A multicentre study to determine the in vitro efficacy of flomoxef against extended-spectrum beta-lactamase producing Escherichia coli in Malaysia.

Background: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance. Methods: Therefore, an inventory surveillance of the ESBL-Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated. Results: A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The blaCTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring blaCTX-M-1 only, 27 isolates (21.3%) co-harbouring blaCTX-M-1 and blaTEM, and ten isolates (7.9%) co-harbouring blaCTX-M-1, blaTEM and blaSHV. A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes.

Phenotypic and genotypic comparison of pathogenic group B Streptococcus isolated from human and cultured tilapia (Oreochromis species) in Malaysia.

Group B Streptococcus (GBS) is a major cause of several infectious diseases in humans and fish. This study was conducted to compare human and fish-derived GBS in terms of their antimicrobial susceptibility, serotype, virulence and pili genes and sequence type (ST), and to determine whether there is a potential linkage of zoonotic transmission in Malaysia. GBS isolated from humans and fish had similar phenotypic characteristics and differed in virulence gene profile, antimicrobial susceptibility, serotype and sequence type. Fish GBS isolates had lower genetic diversity and higher antibiotic susceptibility than human isolates. We report a rare detection of the potentially fish-adapted ST283 in human GBS isolates. Both human and fish ST283 shared several phenotypic and genotypic features, including virulence and pilus genes and antimicrobial susceptibility, illustrating the value of monitoring GBS within the One Health scope. In this study, two human GBS ST283 isolates belonging to the variant common in fish hosts were identified, raising awareness of the zoonotic potential between the different species in Malaysia.

Diversity and Dissemination of Methicillin-Resistant Staphylococcus aureus (MRSA) Genotypes in Southeast Asia.

Methicillin-resistant Staphylococcus aureus (MRSA) is a successful pathogen that has achieved global dissemination, with high prevalence rates in Southeast Asia. A huge diversity of clones has been reported in this region, with MRSA ST239 being the most successful lineage. Nonetheless, description of MRSA genotypes circulating in the Southeast Asia region has, until now, remained poorly compiled. In this review, we aim to provide a better understanding of the molecular epidemiology and distribution of MRSA clones in 11 Southeast Asian countries: Singapore, Malaysia, Thailand, Vietnam, Cambodia, Lao People's Democratic Republic (PDR), Myanmar, Philippines, Indonesia, Brunei Darussalam, and Timor-Leste. Notably, while archaic multidrug-resistant hospital-associated (HA) MRSAs, such as the ST239-III and ST241-III, were prominent in the region during earlier observations, these were then largely replaced by the more antibiotic-susceptible community-acquired (CA) MRSAs, such as ST22-IV and PVL-positive ST30-IV, in recent years after the turn of the century. Nonetheless, reports of livestock-associated (LA) MRSAs remain few in the region.

Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How They All Come Together?

In the past decade, many studies have highlighted the role of metabotropic glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related biological effects such as alcohol consumption, alcohol-seeking and relapse-like behaviors. Taken together, these findings suggest that pharmacological agents acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are present abundantly in brain regions known to be involved in emotion regulation, motivation and drug administration. On a cellular level, they are primarily located at the postsynaptic part of the neuron where the receptor is functionally linked to various downstream proteins that are involved in cell signaling and gene transcription that mediate the alcohol-induced neuroplasticity. As well, the discovery of a functional link between mGlu5 and a specific isozyme, Protein Kinase C epsilon (PKCε) in mediating the attenuating effects of selective negative allosteric modulators of mGlu5 such as methyl- 6(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked interesting speculations. In this article, we shall review the following: the effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being studied both at pre-clinical and clinical stages; and the mechanisms underlying the pharmacological effects of these drugs.

Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus.

