More than a piece of cake: Noun classifier processing in primary progressive aphasia.

INTRODUCTION: Clinical understanding of primary progressive aphasia (PPA) has been primarily derived from Indo-European languages. Generalizing certain linguistic findings across languages is unfitting due to contrasting linguistic structures. While PPA patients showed noun classes impairments, Chinese languages lack noun classes. Instead, Chinese languages are classifier language, and how PPA patients manipulate classifiers is unknown. METHODS: We included 74 native Chinese speakers (22 controls, 52 PPA). For classifier production task, participants were asked to produce the classifiers of high-frequency items. In a classifier recognition task, participants were asked to choose the correct classifier. RESULTS: Both semantic variant (sv) PPA and logopenic variant (lv) PPA scored significantly lower in classifier production task. In classifier recognition task, lvPPA patients outperformed svPPA patients. The classifier production scores were correlated to cortical volume over left temporal and visual association cortices. DISCUSSION: This study highlights noun classifiers as linguistic markers to discriminate PPA syndromes in Chinese speakers. HIGHLIGHTS: Noun classifier processing varies in the different primary progressive aphasia (PPA) variants. Specifically, semantic variant PPA (svPPA) and logopenic variant PPA (lvPPA) patients showed significantly lower ability in producing specific classifiers. Compared to lvPPA, svPPA patients were less able to choose the accurate classifiers when presented with choices. In svPPA, classifier production score was positively correlated with gray matter volume over bilateral temporal and left visual association cortices in svPPA. Conversely, classifier production performance was correlated with volumetric changes over left ventral temporal and bilateral frontal regions in lvPPA. Comparable performance of mass and count classifier were noted in Chinese PPA patients, suggesting a common cognitive process between mass and count classifiers in Chinese languages.

PSORTdb 4.0: expanded and redesigned bacterial and archaeal protein subcellular localization database incorporating new secondary localizations.

Protein subcellular localization (SCL) is important for understanding protein function, genome annotation, and aids identification of potential cell surface diagnostic markers, drug targets, or vaccine components. PSORTdb comprises ePSORTdb, a manually curated database of experimentally verified protein SCLs, and cPSORTdb, a pre-computed database of PSORTb-predicted SCLs for NCBI's RefSeq deduced bacterial and archaeal proteomes. We now report PSORTdb 4.0 (http://db.psort.org/). It features a website refresh, in particular a more user-friendly database search. It also addresses the need to uniquely identify proteins from NCBI genomes now that GI numbers have been retired. It further expands both ePSORTdb and cPSORTdb, including additional data about novel secondary localizations, such as proteins found in bacterial outer membrane vesicles. Protein predictions in cPSORTdb have increased along with the number of available microbial genomes, from approximately 13 million when PSORTdb 3.0 was released, to over 66 million currently. Now, analyses of both complete and draft genomes are included. This expanded database will be of wide use to researchers developing SCL predictors or studying diverse microbes, including medically, agriculturally and industrially important species that have both classic or atypical cell envelope structures or vesicles.

Tonal and orthographic analysis in a Cantonese-speaking individual with nonfluent/agrammatic variant primary progressive aphasia.

Clinical understanding of primary progressive aphasia (PPA) has been established based on English-speaking population. The lack of linguistic diversity in research hinders the diagnosis of PPA in non-English speaking patients. This case report describes the tonal and orthographic deficits of a multilingual native Cantonese-speaking woman with nonfluent/agrammatic variant PPA (nfvPPA) and progressive supranuclear palsy. Our findings suggest that Cantonese-speaking nfvPPA patients exhibit tone production impairments, tone perception deficits at the lexical selection processing, and linguistic dysgraphia errors unique to logographic script writer. These findings suggest that linguistic tailored approaches offer novel and effective tools in identifying non-English speaking PPA individuals.

Multimorbidity and Regional Volumes of the Default Mode Network in Brain Aging.

