Stress modulates pain perception, resulting in either stress-induced analgesia or stress-induced hyperalgesia, as reported in both animal and human studies. The responses to stress include neural, endocrine, and behavioural changes, and built-in coping strategies are in place to address stressors. Peculiar to humans are additional factors that modulate pain that are experienced in times of stress, notably psychological factors that potentially influence the directionality of pain perception.

Background: β-thalassaemia is one of the most common single-gene disorders worldwide. Each ethnic population has its own common mutations, accounting for the majority of cases, with a small number of mutations for the rarer alleles. Due to the heterogeneity of β-thalassaemia and the multi-ethnicity of Malaysians, molecular diagnostics may be expensive and time consuming. Methods: A simple polymerase chain reaction (PCR) approach involving a multiplex amplification refractory mutation system (MARMS) and one amplification refractory mutation system (ARMS), consisting of 20 β-globin gene mutations, were designed and employed to investigate β-thalassaemia patients and carriers. Results: Out of 169 carriers tested with the MARMS, Cd 41/42 (–TTCT), Cd 26 (A–G) HbE, IVS 1–1 (G–T), and IVS 1–5 (G–C) were the most common mutations, accounting for 78.1%. Among the Malays, Cd 26 (A–G) HbE, Cd 41/42 (–TTCT), IVS 1–1 (G–T), and IVS 1–5 (G–C) were the most common mutations, accounting for 81.4%, whereas Cd 41/42 (–TTCT) and IVS 2–654 (C–T) were most common among the Chinese (79.1%). Conclusion: We propose the use of this cheap, easy to interpret, and simple system for the molecular diagnostics of β-thalassaemia among Malaysians at the Institute for Medical Research (IMR)

Background: Depression is one of the common post-menopausal symptoms. In addition to estrogen deficiency, social instability stress may contribute as an additional underlying factor in the development of depressive behaviour in females. Therefore, this study was aimed at examining the influence of social instability stress on depressive behaviour in ovariectomized rats. Methods: The rats were divided into four groups (n = 5 per group); (i) sham-operated control without stress, (ii) sham-operated control with stress, (iii) ovariectomized without stress, and (iv) ovariectomized with stress. These rats were subjected to social instability stress procedures for 15 days prior to an enforced swimming test. Struggling, immobility, and swimming times were recorded promptly. Results: The results were analysed using the one-way analysis of variance (ANOVA) and a P value of < 0.05 was considered as significant. The mean durations of struggling, immobility, and swimming behaviour were significantly distinct among the four groups. Ovariectomized rats exhibited a substantial decrease in struggling and swimming behaviour, and an increase in immobility behaviour in comparison with the sham-operated controls (P < 0.05). Ovariectomized rats with stress displayed a supplementary decrease in struggling and swimming behaviour as well as an advanced increase in immobility behaviour, compared to sham-operated controls with or without stress (P < 0.05). Conclusion: In summary, these findings suggest that ovariectomized rats encountered an augmented amount of depressive behaviour following social instability stress.

Objectives: Alpha thalassaemia is wide spread in Malaysia and is a public health problem. This study aimed to describe the carrier frequencies of α‒thalassaemia and its distribution among major ethnic groups in three states of Malaysia. Methods: Educational forums were organised and study was explained to students from three schools. Students were invited to take part in the screening with parent consent. A total of 8420 adolescent students aged 16 years volunteered to participate in the study. Peripheral blood samples were analysed for complete blood counts, haemoglobin quantification and typing, and serum ferritin levels. Genomic DNA was used for screening alpha thalassaemia alleles by PCR based molecular methods. Results: We identified seven α‒globin gene defects in 341 (4.08%) students: amongst them α+‒ and α0‒thalassaemias were detected in 232 (2.77%) and 107 (1.28%) students respectively. Genotype ‒α3.7/αα was the most prevalent among sub-populations of Malay, indigenous communities of Sahab and Indian, while ‒‒SEA/αα deletion is more prevalent in Malaysian Chinese. It is estimated that 63 pregnancies annually are at risk of Hb Bart’s hydrops fetalis. Conclusions: We have demonstrated the prevalence and mutation patterns of α‒thalassaemia in the 16 year olds in three states of Malaysia. High α0‒thalassaemia deletions amongst the study subjects place these carriers at an increased risk of conceiving fetuses with HbH disease and Hb Bart’s hydrops fetalis should they choose another heterozygous partner. It is therefore highly recommended to institute community screening programmes and provide prospective carriers with genetic counselling to help them make informed choices.

