The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study (ANA-LIS): 5 year results of a Randomized Controlled Trial

PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in subjects diagnosed as primary angle closure suspects (PACS) DESIGN: Prospective, randomized controlled trial PARTICIPANTS: This multi-center, randomized controlled trial (NCT00347178, Clinical trials.gov) enrolled 480 subjects over the age of 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). METHODS: Each subject underwent prophylactic LPI in one randomly selected eye, while the fellow eye served as control. Subjects were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC, defined as presence of peripheral anterior synechiae, and/or intraocular pressure>21 mmHg or acute angle closure [AAC]) or PACG over 5 years. RESULTS: Of the 480 randomized subjects, the majority were Chinese (92.7%) and female (75.8%) with mean age of 62.8±6.9 years. LPI-treated eyes reached endpoint less frequently after five years (24, 5.0%, incidence rate [IR]=11.65 per 1000 eye-years) compared to control eyes (45, 9.4%, IR=21.84 per 1000 eye-years, p=0.001). The adjusted hazards ratio (HR) for progression to PAC was 0.55 (95%CI: 0.37-0.83, p=0.004) in LPI-treated eyes compared to control eyes. Older subjects (per year, HR=1.06, 95%CI: 1.03-1.10, p<0.001) and eyes with higher baseline IOP (per mm Hg, HR=1.35, 95%CI: 1.22-1.50, p<0.0001) were more likely to reach an endpoint. The number needed to treat in order to prevent an endpoint was 22 (95%CI: 12.8-57.5). CONCLUSIONS: In subjects with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI had significantly fewer endpoints compared to control eyes over 5 years. However, the overall incidence of PAC or PACG was low

Residual angle closure one year after laser peripheral iridotomy in primary angle closure suspects

PURPOSE: To determine the incidence and baseline clinical and anterior segment optical coherence tomography (AS-OCT) predictors associated with residual angle closure as assessed by gonioscopy 1 year after laser peripheral iridotomy (LPI) in primary angle closure suspects (PACS). DESIGN: Sub-analysis of randomized controlled trial data METHODS: AS-OCT images (Visante, Carl Zeiss Meditec, Dublin, CA) from 181 PACS subjects ≥ 50 years of age, were analyzed using customized software, prior to, and 1 year after LPI. Other parameters assessed were intraocular pressure (IOP) and axial length (Axl). Residual angle closure was defined as the inability to see the posterior trabecular meshwork for at least 2 quadrants on gonioscopy after LPI. Multivariate regression analysis determined the baseline predictors of residual angle closure 1 year after LPI. RESULTS: The mean age of participants was 62.4 (SD 9.9) years. The majority were female (137, 75.7%) and Chinese 174, 96.1%). At 1 year post LPI, 148 (81.8%) subjects had gonioscopic residual angle closure. Univariate analysis showed that baseline Axl, anterior chamber area, anterior chamber volume, angle opening distance at 750 microns from the scleral spur and angle recess area were smaller while baseline lens vault and iris curvature were larger in residual angle closure subjects (all p80% of PACS had gonioscopic residual angle closure. Greater baseline iris volume and higher IOP at baseline are independent risk factors for residual gonioscopic angle closure

A clinical diagnostic model for predicting influenza among young adult military personnel with febrile respiratory illness in Singapore

10.1371/journal.pone.0017468PLoS ONE63

Evaluation of bleach-sedimentation for sterilising and concentrating Mycobacterium tuberculosis in sputum specimens

