Are we making good use of our public resources? The false-positive rate of screening by fundus photography for diabetic macular oedema.

INTRODUCTION: A large proportion of patients diagnosed with diabetic maculopathy using fundus photography and hence referred to specialist clinics following the current screening guidelines adopted in Hong Kong and United Kingdom are found to be false-positive, implying that they did not have macular oedema. This study aimed to evaluate the false-positive rate of diabetic maculopathy screening using the objective optical coherence tomography scan. METHODS: This was a cross-sectional observational study. Consecutive diabetic patients from the Hong Kong West Cluster Diabetic Retinopathy Screening Programme with fundus photographs graded R1M1 were recruited between October 2011 and June 2013. Spectral-domain optical coherence tomography imaging was performed. Central macular thickness of ≥300 µm and/or the presence of optical coherence tomography signs of diabetic macular oedema were used to define the presence of diabetic macular oedema. Patients with conditions other than diabetes that might affect macular thickness were excluded. The mean central macular thickness in various subgroups of R1M1 patients was calculated and the proportion of subjects with central macular thickness of ≥300 µm was used to assess the false-positive rate of this screening strategy. RESULTS: A total of 491 patients were recruited during the study period. Of the 352 who were eligible for analysis, 44.0%, 17.0%, and 38.9% were graded as M1 due to the presence of foveal 'haemorrhages', 'exudates', or 'haemorrhages and exudates', respectively. The mean (±standard deviation) central macular thickness was 265.1±55.4 µm. Only 13.4% (95% confidence interval, 9.8%-17.0%) of eyes had a central macular thickness of ≥300 µm, and 42.9% (95% confidence interval, 37.7%-48.1%) of eyes had at least one optical coherence tomography sign of diabetic macular oedema. For patients with retinal haemorrhages only, 9.0% (95% confidence interval, 4.5%-13.5%) had a central macular thickness of ≥300 µm; 23.2% (95% confidence interval, 16.6%-29.9%) had at least one optical coherence tomography sign of diabetic macular oedema. The false-positive rate of the current screening strategy for diabetic macular oedema was 86.6%. CONCLUSION: The high false-positive rate of the current diabetic macular oedema screening adopted by the United Kingdom and Hong Kong may lead to unnecessary psychological stress for patients and place a financial burden on the health care system. A better way of screening is urgently needed. Performing additional spectral-domain optical coherence tomography scans on selected patients fulfils this need.

Decreasing efficacy of repeated intravitreal triamcinolone injections in diabetic macular oedema.

BACKGROUND/AIM: Intravitreal triamcinolone (IVTA) results in transient improvements in diabetic macular oedema (DMO), necessitating repeated injections. The authors report a case series of 10 eyes of 10 patients with DMO, who received a repeat injection of 4 mg IVTA, at least 26 weeks after the first injection of the same dose. METHOD: Pre-injection and at 2, 4, 9, and 17 weeks post-injection, best corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography, after the first and repeat injections, were compared using paired t test. Side effects were monitored. RESULTS: BCVA, CFT, intraocular pressure (IOP), and cataract scores were not significantly different before initial and repeat injections (given at 32.5 (SD 3.5) weeks after the first injection). Transient improvements of BCVA and CFT were achieved after both injections. However, after the repeat injection, the BCVA was significantly worse at all time points (p<0.05) and so were the best achieved CFT and the CFT at 4 weeks post-injection (p = 0.034 and 0.011 respectively), compared with the initial injection. Post-injection maximum IOPs and increase in cataract scores were not significantly different between the two injections. CONCLUSION: A repeat injection of 4 mg of IVTA may not be as effective as an initial injection for the treatment of DMO.

A 12-year review on the aetiology and surgical outcomes of paediatric rhegmatogenous retinal detachments in Hong Kong.