INTRODUCTION: The default mode network (DMN) is selectively vulnerable in brain aging. Little is known about the effect of multimorbidity as a whole onto the brain structural integrity. OBJECTIVE: We aimed to investigate the association between multimorbidity and the structural integrity of DMN. METHODS: We enrolled senior volunteers aged between 60 and 80 years in Hualien County during 2014-2018 and conducted in-person interview to collect information on chronic diseases. Fasting blood glucose and glycated hemoglobin (HbA1c) were tested. We assessed multimorbidity burden by the cumulative illness rating scale-geriatric (CIRS-G). MRI brain scans were standardized to measure the regional volume within the DMN. In a cross-sectional design, we employed stepwise regression models to evaluate the effects of age, sex, hyperglycemia, and multimorbidity on the DMN. RESULTS: A total of 170 volunteers were enrolled with a mean age of 66.9 years, female preponderance (71%), an average mini-mental state examination score of 27.6, a mean HbA1c of 6.0, and a mean CIRS-G total score (TS) of 7.2. We found that older age was associated with reduced volumes in the hippocampus, left rostral anterior cingulate cortex, right posterior cingulate, right isthmus, precuneus, and right supramarginal. Higher levels of HbA1c and fasting glucose were associated with a reduced volume in the hippocampus only. A higher CIRS-G-TS was associated with reduced volumes in the left posterior cingulate cortex and right supramarginal gyrus; while a higher CIRS-G severity index was associated with a smaller right precuneus and right supramarginal. CONCLUSIONS: In the DMN, hippocampal volume shows vulnerability to aging and hyperglycemia, whereas the posterior cingulate, supramarginal, and precuneus cortices may be the key sites to reflect the total effects of multimorbidity.

Impact of Comorbidity Burden on Cognitive Decline: A Prospective Cohort Study of Older Adults with Dementia.

INTRODUCTION: The lack of longitudinal data of comorbidity burden makes the association between comorbidity and cognitive decline inconclusive. We aimed to measure comorbidity and assess its effects on cognitive decline in mild to moderate dementia. METHODS: This was a prospective cohort study. The participants were enrolled from the Hualien Tzu Chi Hospital between January 2015 and December 2018. We enrolled 175 older adults with mild to moderate dementia and conducted in-person interviews to follow-up comorbidity and cognitive function annually. The comorbidity burden indices included Cumulative Illness Rating Scale for Geriatrics (CIRS-G), Charlson Comorbidity Index (CCI), and Medication Regimen Complexity Index (MRCI), and cognitive function was measured by Mini-Mental State Examination (MMSE) and clock drawing test. We employed the generalized estimating equations to assess the longitudinal effect of time-varying comorbidity burden on cognitive decline after adjusting for age, sex, and education. RESULTS: Most patients were diagnosed with Alzheimer's disease (88.6%) and in the early stage of dementia (Clinical Dementia Rating [CDR] = 0.5, 57.1%; CDR = 1, 36.6%). Multimorbidity was common (median: 3), and the top 3 most common comorbidities were osteoarthritis (67.4%), hypertension (65.7%), and hyperlipidemia (36.6%). The severity index of CIRS-G was significantly associated with cognitive decline in MMSE after adjusting for age, sex, and education. CCI and MRCI scores were, however, not associated with cognitive function. CONCLUSION: The severity index of CIRS-G outperforms CCI and MRCI in reflecting the longitudinal effect of comorbidity burden on cognitive decline in mild to moderate dementia.

Psychometric properties of the dementia knowledge assessment scale-traditional Chinese among home care workers in Taiwan.

BACKGROUND: The Dementia Knowledge Assessment Scale (DKAS) is a reliable and valid measurement of dementia knowledge for diverse allied health professionals but its traditional Chinese version has not been formally validated yet. The purpose of this study was to translate the DKAS from English to traditional Chinese and evaluate its psychometric properties among home care workers in Taiwan. METHODS: The DKAS scale was translated into traditional Chinese through a forward translation and back translation process following the cross-cultural translation guideline. A total of 285 home care workers in eastern Taiwan were recruited using convenience sample. A total of 252 participants completed the questionnaires, giving a response rate of 88.4%. We tested the construct validity by confirmatory factor analysis (CFA) and evaluated the reliability by internal consistency. RESULTS: The results of the CFA supported the 25-item, four-factor model for the DKAS-TC. The DKAS-TC achieved a good overall Cronbach's alpha of .93 and McDonald's omega of 0.94 with acceptable subscales McDonald's omega ranged from .77 to .82. CONCLUSIONS: The DKAS-TC has adequate construct validity and reliability and can serve as an assessment tool to evaluate the knowledge level of home care workers in a dementia training program in Taiwan. The dementia knowledge level among home care workers in Taiwan was inadequate. There is a need for developing suitable dementia care training tailored to their learning needs and educational levels, and to improve their quality of care for those with dementia.

