Are Current Aspergillus sojae Strains Originated from a Native Aflatoxigenic Aspergillus Species Population Also Present in California?

Aspergillus sojae has long been considered a domesticated strain of Aspergillus parasiticus. This study delineated relationships among the two species and an Aspergillus PWE36 isolate. Of 25 examined clustered aflatoxin genes of PWE36, 20 gene sequences were identical to those of A. sojae, but all had variations to those of A. parasiticus. Additionally, PWE36 developmental genes of conidiation and sclerotial formation, overall, shared higher degrees of nucleotide sequence identity with A. sojae genes than with A. parasiticus genes. Examination of defective cyclopiazonic acid gene clusters revealed that the PWE36 deletion pattern was identical only to those of A. sojae. Using A. sojae SMF134 genome sequence as a reference, visualization of locally collinear blocks indicated that PWE36 shared higher genome sequence homologies with A. sojae than with A. parasiticus. Phylogenetic inference based on genome-wide single nucleotide polymorphisms (SNPs) and total SNP counts showed that A. sojae strains formed a monophyletic clade and were clonal. Two (Argentinian and Ugandan) A. parasiticus isolates but not including an Ethiopian isolate formed a monophyletic clade, which showed that A. parasiticus population is genetically diverse and distant to A. sojae. PWE36 and A. sojae shared a most recent common ancestor (MRCA). The estimated divergence time for PWE36 and A. sojae was about 0.4 mya. Unlike Aspergillus oryzae, another koji mold that includes genetically diverse populations, the findings that current A. sojae strains formed a monophyletic group and shared the MRCA with PWE36 allow A. sojae to be continuously treated as a species for food safety reasons.

Direct and indirect costs for hospitalized patients with dengue in Southern Sri Lanka.

BACKGROUND: The Southern Province of Sri Lanka is endemic with dengue, with frequent outbreaks and occurrence of severe disease. However, the economic burden of dengue is poorly quantified. Therefore, we conducted a cost analysis to assess the direct and indirect costs associated with hospitalized patients with dengue to households and to the public healthcare system. METHODS: From June 2017-December 2018, we prospectively enrolled children and adults with acute dengue hospitalized at the largest, public tertiary-care (1800 bed) hospital in the Southern Province, Sri Lanka. We administered a structured questionnaire to obtain information regarding direct costs spent by households on medical visits, medications, laboratory testing, and travel for seeking care for the illness. Indirect costs lost by households were estimated by identifying the days of work lost by patients and caregivers and school days lost by children. Direct hospital costs were estimated using gross costing approach and adjusted by multiplying by annual inflation rates in Sri Lankan rupees and converted to US dollars. RESULTS: A total of 1064 patients with laboratory-confirmed dengue were enrolled. The mean age (SD) was 35.9 years (15.6) with male predominance (66.2%). The mean durations of hospitalization for adults and paediatric patients were 3.86 (SD = 1.51) and 4 (SD = 1.32) days, respectively. The per-capita direct cost borne by the healthcare system was 233.76 USD, and was approximately 14 times greater than the per-capita direct cost borne by households (16.29 USD, SD = 14.02). The per-capita average number of loss of working days was 21.51 (SD = 41.71), with mean per-capita loss of income due to loss of work being 303.99 USD (SD = 569.77), accounting for over 70% of average monthly income. On average, 10.88 days (SD = 10.97) of school days were missed due to the dengue episode. School misses were expected to reduce future annual income of affected children by 0.44%. CONCLUSIONS: Dengue requiring hospitalization had a substantial economic burden on the public healthcare system in Sri Lanka and the affected households. These findings emphasize the importance of strengthening dengue control activities and improved use of hospital-based resources for care to reduce the economic impact of dengue in Sri Lanka.

A tumour-resident Lgr5+ stem-cell-like pool drives the establishment and progression of advanced gastric cancers.

