Fermented milk with Lactobacillus curvatus SMFM2016-NK alleviates periodontal and gut inflammation, and alters oral and gut microbiota.

This study aimed to analyze the effect of milk fermented with Lactobacillus curvatus SMFM2016-NK on periodontal diseases and gut health in a rat model. To improve the effect of Lb. curvatus SMFM2016-NK-fermented milk administration for relieving periodontitis, the periodontitis rat models were treated with the following for 4 wk: 10% skim milk (normal), periodontitis + 10% skim milk (negative control), periodontitis + Lactobacillus rhamnosus GG-fermented milk (positive control), and periodontitis + Lb. curvatus SMFM2016-NK-fermented milk (PD+LCFM). Transcriptional analysis of inflammatory cytokines [tumor necrosis factor α (TNF-α), IL-1ß, IL-6, and IL-10] was performed via quantitative reverse-transcription PCR. The changes in the oral and gut microbiomes after administering Lb. curvatus SMFM2016-NK-fermented milk were analyzed with metagenomics sequencing using DNA extracted from the oral gingival tissues and feces from the cecum of the rat models. After treatment with Lb. curvatus SMFM2016-NK-fermented milk, the relative gene expression levels of TNFA and IL1B in the gingiva decreased in the PD+LCFM group compared with those in the negative control group. In the oral microbiome, the proportion of the phylum Proteobacteria in the PD+LCFM group was lower than that in the negative control after treatment with Lb. curvatus SMFM2016-NK-fermented milk. For the effect in the gut, the relative gene expression levels of inflammatory cytokines in the colon between the normal and negative control groups were not different; however, the expression levels of TNFA and IL1B in the PD+LCFM and positive control groups, respectively, were lower than those in the negative control group. The composition and diversity of the gut microbiome differed among normal, periodontitis, and Lb. curvatus SMFM2016-NK-fermented milk treatment groups. These results indicate that Lb. curvatus SMFM2016-NK-fermented milk could alleviate periodontal and gut inflammation and change oral and gut microbiota.

Risk factors and renal outcomes of low bone mineral density in patients with non-dialysis chronic kidney disease.

Bone disorder is a common complication of chronic kidney disease (CKD). The clinical usefulness of bone mineral density (BMD) in CKD is not well known. Our study shows that low BMD is associated with physical activity and dietary Na/K intake ratio and can predict poor renal outcome in non-dialysis CKD. PURPOSE: Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD. METHODS: We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by T score: normal (T score ≥ - 1.0), osteopenia (- 1.0 > T score > - 2.5), and osteoporosis (T score ≤ - 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (T score < - 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD). RESULTS: Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12 years; male 61%). Over a median follow-up of 4.3 years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49-0.77)) and spot urine Na/K ratio (1.07 (1.00-1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92-1.41) for osteopenia; 1.43 (1.01-2.04) for osteoporosis, P for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to T score discordance classification. CONCLUSIONS: Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD.

Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Associations of various blood pressure parameters with functional outcomes after endovascular thrombectomy in acute ischaemic stroke.

BACKGROUND AND PURPOSE: High blood pressure (BP) at presentation is associated with poor outcomes in acute ischaemic stroke, but serial BP measurements may better delineate the clinical implications of BP. The aim was to investigate the association between various BP parameters and functional outcomes in acute ischaemic stroke patients treated with endovascular thrombectomy (EVT). METHODS: This study reports a retrospective analysis of a prospective registry of a comprehensive stroke centre. Patients treated with EVT due to large vessel occlusion in the anterior circulation were enrolled. BP was measured hourly during the first 24 h after admission. Associations of various BP parameters, including BP variability, with functional outcomes at 3 months, including good outcomes (modified Rankin Scale score of 0-2), were analysed. RESULTS: Of the 378 enrolled patients (mean age 70 ± 11 years, male 54.2%), 313 (82.8%) achieved successful reperfusion after EVT, and 149 (39.4%) had good outcomes at 3 months. Higher mean systolic BP [each 10 mmHg increase, odds ratio 0.82 (0.69-0.97)] and higher systolic successive variation (SV) [each 10% increase, odds ratio 0.37 (0.18-0.76)] were associated with a reduced likelihood of achieving good outcomes. In addition, reperfusion status after EVT moderated the influence of higher systolic SV on good outcomes (Pint  = 0.05). CONCLUSION: The results showed that a higher mean systolic BP and systolic SV during the first 24 h of EVT reduced the likelihood of good outcomes at 3 months. The effects of these parameters on outcomes are more substantial amongst patients with successful reperfusion after EVT, suggesting that different BP control strategies should be employed according to reperfusion status.

