniforme de los dos. Conclusión: La medición repetida de FeNO durante la misma sesión no es esencial para el cribado del asma en los casos en que la primera medición de FeNO es aceptable y se realiza con el método adecuado

ESRP1 is overexpressed in ovarian cancer and promotes switching from mesenchymal to epithelial phenotype in ovarian cancer cells.

This corrects the article DOI: 10.1038/oncsis.2017.87.

ESRP1 is overexpressed in ovarian cancer and promotes switching from mesenchymal to epithelial phenotype in ovarian cancer cells.

Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2), epithelial cell-specific regulators of alternative splicing, are downregulated during the epithelial-mesenchymal transition (EMT). These factors have roles in tumor progression and metastasis in some cancers; however, their expression and function in ovarian cancer (OC) remain unclear. We found that ESRP1 and ESRP2 mRNAs were expressed at higher levels in OC cells than in immortalized ovarian surface epithelial (IOSE) cells, and confirmed their overexpression in OC tissues at the protein level. The Cancer Genome Atlas (TCGA) data analysis revealed frequent gene amplification of ESRP1 in OC tissues; however, we detected no significant correlation between ESRP1 gene copy number and gene expression in OC cells. Importantly, expression of ESRP1 and ESRP2 was inversely correlated with DNA methylation in OC cells, and ESRP2 overexpression in OC tissues was significantly associated with DNA hypomethylation. Notably, survival analysis using TCGA data from 541 OC tissues revealed that high ESRP1 expression was significantly associated with shorter 5-year survival of patients. Ectopic ESRP1 expression in mesenchymal OC cells promoted cell proliferation but suppressed cell migration. Furthermore, we found that ESRP1 drives a switch from mesenchymal to epithelial phenotype characterized by reduced cell migration in association with induction of epithelial cell-specific variant of CD44 and ENAH. Taken together, our findings suggest that an epigenetic mechanism is involved in ESRP1 overexpression, and that ESRP1 has a role in OC progression.

Is c-Met oncoprotein expression an adverse prognosticator in extrahepatic bile duct cancer treated with curative resection followed by adjuvant chemoradiotherapy?

Purpose: To analyze the expression of c-Met, and to investigate correlations between the expression of c-Met, clinicopathologic variables, and survival in patients undergoing curative surgery followed by adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. Methods: Ninety EHBD cancer patients who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled. Expression of c-Met was assessed with immunohistochemical staining on tissue microarray. The correlation between clinicopathologic variables and survival outcomes was evaluated using Kaplan-Meier method and Cox proportional hazard model. Results: On univariate analysis, 66 patients (76.7 %) showed c-Met expression. c-Met expression had a significant impact on 5-year overall survival (OS) (43.0 % in c-Met(+) vs. 25.0 % in c-Met(-), p = 0.0324), but not on loco-regional relapse-free survival or distant metastasisfree survival (DMFS). However, on multivariate analysis incorporating tumor location and nodal involvement, survival difference was not maintained (p = 0.2940). Tumor location was the only independent prognostic factor predicting OS (p = 0.0089). Hilar location tumors, nodal involvement, and poorly differentiated tumors were all identified as independent prognostic factors predicting inferior DMFS (p = 0.0030, 0.0013, and 0.0037, respectively). Conclusions: This study showed that c-Met expression was not associated with survival outcomes in EHBD cancer patients undergoing curative resection followed by adjuvant chemoradiotherapy. Further studies are needed to fully elucidate the prognostic value of c-Met expression in these patients (AU)

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A new practical desensitization protocol for oxaliplatin-induced immediate hypersensitivity reactions: a necessary and useful approach