Gastric cancer is among the most prevalent and deadliest of cancers globally. To derive mechanistic insight into the pathways governing this disease, we generated a Claudin18-IRES-CreERT2 allele to selectively drive conditional dysregulation of the Wnt, Receptor Tyrosine Kinase and Trp53 pathways within the gastric epithelium. This resulted in highly reproducible metastatic, chromosomal-instable-type gastric cancer. In parallel, we developed orthotopic cancer organoid transplantation models to evaluate tumour-resident Lgr5+ populations as functional cancer stem cells via in vivo ablation. We show that Cldn18 tumours accurately recapitulate advanced human gastric cancer in terms of disease morphology, aberrant gene expression, molecular markers and sites of distant metastases. Importantly, we establish that tumour-resident Lgr5+ stem-like cells are critical to the initiation and maintenance of tumour burden and are obligatory for the establishment of metastases. These models will be invaluable for deriving clinically relevant mechanistic insights into cancer progression and as preclinical models for evaluating therapeutic targets.

Evaluation of the probiotic and functional potential of Lactobacillus agilis 32 isolated from pig manure.

Escherichia coli is a symbiotic bacterium in humans and animals and an important pathogen of humans and animals. Prevention and suppression of E. coli infection is of great concern. In this study, we isolated a strain of Lactobacillus agilis 32 from pig manure and evaluated its biological characteristics, and found that its bacterial survival rate was 25% after 4 h of treatment at pH 2, and under the condition of 0·5% bile concentration, its survival rate exceeds 30%. In addition, L. agilis 32 has a cell surface hydrophobicity of 77·8%, and exhibits 67·1% auto-aggregation and 63·2% aggregation with Enterotoxigenic E. coli 10 (ETEC 10). FITC fluorescence labelling showed that the fluorescence intensity of cecum was significantly higher than that of duodenum, jejunum or colon (P < 0·05), but no significant difference from ileum. Lactobacillus agilis 32 bacterial culture and CFS showed average inhibition zone diameters of 14·2 and 15·4 mm respectively. Lactobacillus agilis 32 CFS treatment can significantly reduce the pathogenicity of ETEC 10. These results show that L. agilis 32 is an active and potential probiotic, and it has a good antibacterial effect on ETEC10, which provides basic research for probiotics to prevent and treat intestinal diarrhoea pathogen infection.

Validation of the Hebrew Version of the Unified Dyskinesia Rating Scale.

BACKGROUND: The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS. METHODS: We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations. RESULTS: The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS. CONCLUSION: The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings.

Genome Sequence of an Aspergillus flavus CA14 Strain That Is Widely Used in Gene Function Studies.

Aspergillus flavus produces aflatoxins that adversely impact human health and the economy. We report the genome sequence of A. flavus CA14 that has been widely used in gene function studies. The information will benefit A. flavus functional genomics studies on fungal development, secondary metabolite production, and fungus-host plant interactions.

Dual culture of atoxigenic and toxigenic strains of Aspergillus flavus to gain insight into repression of aflatoxin biosynthesis and fungal interaction.

Application of atoxigenic strains to compete against toxigenic strains of Aspergillus flavus strains has emerged as one of the practical strategies for reducing aflatoxin contamination in corn, peanut, and tree nuts. The actual mechanism that results in aflatoxin reduction is not fully understood. Real-time RT-PCR and relative quantification of gene expression protocol were applied to elucidate the molecular mechanism. Transcriptional analyses of aflatoxin biosynthetic gene cluster in dual culture of toxigenic and atoxigenic A. flavus strains were carried out. Six targeted genes, aflR, aflJ, omtA, ordA, pksA, and vbs, were downregulated to variable levels depending on paired strains of toxigenic and atoxigenic A. flavus. Consistent with the decreased gene expression levels, the aflatoxin concentrations in dual cultures were reduced significantly in comparison with toxigenic cultures. Fluorescent images showed fungal hyphae in dual culture displayed green fluorescent, and contacts of live hyphae were seen. A coconut agar plate assay was used to show that toxigenic A. flavus colony produced blue fluorescence under long UV exposure, suggesting that aflatoxin is exported outside fungal hyphae. Furthermore, the assay was applied to demonstrate the potential role of thigmo-regulation in fungal interaction.

Aspergillus flavus NRRL 35739, a Poor Biocontrol Agent, May Have Increased Relative Expression of Stress Response Genes.