PURPOSE: To evaluate the aetiology, clinical features, and surgical outcomes of paediatric rhegmatogenous retinal detachments (RRD) in Hong Kong.Patients and methodsThis is a retrospective consecutive case series of all patients aged 18 or under who underwent primary retinal detachment repair in the Hong Kong Eye Hospital from January 2000 to December 2012.ResultsForty-nine eyes of 47 patients were included. The mean age was 14, and the mean follow-up duration was 6.2 years. The most common aetiology for RRD was idiopathic (28.6%), followed by high myopia (24.5%), atopic dermatitis (AD) (18.4%), congenital and developmental abnormalities (16.3%), trauma (8.2%), and intraocular inflammation (4.1%). The mean preoperative visual acuity was LogMAR 1.0±0.8 (Snellen equivalent 6/60). The primary anatomical success rate in this series was 65.3%, and the final anatomical success rate was 85.7%. The mean postoperative visual acuity was LogMAR 0.9±1.2 (Snellen equivalent 6/48). Patients with congenital and developmental abnormalities or AD had worse anatomical and functional outcomes than patients who had no predisposing factor or high myopia. CONCLUSIONS: The primary and overall anatomical success rates in our series were comparable with existing literature. High myopia is the most commonly identifiable risk factor in Hong Kong and AD is associated with a higher re-detachment rates and a poor visual outcome.

Advances of optical coherence tomography in myopia and pathologic myopia.

The natural course of high-axial myopia is variable and the development of pathologic myopia is not fully understood. Advancements in optical coherence tomography (OCT) technology have revealed peculiar intraocular structures in highly myopic eyes and unprecedented pathologies that cause visual impairment. New OCT findings include posterior precortical vitreous pocket and precursor stages of posterior vitreous detachment; peripapillary intrachoroidal cavitation; morphological patterns of scleral inner curvature and dome-shaped macula. Swept source OCT is capable of imaging deeper layers in the posterior pole for investigation of optic nerve pits, stretched and thinned lamina cribrosa, elongated dural attachment at posterior scleral canal, and enlargement of retrobulbar subarachnoid spaces. This has therefore enabled further evaluation of various visual field defects in high myopia and the pathogenesis of glaucomatous optic neuropathy. OCT has many potential clinical uses in managing visual impairing conditions in pathologic myopia. Understanding how retinal nerve fibers are redistributed in axial elongation will allow the development of auto-segmentation software for diagnosis and monitoring progression of glaucoma. OCT is indispensable in the diagnosis of various conditions associated with myopic traction maculopathy and monitoring of post-surgical outcomes. In addition, OCT is commonly used in the multimodal imaging assessment of myopic choroidal neovascularization. Biometry and topography of the retinal layers and choroid will soon be validated for the classification of myopic maculopathy for utilization in epidemiological studies as well as clinical trials.

One world one burn rehabilitation standard.

According to the World Health Organization (WHO) burns are a huge global health problem resulting in death and devastation to those who survive large burns as they are faced with significant functional limitations that prevent purposeful and productive living. Members of the International Society for Burn Injuries (ISBI) Rehabilitation Committee conducted a needs assessment survey in order to characterize how burn rehabilitation is implemented worldwide and how the international burn rehabilitation community can help improve burn rehabilitation in identified geographic locations which need assistance in rehabilitating burn survivors successfully. The results of this survey indicated that poor and in some cases resource limited environments (RLEs) around the world seem to lack the financial, educational and material resources to conduct burn rehabilitation successfully. It appears that there are vast discrepancies in the areas of education, training and capacity to conduct research to improve the care of burn survivors as evidenced by the variation in responses between the RLEs and developed countries around the globe. In some cases, the problem is not knowledge, skill and ability to practice burn rehabilitation, but rather having the resources to do so due to financial difficulties.

alpha-Latrotoxin releases calcium in frog motor nerve terminals.

alpha-Latrotoxin (alpha-LTX) is a neurotoxin that accelerates spontaneous exocytosis independently of extracellular Ca(2+). Although alpha-LTX increases spontaneous transmitter release at synapses, the mechanism is unknown. We tested the hypothesis that alpha-LTX causes transmitter release by mobilizing intracellular Ca(2+) in frog motor nerve terminals. Transmitter release was measured electrophysiologically and with the vesicle marker FM1-43; presynaptic ion concentration dynamics were measured with fluorescent ion-imaging techniques. We report that alpha-LTX increases transmitter release after release of a physiologically relevant concentration of intracellular Ca(2+). Neither the blockade of Ca(2+) release nor the depletion of Ca(2+) from endoplasmic reticulum affected Ca(2+) signals produced by alpha-LTX. The Ca(2+) source is likely to be mitochondria, because the effects on Ca(2+) mobilization of CCCP (which depletes mitochondrial Ca(2+)) and of alpha-LTX are mutually occlusive. The release of mitochondrial Ca(2+) is partially attributable to an increase in intracellular Na(+), suggesting that the mitochondrial Na(+)/Ca(2+) exchanger is activated. Effects of alpha-LTX were not blocked when Ca(2+) increases were reduced greatly in saline lacking both Na(+) and Ca(2+) and by application of intracellular Ca(2+) chelators. Therefore, although increases in intracellular Ca(2+) may facilitate the effects of alpha-LTX on transmitter release, these increases do not appear to be necessary. The results show that investigations of Ca(2+)-independent alpha-LTX mechanisms or uses of alpha-LTX to probe exocytosis mechanisms would be complicated by the release of intracellular Ca(2+), which itself can trigger exocytosis.

Evaluation of fluorinated indole derivatives for electron-capture negative ionization mass spectrometry: application to the measurement of endogenous 5-methoxyindole-3-acetic acid in rat.

A series of N-trifluoroacetyl/pentafluoropropionyl-O-trifluoroethyl/ pentafluoropropyl/heptafluorobutyl ester derivatives of 5-methoxyindole-3-acetic acid (5MIAA) were synthesized. Under electron-capture negative ionization conditions, the N-trifluoroacetyl derivatives were found to yield relatively abundant, analyte-specific M-. molecular ions and [M-HF]-., [M-HF-CF2CO]-. and [M-CF3CO]- fragment ions, while the N-pentafluoropropionyl derivatives yielded predominantly the reagent-specific pentafluoroacylium C2F5CO- ion. 5-[2H3]Methoxyindole-3-acetic acid was prepared in high yield by a new synthetic procedure and used as the internal standard in subsequent gas chromatographic/mass spectrometric analysis. Using the N-trifluoroacetyl-O-pentafluoropropyl ester derivative, femtomole to low picomole per gland/organ per g ml-1 levels of endogenous 5MIAA were identified and determined in the rat pineal gland, retina, whole brain and serum.

Identification and diurnal studies of pineal and serum 5-methoxytryptamine in the rat and quail.

Picomole to femtomole per gland/ml levels of 5-methoxytryptamine (5MT) in the pineal gland and serum of the rat and quail were determined, in the absence of a monoamine oxidase inhibitor, by using the ultra-sensitive technique of capillary column gas chromatography/electron-capture negative ion chemical ionization mass spectrometry. Diurnal rhythms of pineal 5MT with high levels at mid-light and low levels at mid-dark were found in both species, while serum 5MT levels showed less or no diurnal variations. The definitive presence of 5MT in the pineal gland and blood circulation provides further evidence that it is potentially a neurohormone. Whether 5MT is implicated in the photoperiodic responses and/or other physiological functions of animals, however, remains to be investigated.

Separation of N-nitrosoamino acids by C18 reversed-phase ion-pair high-performance liquid chromatography and compatible detection by electrospray ionization mass spectrometry.

Four non-volatile N-nitrosoamino acids, namely N-nitrososarcosine, N-nitrosoproline, N-nitrosothiazolidine-4-carboxylic acid and N-nitroso-2-methyl-thiazolidine-4-carboxylic acid were separated by C18 reversed-phase ion-pair high-performance liquid chromatography (HPLC) using 1.4 mM C16-cetyltrimethylammonium chloride in methanol-water-acetonitrile (60:35:5, v/v) as the mobile phase. The N-nitrosoamino acids were sensitively detected by negative electrospray ionization mass spectrometry (ESI-MS) in the form of the deprotonated carboxylate anion, [M-H]-. Compatibility problems associated with HPLC separation and ESI-MS detection, such as formation of solvent cluster ions and the effects of co-eluting anions of the ion-pairing reagent, were systematically investigated. The optimized experimental conditions for separation and detection of N-nitrosoamino acids were described.

Effects of culture with TNF-alpha, TGF-beta and insulin on sulphotransferase (SULT 1A1 and 1A3) activity in human colon and neuronal cell lines.

The aim of the study was to determine whether the expression of sulphotransferase enzymes could be affected by the presence of cytokines or peptide hormones. The effects of cytokines (TNF-alpha and TGF-beta) and insulin on sulphotransferase (SULT 1A1 and 1A3) activity were studied in a human neuronal cell line (SK-N-SH) and a human gastrointestinal tract cell line (HT-29). Cells were cultured with varying concentrations of TNF-alpha, TGF-beta or insulin for 24 h; the SULT 1A1 isoform in the 2 cell lines showed different optimal substrate concentrations. There were no direct effects of cytokines on enzyme activity. Culture with TNF-alpha increased activity of both SULT 1A1 and 1A3 in the HT-29 cells; TGF-beta also increased activities of both isoforms but to a lesser extent; insulin increased activity of SULT 1A1 only. The cytokines and insulin had relatively little effect on sulphotransferase activity in the neuronal cell line. These results suggest that, unlike neuronal cells, gastrointestinal cells may respond to physiological states by altering sulphotransferase activity. As certain substrates such as diet-derived heterocyclic amines are bioactivated by sulphation to produce carcinogenic metabolites this may be a factor in the increased incidence of colorectal cancer in patients with inflammatory bowel disease or diabetes.

Chemical characteristics of aerosols at coastal station in Hong Kong. II. Environmental behavior of trace elements during the April 1995 to April 1996.

An one-year of sampling aerosol program was carried out during the period of April 1995 to April 1996 at coastal region, Cape D'Aguilar, in Hong Kong. The trace element composition of aerosol particles (TSP and PM10) were measured and analyzed by using the Instrumental Neutron Activation Analysis (INAA) and Inductive Couple Plasma-Mass Spectrometry (ICP-MS) techniques. The results showed that the polluted elements such as: V, Zn, As, Pb, Cd, Sb, I, Se, Bi, with high enrichment factor (E. F) values, are derived from anthropogenic sources, while Sc, Al, Fe, Mn, Sm, La, Sr are less than 10 in E. F, these elements are related the crust and soil. The concentration of the trace elements are present seasonal variation i.e. summer low and winter high, whereas the V or noncrustal V (V*) present summer high and winter low, this phenomenon might be explained by local or regional oil combustion sources. Use three type of elemental ratio, e.g. La/Sm, Mn*/V* and Bi/Al indicate that both TSP and PM10 of La/Sm ratios are mainly related to soil and dust, Mn*/V* are probably represent fossil combustion and Bi/Al are possibly associated with refuse incineration, ferromanganese alloys and aluminum production. The varimax rotation factor analysis for trace elements was performed. By means of the absolute principal component analysis (APCA) and multiple regression, the contribution of trace elements to possible sources and overall means of trace elements were estimated. The results showed that the present station is impacted by the anthropogenic species, although the quantities are different during the summertime and wintertime.

Detection of changes of scar thickness under mechanical loading using ultrasonic measurement.

The intervention of pressure therapy on management of hypertrophic scar (HS) after burn is based on the theoretical assumption that the mechanical force added onto the scar tissue will reduce the growth of myofibroblasts which create the collagen clusters and the interstitial space, and to realign fibrous tissues, thus reducing the thickness of HS. In this experimental study, a high frequency ultrasound imaging system (12 MHz) was applied to measure the real time changes of thickness of the post burn HS under a mechanical loading system with similar pressure generated to the scar tissue. The validity of the ultrasound system in measurement of the changes of scar thickness underneath the tissue was tested on the porcine skin in vitro followed by measurement of human skin in vivo. Results showed that the ultrasound measurement of thickness had both good validity (r(2)=0.98, p<0.0001) and good intra-rater reliability (ICC=0.89). Then, the system was used to test the thickness of 14 human HS samples in vivo among 7 subjects. External loading force with similar pressure range (10-45 mmHg) was then applied to these scar samples via ultrasound probe with rectangular contacting area at 4 cm(2) and each loading force was maintained unchange for 2 min over the scar tissue. The real time scar thickness was documented. Results showed that the mean scar thickness was found to be significantly decreased when the loading force applied was increased from 5 to 35 mmHg (with 10 mmHg interval) (p<0.001). A significant negative correlation between the pressure level and scar thickness was observed (r(2)=0.96, p=0.005). The decline of thickness was found more significant between 0 mmHg and 15 mmHg. The findings were in line with the postulate that pressure therapy is effective in reducing the thickness of HS. A long term followup study should be administered to determine the prolonged effect of pressure intervention.

The effect of a computerized visual perception and visual-motor integration training program on improving Chinese handwriting of children with handwriting difficulties.

This study aimed to investigate the effect of a computerized visual perception and visual-motor integration training program to enhance Chinese handwriting performance among children with learning difficulties, particularly those with handwriting problems. Participants were 26 primary-one children who were assessed by educational psychologists and occupational therapists to have handwriting difficulties. They were matched according to their age and then randomly assigned into either the control group or the experimental group. Subjects in the experimental group (n=13) would receive eight sessions of computerized visual perception and visual-motor integration training together with a home training program while those in the control group (n=13) would only receive conventional handwriting training by teachers, which focused mainly on remedial handwriting exercises. Results from repeated measure ANOVA revealed that children in the experimental group showed improvements in their visual perception skills as well as in their handwriting time. Both the "On Paper" time and "In Air" time of this group were improved when compared to the control group. However, no significant differences were found in visual-motor integration skill and handwriting legibility between the two groups after the intervention. This computerized training program focusing on visual perception and visual-motor integration training appeared to be effective in enhancing the handwriting time among children with handwriting difficulties. However, the training program did not seem to improve the legibility of children.

Surgically induced astigmatism in phacoemulsification, pars plana vitrectomy, and combined phacoemulsification and vitrectomy: a comparative study.

PURPOSE: To study the surgically induced astigmatism (SIA) in combined phacoemulsification and vitrectomy, and compare with that when either procedure is performed alone. METHODS: This is a prospective comparative interventional trial comprising of 60 eyes of 60 consecutive patients with cataract and/or vitreo-retinal pathology. They were divided equally into three groups based on the type of procedure: Group A, phacoemulsification alone group, using a 3.0-3.2 mm wide unsutured sclero-corneal tunnel incision at 1.0 mm post-limbus at 10 o'clock; Group B, par plana vitrectomy alone group, using three sclerotomies at 3.5 mm post-limbus at 2, 8, and 10 o'clock (right eye) or at 2, 4, and 10 o'clock (left eye) positions; and Group C, combined phacoemulsification and pars plana vitrectomy group. Main outcome measures were the amplitude (K-induced) and the axis of SIA calculated by rectangular coordinate method using the Holladay-Cravy-Koch formula. RESULTS: The mean K-induced amplitudes were 0.19+/-0.14 D, 0.17+/-0.11 D, and 0.23+/-0.19 D for groups A, B, and C, respectively. The range of K-induced amplitudes for the entire cohort was 0.00-0.77 D. No overall statistically significant differences in the pre- and postoperative topographic astigmatism amplitudes and the K-induced between groups A, B, and C were found (all P>0.05). Minor shifts, of doubtful clinical significance, in the axes of SIA were present. CONCLUSIONS: Combined phacoemulsification and pars plana vitrectomy does not induce significant astigmatic change per se, and its amount is similar to that when either procedure is performed alone.

The effect of a job placement and support program for workers with musculoskeletal injuries: a randomized control trial (RCT) study.

BACKGROUND: This is a randomized clinical trial (RCT) to investigate the efficacy of a job placement and support program designed for workers with musculoskeletal injuries and having difficulties in resuming the work role. The program was planned to help injured workers to successfully return to work (RTW) by overcoming the difficulties and problems during the process of job seeking and sustaining a job using a case management approach. METHODOLOGY: A total of 66 injured workers were recruited and randomly assigned into the job placement and support group (PS group) or the self-placement group (SP group). A three-week job placement and support program was given to subjects in the PS group while subjects in the control group (SP group) were only given advice on job placement at a workers' health center. The PS program was comprised of an individual interview, vocational counseling, job preparation training, and assisted placement using the case management approach. The Chinese Lam Assessment of Stages of Employment Readiness (C-LASER), the Chinese State Trait and Anxiety Inventory (C-STAI), and the SF-36 were the outcome measures for the two groups before and after the training program to observe the changes in subjects' work readiness status, emotional status and their health related quality of life pre- and post-training program. The rate of return to work was measured for both groups of subjects after the training program. RESULTS: The results indicated that the rate of success in RTW (73%) was significantly higher in the job placement (PS) group than that of the self-placement (SP) group (51.6%) with P < 0.05. Significant differences were also found in C-STAI (P < 0.05), SF-36 (P < 0.05) and C-LASER scores on action (P < 0.05) between the two groups. CONCLUSION: The job placement (PS) program appeared to have enhanced the employability of injured workers. Workers who participated in the program also showed higher levels of work readiness and emotional status in coping with their work injuries.

CD4+ T-cell responses to Epstein-Barr virus nuclear antigen EBNA1 in Chinese populations are highly focused on novel C-terminal domain-derived epitopes.

Epstein-Barr virus nuclear antigen EBNA1, the one viral protein uniformly expressed in nasopharyngeal carcinoma (NPC), represents a prime target for T-cell-based immunotherapy. However, little is known about the EBNA1 epitopes, particularly CD4 epitopes, presented by HLA alleles in Chinese people, the group at highest risk for NPC. We analyzed the CD4+ T-cell responses to EBNA1 in 78 healthy Chinese donors and found marked focusing on a small number of epitopes in the EBNA1 C-terminal region, including a DP5-restricted epitope that was recognized by almost half of the donors tested and elicited responses able to recognize EBNA1-expressing, DP5-positive target cells.

Theoretical study of alpha/beta-alanine and their protonated/alkali metal cationized complexes.

Density functional theory has been employed to model the structure and the relative stabilities of alpha/beta-alanine conformers and their protonated and alkali metal cationized complexes. In general, we find that the behavior of the beta-alanine (beta-Ala) system is quite similar to that of alpha-alanine (alpha-Ala). However, the presence of the methylene group (-CH2-) at the beta position in beta-Ala leads to a few key differences. First, the intramolecular hydrogen bonding patterns are different between free alpha- and beta-Ala. Second, the stability of zwitterionic species (in either the free ligand or alkali metal cationized complexes) is often enhanced in beta-Ala. Third, the preferred mode of alkali metal cation (M+) binding may also differ in alpha- and beta-Ala. Natural energy decomposition analysis has been applied here to gain further insight into the effects of the ligand, cation size, and mode of binding on the nature of interaction in these M+-Ala complexes.

CD4+ T-cell responses to Epstein-Barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines.

There is considerable interest in the potential of Epstein-Barr virus (EBV) latent antigen-specific CD4+ T cells to act as direct effectors controlling EBV-induced B lymphoproliferations. Such activity would require direct CD4+ T-cell recognition of latently infected cells through epitopes derived from endogenously expressed viral proteins and presented on the target cell surface in association with HLA class II molecules. It is therefore important to know how often these conditions are met. Here we provide CD4+ epitope maps for four EBV nuclear antigens, EBNA1, -2, -3A, and -3C, and establish CD4+ T-cell clones against 12 representative epitopes. For each epitope we identify the relevant HLA class II restricting allele and determine the efficiency with which epitope-specific effectors recognize the autologous EBV-transformed B-lymphoblastoid cell line (LCL). The level of recognition measured by gamma interferon release was consistent among clones to the same epitope but varied between epitopes, with values ranging from 0 to 35% of the maximum seen against the epitope peptide-loaded LCL. These epitope-specific differences, also apparent in short-term cytotoxicity and longer-term outgrowth assays on LCL targets, did not relate to the identity of the source antigen and could not be explained by the different functional avidities of the CD4+ clones; rather, they appeared to reflect different levels of epitope display at the LCL surface. Thus, while CD4+ T-cell responses are detectable against many epitopes in EBV latent proteins, only a minority of these responses are likely to have therapeutic potential as effectors directly recognizing latently infected target cells.