Background and Objective: Desensitization protocols for patients with immediate hypersensitivity reactions (IHSRs) have proven to be effective, but they are not widely used in clinical practice because of impracticalities such as high cost, long procedure duration, and a lack of trained personnel. We aimed to determine the clinical characteristics of oxaliplatin-induced IHSRs and assess measures to protect against these reactions and to validate a new practical desensitization protocol. Methods: We retrospectively reviewed 2640 cases of oxaliplatin IHSRs in 271 oxaliplatin users and prospectively used a newly designed desensitization protocol 32 times in 12 patients with hypersensitivity to platinum-based chemotherapy. The protocol consisted of increases in infusion rate every 15 minutes, regardless of the concentration of the chemotherapy agent in the infusion bags. Results: Of the 271 patients administered oxaliplatin, 45 (16.6%) experienced IHSRs. Of 39 patients who experienced an IHSR but needed to continue oxaliplatin, 6 (15.4%) stopped treatment due to the reaction, and 33 (84.6%) continued despite the risk of further reactions. The new desensitization protocol was successfully completed in 12 patients (100%), but it was ineffective in 3 patients (all with a negative skin prick test), who experienced fever without urticaria. Conclusions: Many patients who experience oxaliplatin-induced IHSRs are required to stop first-line oxaliplatin-based chemotherapy or to continue without desensitization, with the associated risks. Our new desensitization protocol is practical and easy to use in clinical practice (AU)

Introducción y Objetivos: El protocolo de desensibilización en los pacientes con reacciones de hipersensibilidad inmediata a quimioterápicos resulta efectivo, sin embargo no se aplica en muchos hospitales debido a su alto coste, consumo de tiempo y falta de personal entrenado. El motivo de este trabajo fue analizar las características clínicas y las medidas habitualmente adoptadas en esta patología y validar un nuevo protocolo de desensibilización a oxaliplatino. Métodos: Para ello revisamos retrospectivamente 2.640 reacciones de hipersensibilidad inmediata a oxaliplatino en 271 pacientes sometidos a tratamiento con este quimioterápico. De forma prospectiva, aplicamos un nuevo protocolo de desensibilización 32 veces en 12 pacientes con hipersensibilidad inmediata a quimioterapia basada en oxaliplatino. Este nuevo protocolo se realizó con la administración escalonada de la concentración determinada cada 15 minutos. Resultados: En cuanto a los resultados obtenidos, de los 271 pacientes a los que se administró oxaliplatino, 45 (16,6%) presentaron reacciones de hipersensibilidad inmediata. De los 39 que necesitaron seguir el tratamiento con oxaliplatino, 6 (15,4%) abandonaron el tratamiento y 33 (84,6%) continuaron. El nuevo protocolo de desensibilización se completó en 12 pacientes (100%) si bien tres de ellos manifestaron fiebre sin urticaria y una respuesta negativa en la prueba cutánea. Conclusiones: En conclusión, una proporción importante de pacientes que sufren reacciones de hipersensibilidad a oxaliplatino interrumpen el tratamiento o lo mantienen sin ser sometidos a protocolos de desensibilización. El protocolo de desensibilización que proponemos en este estudio es fácil y muestra resultados satisfactorios en la práctica clínica (AU)

Locoregional recurrence after curative intent resection for intrahepatic cholangiocarcinoma: implications for adjuvant radiotherapy

Backgrounds. As for intrahepatic cholangiocarcinoma, the most frequent site of failure after curative intent resection is the liver. We identified the risk factors for locoregional recurrence after curative intent resection for intrahepatic cholangiocarcinoma. Methods. Medical records of 115 patients treated with surgical resection alone for intrahepatic cholangiocarcinoma from November 2000 to December 2010 were retrospectively reviewed. Locoregional failure was defined as recurrence within 20 mm from resection margin or regional lymph node. Overall survival and locoregional recurrence rates were analyzed using Kaplan–Meier methods, and the prognostic factors were analyzed using Cox proportional hazards model. Results. Median follow-up duration of surviving patients was 61 months (range 8–139). Sixty-six patients had recurrence, and 45 of 66 patients (68 %) had locoregional recurrence. The 5-year overall survival and locoregional control rates were 49.1 and 51.6 %, respectively. ≥T2b disease and R1 resection were associated with locoregional recurrence in multivariate analysis. Patients were divided into two groups whether these risk factors exist or not. The 5-year locoregional control rates of low (no risk factor n = 64) and high (1 or 2 risk factors n = 51) risk groups were 62.5 and 34.7 %, respectively (P = 0.001). Conclusions. After curative intent resection, locoregional control and survival of patients with intrahepatic cholangiocarcinoma were far from satisfactory. Further studies are needed to evaluate the potential benefit of adjuvant locoregional treatment such as radiotherapy for patients with high-risk factors (≥T2b disease or R1 resection) (AU)

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Antifungal effect of gamma irradiation and sodium dichloroisocyanurate against Penicillium expansum on pears.

