Agar and agarose have wide applications in food and pharmaceutical industries. Knowledge on the genome of red seaweeds that produce them is still lacking. To fill the gap in genome analyses of these red algae, we have sequenced the nuclear and organellar genomes of an agarophyte, Gracilaria changii. The partial nuclear genome sequence of G. changii has a total length of 35.8Mb with 10,912 predicted protein coding sequences. Only 39.4% predicted proteins were found to have significant matches to protein sequences in SwissProt. The chloroplast genome of G. changii is 183,855bp with a total of 201 open reading frames (ORFs), 29 tRNAs and 3 rRNAs predicted. Five genes: ssrA, leuC and leuD CP76_p173 (orf139) and pbsA were absent in the chloroplast genome of G. changii. The genome information is valuable in accelerating functional studies of individual genes and resolving evolutionary relationship of red seaweeds.
Seaweeds survive in marine waters with high sulfate concentration compared to those living at freshwater habitats. The cell wall polymer of Gracilaria spp. which supplies more than 50% of the world agar is heavily sulfated. Since sulfation reduces the agar quality, it is interesting to investigate the effects of sulfate deprivation on the sulfate contents of seaweed and agar, as well as the metabolic pathways of these seaweeds. In this study, two agarophytes G. changii and G. salicornia were treated under sulfate deprivation for 5 days. The sulfate contents in the seaweed/agar were generally lower in sulfate-deprivated samples compared to those in the controls, but the differences were only statistically significant for seaweed sample of G. changii and agar sample of G. salicornia. RNA sequencing (RNA-Seq) of sulfate-deprivated and untreated seaweed samples revealed 1,292 and 3,439 differentially expressed genes (DEGs; ≥1.5-fold) in sulfate-deprivated G. changii and G. salicornia, respectively, compared to their respective controls. Among the annotated DEGs were genes involved in putative agar biosynthesis, sulfur metabolism, metabolism of sulfur-containing amino acids, carbon metabolism and oxidative stress. These findings shed light on the sulfate deprivation responses in agarophytes and help to identify candidate genes involved in agar biosynthesis.
BACKGROUND: Tuberculosis (TB) is generally well controlled in Malaysia, but remains an important problem in the nation's eastern states. In order to better understand factors contributing to high TB rates in the eastern state of Sabah, our aims were to describe characteristics of patients with TB at a large outpatient clinic, and determine the prevalence of HIV co-infection. Additionally, we sought to test sensitivity and specificity of the locally-available point-of-care HIV test kits.
METHODS: We enrolled consenting adults with smear-positive pulmonary TB for a 2-year period at Luyang Clinic, Kota Kinabalu, Malaysia. Participants were questioned about ethnicity, smoking, prior TB, disease duration, symptoms and comorbidities. Chest radiographs were scored using a previously devised tool. HIV was tested after counselling using 2 point-of-care tests for each patient: the test routinely in use at the TB clinic (either Advanced Quality™ Rapid Anti-HIV 1&2, FACTS anti-HIV 1/2 RAPID or HIV (1 + 2) Antibody Colloidal Gold), and a comparator test (Abbott Determine™ HIV-1/2, Inverness Medical). Positive tests were confirmed by enzyme immunoassay (EIA), particle agglutination and line immunoassay.
RESULTS: 176 participants were enrolled; 59 (33.5%) were non-Malaysians and 104 (59.1%) were male. Smoking rates were high (81/104 males, 77.9%), most had cavitary disease (51/145, 64.8%), and 81/176 (46.0%) had haemoptysis. The median period of symptoms prior to treatment onset was 8 weeks. Diabetes was present in 12. People with diabetes or other comorbidities had less severe TB, suggesting different healthcare seeking behaviours in this group. All participants consented to HIV testing: three (1.7%) were positive according to Determine™ and EIA, but one of these tested negative on the point-of-care test available at the clinic (Advanced Quality™ Rapid Anti-HIV 1&2). The low number of positive tests and changes in locally-available test type meant that accurate estimates of sensitivity and specificity were not possible.
CONCLUSION: Patients had advanced disease at diagnosis, long diagnostic delays, low HIV co-infection rates, high smoking rates among males, and migrants may be over-represented. These findings provide important insights to guide local TB control efforts. Caution is required in using some point-of-care HIV tests, and ongoing quality control measures are of major importance.
Study site: Klinik Kesihatan Luyang (Tuberculosis Clinic), Kota Kinabalu, Sabah, Malaysia,
Agar is a jelly-like biopolymer synthesized by many red seaweeds as their major cell wall component. Due to its excellent rheological properties, it has been exploited commercially for applications in food, cosmetic, pharmaceutical, biomedical and biotechnology industries. Despite its multiple uses, the biosynthesis of this phycocolloid is not fully understood. The current knowledge on agar biosynthesis is inferred from plant biochemistry and putative pathways for ulvan and alginate biosynthesis in green and brown seaweeds, respectively. In this review, the gaps in our current knowledge on agar biosynthetic pathway are discussed, focusing on the biosynthesis of agar precursors, elongation of agar polysaccharide chain and side chain modification. The development of molecular markers for the screening of desired seaweeds for industrial exploitation is also discussed.