Biocontrol of the mycotoxin aflatoxin utilizes non-aflatoxigenic strains of Aspergillus flavus, which have variable success rates as biocontrol agents. One non-aflatoxigenic strain, NRRL 35739, is a notably poor biocontrol agent. Its growth in artificial cultures and on peanut kernels was found to be slower than that of two aflatoxigenic strains, and NRRL 35739 exhibited less sporulation when grown on peanuts. The non-aflatoxigenic strain did not greatly prevent aflatoxin accumulation. Comparison of the transcriptomes of aflatoxigenic and non-aflatoxigenic A. flavus strains AF36, AF70, NRRL 3357, NRRL 35739, and WRRL 1519 indicated that strain NRRL 35739 had increased relative expression of six heat shock and stress response proteins, with the genes having relative read counts in NRRL 35739 that were 25 to 410 times more than in the other four strains. These preliminary findings tracked with current thought that aflatoxin biocontrol efficacy is related to the ability of a non-aflatoxigenic strain to out-compete aflatoxigenic ones. The slower growth of NRRL 35739 might be due to lower stress tolerance or overexpression of stress response(s). Further study of NRRL 35739 is needed to refine our understanding of the genetic basis of competitiveness among A. flavus strains.

Volatile 1-octen-3-ol increases patulin production by Penicillium expansum on a patulin-suppressing medium.

1-Octen-3-ol is one of the most abundant volatile compounds associated with fungi and functions as a germination and growth inhibitor in several species. By investigating its effect on the biosynthesis of patulin, a mycotoxin made by Penicillium expansum, it was found that a sub-inhibitory level of volatile 1-octen-3-ol increased accumulation of patulin on a medium that normally suppresses the mycotoxin. Transcriptomic sequencing and comparisons of control and treated P. expansum grown on potato dextrose agar (PDA; patulin permissive) or secondary medium agar (SMA; patulin suppressive) revealed that the expression of gox2, a gene encoding a glucose oxidase, was significantly affected, decreasing 10-fold on PDA and increasing 85-fold on SMA. Thirty other genes, mostly involved in transmembrane transport, oxidation-reduction, and carbohydrate metabolism were also differently expressed on the two media. Transcription factors previously found to be involved in regulation of patulin biosynthesis were not significantly affected despite 1-octen-3-ol increasing patulin production on SMA. Further study is needed to determine the relationship between the upregulation of patulin biosynthesis genes and gox2 on SMA, and to identify the molecular mechanism by which 1-octen-3-ol induced this effect.

Influence of R and S enantiomers of 1-octen-3-ol on gene expression of Penicillium chrysogenum.

Inhibition of spore germination offers an attractive and effective target for controlling fungal species involved in food spoilage. Mushroom alcohol (1-octen-3-ol) functions as a natural self-inhibitor of spore germination for many fungi and, therefore, provides a useful tool for probing the molecular events controlling the early stages of fungal growth. In Penicillium spp., the R and S enantiomers of 1-octen-3-ol delayed spore germination and sporulation in four species of Penicillium involved in soils of fruit and grains, but to different degrees. Because of its well-annotated genome, we used Penicillium chrysogenum to perform a comprehensive comparative transcriptomic analysis of cultures treated with the two enantiomers. Altogether, about 80% of the high-quality reads could be mapped to 11,396 genes in the reference genome. The top three active pathways were metabolic (978 transcripts), biosynthesis of secondary metabolites (420 transcripts), and microbial metabolism in diverse environments (318 transcripts). When compared to the control, treatment with (R)-(-)-1-octen-3-ol affected the transcription levels of 91 genes, while (S)-(+)-1-octen-3-ol affected only 41 genes. Most of the affected transcripts were annotated and predicted to be involved in transport, establishment of localization, and transmembrane transport. Alternative splicing and SNPs' analyses indicated that, compared to the control, the R enantiomer had greater effects on the gene expression pattern of Penicillium chrysogenum than the S enantiomer. A qRT-PCR analysis of 28 randomly selected differentially expressed genes confirmed the transcriptome data. The transcriptomic data have been deposited in NCBI SRA under the accession number SRX1065226.

Transcriptional Regulation of Aflatoxin Biosynthesis and Conidiation in Aspergillus flavus by Wickerhamomyces anomalus WRL-076 for Reduction of Aflatoxin Contamination.