Haemoglobin S D-Punjab is a rare compound heterozygous haemoglobinopathy characterised by the presence of two β globin gene variants: β6(GAG→GTG) and β121(GAA→CAA). These patients’ clinical and haematological features mimic haemoglobin S disease. We describe the first case of doubly heterozygous HbSD-Punjab from Malaysia managed with regular blood transfusion at the age of one. This case highlights the propensity for occurrence of rare phenotypes within our multi-ethnic population and emphasises the importance of accurate genotyping to avoid erroneous counselling, and to plan an effective patient management strategy before complication evolves.

Introduction: Minocycline has been demonstrated to have potent effects on neurologic structures and functions in several animal models. However, its neuroprotective properties following a single injection of lipopolysaccharide (LPS) in an adult rat model have not been clearly elucidated. This study investigated minocycline’s neuroprotective effects in the LPS-induced neuroinflammation rat model. Methods: Fifty adult male Sprague Dawley rats were split into five groups at random: (i) control, (ii) distilled water-treated LPS, (iii) 25 mg/kg minocycline-treated LPS, (iv) 50 mg/kg minocycline-treated LPS, and (v) 10 mg/kg memantine-treated LPS. On day 5, LPS (5 mg/kg) was given intraperitoneally once, whereas minocycline and memantine were given once daily for 14 days. Results: LPS was found to significantly induce β-amyloid peptide deposition and neuronal damage, and impair recognition memory, while administration of minocycline dose-dependently reversed these effects. These data suggest that LPS-induced recognition memory impairment by inducing β-amyloid peptide deposition and neuronal damage in the cortical and hippocampal areas. Furthermore, we compared minocycline with memantine administration, and these data suggested better effects in minocycline (50 mg/kg) and comparable effects between minocycline (25 mg/kg) and memantine (10 mg/kg) treatments in reducing β-amyloid peptide deposition, neuronal damage and recognition memory impairment induced by LPS. Conclusion: Minocycline may be a strong contender as an effective preventive-therapeutic drug for neuroinflammatory diseases such as Alzheimer’s disease (AD) based on these findings.

OBJECTIVE: This study was done to determine whether Tualang honey could prevent the altered nociceptive behaviour, with its associated changes of oxidative stress markers and morphology of the spinal cord, among the offspring of prenatally stressed rats. METHODS: Pregnant rats were divided into three groups: control, stress, and stress treated with Tualang honey. The stress and stress treated with Tualang honey groups were subjected to restraint stress from day 11 of pregnancy until delivery. Ten week old male offspring (n = 9 from each group) were given formalin injection and their nociceptive behaviours were recorded. After 2 h, the rats were sacrificed, and their spinal cords were removed to assess oxidative stress activity and morphology. Nociceptive behaviour was analysed using repeated measures analysis of variance (ANOVA), while the levels of oxidative stress parameters and number of Nissl-stained neurons were analysed using a one-way ANOVA. RESULTS: This study demonstrated that prenatal stress was associated with increased nociceptive behaviour, changes in the oxidative stress parameters and morphology of the spinal cord of offspring exposed to prenatal stress; administration of Tualang honey reduced the alteration of these parameters. CONCLUSION This study provides a preliminary understanding of the beneficial effects of Tualang honey against the changes in oxidative stress and neuronal damage in the spinal cord of the offspring of prenatally stressed rats.