Document classification aims to assign one or more classes to a document for ease of management by understanding the content of a document. Hierarchical attention network (HAN) has been showed effective to classify documents that are ambiguous. HAN parses information-intense documents into slices (i.e., words and sentences) such that each slice can be learned separately and in parallel before assigning the classes. However, introducing hierarchical attention approach leads to the redundancy of training parameters which is prone to overfitting. To mitigate the concern of overfitting, we propose a variant of hierarchical attention network using adversarial and virtual adversarial perturbations in 1) word representation, 2) sentence representation and 3) both word and sentence representations. The proposed variant is tested on eight publicly available datasets. The results show that the proposed variant outperforms the hierarchical attention network with and without using random perturbation. More importantly, the proposed variant achieves state-of-the-art performance on multiple benchmark datasets. Visualizations and analysis are provided to show that perturbation can effectively alleviate the overfitting issue and improve the performance of hierarchical attention network.
OBJECTIVES: To determine treatment outcomes and associated predictors of all patients registered in 2012 with the Malaysian National Tuberculosis (TB) Surveillance Registry.
METHODS: Sociodemographic and clinical data were analysed. Unfavourable outcomes included treatment failure, transferred out and lost to follow-up, treatment defaulters, those not evaluated and all-cause mortality.
RESULTS: In total, 21 582 patients were registered. The mean age was 42.36 ± 17.77 years, and 14.2% were non-Malaysians. The majority were new cases (93.6%). One fifth (21.5%) had unfavourable outcomes; of these, 46% died, 49% transferred out or defaulted and 1% failed treatment. Predictors of unfavourable outcomes were older age, male sex, foreign citizenship, lower education, no bacille Calmette-Guérin (BCG) vaccination scar, treatment in tertiary settings, smoking, previous anti-tuberculosis treatment, human immunodeficiency virus infection, not receiving directly observed treatment, advanced chest radiography findings, multidrug-resistant TB (MDR-TB) and extra-pulmonary TB. For all-cause mortality, predictors were similar except for rural dwelling and nationality (higher mortality among locals). Absence of BCG scar, previous treatment for TB and MDR-TB were not found to be predictors of all-cause mortality. Indigenous populations in East Malaysia had lower rates of unfavourable treatment outcomes.
CONCLUSIONS: One fifth of TB patients had unfavourable outcomes. Intervention strategies should target those at increased risk of unfavourable outcomes and all-cause mortality.
This study aimed to develop an intervention to reduce medical errors and to determine if the intervention can reduce medical errors in public funded primary care clinics. A controlled interventional trial was conducted in 12 conveniently selected primary care clinics. Random samples of outpatient medical records were selected and reviewed by family physicians for documentation, diagnostic, and management errors at baseline and 3 months post intervention. The intervention package comprised educational training, structured process change, review methods, and patient education. A significant reduction was found in overall documentation error rates between intervention (Pre 98.3% [CI 97.1-99.6]; Post 76.1% [CI 68.1-84.1]) and control groups (Pre 97.4% [CI 95.1-99.8]; Post 89.5% [85.3-93.6]). Within the intervention group, overall management errors reduced from 54.0% (CI 49.9-58.0) to 36.6% (CI 30.2-43.1) and medication error from 43.2% (CI 39.2-47.1) to 25.2% (CI 19.9-30.5). This low-cost intervention was useful to reduce medical errors in resource-constrained settings.
Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results.
Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study.
Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5-9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM.
Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB.
Study site: Tuberculosis clinic, Klinik Kesihatan Luyang, Kota Kinabalu, Sabah, Malaysia
Patient safety is vital in patient care. There is a lack of studies on medical errors in primary care settings. The aim of the study is to determine the extent of diagnostic inaccuracies and management errors in public funded primary care clinics.
BACKGROUND: Vitamin D deficiency (low plasma 25-hydroxyvitamin D [25D] concentration) is often reported in tuberculosis. Adjunctive vitamin D has been tested for its potential to improve treatment outcomes, but has proven largely ineffective. To better understand vitamin D in tuberculosis, we investigated determinants of 25D and its immunologically active form, 1,25-dihydroxyvitamin D (1,25D), their inter-relationship in tuberculosis, longitudinal changes and association with outcome.
METHODS: In a prospective observational study of adults with smear-positive pulmonary tuberculosis in Sabah, Malaysia, we measured serial 25D, 1,25D, vitamin D-binding protein (VDBP), albumin, calcium, parathyroid hormone, chest x-ray, week 8 sputum smear/culture and end-of-treatment outcome. Healthy control subjects were enrolled for comparison.
RESULTS: 1,25D was elevated in 172 adults with tuberculosis (mean 229.0 pmol/L, 95% confidence interval: 215.4 - 242.6) compared with 95 controls (153.9, 138.4-169.4, p