Aspergillus flavus is a ubiquitous saprophytic fungus found in soils across the world. The fungus is the major producer of aflatoxin (AF) B1, which is toxic and a potent carcinogen to humans. Aflatoxin B1 (AFB1) is often detected in agricultural crops such as corn, peanut, almond, and pistachio. It is a serious and recurrent problem and causes substantial economic losses. Wickerhamomyces anomalus WRL-076 was identified as an effective biocontrol yeast against A. flavus. In this study, the associated molecular mechanisms of biocontrol were investigated. We found that the expression levels of eight genes, aflR, aflJ, norA, omtA, omtB, pksA, vbs, and ver-1 in the aflatoxin biosynthetic pathway cluster were suppressed. The decreases ranged from several to 10,000 fold in fungal samples co-cultured with W. anomalus. Expression levels of conidiation regulatory genes brlA, abaA, and wetA as well as sclerotial regulatory gene (sclR) were all down regulated. Consistent with the decreased gene expression levels, aflatoxin concentrations in cultural medium were reduced to barely detectable. Furthermore, fungal biomass and conidial number were significantly reduced by 60% and more than 95%, respectively. The results validate the biocontrol efficacy of W. anomalus WRL-076 observed in the field experiments.

Biocontrol strain Aspergillus flavus WRRL 1519 has differences in chromosomal organization and an increased number of transposon-like elements compared to other strains.

Aflatoxins are toxic secondary metabolites produced by members of the genus Aspergillus, most notably A. flavus. Non-aflatoxigenic strains of A. flavus are commonly used for biocontrol of the aflatoxigenic strains to reduce aflatoxins in corn, cotton, peanuts and tree nuts. However, genomic differences between aflatoxigenic strains and non-aflatoxigenic strains have not been reported in detail, though such differences may further elucidate the evolutionary histories of certain biocontrol strains and help guide development of other useful strains. We recently reported the genome and transcriptome sequencing of A. flavus WRRL 1519, a strain isolated from almond that does not produce aflatoxins or cyclopiazonic acid due to deletions in the biosynthetic gene clusters. Continued bioinformatics analyses focused on comparing strain WRRL 1519 to the aflatoxigenic strain NRRL 3357. The genome assembly of strain WRRL 1519 was improved by anchoring 84 of the 127 scaffolds to the putative nuclear chromosomes of strain NRRL 3357. The five largest areas of extrachromosomal mismatches observed between WRRL 1519 and NRRL 3357 were not similar to any of the mismatches that were observed with pairwise comparisons of NRRL 3357 to other non-aflatoxigenic strains NRRL 21882, NRRL 30797 or NRRL 18543. Comparisons of predicted secondary metabolite gene clusters uncovered two other biosynthetic gene clusters in which strain WRRL 1519 had large deletions compared to the homologous clusters in NRRL 3357. Additionally, there was a marked overrepresentation of repetitive sequences in WRRL 1519 compared to other inspected A. flavus strains. This is the first report of detection of a large number of putative retrotransposons in any A. flavus strain, initially suggesting that retrotransposons may contribute to the natural occurrence of genetic variation and biocontrol strains. However, the transposons may not be significantly associated with the chromosomal differences. Future experimentation and continued bioinformatics analyses will potentially illuminate causes of the differences and may reveal whether transposon activity in A. flavus can lead to random natural occurrences of non-aflatoxigenic strains.

Genome sequence and comparative analyses of atoxigenic Aspergillus flavus WRRL 1519.

Aflatoxins are toxic secondary metabolites produced by Aspergillus flavus and a few other closely related species of Aspergillus. These highly toxigenic and carcinogenic mycotoxins contaminate global food and feed supplies, posing widespread health risks to humans and domestic animals. Field application of nonaflatoxigenic strains of A. flavus to compete against aflatoxigenic strains has emerged as one of the best management practices for reducing aflatoxins contamination, yielding successful commercial products for corn, cotton seed, and peanuts. In this study, we sequenced the genome and transcriptome of atoxigenic (does not produce aflatoxin or cyclopiazonic acid) A. flavus strain WRRL 1519 isolated from a tree nut orchard to define the genetic characteristics of the strain in relation to aflatoxigenic and other nonaflatoxigenic A. flavus strains. WRRL 1519 strain was similar to other strains in size (38.0 Mb), GC content (47.2%), number of predicted secondary metabolite gene clusters (46), and number of putative proteins (12 121). About 87.4% of the predicted proteome had high shared identity with protein sequences derived from other A. flavus genomes. However, the atoxigenic A. flavus strain WRRL 1519 had deletions, or low shared identity, for many genes in the clusters required for aflatoxins and cyclopiazonic acid (CPA) synthesis. Over half of the aflatoxin synthesis gene cluster was missing, and none of the components of the CPA gene cluster were identified with high sequence similarity. Importantly, the strain appeared to maintain functional sequences of several genes thought to be required for high infectivity. Since the ability to grow on target crop is an important attribute for a successful biocontrol agent, these results indicate that the nonaflatoxigenic A. flavus strain WRRL 1519 would be a good candidate as a biocontrol agent for reducing aflatoxin and CPA accumulation in high-value nut crops.