UNLABELLED: Gamma irradiation (GI) was evaluated for its in vitro and in vivo antifungal activity against Penicillium expansum on pear fruits. GI showed a complete inhibition of spore germination, germ tube elongation and mycelial of P. expansum, especially 1·8 kGy. GI affected the membrane integrity and cellular leakage of conidia in a dose-dependent manner. Furthermore, the leakage of protein and sugar from mycelia increased along with the dose. GI was evaluated at lower doses in combination with a chlorine donor, sodium dichloro-s-triazinetrione (NaDCC), to examine the inhibition of P. expansum. Interestingly, only a combined treatment with 0·2 kGy of GI and 70 ppm of NaDCC exhibited significant synergistic antifungal activity. The mechanisms by which the combined treatment decreased the blue mould decay of pear fruits could directly associated with the disruption of the cell membrane of the fungal pathogen, resulting in a loss of cytoplasmic materials from the hyphae. SIGNIFICANCE AND IMPACT OF THE STUDY: Gamma irradiation (GI) is used as an effective nonchemical approach to inactive pathogens. This study investigated the antifungal effect of gamma irradiation and its combined treatment with a chlorine donor on this fungal pathogen, both in vitro and in vivo. This study emphasized that the integration of low-dose GI and a chlorine donor, NaDCC, exhibited a significant antifungal effect, and that its mechanisms are directly associated with membrane integrity of fungal spores, promising that GI has the potential to be an antifungal approach.

Association of obesity with serum leptin, adiponectin, and serotonin and gut microflora in beagle dogs.

BACKGROUND: Serotonin (5-hydroxytryptamine, 5HT) is involved in hypothalamic regulation of energy consumption. Also, the gut microbiome can influence neuronal signaling to the brain through vagal afferent neurons. Therefore, serotonin concentrations in the central nervous system and the composition of the microbiota can be related to obesity. OBJECTIVE: To examine adipokine, and, serotonin concentrations, and the gut microbiota in lean dogs and dogs with experimentally induced obesity. ANIMALS: Fourteen healthy Beagle dogs were used in this study. METHODS: Seven Beagle dogs in the obese group were fed commercial food ad libitum, over a period of 6 months to increase their weight and seven Beagle dogs in lean group were fed a restricted amount of the same diet to maintain optimal body condition over a period of 6 months. Peripheral leptin, adiponectin, 5HT, and cerebrospinal fluid (CSF-5HT) levels were measured by ELISA. Fecal samples were collected in lean and obese groups 6 months after obesity was induced. Targeted pyrosequencing of the 16S rRNA gene was performed using a Genome Sequencer FLX plus system. RESULTS: Leptin concentrations were higher in the obese group (1.98 ± 1.00) compared to those of the lean group (1.12 ± 0.07, P = .025). Adiponectin and 5-hydroytryptamine of cerebrospinal fluid (CSF-5HT) concentrations were higher in the lean group (27.1 ± 7.28) than in the obese group (14.4 ± 5.40, P = .018). Analysis of the microbiome revealed that the diversity of the microbial community was lower in the obese group. Microbes from the phylum Firmicutes (85%) were predominant group in the gut microbiota of lean dogs. However, bacteria from the phylum Proteobacteria (76%) were the predominant group in the gut microbiota of dogs in the obese group. CONCLUSIONS AND CLINICAL IMPORTANCE: Decreased 5HT levels in obese group might increase the risk of obesity because of increased appetite. Microflora enriched with gram-negative might be related with chronic inflammation status in obese dogs.

Nitric oxide induces apoptosis in human gingival fibroblast through mitochondria-dependent pathway and JNK activation.