INTRODUCTION: REM sleep deprivation is associated with impairment in learning and memory, and nicotine treatment has been shown to attenuate this effect. Recent studies have demonstrated the importance of DREAM protein in learning and memory processes. This study investigates the association of DREAM protein in REM sleep-deprived rats hippocampus upon nicotine treatment. METHODS: Male Sprague Dawley rats were subjected to normal condition, REM sleep deprivation and control wide platform condition for 72 hr. During this procedure, saline or nicotine (1 mg/kg) was given subcutaneously twice a day. Then, Morris water maze (MWM) test was used to assess learning and memory performance of the rats. The rats were sacrificed and the brain was harvested for immunohistochemistry and Western blot analysis. RESULTS: MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein. CONCLUSION: This study suggests that changes in DREAM protein expression in CA1, CA2, CA3, and DG regions of rat's hippocampus and mean relative level of DREAM protein may involve in the mechanism of nicotine treatment-prevented REM sleep deprivation-induced learning and memory impairment in rats.

Characterization of a Group B Streptococcus infection based on the demographics, serotypes, antimicrobial susceptibility and genotypes of selected isolates from sterile and non-sterile isolation sites in three major hospitals in Malaysia.

BACKGROUND/PURPOSE: The purpose of this study is to characterize GBS isolates that were collected from three major hospitals in a densely populated area of Klang Valley for their demographics, serotypes, antibiotic susceptibility patterns and genetic background. METHODS: Sixty GBS isolates from sterile and non-sterile samples in three major hospitals in the Klang Valley area of Malaysia were collected by convenience sampling from 2012 until March 2014. These isolates were studied for their antimicrobial susceptibilities, serotypes and genotypes. Patients' demographic data and clinical information were collected from lab request forms. RESULTS: Diabetes mellitus was the only underlying condition (7 patients, 23.3%); the remaining samples were from patients who were immunocompromised due to medications. Fifty-nine (98%) isolates were sensitive to penicillin, while 78.3% and 88.3% of the isolates were sensitive to erythromycin and clindamycin, respectively. Serotype Ia was the most common serotype (n=27, 45%), followed by serotype III (n=10, 16.7%), V (n=9, 15%), VI (n=8, 13.3%), VIII (n=2, 3.3%) and VII (n=1, 1.7%). Random Amplified Polymorphic DNA (RAPD) typing showed a diverse genetic pedigree for all isolates, including four major groups that clustered according to geographical location. CONCLUSION: This preliminary study determines the prevalence of limited common serotypes and antimicrobial resistance in distinct GBS isolates. Nonetheless, the RAPD clustering pattern suggests a close genetic lineage of the GBS isolates based on their isolation sites and location of hospitals.

Thermal Change and the Dynamics of Multi-Host Parasite Life Cycles in Aquatic Ecosystems.

Altered thermal regimes associated with climate change are impacting significantly on the physical, chemical, and biological characteristics of the Earth's natural ecosystems, with important implications for the biology of aquatic organisms. As well as impacting the biology of individual species, changing thermal regimes have the capacity to mediate ecological interactions between species, and the potential for climate change to impact host-parasite interactions in aquatic ecosystems is now well recognized. Predicting what will happen to the prevalence and intensity of infection of parasites with multiple hosts in their life cycles is especially challenging because the addition of each additional host dramatically increases the potential permutations of response. In this short review, we provide an overview of the diverse routes by which altered thermal regimes can impact the dynamics of multi-host parasite life cycles in aquatic ecosystems. In addition, we examine how experimentally amenable host-parasite systems are being used to determine the consequences of changing environmental temperatures for these different types of mechanism. Our overarching aim is to examine the potential of changing thermal regimes to alter not only the biology of hosts and parasites, but also the biology of interactions between hosts and parasites. We also hope to illustrate the complexity that is likely to be involved in making predictions about the dynamics of infection by multi-host parasites in thermally challenged aquatic ecosystems.

The effects of acute ethanol administration on ethanol withdrawal-induced anxiety-like syndrome in rats: A biochemical study.