Late-onset bulky naevocytoma of the perineum masquerading as a malignant melanoma.

Bulky naevocytoma of the perineum is a very rare variant of giant congenital melanocytic naevus (GCMN). It presents as a bulky naevocytic tumour in the perineal region with characteristic histological findings, such as extensive areas with a neural appearance called 'lames foliacees', formation of a pseudofollicular structure and extension of naevus cells between collagen bundles in a row called 'Indian-file' pattern. We report a case of late-onset bulky naevocytoma of the perineum in a 13-year-old girl. The patient presented with two bulky, pedunculated, heavily pigmented masses in the vulvar area that developed in a pre-existing GCMN lesion, which began around puberty and caused severe gait disturbance. Given the possibility of malignant transformation, we conducted staged reduction surgery of the tumour masses, which were found to be intradermal naevi without evidence of malignancy. The patient's gait disturbance improved markedly after surgery.

Population genetic characterization of the Japanese oak silkmoth, Antheraea yamamai (Lepidoptera: Saturniidae), using novel microsatellite markers and mitochondrial DNA gene sequences.

The Japanese oak silkmoth, Antheraea yamamai Guérin-Méneville, 1861 (Lepidoptera: Saturniidae), is an important natural resource of industrial value for silk fiber production. Owing to a lack of geographic and population genetic information, systematic domestication of An. yamamai has not been possible yet. In this study, 10 microsatellite markers developed using next-generation sequencing and two mitochondrial DNA (mtDNA) gene sequences (COI and ND4) were used to investigate the genetic variation and geographic structure of An. yamamai populations in South Korea. The two mtDNA gene sequences revealed very low total genetic variation and, consequently, low geographic variation, validating the use of more variable molecular markers. Genotyping of 76 An. yamamai individuals from nine localities in South Korea showed that the observed number of alleles at each locus ranged from 3 to 26, the polymorphism information content was 0.2990-0.9014, the observed and expected heterozygosities were 0.3252-0.9076 and 0.2500-0.9054, respectively, and FIS was -0.654-0.520. The population-based FIS, FST, RST, and global Mantel tests all suggested that the An. yamamai populations were overall well-interconnected, suggesting that any population can be used as a genetic source for domestication. Nevertheless, STRUCTURE analyses using microsatellite data and mtDNA sequences indicated the presence of two genetic pools in many populations, although a plausible explanation for this observation requires further studies.

Cognitive remediation for individuals with psychosis: efficacy and mechanisms of treatment effects.

BACKGROUND: The popularity of cognitive remediation (CR) interventions for individuals with psychosis is in part based on the well-established link between cognition and functioning and the assumption that by targeting cognition, function can improve. While numerous trials have reported CR's efficacy, it is still not considered an evidence-based treatment. Importantly, little is known about the mechanisms through which it may affect functioning. METHOD: In this study, we evaluated CR's proximal and distal effects, and examined potential mechanisms. A total of 75 individuals with psychotic disorders were randomized to a combination of strategy-based and drill-and-practice CR or wait-list control, with assessments of training task performance, neurocognition, functional capacity, symptoms and functioning conducted at baseline, end of the 2-month intervention, and 2-month follow-up. RESULTS: Compared with treatment as usual, CR was associated with large post-training improvements on training tasks targeting attention, visuospatial memory, and verbal learning and memory, with persisting group differences at the 2-month follow-up. These generalized to mostly large improvements on neuropsychological measures targeting visuospatial memory, verbal learning and memory, delayed verbal memory and verbal working memory. While there were no CR-associated improvements on measures of functional capacity, symptoms, or a self-report measure of independent living skills, there was an effect on an interviewer-rated measure of functioning (Quality of Life Scale), which appeared primarily driven by the Intrapsychic Foundations subscale. Finally, for those randomized to CR, there were significant, medium-sized correlations between training task improvement, neuropsychological improvement and functioning measures. CONCLUSIONS: This suggests a complex, multifactorial relationship between CR, and cognitive and functional change.

RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder.

RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.

Mosaic double aneuploidy (45,X/47,XX,+8) with aortic dissection.