The effects of a family-centered psychosocial-based nutrition intervention in patients with advanced cancer: the PiCNIC2 pilot randomised controlled trial.

BACKGROUND: Malnutrition in advanced cancer patients is common but limited and inconclusive data exists on the effectiveness of nutrition interventions. Feasibility and acceptability of a novel family-based nutritional psychosocial intervention were established recently. The aims of this present study were to assess the feasibility of undertaking a randomised controlled trial of the latter intervention, to pilot test outcome measures and to explore preliminary outcomes. METHODS: Pilot randomised controlled trial recruiting advanced cancer patients and family caregivers in Australia and Hong Kong. Participants were randomised and assigned to one of two groups, either a family-centered nutritional intervention or the control group receiving usual care only. The intervention provided 2-3 h of direct dietitian contact time with patients and family members over a 4-6-week period. During the intervention, issues with nutrition impact symptoms and food or eating-related psychosocial concerns were addressed through nutrition counselling, with a focus on improving nutrition-related communication between the dyads and setting nutritional goals. Feasibility assessment included recruitment, consent rate, retention rate, and acceptability of assessment tools. Validated nutritional and quality of life self-reported measures were used to collect patient and caregiver outcome data, including the 3-day food diary, the Patient-Generated Subjective Global Assessment Short Form, the Functional Assessment Anorexia/Cachexia scale, Eating-related Distress or Enjoyment, and measures of self-efficacy, carers' distress, anxiety and depression. RESULTS: Seventy-four patients and 54 family caregivers participated in the study. Recruitment was challenging, and for every patient agreeing to participate, 14-31 patients had to be screened. The consent rate was 44% in patients and 55% in caregivers. Only half the participants completed the trial's final assessment. The data showed promise for some patient outcomes in the intervention group, particularly with improvements in eating-related distress (p = 0.046 in the Australian data; p = 0.07 in the Hong Kong data), eating-related enjoyment (p = 0.024, Hong Kong data) and quality of life (p = 0.045, Australian data). Energy and protein intake also increased in a clinically meaningful way. Caregiver data on eating-related distress, anxiety, depression and caregiving burden, however, showed little or no change. CONCLUSIONS: Despite challenges with participant recruitment, the intervention demonstrates good potential to have positive effects on patients' nutritional status and eating-related distress. The results of this trial warrant a larger and fully-powered trial to ascertain the effectiveness of this intervention. TRIAL REGISTRATION: The trial was registered with the Australian & New Zealand Clinical Trials Registry, registration number ACTRN12618001352291 .

A Study of Seven Patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) in Eastern Taiwan: A Case Series with Literature Review.

PURPOSE: CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common cause of heritable vascular dementia. Recognizing the disease before the full-blown clinical features is challenging, so our case series high light clinical characteristics, screening tools and diagnostic process of the patients with CADASIL. CASE REPORT: Our case series reports neurocognitive features, neuroimaging, and exemplary pedigrees of seven patients with genetically confirmed CADASIL, in which six patients presented with dementia and the other one presented with migraine. CONCLUSION: Our report is the single-center experience of our hospital in eastern Taiwan, where access to medical care and genetic test is relatively limited compared to other parts of Taiwan. We had also compared the utility of Davous' CADASIL criteria and the CADASIL scale, and both can be used as sensitive screening tools before genetic tests, especially in the area with limited medical access.

Cervical dystonia incidence and diagnostic delay in a multiethnic population.

BACKGROUND: Current cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized. OBJECTIVES: To determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization. METHODS: We identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration. RESULTS: CD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68). CONCLUSIONS: CD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society.

Barriers to advance care planning: a qualitative study of seriously ill Chinese patients and their families.

BACKGROUND: Advance care planning (ACP) facilitates identification and documentation of patients' treatment preferences. Its goal aligns with that of palliative care - optimizing quality of life of seriously ill patients. However, concepts of ACP and palliative care remain poorly recognized in Chinese population. This study aims at exploring barriers to ACP from perspective of seriously ill patients and their family caregivers. METHODS: This is a qualitative study conducted in a Palliative Day Care Centre of Hong Kong between October 2016 and July 2017. We carried out focus groups and individual interviews for the seriously ill patients and their family caregivers. A semi-structured interview guide was used to explore participants' experiences and attitudes about ACP. Qualitative content analysis was adopted to analyze both manifest content and latent content. RESULTS: A total of 17 patients and 13 family caregivers participated in our study. The qualitative analysis identified four barriers to ACP: 1) limited patients' participation in autonomous decision making, 2) cognitive and emotional barriers to discussion, 3) lack of readiness and awareness of early discussion, and 4) unprepared healthcare professionals and healthcare system. CONCLUSIONS: Participations of seriously ill patients, family caregivers and healthcare workers in ACP initiation are lacking respectively. A series of interventions are necessary to resolve the barriers.