Withdrawal from long-term ethanol consumption results in overexcitation of glutamatergic neurotransmission in the amygdala, which induces an anxiety-like syndrome. Most alcoholics that suffer from such symptoms frequently depend on habitual drinking as self-medication to alleviate their symptoms. Metabotropic glutamate receptor subtype 5 (mGlu5) and protein kinase C (PKC) epsilon have been reported to mediate acute and chronic effects of ethanol. This study explores the changes in mGlu5 and PKC epsilon in the amygdala following acute administration of ethanol during ethanol withdrawal (EW) induced anxiety. Male Wistar rats were fed a modified liquid diet containing low-fat cow milk, sucrose, and maltodextrin, with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into EW, the rats were intraperitoneally injected with normal saline and ethanol (2.5 g/kg, 20% v/v), and exposed to open-field and elevated plus maze tests. Then, amygdala tissue was dissected from the rat brain for Western blot and gene expression studies. EW-induced anxiety was accompanied by a significant increase in mGlu5, total PKC epsilon, and phosphorylated PKC epsilon protein levels, and also of mRNA of mGlu5 (GRM5) in the amygdala. Acute administration of ethanol significantly attenuated EW-induced anxiety as well as an EW-induced increase in GRM5. The acute challenge of ethanol to EW rats had little effect on the phosphorylated and total protein levels of PKC epsilon in the amygdala. Our results demonstrate that amygdala PKC epsilon may not be directly involved in the development of anxiety following EW.

INFLUENZA VACCINATION UPTAKE AMONG HEALTHCARE WORKERS AT A MALAYSIAN TEACHING HOSPITAL.

Annual influenza vaccination is the most important preventive strategy against influenza illness in healthcare workers (HCWs), who could acquire influenza from and transmit influenza to patients and other HCWs. Despite the well established benefits and strong recommendations for influenza vaccination for all HCWs, influenza vaccination uptake at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) for the past 3 years has been low and is decreasing. We aimed to determine the factors associated with influenza vaccination uptake among HCWs at UKMMC. We conducted a cross sectional study via questionnaire among 211 randomly selected HCWs, consisting of 106 HCWs who were vaccinated in 2011 and 105 HCWs who were not vaccinated in 2010 or 2011. We had a 100% response rate. Influenza vaccination uptake was significantly associated with age and previous vaccination history, with older HCWs being more likely to be vaccinated (adjusted OR = 12.494; 95% CI:6.278-24.863; p < 0.001) and HCWs with previous vaccination history being more likely to be vaccinated (adjusted OR = 1.038; 95% CI:1.001-1.077; p = 0.045). Influenza vaccination uptake was not associated with gender (p = 0.926) or job category (p = 0.220). Publicity at the workplace was the main source of information about the vaccine (51.2% of respondents), followed by colleagues (29.9%). Despite the low uptake, 85.3% of respondents believed influenza vaccination was important for disease prevention. The most common reason given for vaccination was protection against influenza infection (73.6%). The most common reason for not having the vaccine was time constraints (56.2%). An evidenced-based strategy needs to be developed to improve vaccine uptake or having mandatory vaccination.

Preconditioning effect of (S)-3,5-dihydroxyphenylglycine on ischemic injury in middle cerebral artery occluded Sprague-Dawley rats.

Glutamate receptors are the integral cellular components associated with excitotoxicity mechanism induced by the ischemic cascade events. Therefore the glutamate receptors have become the major molecular targets of neuroprotective agents in stroke researches. Recent studies have demonstrated that a Group I metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) preconditioning elicits neuroprotection in the hippocampal slice cultures exposed to toxic level of N-methyl-d-aspartate (NMDA). We further investigated the preconditioning effects of (S)-3,5-DHPG on acute ischemic stroke rats. One 10 or 100µM of (S)-3,5-DHPG was administered intrathecally to Sprague-Dawley adult male rats, 2h prior to induction of acute ischemic stroke by middle cerebral artery occlusion (MCAO). After 24h, neurological deficits were evaluated by modified stroke severity scores and grid-walking test. All rats were sacrificed and infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining. The serum level of neuron-specific enolase (NSE) of each rat was analyzed by enzyme-linked immunosorbent assay (ELISA). One and 10µM of (S)-3,5-DHPG preconditioning in the stroke rats showed significant improvements in motor impairment (P<0.01), reduction in the infarct volume (P<0.01) and reduction in the NSE serum level (P<0.01) compared to the control stroke rats. We conclude that 1 and 10µM (S)-3,5-DHPG preconditioning induced protective effects against acute ischemic insult in vivo.