Introduction: Increased nociceptive responses were shown in the offspring of prenatally stressed rats. Reports have demonstrated the anti-nociceptive effects of Tualang honey in the rat offspring. The present study was done to determine whether the modulation of nociceptive behaviour by Tualang honey was mediated by modulating changes in the histology, oxidative stress parameters and N-methyl-D-aspartate (NMDA) receptors in the thalamus of the rat offspring. Methods: Eighteen Sprague Dawley pregnant rats were randomly assigned to control (C), stress (S) and stress-treated with Tualang honey (SH) groups. Stress was given in a form of restraint stress.Tualang honey was given to SH group from first day of pregnancy until delivery. Thirty-three adult male offspring were subjected to formalin test before they were sacrificed. Nociceptive behaviour score, number of neurons, level of oxidative stress parameters and NMDA receptors in the thalamus were analysed by using one-way ANOVA. Results: The study demonstrated a significant decrease in mean nociceptive behaviour score (p<0.05) with lower malondialdehyde (MDA, p<0.05) and higher superoxide dismutase SOD and catalase levels in the thalamus of SH group compared to S group (p<0.05). There was also increased Nissl positive neurons in the thalamus of SH group compared to S group. There was no significant difference in NMDA receptor level between S and SH groups. Conclusion: The modulation of nociceptive responses in the prenatally stressed rat offspring by Tualang honey was associated with improvement in oxidative stress parameters and histology of the thalamus in the rat offspring exposed to prenatal stress.

Introduction: Studies show that adolescents are more reward sensitive compared to other age groups. The nucleus accumbens (NAcc) has been identified as a key brain area involved in reward through its connectivity to other reward-related brain areas. Our study aimed to characterise the white matter structural connectivity of nucleus accumbens with brain areas that are most often associated with reward in female adolescents. Methods: Fifteen healthy female Malay adolescents were recruited and underwent diffusion-weighted brain scanning. Two behaviour scales were also given to verify typical reward responsiveness. Then, probabilistic tractography and NAcc segmentation were performed on the data using FMRIB Software Library (FSL). Probabilistic tractography was performed to determine the relative connection probability of nucleus accumbens (NAcc) to areas shown to be associated with reward, namely amygdala, anterior cingulate cortex (ACC), medial orbitofrontal cortex (mOFC), hippocampus, ventrolateral prefrontal cortex (vlPFC) and dorsolateral prefrontal cortex (dlPFC). Connectivity-based segmentation of NAcc was performed to determine the spatial distribution of its connectivity with the target brain areas according to the highest connection probability. Results: The highest relative connection probability was found between NAcc to mOFC, while the NAcc parcellation showed the widest distribution of connection to mOFC compared to the other five targets on both sides of the brain. Conclusion: Our findings demonstrated the strongest structural connectivity and widest distribution between NAcc and mOFC compared with other brain areas related to reward. This study’s findings could be used as baseline to compare with people with atypical reward circuit problems.

Introduction: Trauma is a Global threat and the 5th highest cause of all-cause mortality in Malaysia caused predominantly due to road traffic accidents. Majority of trauma victims are young adults aged between 21-40 years old. In Malaysia, 24 out of 100,000 population die annually due to trauma, rating us amongst the highest in South East Asia. These alarming figures justify aggressive preventive and mitigation strategies. The aim of this paper is to promote the implementation of evidence-based interventions that will reduce the rate of preventable death because of trauma. Tranexamic acid is one of the few interventions in the early management of severe trauma with level-one evidence. Tranexamic acid has been proven to reduce all causes of mortality and mortality due to bleeding. Evidence proves that it is most effective when administered early, particularly within the 1st hour of trauma. This proposed guideline is formulated based upon quality evidence from multicentre studies, clinical practices in other countries and consideration of the local demographic factors with the intent of enabling an easy and simple pathway to administer tranexamic acid early in the care of the severely injured. Conclusion: The guideline highlights select pre-hospital criteria’s and the methods for drug administration. The authors recognise that some variants may be present amongst certain institutions necessitating minor adaptations, nevertheless the core principles of advocating tranexamic acid early in the course of pre-hospital trauma should be adhered to.