Diagnostic diversity among patients with cognitive complaints: A 3-year follow-up study in a memory clinic.

OBJECTIVES: To describe the distribution and estimate the mortality risks of degenerative dementias and nondegenerative conditions in a memory clinic. METHODS: We enrolled 727 consecutive patients with cognitive complaints who visited the memory clinic in Buddhist Tzu Chi General Hospital during 2013 to 2016. Three main diagnostic groups were defined: pure type dementia, in which only one type of dementia was diagnosed, such as Alzheimer disease (AD), vascular dementia (VaD), Parkinson disease with dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD); mixed type dementia; and nondegenerative conditions. We described the frequency of different diagnoses and employed Cox proportional hazards regression models to examine the mortality risks for each diagnostic group after adjusting for age, sex, education, and cognitive status. All patients alive on or after September 30, 2018, were censored in the analysis. RESULTS: Two-thirds of patients (n = 496, 68.2%) were diagnosed with degenerative dementias. Pure type to mixed type dementia ratio was about 2: 1. AD remained the most common pure dementia subtype, followed by VaD and PDD. Among all nondegenerative conditions, depression/anxiety and subjective cognitive decline were the most common diagnoses. During a mean follow-up of 3.4 years, 150 deaths were documented, and the mortality risk was 61 deaths/1000 person-years. Mortality risks were associated with age, sex, education, and cognitive function at diagnosis but did not differ by diagnostic group. CONCLUSIONS: Clinical diagnoses for patients with cognitive complaints are diverse, and nearly one-third are of nondegenerative conditions. Baseline cognitive function is a stronger predictor for survival than clinical diagnosis.

CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database.

The Comprehensive Antibiotic Resistance Database (CARD; http://arpcard.mcmaster.ca) is a manually curated resource containing high quality reference data on the molecular basis of antimicrobial resistance (AMR), with an emphasis on the genes, proteins and mutations involved in AMR. CARD is ontologically structured, model centric, and spans the breadth of AMR drug classes and resistance mechanisms, including intrinsic, mutation-driven and acquired resistance. It is built upon the Antibiotic Resistance Ontology (ARO), a custom built, interconnected and hierarchical controlled vocabulary allowing advanced data sharing and organization. Its design allows the development of novel genome analysis tools, such as the Resistance Gene Identifier (RGI) for resistome prediction from raw genome sequence. Recent improvements include extensive curation of additional reference sequences and mutations, development of a unique Model Ontology and accompanying AMR detection models to power sequence analysis, new visualization tools, and expansion of the RGI for detection of emergent AMR threats. CARD curation is updated monthly based on an interplay of manual literature curation, computational text mining, and genome analysis.

Unfolding and displaying the influencing factors of advance directives from the stakeholder's perspective: A concept mapping approach.

AIMS: To develop a culturally relevant conceptual map to discover perceptions of a statutory form of advance directive (AD) for Hong Kong Chinese. DESIGN: This was the first study on AD using a concept mapping approach with two phases. METHODS: The data collection of the two phases was conducted from February 2016-February 2017. In Phase I, 96 participants were recruited using purposive sampling. In Phase II, multi-dimensional scaling and hierarchical cluster analysis were used to create a concept map based on quantitative data. RESULTS: The map depicted six clusters of factors affecting the acceptance of AD, with their importance rating in decreasing order: Conditional factor, value system, process of AD, physical and illness factor, personal situation factor, and socio-cultural factor. CONCLUSION: The study adopted a comprehensive approach to unfolding the multi-faceted factors affecting the acceptance of ADs by stakeholders. Strategies targeting the clusters could be developed to facilitate the discussion and completion of AD.

High-throughput detection of RNA processing in bacteria.