REM sleep deprivation induces changes of Down Regulatory Antagonist Modulator (DREAM) expression in the ventrobasal thalamic nuclei of Sprague-Dawley rats

REM sleep is a crucial component of sleep. Animal studies indicate that rapid eye movement (REM) sleep deprivation elicits changes in gene expression. Down regulatory antagonist modulator (DREAM) is a protein which down regulates other gene transcriptions by binding to the downstream response element site. The aim of this study is to examine the effect of REM sleep deprivation on DREAM expression in ventrobasal thalamic nuclei (VB) of rats. Seventy-two male Sprague-Dawley rats were divided into four major groups consisting of free-moving control rats (FMC) (n = 18), 72-h REM sleep-deprived rats (REMsd) (n = 18), 72-h REM sleep-deprived rats with 72-h sleep recovery (RG) (n = 18), and tank control rats (TC) (n = 18). REM sleep deprivation was elicited using the inverted flower pot technique. DREAM expression was examined in VB by immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) studies. The DREAM-positive neuronal cells (DPN) were decreased bilaterally in the VB of rats deprived of REM sleep as well as after sleep recovery. The nuclear DREAM extractions were increased bilaterally in animals deprived of REM sleep. The DREAM messenger RNA (mRNA) levels were decreased after sleep recovery. The results demonstrated a link between DREAM expression and REM sleep deprivation as well as sleep recovery which may indicate potential involvement of DREAM in REM sleep-induced changes in gene expression, specifically in nociceptive processing

REM sleep deprivation induces changes of down regulatory antagonist modulator (DREAM) expression in the ventrobasal thalamic nuclei of sprague-dawley rats.

REM sleep is a crucial component of sleep. Animal studies indicate that rapid eye movement (REM) sleep deprivation elicits changes in gene expression. Down regulatory antagonist modulator (DREAM) is a protein which downregulates other gene transcriptions by binding to the downstream response element site. The aim of this study is to examine the effect of REM sleep deprivation on DREAM expression in ventrobasal thalamic nuclei (VB) of rats. Seventy-two male Sprague-Dawley rats were divided into four major groups consisting of free-moving control rats (FMC) (n = 18), 72-h REM sleep-deprived rats (REMsd) (n = 18), 72-h REM sleep-deprived rats with 72-h sleep recovery (RG) (n = 18), and tank control rats (TC) (n = 18). REM sleep deprivation was elicited using the inverted flower pot technique. DREAM expression was examined in VB by immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) studies. The DREAM-positive neuronal cells (DPN) were decreased bilaterally in the VB of rats deprived of REM sleep as well as after sleep recovery. The nuclear DREAM extractions were increased bilaterally in animals deprived of REM sleep. The DREAM messenger RNA (mRNA) levels were decreased after sleep recovery. The results demonstrated a link between DREAM expression and REM sleep deprivation as well as sleep recovery which may indicate potential involvement of DREAM in REM sleep-induced changes in gene expression, specifically in nociceptive processing.

Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats.

Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.

The Effects of Pre-emptive Administration of Ketamine and norBNI on Pain Behavior, c-Fos, and Prodynorphin Protein Expression in the Rat Spinal Cord after Formalin-induced Pain Is Modulated by the DREAM Protein.