Chromosomal aneuploidy is considerably frequent and may involve either autosomes or sex chromosomes. While double aneuploidy involving both autosomal and sex chromosomes is rare, several reports described the cases of sex chromosomal aneuploidies in combination with trisomy 21, such as Down-Klinefelter and Down-Turner syndrome. However, trisomy 8-Turner syndrome has been rarely described to date. Here we report a case of a 28-year-old female with mosaic trisomy 8-Turner syndrome. The patient was referred to our hospital for aortic dissection. On physical evaluation, features of her phenotype, which included short stature, webbed neck and cubitus valgus, suggested congenital anomalies such as Turner syndrome. Chest CT revealed aortic dissection with bicuspid aortic valve and coarctation. G-banding cytogenetic analysis of peripheral blood showed mosaicism with two cell lines (45,X[17]/47,XX,+8[33]). FISH analysis indicated that 15% of the cells were of monosomy X karyotype and 85% of the cells were with XX karyotype and trisomy 8 was detected only in XX cells. Though the patient exhibited clinical features of Turner syndrome, somatic stigmas present were not clearly distinguishable from those of trisomy 8, such as short stature, skeletal and cardiac abnormalities. Observations from most of the double aneuploidy cases indicated that the patient's phenotype was not necessarily in correlation to the ratio of autosomal and sex chromosomal aberrations. Mosaicism in trisomy 8-Turner syndrome was rarely documented and we believe this is the first reported case of mosaicism in trisomy 8-Turner syndrome presenting with aortic dissection and surviving into adulthood.

Prediction of hemorrhagic transformation in acute ischaemic stroke by micro- and macroalbuminuria after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is one of the most problematic complications to arise from intravenous thrombolysis (IVT). This study was conducted to assess whether micro- and macroalbuminuria could be associated with HT after IVT in patients with acute ischaemic stroke, and to investigate whether the value of urinary albumin-to-creatinine ratios would correlate with the degree of HT. METHODS: This was a retrospective study of stroke patients who had undergone IVT within 3 h of symptom onset. Albuminuria assessment was based on random morning spot urine collection with patients in a fasting state, the first morning after IVT. Multiple logistic regression analysis was used to evaluate whether the presence of micro- and macroalbuminuria might be independent predictors of HT. RESULTS: One-hundred and fifty-four patients were included in the study. Fifty-one patients had HT. The presence of micro- or macroalbuminuria was associated with HT after adjustment for variables with clinical significance (adjusting for age, atrial fibrillation, platelet counts, baseline National Institutes of Health Stroke Scale score, hypertension and diabetes mellitus; odds ratio, 2.542; 95% confidence interval, 1.106-5.841; P = 0.028). There were significant relationships between the presence of micro- and macroalbuminuria and types of HT. CONCLUSION: In conclusion, the results of this study suggest that the presence of micro- and macroalbuminuria after IVT could be a predictor of severe HT in patients with acute ischaemic stroke.

Isolation and characterization of a proteinaceous antifungal compound from Lactobacillus plantarum YML007 and its application as a food preservative.

UNLABELLED: Korean kimchi is known for its myriad of lactic acid bacteria (LAB) with diverse bioactive compounds. This study was undertaken to isolate an efficient antifungal LAB strain among the isolated kimchi LABs. One thousand and four hundred LABs isolated from different kimchi samples were initially screened against Aspergillus niger. The strain exhibiting the highest antifungal activity was identified as Lactobacillus plantarum YML007 by 16S rRNA sequencing and biochemical assays using API 50 CHL kit. Lact. plantarum YML007 was further screened against Aspergillus oryzae, Aspergillus flavus, Fusarium oxysporum and other pathogenic bacteria. The morphological changes during the inhibition were assessed by scanning electron microscopy. Preliminary studies on the antifungal compound demonstrated its proteinaceous nature with a molecular weight of 1256·617 Da, analysed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF). The biopreservative activity of Lact. plantarum YML007 was evaluated using dried soybeans. Spores of A. niger were observed in the negative control after 15 days of incubation. However, fungal growth was not observed in the soybeans treated with fivefold concentrated cell-free supernatant of Lact. plantarum YML007. The broad activity of Lact. plantarum YML007 against various food spoilage moulds and bacteria suggests its scope as a food preservative. SIGNIFICANCE AND IMPACT OF THE STUDY: After screening 1400 kimchi bacterial isolates, strain Lactobacillus plantarum YML007 was selected with strong antifungal activity against various foodborne pathogens. From the preliminary studies, it was found that the bioactive compound is a low molecular weight novel protein of 1256·617 Da. Biopreservative potential of Lact. plantarum YML007 was demonstrated on soybean grains, and the results point out YML007 as a potent biopreservative having broad antimicrobial activity against various foodborne pathogens.