AIM: To investigate the molecular mechanisms of nitric oxide (NO)-induced cytotoxic effect in human gingival fibroblast (HGF) cells. METHODOLOGY: After sodium nitroprusside (SNP), as NO donor, was treated to HGF, viability was measured by MTT assay and apoptosis was determined by TUNEL and DNA fragmentation assay. Mitochondrial membrane potential was detected using confocal microscopy, and caspase activity assay was measured by spectrophotometer. Mitogen-activated protein kinases (MAPK) activation, Bax/Bcl-2 ratio and cytochrome c release were analysed by Western blot analyses. Cells were exposed to MAPK inhibitors (U0126, SB203580 and SP600125) before SNP treatment to investigate the effects of MAPK kinases on the NO-induced apoptosis in HGF. Statistical analysis was performed using one-way analysis of variance with the Student-Newman-Keuls post hoc test for multiple group comparison. RESULTS: Apoptosis was significantly increased (P = 0.011 and 0.0004, respectively) in the presence of SNP (1 and 3 mmol L(-1) ) after 12 h in HGF. However, 1H-[1,2,4] oxadiatolo [4, 3-a] cluinoxaline-1-one (ODQ), a soluble guanylate cyclase inhibitor, did not block the decrement of cell viability by NO. SNP treatment induced the loss of mitochondrial membrane potential, release of cytochrome c, increased Bax/Bcl-2 ratio and activation of caspases in HGF. Also, SNP treatment increased phosphorylation of MAPKinases and c-Jun N-terminal kinase (JNK) inhibitor (5 and 10 µmol L(-1) ) rescued cell viability decreased by SNP in HGF (P = 0.024 and 0.0149, respectively). CONCLUSION: Nitric oxide induced apoptosis in human gingival fibroblast through the mitochondria-mediated pathway by regulation of Bcl-2 family and JNK activation.

Exclusive radiotherapy for gliomatosis cerebri: long-term follow-up at a single institution

PURPOSE: To evaluate the efficacy of radiotherapy and factors affecting the prognosis of gliomatosis cerebri. METHODS: Twenty-eight patients with pathologically confirmed gliomatosis cerebri underwent radiotherapy between August 1988 and September 2003. The median age of the patients was 39 years (range 18-67). Performance status was good (ECOG score ≤2) in 23 patients (82 %). The extent of radiotherapy was partial brain in 17 patients, whole brain in 2 patients, and whole brain followed by partial brain in 9 patients. The median radiation dose was 55.8 Gy (range 46.8-70.4). The median duration of follow-up was 136 months for survivors (range 39-191). RESULTS: The median overall and progression-free survival times of all patients were 20 and 11 months, respectively. When initial response to radiotherapy was grouped as improved, stationary, and aggravated, the median overall survival times in patients with improved, stationary, and aggravated responses were 76, 20, and 7 months, respectively (p = 0.0129). However, radiation parameters such as dose and irradiation volume had no impact on overall survival. On multivariate analysis, both performance status and initial response to radiotherapy were significant prognostic factors affecting overall survival (p = 0.0249 and 0.0065, respectively). CONCLUSIONS: This study showed that gliomatosis cerebri could be effectively treated with radiotherapy and that initial response to radiotherapy was a significant prognostic factor affecting the survival (AU)

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In vitro differentiation of human liver-derived stem cells with mesenchymal characteristics into immature hepatocyte-like cells.

Liver transplantation is severely limited by donor shortage although it is the only effective treatment for end-stage liver disease. So the best alternative is hepatocyte transplantation. For obtaining human hepatocytes, some stem cells originating from extrahepatic or intraheptic tissues have been isolated and characterized. Previously we have reported that human liver-derived stem cells (HLSCs) could be isolated and expanded from donated livers unsuitable for transplantation; they expressed some markers of mesenchymal stem cells but neither hematopoietic nor oval cells. In this study, we isolated and expanded HLSCs with mesenchymal characteristics from another adult human liver. They showed mesenchymal morphology and grew well under serum condition similar to our previous reports. Also, they expressed some markers of mesenchymal stem cells, such as CD44, CD73, CD90, and CD105, through fluorescence-activated cell sorting analysis. When HLSCs were sequentially exposed to fibroblast growth factor-1 (FGF-1), FGF-4, and hepatocyte growth factor (HGF) followed by FGF-4, HGF, oncostatin M, and dexamethasone, they became round or polygonal, and expressed some hepatic markers such as albumin and α1-antitrypsin in the gene or protein level. Also, they showed urea synthesis activity 7 days after treatment of FGF-4, HGF, oncostatin M, and dexamethasone. These results provided that HLSCs would be a useful cell source in the field of regenerative medicine as well as liver cell biology.