Development of a droplet digital PCR assay for population analysis of aflatoxigenic and atoxigenic Aspergillus flavus mixtures in soil.

Aflatoxin B1 is a potent hepatotoxin and carcinogen that poses a serious safety hazard to both humans and animals. Aspergillus flavus is the most common aflatoxin-producing species on corn, cotton, peanuts, and tree nuts. Application of atoxigenic strains to compete against aflatoxigenic strains of A. flavus has emerged as one of the most practical strategies for ameliorating aflatoxin contamination in food. Genes directly involved in aflatoxin biosynthesis are clustered on an 82-kb region of the genome. Three atoxigenic strains (CA12, M34, and AF123) were each paired with each of four aflatoxigenic strains (CA28, CA42, CA90, and M52), inoculated into soil and incubated at 28 °C for 2 weeks and 1 month. TaqMan probes, omtA-FAM, and norA-HEX were designed for developing a droplet digital PCR (ddPCR) assay to analyze the soil population of mixtures of A. flavus strains. DNA was extracted from each soil sample and used for ddPCR assays. The data indicated that competition between atoxigenic and aflatoxigenic was strain dependent. Variation in competitive ability among different strains of A. flavus influenced the population reduction of the aflatoxigenic strain by the atoxigenic strain. Higher ratios of atoxigenic to aflatoxigenic strains increased soil population of atoxigenic strains. This is the first study to demonstrate the utility of ddPCR to quantify mixtures of both atoxigenic and aflatoxigenic A. flavus strains in soil and allows for rapid and accurate determination of population sizes of atoxigenic and aflatoxigenic strains. This method eliminates the need for isolation and identification of individual fungal isolates from experimental soil samples.

First report of an atypical new Aspergillus parasiticus isolates with nucleotide insertion in aflR gene resembling to A. sojae.

Aflatoxins are toxic and carcinogenic secondary metabolites produced primarily by the filamentous fungi Aspergillus flavus and Aspergillus parasiticus and cause toxin contamination in food chain worldwide. Aspergillus oryzae and Aspergillus sojae are highly valued as koji molds in the traditional preparation of fermented foods, such as miso, sake, and shoyu. Koji mold species are generally perceived of as being nontoxigenic and are generally recognized as safe (GRAS). Fungal isolates were collected from a California orchard and a few were initially identified to be A. sojae using ß-tubulin gene sequences blasted against NCBI data base. These new isolates all produced aflatoxins B1, B2, G1, and G2 and were named as Pistachio Winter Experiment (PWE) strains. Thus, it is very important to further characterize these strains for food safety purposes. The full length of aflR gene of these new isolates was sequenced. Comparison of aflR DNA sequences of PWE, A. parasiticus and A. sojae, showed that the aflatoxigenic PWE strains had the six base insertion (CTCATG) similar to domesticated A. sojae, but a pre-termination codon TGA at nucleotide positions 1153-1155 was absent due to a nucleotide codon change from T to C. Colony morphology and scanning microscopic imaging of spore surfaces showed similarity of PWE strains to both A. parasiticus and A. sojae. Concordance analysis of multi locus DNA sequences indicated that PWE strains were closely linked between A. parasiticus and A. sojae. The finding documented the first report that such unique strains have been found in North America and in the world.

Relationship between Homocysteine and Muscle Strength Decline: The Baltimore Longitudinal Study of Aging.