BACKGROUND: Understanding the RNA processing of an organism's transcriptome is an essential but challenging step in understanding its biology. Here we investigate with unprecedented detail the transcriptome of Pseudomonas aeruginosa PAO1, a medically important and innately multi-drug resistant bacterium. We systematically mapped RNA cleavage and dephosphorylation sites that result in 5'-monophosphate terminated RNA (pRNA) using monophosphate RNA-Seq (pRNA-Seq). Transcriptional start sites (TSS) were also mapped using differential RNA-Seq (dRNA-Seq) and both datasets were compared to conventional RNA-Seq performed in a variety of growth conditions. RESULTS: The pRNA-Seq library revealed known tRNA, rRNA and transfer-messenger RNA (tmRNA) processing sites, together with previously uncharacterized RNA cleavage events that were found disproportionately near the 5' ends of transcripts associated with basic bacterial functions such as oxidative phosphorylation and purine metabolism. The majority (97%) of the processed mRNAs were cleaved at precise codon positions within defined sequence motifs indicative of distinct endonucleolytic activities. The most abundant of these motifs corresponded closely to an E. coli RNase E site previously established in vitro. Using the dRNA-Seq library, we performed an operon analysis and predicted 3159 potential TSS. A correlation analysis uncovered 105 antiparallel pairs of TSS that were separated by 18 bp from each other and were centered on single palindromic TAT(A/T)ATA motifs (likely - 10 promoter elements), suggesting that, consistent with previous in vitro experimentation, these sites can initiate transcription bi-directionally and may thus provide a novel form of transcriptional regulation. TSS and RNA-Seq analysis allowed us to confirm expression of small non-coding RNAs (ncRNAs), many of which are differentially expressed in swarming and biofilm formation conditions. CONCLUSIONS: This study uses pRNA-Seq, a method that provides a genome-wide survey of RNA processing, to study the bacterium Pseudomonas aeruginosa and discover extensive transcript processing not previously appreciated. We have also gained novel insight into RNA maturation and turnover as well as a potential novel form of transcription regulation. NOTE: All sequence data has been submitted to the NCBI sequence read archive. Accession numbers are as follows: [NCBI sequence read archive: SRX156386, SRX157659, SRX157660, SRX157661, SRX157683 and SRX158075]. The sequence data is viewable using Jbrowse on www.pseudomonas.com .

Cognitive Impairment and Glycemic Control in Elderly Patients Under Health-Care Case Management.

We aim to test whether the association between glucose control and cognitive function still holds true in elderly patients with diabetes mellitus (DM) and Alzheimer disease (AD) under health-care case management. We enrolled 100 patients with DM (mean age: 74.6 years; male: 49%) and 102 patients with AD (mean age: 77.9 years; male: 41.2%) consecutively from the Diabetes Shared Care Program and the memory clinic. These patients were followed up every 3 months with scheduled examinations. Most patients with AD were at early stage and DM was a common comorbidity (n = 42). In the DM group, there were 76 patients with subjective cognitive decline and 19 patients with mild cognitive impairment, but none sought further consultation. After adjusting for age, sex, education, and comorbidity, higher levels of glycated hemoglobin (HbA1C) were not associated with lower Mini-Mental State Examination (MMSE) scores in the DM group (coefficient: 0.03; 95% confidence interval [CI]: -0.44 to 0.50) and lower MMSE scores were not associated with higher HbA1C in the AD group either (coefficient: -0.05; 95% CI: -0.11 to 0.01). When additionally accounting for the variability of HbA1C in the DM group, higher standard deviation of HbA1C was associated with poor clock drawing test scores, but not MMSE. The coexistence of AD-DM was common, but the association between hyperglycemia and cognitive impairment was not seen in patients under regular health monitoring.

PSORTdb: expanding the bacteria and archaea protein subcellular localization database to better reflect diversity in cell envelope structures.

Protein subcellular localization (SCL) is important for understanding protein function, genome annotation, and has practical applications such as identification of potential vaccine components or diagnostic/drug targets. PSORTdb (http://db.psort.org) comprises manually curated SCLs for proteins which have been experimentally verified (ePSORTdb), as well as pre-computed SCL predictions for deduced proteomes from bacterial and archaeal complete genomes available from NCBI (cPSORTdb). We now report PSORTdb 3.0. It features improvements increasing user-friendliness, and further expands both ePSORTdb and cPSORTdb with a focus on improving protein SCL data in cases where it is most difficult-proteins associated with non-classical Gram-positive/Gram-negative/Gram-variable cell envelopes. ePSORTdb data curation was expanded, including adding in additional cell envelope localizations, and incorporating markers for cPSORTdb to automatically computationally identify if new genomes to be analysed fall into certain atypical cell envelope categories (i.e. Deinococcus-Thermus, Thermotogae, Corynebacteriales/Corynebacterineae, including Mycobacteria). The number of predicted proteins in cPSORTdb has increased from 3,700,000 when PSORTdb 2.0 was released to over 13,000,000 currently. PSORTdb 3.0 will be of wider use to researchers studying a greater diversity of monoderm or diderm microbes, including medically, agriculturally and industrially important species that have non-classical outer membranes or other cell envelope features.