Case report: congenital rubella syndrome: a rare but persistent concern in the United States.

In countries such as the United States where rubella virus infections are rare, congenital rubella syndrome (CRS) may not be recognized in a timely manner. However, the syndrome still appears in this country, often in infants of mothers emigrating from countries with absent or suboptimal national vaccination programs. We describe a case of CRS in a term baby born to a recent US immigrant who developed a primary varicella infection in late pregnancy and demonstrated IgG titers to rubella at delivery. At presentation, the neonate had both classical findings as well as less reported vascular and neurological abnormalities seen in infants with CRS.

Chunggan extract (CGX), methionine-and choline-deficient (MCD) diet-induced hepatosteatosis and oxidative stress in C57BL/6 mice.

In the present study, we aimed to evaluate the hepatoprotective and antioxidant effects of Chunggan extract (CGX) in an animal model of hepatosteatosis. The C57BL/6N mice were fed either methionine- and choline-sufficient (MCS) diet (n = 10) or a methionine- and choline-deficient (MCD) diet (n = 50) for 4 weeks, and then they were treated orally with CGX (100 or 200 mg/kg), ursodeoxycholic acid (80 mg/kg, as a positive control), or distilled water (DW, MCS diet group, and MCD diet group) for the final 2 weeks (once per day). The MCD diet induced severe hepatic injury with the typical features of hepatosteatosis in both serum and hepatic tissues. CGX treatment significantly attenuated these alterations in the serum levels including triglyceride (TG), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin. Moreover, CGX also efficiently prevented from the hepatic TG accumulation in the hepatic tissue, evidenced by histopathological findings, compared with the MCD diet. In addition, CGX treatment significantly ameliorated the excessive oxidative stress and antioxidant markers in the serum as well as the hepatic levels of reactive oxygen species, the levels of malondialdehyde, the protein carbonyl, and total antioxidant capacity, and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. In conclusion, our results indicate the experimental relevance of CGX for potential clinical application in patients with hepatosteatotic disorders and a possible mechanism related to its antioxidant properties.

Atopic dermatitis-mitigating effects of new Lactobacillus strain, Lactobacillus sakei probio 65 isolated from Kimchi.

AIMS: Atopic dermatitis (AD) is an inflammatory skin disease. Probiotics have been reported to modulate immune responses and thus are now being suggested as potential treatments for allergies. In this study, we investigated the inhibitory effects of Lactobacillus sakei probio 65 isolated from Kimchi on artificially inducing AD in NC/Nga mice. METHODS AND RESULTS: Oral administration of viable or heat-inactivated Lact. sakei probio 65 improved the condition of skin and reduced scratching frequency. Serum levels of IgE and cutaneous T-cell-attracting chemokine (CTACK) were significantly decreased by this therapy. Dead Lact. sakei probio 65 also decreased IL-4 and IL-6 serum concentrations. Moreover, both live and dead Lact. sakei probio 65 inhibited the expression of Thymus and activation-regulated chemokine and CTACK in AD-like skin lesions. The increased levels of Foxp3 expression in the lesional skin and ears were also suppressed by Lact. sakei probio 65. In addition, Lact. sakei probio 65 inhibited ß-hexosaminidase release and the secretion of IL-4, TNF-α and IL-6 from RBL-2H3 cells. CONCLUSIONS: Oral treatment with both viable and heat-inactivated Lact. sakei probio 65 inhibits skin inflammation and AD-like skin lesions, as well as mast cell activation. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus sakei probio 65 has an inhibitory effect on atopic dermatitis-like skin lesions and may represent an effective new anti-inflammatory agent.

A practical MRI grading system for cervical foraminal stenosis based on oblique sagittal images.