Background: Decreased muscle strength is strongly associated with future mobility limitations in older adults. Homocysteine is a risk factor for vascular disease and may exacerbate muscle strength decline. The present study aimed to examine the association between homocysteine levels and muscle strength in adults aged 50 years or older. Methods: Data were from 1,101 participants of The Baltimore Longitudinal Study of Aging between December 2004 and March 2015. Muscle strength was measured using grip strength. Mixed effects linear regression was used to estimate the association between homocysteine and muscle strength in men and women, separately. Results: Total mean follow-up time was 4.7 ± 3.1 years, range from 0 to 10.1 years. Baseline mean grip strength was 39.9 kg for men and 25.5 kg for women. Grip strength declined over the follow-up time for both men and women. Among women, there was a significant inverse relationship between homocysteine and grip strength, where grip strength declined as a function of increasing homocysteine over time (ß = -0.05, p = .031). Among men, an increase of 1 µmol/L in homocysteine was associated with -0.10 kg decrease in grip strength, though not significantly. Conclusions: In this study of healthy older adults aged 50 years or older, higher homocysteine was related to lower muscle strength in women. This is the first study to characterize the relationship over a long follow-up period. Future research should focus on assessing homocysteine as a marker of physical function decline and translating the relationship into clinical and public health practice.

Validation of the Hebrew version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.

BACKGROUND: The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one. METHODS: The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version. RESULTS: The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors. CONCLUSIONS: The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS.

Transarterial embolisation for congenital renal arteriovenous malformations improves clinical condition even with partial obliteration.

AIM: To evaluate the efficacy and safety of transarterial embolisation (TAE), used to treat congenital renal arteriovenous malformations (CRAVMs). MATERIALS AND METHODS: The medical records were searched retrospectively to identify patients who underwent TAE to treat CRAVM from January 2003 to August 2015. Patient demographics, clinical presentations, and imaging findings were reviewed. TAE outcomes, including complete or partial obliteration, clinical success, complications, renal function changes, and relapse of symptoms or signs after the final TAE, were assessed. RESULTS: Over the 12-year period, 16 patients (nine male, seven female; median age, 47 years) who underwent 21 TAE procedures to treat 16 CRAVMs were enrolled in the study. The most common clinical presentation was haematuria (81.3%). Thirteen patients (81.3%) had cirsoid and three (18.7%) had aneurysmal CRAVMs. Of the 16 CRAVMs, 11 (68.8%) were peripheral, four (25%) were central, and one (6.3%) was both peripheral and central. The complete obliteration rate was 56.3%. The clinical success rate was 87.5% over a median follow-up period of 398.5 days. Two (9.5%) major complications and 14 (66.7%) minor complications were encountered. No statistically significant change in renal function was evident after TAE. CONCLUSION: TAE was safe and effective when used to treat CRAVM; the complication profile was acceptable and renal function was preserved. TAE improved the clinical condition of CRAVM patients even when obliteration was only partial.

Autonomic and electrocardiographic findings in Parkinson's disease.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and signs. Many reports suggest that diminished heart rate variability occurs early, even prior to the cardinal signs of PD. In a longitudinal study of PD, we evaluated whether heart rate variability (HRV) obtained using a 10-second ECG tracing, and the electrocardiographic QT-interval would be associated with PD severity and progression. Subjects were derived from a longitudinal study of 1741 individuals with early, stable PD. The severity of PD was measured using the global statistical test (GST). In a subset, the heart rate corrected QT-interval (QTcB) was calculated for each electrocardiogram (ECG). The HRV was measured for each ECG and then transformed to fit a normal distribution. The baseline analysis included 653 subjects, with 256 completing the 5-year follow up study. There was an association (P<0.05) between QTcB and PD severity in individuals that were taking QT-interval affecting drugs. A longer QT-interval at baseline was associated with more advanced PD at 5years (P<0.05), and greater disease progression over 5years (P<0.05). There was an association between diminished HRV and an orthostatic decrease in standing blood pressure at baseline in individuals with PD (P<0.05). HRV was not associated with PD severity or progression. In conclusion, we were able to detect measurable associations between the QTcB interval and PD severity, PD severity 5years later, and the change in disease over time. However, routine ECG tracings appear inadequate for the evaluation of autonomic function in PD.