Enhanced annotations and features for comparing thousands of Pseudomonas genomes in the Pseudomonas genome database.

The Pseudomonas Genome Database (http://www.pseudomonas.com) is well known for the application of community-based annotation approaches for producing a high-quality Pseudomonas aeruginosa PAO1 genome annotation, and facilitating whole-genome comparative analyses with other Pseudomonas strains. To aid analysis of potentially thousands of complete and draft genome assemblies, this database and analysis platform was upgraded to integrate curated genome annotations and isolate metadata with enhanced tools for larger scale comparative analysis and visualization. Manually curated gene annotations are supplemented with improved computational analyses that help identify putative drug targets and vaccine candidates or assist with evolutionary studies by identifying orthologs, pathogen-associated genes and genomic islands. The database schema has been updated to integrate isolate metadata that will facilitate more powerful analysis of genomes across datasets in the future. We continue to place an emphasis on providing high-quality updates to gene annotations through regular review of the scientific literature and using community-based approaches including a major new Pseudomonas community initiative for the assignment of high-quality gene ontology terms to genes. As we further expand from thousands of genomes, we plan to provide enhancements that will aid data visualization and analysis arising from whole-genome comparative studies including more pan-genome and population-based approaches.

The Initial Symptom and Motor Progression in Spinocerebellar Ataxias.

The aim of this study is to determine whether the initial symptom associates with motor progression in spinocerebellar ataxias (SCAs). SCAs are clinically heterogeneous and the initial presentation may represent different subtypes of SCA with different motor progression. We studied 317 participants with SCAs1, 2, 3, and 6 from the Clinical Research Consortium for SCAs (CRC-SCA) and repeatedly measured the severity of ataxia for 2 years. SCA patients were divided into gait-onset and non-gait-onset (speech, vision, and hand dexterity) groups based on the initial presentation. In addition to demographic comparison, we employed regression models to study ataxia progression in these two groups after adjusting for age, sex, and pathological CAG repeats. The majority of SCA patients had gait abnormality as an initial presentation. The pathological CAG repeat expansions were similar between the gait-onset and non-gait-onset groups. In SCA1, gait-onset group progressed slower than non-gait-onset group, while gait-onset SCA6 group progressed faster than their counterpart. In addition, the disease presented 9 years later for SCA2 gait-onset group than non-gait-onset group. Initial symptoms of SCA3 did not influence age of onset or disease progression. The initial symptom in each SCA has a different influence on age of onset and motor progression. Therefore, gait and non-gait-onset groups of SCAs might represent different subtypes of the diseases.

IslandViewer 3: more flexible, interactive genomic island discovery, visualization and analysis.

IslandViewer (http://pathogenomics.sfu.ca/islandviewer) is a widely used web-based resource for the prediction and analysis of genomic islands (GIs) in bacterial and archaeal genomes. GIs are clusters of genes of probable horizontal origin, and are of high interest since they disproportionately encode genes involved in medically and environmentally important adaptations, including antimicrobial resistance and virulence. We now report a major new release of IslandViewer, since the last release in 2013. IslandViewer 3 incorporates a completely new genome visualization tool, IslandPlot, enabling for the first time interactive genome analysis and gene search capabilities using synchronized circular, horizontal and vertical genome views. In addition, more curated virulence factors and antimicrobial resistance genes have been incorporated, and homologs of these genes identified in closely related genomes using strict filters. Pathogen-associated genes have been re-calculated for all pre-computed complete genomes. For user-uploaded genomes to be analysed, IslandViewer 3 can also now handle incomplete genomes, with an improved queuing system on compute nodes to handle user demand. Overall, IslandViewer 3 represents a significant new version of this GI analysis software, with features that may make it more broadly useful for general microbial genome analysis and visualization.