BACKGROUND: We investigated the effects of pre-emptive administration of ketamine and norBNI on pain behavior and the expression of DREAM, c-Fos, and prodynorphin proteins on the ipsilateral side of the rat spinal cord at 2 and 4 hours after formalin injection. METHODS: Eighty-four male Sprague Dawley rats were divided into 4 major groups consisting of control rats (C) (n = 12), rats given only formalin injections (F) (n = 24), and rats treated with pre-emptive administration of either ketamine (K+F) (n = 24) or norBNI (N+F) (n = 24). The non-control groups were further divided into subgroups consisting of rats that were sacrificed at 2 and 4 hours (n = 12 for each group) after formalin injection. Pain behavior was recorded for 1 hour. After 2 and 4 hours, the rats were sacrificed and the spinal cords (L4-L5 sections) were removed for immunohistochemistry and Western blot analysis. RESULTS: The pain behavior response was reduced in the K+F group compared to the other groups during the second phase of the formalin pain response. We detected an increase in the nuclear DREAM protein level in the K+F group at 2 and 4 hours and a transient decrease in the N+F group at 2 hours; however, it increased at 4 hours after injection. Fos-like immunoreactivity (FLI) and Prodynorphin-like immunoreactivity (PLI) neurons decreased in the K+F group but increased in the N+F group at 2 hours after injection. While FLI decreased, PLI increased in all groups at 4 hours after injection. CONCLUSIONS: We suggest that NMDA and kappa opioid receptors can modulate DREAM protein expression, which can affect pain behavior and protein transcriptional processes at 2 hours and bring about either harmful or protective effects at 4 hours after formalin injection.

Clinical use of Malay Version of Vertigo Symptom Scale (MWSS) in patients with peripheral vestibular disorder (PVD).

INTRODUCTION: The Vertigo symptom scale (VSS) is a well established tool for the evaluation of vestibular disorders and the associated symptoms of autonomic arousal and somatosensation. By using a validated Malay version of vertigo symptom scale (MVVSS) questionnaire, the severity of the vertigo from patients' perspective can be determined and rated. Before MVVSS can be applied clinically among Malaysians, it was of interest to determine its clinical value in identifying vestibular disorders. METHOD: Forty normal and 65 PVD subjects participated in this cross-sectional study. Normal subjects were recruited amongst Universiti Sains Malaysia (USM) staff and students who had no history of ear and vestibular disorders. RESULTS: Mean total score of MVVSS in normal and PVD subjects were 13.9 +/- 11.1 and 30.1 +/- 20.9, respectively. When the total scores of normal and PVD group were compared, the Mann-Whitney U test showed that there was a significant difference between the two groups (p < 0.05). This is consistent with previous studies. It was also of interest to see if subtypes of PVD [benign paroxymal positional vertigo (BPPV), Meniere's disease, labyrinthitis and unknown] have different MVVSS results. However, analysis of variance (ANOVA) found no significant difference in term of outcomes of MVVSS among the different PVD pathologies. Using receiver operating characteristic curve (ROC) method, the sensitivity and specificity of MVVSS were 71% and 60%, respectively. CONCLUSION: MVVSS is able to discriminate clinically among the normal and PVD subjects. However, it is not a good indicator for differential diagnosis of PVD subtypes, at least in this study. Its sensitivity and specificity in clinical diagnosis are reasonably high. Perhaps a bigger sample size would be useful to further study the clinical usefulness of MVVSS.

Increases in mRNA and DREAM protein expression in the rat spinal cord after formalin induced pain.

Downstream Regulatory Element Antagonist Modulator (DREAM) protein modulates pain by regulating prodynorphin gene transcription. Therefore, we investigate the changes of mRNA and DREAM protein in relation to the mRNA and prodynorphin protein expression on the ipsilateral side of the rat spinal cord after formalin injection (acute pain model). DREAM like immunoreactivity (DLI) was not significantly different between C and F groups. However, we detected the upregulation of mean relative DREAM protein level in the nuclear but not in the cytoplasmic extract in the F group. These effects were consistent with the upregulation of the relative DREAM mRNA level. Prodynorphin like immunoreactivity (PLI) expression increased but the relative prodynorphin mRNA level remained unchanged. In conclusion, we suggest that upregulation of DREAM mRNA and protein expression in the nuclear compartment probably has functional consequences other than just the repression of prodynorphin gene. It is likely that these mechanisms are important in the modulation of pain.

Profound swim stress-induced analgesia with ketamine.

The potential of ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, in preventing central sensitization has led to numerous studies. Ketamine is increasingly used in the clinical setting to provide analgesia and prevent the development of central sensitization at subanaesthetic doses. However, few studies have looked into the potential of ketamine in combination with stress-induced analgesia. This study looks at the effects of swim stress, which is mediated by opioid receptor, on ketamine analgesia using formalin test. Morphine is used as the standard analgesic for comparison. Adult male Sprague-Dawley rats were assigned to 6 groups: 3 groups (stressed groups) were given saline 1ml/kg intraperitoneally (ip), morphine 10mg/kg ip or ketamine 5mg/kg ip and subjected to swim stress; 3 more groups (non-stressed groups) were given the same drugs without swim stress. Formalin test, which involved formalin injection as the pain stimulus and the pain score recorded over time, was performed on all rats ten minutes after cessation of swimming or 30 minutes after injection of drugs. Combination of swim stress and ketamine resulted in complete analgesia in the formalin test which was significantly different from ketamine alone (p<0.05) and saline with stress (p<0.01). There is no significant difference between ketamine stressed and morphine stressed. These results indicate that ketamine and swim stress act synergistically to produce profound analgesia in the formalin test. This suggests that in the clinical setting, under stressful situations such as operative stress, ketamine is capable of producing profound analgesia at a subanaesthetic dose.

Expanding nursing education through e-learning: A case study in Malaysia.

The School of Health Sciences, Universiti Sains Malaysia (SHS) is planning to expand its contribution to produce more graduate nurses by offering a nursing degree through e-learning. After three years of using e-learning by four lecturers in seven nursing courses, we conducted a study to get the lecturers feedback and to compare the students' preference and their actual experiences in e-learning. Lecturers' feedback were collected based on six open-ended questions. Feedback from all the 36 final year nursing students were collected using Constructivist On-line Learning Environment Survey (COLLES)--the Student Experience/Preferred Form. Results show that lecturers and students have positive perception on e-learning. They perceive e-learning as a powerful and effective tool for expanding nursing education to meet the demand for a labour force that is knowledgeable, highly skilled and equipped with positive values. We believe blended learning is the most suitable approach to implement e-learning and social constructivism theory provides the dynamic view of learning. To increase success in e-learning implementation for the nursing programme, lecturers should be educated regarding proper instructional design so that their content delivery blends well with the technology and pedagogy.

Accreditation of undergraduate medical training programs: practices in nine developing countries as compared with the United States.

CONTEXT AND OBJECTIVES: Undergraduate medical training program accreditation is practiced in many countries, but information from developing countries is sparse. We compared medical training program accreditation systems in nine developing countries, and compared these with accreditation practices in the United States of America (USA). METHODS: Medical program accreditation practices in nine developing countries were systematically analyzed using all available published documents. Findings were compared to USA accreditation practices. FINDINGS: Accreditation systems with explicitly defined criteria, standards and procedures exist in all nine countries studied: Argentina, India, Kenya, Malaysia, Mongolia, Nigeria, Pakistan, Philippines and South Africa. Introduction of accreditation processes is relatively recent, starting in 1957 in India to 2001 in Malaysia. Accrediting agencies were set up in these countries predominantly by their respective governments as a result of legislation and acts of Parliament, involving Ministries of Education and Health. As in the USA, accreditation: (1) serves as a quality assurance mechanism promoting professional and public confidence in the quality of medical education, (2) assists medical schools in attaining desired standards, and (3) ensures that graduates' performance complies with national norms. All nine countries follow similar accreditation procedures. Where mandatory accreditation is practiced, non-compliant institutions may be placed on probation, student enrollment suspended or accreditation withdrawn. CONCLUSION: Accreditation systems in several developing countries are similar to those in the developed world. Data suggest the trend towards instituting quality assurance mechanisms in medical education is spreading to some developing countries, although generalization to other areas of the world is difficult to ascertain.

c-fos and its Consequences in Pain.

The discovery that c-fos, a proto-oncogene, has a role in pain, has triggered extensive research on the consequences of c-fos expression. It has been shown that c-fos, through its protein form, FOS, leads to expression of dynorphin gene and subsequently dynorphin protein which is implicated in the development of a pain state. This mini review looks at the properties of c-fos and the consequences of its expression following noxious (painful) stimulation.