OBJECTIVE: To propose a new and practical MRI grading method for cervical neural foraminal stenosis and to evaluate its reproducibility. METHODS: We evaluated 50 patients (37 males and 13 females, mean age 49 years) who visited our institution and underwent oblique sagittal MRI of the cervical spine. A total of 300 foramina and corresponding nerve roots in 50 patients were qualitatively analysed from C4-5 to C6-7. We assessed the grade of cervical foraminal stenosis at the maximal narrowing point according to the new grading system based on T2 weighted oblique sagittal images. The incidence of each of the neural foraminal stenosis grades according to the cervical level was analysed by χ(2) tests. Intra- and interobserver agreements between two radiologists were analysed using kappa statistics. Kappa value interpretations were poor (κ<0.1), slight (0.1≤κ≤0.2), fair (0.2<κ≤0.4), moderate (0.4<κ≤0.6), substantial (0.6<κ≤0.8) and almost perfect (0.8<κ≤1.0). RESULTS: Significant stenoses (Grades 2 and 3) were rarely found at the C4-5 level. The incidence of Grade 3 at the C5-6 level was higher than that at other levels, a difference that was statistically significant. The overall intra-observer agreement according to the cervical level was almost perfect. The agreement at each level was almost perfect, except for only substantial agreement at the right C6-7 by Reader 2. No statistically significant differences were seen according to the cervical level. Overall kappa values of interobserver agreement according to the cervical level were almost perfect. In addition, the agreement of each level was almost perfect. Overall intra- and interobserver agreement for the presence of foraminal stenosis (Grade 0 vs Grades 1, 2 and 3) and for significant stenosis (Grades 0 and 1 vs Grades 2 and 3) showed similar results and were almost perfect. However, only substantial agreement was seen in the right C6-7. CONCLUSION: A new grading system for cervical foraminal stenosis based on oblique sagittal MRI provides reliable assessment and good reproducibility. This new grading system is a useful and easy method for the objective evaluation of cervical neural foraminal stenosis by radiologists and clinicians. ADVANCES IN KNOWLEDGE: The use of the new grading system for cervical foraminal stenosis based on oblique sagittal MRI can be a useful method for evaluating cervical neural foraminal stenosis.

Clinical correlation of a new practical MRI method for assessing central lumbar spinal stenosis.

OBJECTIVE: To evaluate interobserver agreement and determine whether a new MRI grading system agrees with symptoms and neurological signs. METHODS: We examined 160 patients (72 males and 88 females; mean age 57 years) who underwent MRI of the lumbar spine at our institution and were evaluated by two musculoskeletal radiologists. The presence and grade of central lumbar spinal stenosis (CLSS) at L3-4, L4-5 and L5-S1 were assessed according to a new grading system, the Lee system. The results were correlated with clinical manifestations and neurological examinations [positive neurological manifestation (PNM) and negative neurological manifestation (NNM)]. Statistical analyses were performed using kappa statistics and non-parametric correlation analysis (Spearman's correlation). RESULTS: Interobserver agreement in the grading of CLSS between the two readers was substantial (κ=0.780). Interobserver agreement of the L4-5 level and older age group was high (0.789, 0.814). The correlation coefficient (R) of Reader 1 between MRI Grades 0, 1, 2 or 3 and neurological manifestations (negative or positive) was 0.654; the R of Reader 2 was 0.591. In the younger age group (<57 years), the R of Reader 1 was 0.634 and the R of Reader 2 was 0.500. In the older age group (≥57 years), the R of Reader 1 was 0.650 and the R of Reader 2 was 0.645. Correlation coefficients were higher at the L3-4 level (0.612-0.678) than at other levels but did not show statistical significance (p>0.05). CONCLUSION: Interobserver agreement for the new CLSS grading system was substantial. Grade 0 was associated with NNMs and Grade 3 with PNMs in this cohort. Grade 2 demonstrates more cases of PNM than NNM but requires further evaluation. Correlations between MRI grades and clinical manifestations were moderate and slightly higher in older patients. ADVANCES IN KNOWLEDGE: The new practical MRI grading method can be useful in the categorisation of CLSS and shows strong clinical correlation.