The serum ferritin level is an important predictor of hemorrhagic transformation in acute ischaemic stroke.

BACKGROUND AND PURPOSE: Because hemorrhagic transformation (HT) is associated with morbidity and mortality, we need a better understanding of the factors that predict HT after ischaemic stroke. HT is a well-known factor that limits the use of thrombolytics and it negates the effect of treatment. This study investigated whether a high serum ferritin level is associated with HT in acute ischaemic stroke. METHODS: Seven hundred and fifty-two consecutive patients with acute ischaemic stroke within 24 h after a vascular event were enrolled. HT was diagnosed using magnetic resonance imaging (MRI) or computed tomography (CT) and the HT was classified into hemorrhagic infarction (HI) type 1, 2 and parenchymal hematoma (PH) type 1, 2. HT was also classified into no HT, asymptomatic HT, minor symptomatic HT (sHT), and major sHT. RESULTS: Computed tomography or MR showed HT in 90 patients (HI in 58 and PH in 32; asymptomatic in 53, minor symptomatic in 23 and major symptomatic in 14). The ferritin levels were higher in the patients who developed HT, PH and sHT. After adjustment for confounding variables, multivariate analysis showed that a high ferritin level remained an independent predictor of HT in the patients with acute ischaemic stroke (P < 0.001). Serum ferritin levels higher than 171.8 ng/ml were independently associated with sHT. CONCLUSIONS: This study suggests that a high ferritin level is an important predictor of HT, PH, and sHT in patients with acute ischaemic stroke. Lowering the ferritin level with iron-modifying agents or using free radical scavengers could be helpful to prevent HT in ischaemic stroke.

Curcumin suppresses Streptococcus mutans adherence to human tooth surfaces and extracellular matrix proteins.

Streptococcus mutans is the key causative agent of caries and infective endocarditis. The first step in biofilm development and the consequent initiation of further disease is bacterial adherence to host cell surfaces. Therefore, the aim of this study was to evaluate the inhibitory effect of curcumin on S. mutans adherence to extracellular matrices and tooth surfaces. The effect of curcumin on the ability of S. mutans to adhere to glass surfaces coated with collagen and fibronectin was tested in order to determine whether the decrease of the bacterial adhesion by curcumin is achieved by hindering the bacteria in adhering to collagen and/or fibronectin. Also, human teeth inoculated with S. mutans were treated with curcumin in vitro in order to assess the relevance of the anti-adhesive effect to oral conditions in vivo. The minimum inhibitory concentration (MIC) at which curcumin completely inhibited bacterial growth was 128 µg/mL. The addition of curcumin below the MIC diminished bacterial adherence onto both collagen- and fibronectin-coated glass surfaces and human tooth surfaces. It appears that the anti-adhesive effect of curcumin against S. mutans is mediated through collagen and fibronectin. These results support the widespread use of curcumin as a food-based antimicrobial agent.

Antimicrobial activities of therapeutic herbal plants against Listeria monocytogenes and the herbal plant cytotoxicity on Caco-2 cell.

AIMS: This study investigated the antimicrobial effect of various therapeutic herbal plants on Listeria monocytogenes, and their cytotoxicity effect on mammalian cells. METHODS AND RESULTS: The extracts from 69 therapeutic herbal plants were used to investigate the effect on the growth inhibition of L. monocytogenes, and their minimal inhibition concentrations and minimal bactericidal concentrations were determined. Among the plants, Psoraleae semen L. (Bogolji) and Sophorae radix L. (Gosam) extracts, which showed obvious antilisterial activity, were examined for the stability to heat, NaCl and acidic condition. Moreover, cytotoxicities of Bogolji and Gosam were tested, using Caco-2 cells. L. monocytogenes growth was completely inhibited by Bogolji and Gosam extracts at 3.2-6.3 and 50-100 AU ml(-1), respectively, and heat, NaCl and acidic condition did not affect the antilisterial activity of Bogolji and Gosam. Cytotoxic activities were observed only at high concentration (50 AU ml(-1)) of Bogolji extract. CONCLUSION: Bogolji and Gosam could be considered as potential phytochemicals to control L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: Use of therapeutic herbal plants should be useful in controlling L. monocytogenes, because most consumers have better acceptance for phytochemicals than synthetic chemicals.