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Bleach-sedimentation may improve microscopy for diagnosing tuberculosis by sterilising sputum and concentrating Mycobacterium tuberculosis. We studied gravity bleach-sedimentation effects on safety, sensitivity, speed and reliability of smear-microscopy. Methods This blinded, controlled study used sputum specimens (n = 72) from tuberculosis patients. Bleach concentrations and exposure times required to sterilise sputum (n = 31) were determined. In the light of these results, the performance of 5 gravity bleach-sedimentation techniques that sterilise sputum specimens (n = 16) were compared. The best-performing of these bleach-sedimentation techniques involved adding 1 volume of 5% bleach to 1 volume of sputum, shaking for 10-minutes, diluting in 8 volumes distilled water and sedimenting overnight before microscopy. This technique was further evaluated by comparing numbers of visible acid-fast bacilli, slide-reading speed and reliability for triplicate smears before versus after bleach-sedimentation of sputum specimens (n = 25). Triplicate smears were made to increase precision and were stained using the Ziehl-Neelsen method. Results M. tuberculosis in sputum was successfully sterilised by adding equal volumes of 15% bleach for 1-minute, 6% for 5-minutes or 3% for 20-minutes. Bleach-sedimentation significantly decreased the number of acid-fast bacilli visualised compared with conventional smears (geometric mean of acid-fast bacilli per 100 microscopy fields 166, 95%CI 68-406, versus 346, 95%CI 139-862, respectively; p = 0.02). Bleach-sedimentation diluted paucibacillary specimens less than specimens with higher concentrations of visible acid-fast bacilli (p = 0.02). Smears made from bleach-sedimented sputum were read more rapidly than conventional smears (9.6 versus 11.2 minutes, respectively, p = 0.03). Counting conventional acid-fast bacilli had high reliability (inter-observer agreement, r = 0.991) that was significantly reduced (p = 0.03) by bleach-sedimentation (to r = 0.707) because occasional strongly positive bleach-sedimented smears were misread as negative. Conclusions Gravity bleach-sedimentation improved laboratory safety by sterilising sputum but decreased the concentration of acid-fast bacilli visible on microscopy, especially for sputum specimens containing high concentrations of M. tuberculosis. Bleach-sedimentation allowed examination of more of each specimen in the time available but decreased the inter-observer reliability with which slides were read. Thus bleach-sedimentation effects vary depending upon specimen characteristics and whether microscopy was done for a specified time, or until a specified number of microscopy fields had been read. These findings provide an explanation for the contradictory results of previous studies.Peer Reviewe

The Role of Histone H4 Biotinylation in the Structure of Nucleosomes

Background: Post-translational modifications of histones play important roles in regulating nucleosome structure and gene transcription. It has been shown that biotinylation of histone H4 at lysine-12 in histone H4 (K12Bio-H4) is associated with repression of a number of genes. We hypothesized that biotinylation modifies the physical structure of nucleosomes, and that biotin-induced conformational changes contribute to gene silencing associated with histone biotinylation. Methodology/Principal Findings: To test this hypothesis we used atomic force microscopy to directly analyze structures of nucleosomes formed with biotin-modified and non-modified H4. The analysis of the AFM images revealed a 13% increase in the length of DNA wrapped around the histone core in nucleosomes with biotinylated H4. This statistically significant (p,0.001) difference between native and biotinylated nucleosomes corresponds to adding approximately 20 bp to the classical 147 bp length of nucleosomal DNA. Conclusions/Significance: The increase in nucleosomal DNA length is predicted to stabilize the association of DNA with histones and therefore to prevent nucleosomes from unwrapping. This provides a mechanistic explanation for the gene silencing associated with K12Bio-H4. The proposed single-molecule AFM approach will be instrumental for studying the effects of various epigenetic modifications of nucleosomes, in addition to biotinylation

SHP-2 Promotes the Maturation of Oligodendrocyte Precursor Cells Through Akt and ERK1/2 Signaling In Vitro

Background: Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs), which are responsible for myelination. Myelin is essential for saltatory nerve conduction in the vertebrate nervous system. However, the molecular mechanisms of maturation and myelination by oligodendrocytes remain elusive. Methods and Findings: In the present study, we showed that maturation of oligodendrocytes was attenuated by sodium orthovanadate (a comprehensive inhibitor of tyrosine phosphatases) and PTPi IV (a specific inhibitor of SHP-2). It is also found that SHP-2 was persistently expressed during maturation process of OPCs. Down-regulation of endogenous SHP-2 led to impairment of oligodendrocytes maturation and this effect was triiodo-L-thyronine (T3) dependent. Furthermore, overexpression of SHP-2 was shown to promote maturation of oligodendrocytes. Finally, it has been identified that SHP-2 was involved in activation of Akt and extracellular-regulated kinases 1 and 2 (ERK1/2) induced by T3 in oligodendrocytes

Season of Sampling and Season of Birth Influence Serotonin Metabolite Levels in Human Cerebrospinal Fluid

BACKGROUND: Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. METHODOLOGY/PRINCIPAL FINDINGS: Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050), with predicted maximum (PC(max)) and minimum (PC(min)) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PC(max) = 172 and PC(min) = 126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. CONCLUSION: In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall