Prevalence and barriers of reporting needle-stick injures amongst government pharmacists working in Perak, Malaysia.

INTRODUCTION: Needle-stick injuries (NSIs) are common amongst healthcare workers including pharmacists. Studies have reported a range of 0-5.65 per 1,000 pharmacists handling vaccinations that suffered at least one incident of NSI. The objective of this study was to determine the prevalence of NSI and the barriers encountered in reporting it amongst government pharmacists working in Perak. MATERIALS AND METHODS: This was a cross-sectional study conducted amongst all government pharmacists in Perak. We excluded those who did not consent or were unreachable electronically. The researchers provided an online link that was forwarded to all heads of departments in Perak via social media. The respondents answered their demographic details, questions assessing their knowledge of NSI transmissible diseases, needle-stick handling practices, detail experiences of them suffering an NSI (all self-developed questionnaires), and their barriers in reporting an NSI (validated questionnaire). All responses were auto-tabulated in an excel sheet. A sample size of 516 pharmacists was needed for this study. A respondent was deemed to have inadequate knowledge when they answered any question wrongly about NSI knowledge-related questions and inappropriate practice in needle handling when respondents answered any questions wrongly for questions assessing practices. RESULTS: A total of 524 pharmacists participated. The overall prevalence of NSI was 23.1% (n=121), of which, those with contaminated NSI were 10.3% (n=54, 95%CI: 7.9-13.30). Twothirds of the participants (66.6%) had inadequate knowledge and nearly all of them were unable to describe the appropriate needle-handling practices (94.7%). Amongst the reported barriers were "not knowing whose duty it was to report an NSI" (45.5%) and "busy schedules" (44.7%). CONCLUSION: One in every five pharmacists in the state of Perak had a history of NSI, and 1 in every 10 had sustained a contaminated NSI. The barriers to reporting a NSI were mainly due to uncertainty about whose responsibility to report the incident and being too busy to report it.

Development and validation of TaqMan real-time PCR for the detection of Burkholderia pseudomallei isolates from Malaysia.

Rapid detection of Burkholderia pseudomallei, the etiologic agent of melioidosis, allows for timely initiation of appropriate treatment and better clinical outcomes. In the current gold standard, the culture method is time consuming and suffers from low sensitivity. Meanwhile, previously reported molecular assays are fast and sensitive, but their performance on isolates from Malaysia, an endemic region of melioidosis is under reported. This study designed oligonucleotides targeting orf2 of Type III secretion system (TTSS) genes cluster for the detection of Malaysian B. pseudomallei isolates and evaluated the assay on 95 local B. pseudomallei strains, 58 other microorganisms and 71 clinical specimens from patients. The developed assay exclusively detected all tested B. pseudomallei isolates with a detection limit of 20 fg per reaction (equivalent to ~2.5 copies). Subsequent testing on clinical samples showed that the assay detected all confirmed specimens with the growth of B. pseudomallei (n = 10/10). None of the negative specimens had a detectable signal of our TTSS-orf2 assay (n = 0/61). In conclusion, the present study provides crucial preliminary data for a subsequent study and should be considered as a potential alternative to current time-consuming culture method for the detection of B. pseudomallei.

Prevalence and Distribution of Anti-Amoebic IgG Antibody among Orang Asli (Aborigines) in Peninsular Malaysia.

Entamoeba species are commonly detected in stool samples of Orang Asli due to their substandard living conditions and poor hygiene. Among the Entamoeba spp., Entamoeba histolytica is the only known primary pathogenic species. This study determined the prevalence and distribution of anti-amoebic IgG antibody among Orang Asli in Peninsular Malaysia. The results would reflect the prevalence of amoebiasis in the population. This study analysed a total of 375 serum samples from archives of two Orang Asli projects conducted between 2011 and 2014. They were from six different states in Malaysia, namely Johor, Kedah, Kelantan, Pahang, Perak, and Selangor. Anti-amoebic IgG antibody was detected using an enzymelinked immunosorbent assay (ELISA) with crude soluble antigen produced from axenically grown E. histolytica trophozoites. From the analysis, the overall seropositivity was approximately 71% (266/375), while the seropositivity rates for each of the three Orang Asli tribes i.e. Senoi, Negrito and Proto-Malay, were 66% (137/208), 92% (103/112), and 43% (17/ 41) respectively. Orang Asli from Kedah [95% (52/55)] showed the highest seropositivity, followed by Kelantan [79% (54/68)], Perak [73% (78/107)], Pahang [60% (57/95)], Selangor [56% (14/25)], and Johor [48% (10/21)]. Orang Asli from rural [76% (192/254)] and peripheral urban [65% (69/106)] areas showed significantly higher seropositivity (p=0.002) than those from urban areas [36% (4/11)]. The high prevalences of anti-amoebic IgG antibody in these Orang Asli populations comprised both active and past infections. This study provides current insights of amoebiasis in selected Orang Asli settlements in Peninsular Malaysia. The high seropositivity of anti-amoebic IgG antibody suggests that the settlements are endemic for amoebiasis and there is a high risk of acquiring E. histolytica infection among the dwellers.

Structural basis of the interaction of the breast cancer oncogene LMO4 with the tumour suppressor CtIP/RBBP8.

LIM-only protein 4 (LMO4) is strongly linked to the progression of breast cancer. Although the mechanisms underlying this phenomenon are not well understood, a role is emerging for LMO4 in regulation of the cell cycle. We determined the solution structure of LMO4 in complex with CtIP (C-terminal binding protein interacting protein)/RBBP8, a tumour suppressor protein that is involved in cell cycle progression, DNA repair and transcriptional regulation. Our data reveal that CtIP and the essential LMO cofactor LDB1 (LIM-domain binding protein 1) bind to the same face on LMO4 and cannot simultaneously bind to LMO4. We hypothesise that overexpression of LMO4 may disrupt some of the normal tumour suppressor activities of CtIP, thereby contributing to breast cancer progression.

The FGFR4 Y367C mutant is a dominant oncogene in MDA-MB453 breast cancer cells.

Mutational analysis of oncogenes is critical for our understanding of cancer development. Oncogenome screening has identified a fibroblast growth factor receptor 4 (FGFR4) Y367C mutation in the human breast cancer cell line MDA-MB453. Here, we investigate the consequence of this missense mutation in cancer cells. We show that MDA-MB453 cells harbouring the mutation are insensitive to FGFR4-specific ligand stimulation or inhibition with an antagonistic antibody. Furthermore, the FGFR4 mutant elicits constitutive phosphorylation leading to an activation of the mitogen-activated protein kinase cascade as shown by an enhanced Erk1/2 phosphorylation. Cloning and ectopic expression of the FGFR4 Y367C mutant in HEK293 cells revealed high pErk levels and enhanced cell proliferation. Based on these findings, we propose that FGFR4 may be a driver of tumour growth, particularly when highly expressed or stabilized and constitutively activated through genetic alterations. As such, FGFR4 presents an option for further mutational screening in tumours and is an attractive cancer target with the therapeutic potential.

Local and global stabilization of coordination by sensory information.

In studies of rhythmic coordination, where sensory information is often generated by an auditory stimulus, spatial and temporal variability are known to decrease at points in the movement cycle coincident with the stimulus, a phenomenon known as anchoring (Byblow et al. 1994). Here we hypothesize that the role of anchoring may be to globally stabilize coordination under conditions in which it would otherwise undergo a global coordinative change such as a phase transition. To test this hypothesis, anchoring was studied in a bimanual coordination paradigm in which either inphase or antiphase coordination was produced as auditory pacing stimuli (and hence movement frequency) were scaled over a wide range of frequencies. Two different anchoring conditions were used: a single-metronome condition, in which peak amplitude of right finger flexion coincided with the auditory stimulus; and a double-metronome condition, in which each finger reversal (flexion and extension) occurred simultaneously with the auditory stimuli. Anchored reversal points displayed lower spatial variation than unanchored reversal points, resulting in more symmetric phase plane trajectories in the double- than the single-metronome condition. The global coordination dynamics of the double-metronome condition was also more stable, with transitions from antiphase to inphase occurring less often and at higher movement frequencies than in the single-metronome condition. An extension of the Haken-Kelso-Bunz model of bimanual coordination is presented briefly which includes specific coupling of sensory information to movement through a process we call parametric stabilization. The parametric stabilization model provides a theoretical account of both local effects on the individual movement trajectories (anchoring) and global stabilization of observed coordination patterns, including the delay of phase transitions.

Functional stabilization of unstable fixed points: human pole balancing using time-to-balance information.

Humans are often faced with tasks that require stabilizing inherently unstable situations. The authors explored the dynamics of human functional stabilization by having participants continually balance a pole until a minimum time criterion was reached. Conditions were manipulated with respect to geometry, mass, and characteristic "fall time" of the pole. Distributions of timing between pole and hand velocities showed strong action-perception coupling. When actions demonstrated a potential for catastrophic failure, the period of hand oscillation correlated well with the perceptual quantity "time to balance" (tau(bal) = theta/theta), but not other quantities such as theta and theta alone. This suggests that participants were using available tau(bal) information during critical conditions, although they may not have been attending to this type of perceptual information during typical, noncritical motions of successful performance. In a model analysis and simulation, the authors showed how discrete tau(bal) information may be used to adjust the parameters of a controller to perform this task.

Parametric stabilization of biological coordination: a theoretical model.

In human coordination studies information from the environment may not only pace rhythmic behavior, but also contribute to the observed dynamics, e.g. aphenomenon known as anchoring in the literature. For the paradigmatic caseof bimanual coordination we study these contributions mathematically and develop a model of the interaction between the limb's intrinsic dynamics and environmental signals from a metronome in terms of oscillator equations. We discuss additive versus multiplicative metronomeimpact and show the latter to be more appropriate.Our model describes single limb-metronome interaction, as well as multilimb-metronome interaction. We establish a parametricstabilization term which preserves the characteristicsof bimanual coordination and additionally explains the varyingstability of movement under different metronome conditions, the frequency dependence of the amplitudes of finger movements, anchoring phenomena andgeometries of phase space trajectories. Predictions of our model are tested against experimental observations.

In vitro assessment of water vapour transmission of synthetic wound dressings.

The water vapour transmission rate (WVTR) of 14 commercially available wound dressings (11 hydrocolloids, 2 hydrogels and 1 polyurethane film) was evaluated over 24 and 48 h periods using a modified ASTM standard method (ASTM E96-90). For the 48 h studies a novel microcomputer-controlled apparatus was employed. The dressings exhibited a wide range of WVTRs (76-9360 g m-2 d-1 at 24 h under forced air convection of 0.4 m s-1). The influence of air velocity of 0.4 m s-1 was not significant if the WVTR of the dressing was less than 880 g m-2 d-1 when measured under static air conditions. The influence of outer barrier layers and additional bandages on WVTR was also examined.

Inhibiting and stimulating effects of TGF-beta 1 on osteoclastic bone resorption in fetal mouse bone organ cultures.

The effects of TGF-beta 1 on osteoclastic resorption of fetal mouse calvaria and long bones at various stages of development was studied in organ culture. In resorbing calvariae and long bones with an established marrow cavity TGF-beta 1 (4-10 ng/ml) had a stimulating effect on 45Ca release that was partially inhibited by indomethacin. In primitive long bones, however, which were explanted before osteoclast invasion and excavation of a marrow cavity had started, TGF-beta 1 (1-4 ng/ml) inhibited 45Ca release by an indomethacin-insensitive mechanism. Histomorphometry of long bones after staining for tartrate-resistant acid phosphatase (TRAP) revealed that TGF-beta 1 treatment inhibited the migration of TRAP-positive cells from periosteum to developing marrow cavity and inhibited cell fusion. However, the formation of (mononuclear) TRAP-positive cells in the periosteum-perichondrium was strongly enhanced. These data suggest that TGF-beta 1 modulates various steps in the cascade of osteoclast development, recruitment, and activation in different ways, involving both prostaglandin-mediated and prostaglandin-independent pathways. Therefore the net effect of exogenous TGF-beta 1 on osteoclastic resorption in bone organ cultures depends on the relative prevalence of osteoclast progenitors, precursors, and mature osteoclasts in the tissue under study.