First Report of Stolbur Phytoplasma Infection in Commercial Freesia hybrida Cultivars.

In January 2012, disease symptoms including chlorosis, leaf crinkle, leaf curving and stunting of whole plants, virescence, and curving and necrosis of flower stalks were observed in Freesia hybrida cvs. Evone, Honey Moon, Golden Gem, and Pallas in Icheon and Suwon (Gyeonggi Province in Korea). To determine a possible phytoplasma infection, the symptomatic freesia plants were examined for the presence of phytoplasma 16S rDNA fragment by PCR with the primer pair P1/P6 (2) and R16F1/R16R1 (in nested PCR), which amplifies phytoplasma 16S rDNA regions (4). An expected PCR product of ~1,096 bp was obtained from the symptomatic freesia plants, and they were designated as FreLN, Fre-phy-Ev4, Fre-phy-Ev6, Fre-phy-GG, Fre-phy-HM, and Fre-phy-Pal. The PCR products were sequenced and registered as GenkBank accessions AB695174 and AB709951-55. The sequence corresponding to symptomatic freesia had 98.8 to 99.4% identity with Stolbur phytoplasma strains in the 16S rDNA region, and it had only 95.7 to 96.3% identity with AY phytoplasma strains. In the ultra-thin sections of the leaf midribs, globous phytoplasmal bodies 54 to 214 nm in size were observed in sieve tube elements of phloem tissue. Fre-Phy-Ev6 and Fre-Phy-HM were doube-infected with Stolbur phytoplasma and Freesia mosaic virus (FreMV). Fre-Phy-Ev6 and Fre-Phy-HM revealed necrosis of flower stalks and flower color breaking besides curving of flower stalks. Therefore, flower color breaking and flower stalk necrosis were assumed to be caused by FreMV (1). Symptoms of chlorosis and stunting of whole plants shown in FreLN and virescence of Fre-phy-GG were typical symptoms of phytoplasmal diseases, while leaf crinkle, leaf curving, and curving of flower stalks appeared to be unique symptoms in F. hybrida. Stolbur phytoplasma was abundant in commercial freesia cultivation fields. Some of the cultivars, such as cv. Pallas, showed only curving of leaf and flower stalks without any typical symptom of phytoplasmal diseases. A phytoplasmal disease was reported in Poland in 2001 from F. hybrida exhibiting leaf chlorotic and necrotic spots, and classified as AY I-B based on RFLP analysis of PCR products (3). To our knowledge, this is the first report of Stolbur phytoplasma in F. hybrida. This result is significant because F. hybrida could be the infection source of Stolbur phytoplasma disease in floricultural crops. Interestingly, we found a prevalence of Stolbur phytoplasma in Petunia hybrida cultivars (GenBank Accession Nos. AB713757 to AB713758). High nucleotide sequence identity of 99.8% in the 16S rDNA region of Stolbur phytoplasma isolates from petunia and freesia support the inference that those Stolbur phytoplasma isolates could infect both floricultural crops. References: (1) A. A. Brunt. Freesia. Page 274 in: Virus and virus-like Diseases of Bulb and Flower Crops, John Wiley & Sons, Chichester, 1995. (2) S. Deng and C. Hiruki. J. Microbiol. Methods. 14:53, 1991. (3) M. Kaminska and H. Sliwa. Plant Dis. 85:336, 2001. (4) I. M. Lee et al. Phytopathology 84:559, 1994.

Clinical implications of collateral middle cerebral artery flow in acute ischaemic stroke with internal carotid artery occlusion.

BACKGROUND AND PURPOSE: The presence of collateral middle cerebral artery (MCA) flow via the primary collateral pathway is thought to protect against the progression of cerebral ischaemia. However, there have been few reports on early clinical outcomes according to the presence of collateral MCA flow in acute ischaemic stroke (AIS) with internal carotid artery (ICA) occlusion. Therefore, we sought to investigate the early clinical outcomes and lesion patterns according to the presence of collateral MCA flows in AIS with ICA occlusion. METHODS: This is a retrospective study of patients with AIS with ICA occlusion consecutively admitted to our stroke center between October 2008 and March 2010. Patients were included if they were admitted within 12 h of symptom onset with AIS and symptomatic ICA occlusion. Collateral MCA flow was defined as the presence of MCA signals from proximal M1 to distal MCA branches ipsilateral to the ICA occlusion by magnetic resonance angiography. Early neurological deterioration (END) was defined as a 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score and persistent neurological deterioration for at least 24 h or newly developed neurological symptoms within 7 days. RESULTS: Sixty-five patients (42 men, 23 women) were finally included. Initial NIHSS scores were significantly lower, and favorable outcomes at 3 months were better in patients with collateral MCA flow than in those without (P < 0.001). Initial lesion patterns were different according to the collateral MCA flow. However, patients with mild AIS might more frequently deteriorate than those with moderate to severe AIS. CONCLUSIONS: In our study, collateral MCA flow reduced initial stroke severity and was associated with favorable outcomes at 3 months but did not seem to protect against END in mild AIS patients with ICA occlusion. Therefore, the results of this study suggest that mild AIS patients with ICA occlusion should be carefully managed because their conditions may deteriorate.

Reduced pre-pregnancy proteinuria is associated with improving postnatal maternal renal outcomes in IgA nephropathy women.

AIMS: In patients with immunoglobulin A (IgA) nephropathy, postnatal renal outcomes vary depending on kidney function and proteinuria. However, whether a decrease in proteinuria prior to conception improves postnatal maternal renal outcomes is unknown. METHODS: This was a single-center retrospective study. A total of 52 pregnant women with biopsy-proven IgA nephropathy were enrolled in the study between January 2004 and December 2009. We collected data on proteinuria, which had been measured 1 year prior to conception, at conception, during pregnancy, and postnatally. The study outcomes included changes in estimated glomerular filtration rate (eGFR) and proteinuria. RESULTS: The median serum creatinine, eGFR, and proteinuria levels at conception were 0.8 (0.5 - 2.6) mg/dl, 91.2 (24.1 - 157.0) ml/min, 0.7 (0.0 - 3.5) g/g, respectively. Compared with values measured at conception, serum creatinine (0.8 - 1.0 mg/dl, p < 0.01) and proteinuria (0.7 - 1.5 g/g, p < 0.01) increased significantly postnatally, while eGFR decreased (91.2 - 77.8 ml/min, p < 0.01). In a multiple linear regression analysis, proteinuria at conception were independently associated with a faster decline in postnatal maternal eGFR (ß = 4.50, p < 0.05). In addition, a less decline in maternal eGFR was observed in patients with a reduction in proteinuria (> 30%) prior to pregnancy, compared with those with a less reduction (≤ 30%). As for newborn outcomes, preterm delivery, caesarean section, low birth weight < 2,500 g, and need for neonatal intensive care were 15.4%, 46.2%, 25.0% and 7.7%, respectively. CONCLUSIONS: This study showed that in women with IgA nephropathy, proteinuria was significantly associated with the deterioration of postnatal maternal renal outcomes. Our study also suggests that a strategy for reducing proteinuria prior to pregnancy is required to preserve kidney function after delivery.

Inhibition of myeloid cell leukemia-1 by tolfenamic acid induces apoptosis in mucoepidermoid carcinoma.

OBJECTIVES: The aim of this study was to evaluate the role of tolfenamic acid (Tol) and ampiroxicam (Amp) in the apoptotic regulation of YD-15 salivary mucoepidermoid carcinoma (MEC). MATERIALS AND METHODS: The effect of Tol on apoptosis and its mechanism were examined using a 3-(4,5-dimethylthiazol-2-yl)-5-(2,4-disulfophenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, Sub-G(1) population, Western blot analysis, 4'-6-Diamidino-2-phenylindole staining, reverse transcriptase polymerase chain reaction, immunostaining and small interfering RNA transfection. RESULTS: Tol inhibited cell growth of YD-15 cells but Amp did not. Tol induces apoptosis in YD-15 cells as evidenced by nuclear fragmentation, accumulation of the sub-G1 phase and the activation of caspase 3. Tol inhibited myeloid cell leukemia-1 (MCL-1) at the protein and mRNA levels. The treatment of MCL-1 siRNA to YD-15 cells resulted in the activation of caspase 3 and the inhibition of cell growth. Moreover, MCL-1 was regulated by specificity protein 1, but not by mitogen-activated protein kinases. CONCLUSION: These results suggest that Tol could be a potent anti-cancer drug for YD-15 MEC cells that acts by regulating the MCL-1 protein.