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The blood-brain barrier (BBB) is a complex, dynamic, and adaptable barrier between the peripheral blood system and the central nervous system. While this barrier protects the brain and spinal cord from inflammation and infection, it prevents most drugs from reaching the brain tissue. With the expanding interest in the pathophysiology of BBB, the development of in vitro BBB models has dramatically evolved. However, due to the lack of a standard model, a range of experimental protocols, BBB-phenotype markers, and permeability flux markers was utilized to construct in vitro BBB models. Several neuroinfectious diseases are associated with BBB dysfunction. To conduct neuroinfectious disease research effectively, there stems a need to design representative in vitro human BBB models that mimic the BBB's functional and molecular properties. The highest necessity is for an in vitro standardised BBB model that accurately represents all the complexities of an intact brain barrier. Thus, this in-depth review aims to describe the optimization and validation parameters for building BBB models and to discuss previous research on neuroinfectious diseases that have utilized in vitro BBB models. The findings in this review may serve as a basis for more efficient optimisation, validation, and maintenance of a structurally and functionally intact BBB model, particularly for future studies on neuroinfectious diseases.

Objectives. Endothelin-1 (ET-1), the most potent endogenous vasoconstrictor, generated by enzymatic cleavage catalyzed by an endothelin-converting enzyme (ECE), plays a significant role in the regulation of hypertension. Methods. This study investigates the effect of endothelin-1 (Lys198Asn/rs5370) and ECE (rs212526 C/T) gene polymorphisms with essential hypertension (EH) among Malay ethnics. To determine the association of gene polymorphism, 177 hypertensives and controls (196) were genotyped using Taqman method. Results. A significant difference was observed in ET-1 rs5370 and ECE rs212526 gene polymorphisms between EH and control subjects (P < 0.001). A significantly high body mass index (BMI), waist-to-hip ratio, fasting plasma glucose, hemoglobin A1c, systolic and diastolic blood pressure, and lipid profiles were observed among the EH patients when compared to controls (P < 0.05). Moreover, T allele (rs5370) carriers in males have a high risk for EH. There was no significant association between gender in ECE C/T polymorphisms (P > 0.05). Conclusion. Based on our result, it is evident that the T allele of ET-1 rs5370 polymorphism and C allele of ECE rs212526 have a significant genetic risk factor in EH among Malay subjects, and BMI and age are associated with hypertension.

Objective: To evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as a migraine prevention by conducting a systematic review and meta-analysis. Background: The efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as preventive migraine treatment remains debatable. Methods: PubMed, Scopus, CINAHL, CENTRAL, and BioMed Central databases were searched from their inception until December 2020. Randomised trials comparing high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex with sham for migraine prevention were included. The risk of bias was assessed using the Cochrane guidelines. Headache days, pain intensity, acute medication intake, and disability were extracted as study outcomes and the mean difference with a random-effects model was used to determine the effect size. Results: Meta-analysis revealed that high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex significantly reduced acute medication intake (Mean Difference = 9.78, p = 0.02, 95%CI: 1.60, 17.96, p = 0.02) and functional disability (Mean Difference = 8.00, p < 0.05, 95%CI: 4.21, 11.79). However, no differences were found in headache days and pain intensity reduction, although there was a slight trend favouring high-frequency repetitive transcranial magnetic stimulation. Conclusion: High-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex may be effective in reducing acute medication intake and disability. However, more studies are needed to strengthen this preliminary evidence.

Objective: To evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as a migraine prevention by conducting a systematic review and meta-analysis. Background: The efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as preventive migraine treatment remains debatable. Methods: PubMed, Scopus, CINAHL, CENTRAL, and BioMed Central databases were searched from their inception until December 2020. Randomised trials comparing high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex with sham for migraine prevention were included. The risk of bias was assessed using the Cochrane guidelines. Headache days, pain intensity, acute medication intake, and disability were extracted as study outcomes and the mean difference with a random-effects model was used to determine the effect size. Results: Meta-analysis revealed that high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex significantly reduced acute medication intake (Mean Difference = 9.78, p = 0.02, 95%CI: 1.60, 17.96, p = 0.02) and functional disability (Mean Difference = 8.00, p < 0.05, 95%CI: 4.21, 11.79). However, no differences were found in headache days and pain intensity reduction, although there was a slight trend favouring high-frequency repetitive transcranial magnetic stimulation. Conclusion: High-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex may be effective in reducing acute medication intake and disability. However, more studies are needed to strengthen this preliminary evidence.

Background: Type 2 Diabetes mellitus (T2DM) is a chronic metabolic disorder. It is a major non-communicable disease affecting 463 million people globally in 2019 and is expected to be double to about 700 million by 2045. The majority are Asians with Indian ethnicity in Malaysia reported as the highest prevalence of T2DM. Cardiovascular disease, renal failure, blindness and neuropathy, as well as premature death are the known morbidity and mortality resulted from T2DM. T2DM is characterized by the dysfunctional insulin physiology that causes reduction of glucose transport into the cells which lead to hyperglycaemia. Hence, one of the important treatments is an oral antidiabetic drug that lowers the serum glucose level in patients with T2DM. This drug will be transported across cell membranes by organic cation transporters (OCT). Therefore, it is important to identify the OCT candidate gene polymorphisms related to T2DM especially among the Indian ethnicity in Malaysia. Methods: Blood samples were collected from 132 T2DM patients and 133 controls. Genotyping of OCT1 (rs628031), OCT2 (rs145450955), OCT3 (rs3088442 and rs2292334) was performed using (PCR-RFLP). Results: No association was observed for genotypic and allelic distributions in all the gene polymorphisms of OCT genes (P > 0.05). However, a logistic regression analysis stratified by gender in a dominant model showed a significant difference for OCT3 among males with T2DM (P = 0.006). Significant association was also observed for OCT3 when stratified to subjects aged > 45 years old (P = 0.009). Conclusion: Based on these findings, the association of OCT3 (rs2292334) could be considered as a possible genetic risk factor for the development of T2DM among Indian males alone.

Pure alexia without agraphia is characterized by impaired reading due to damage to the occipitotemporal cortex with preserved writing skills. In this case report, we investigate the effect of multiple oral re-reading (MOR) therapy adjunct with transcranial direct current stimulation (tDCS) in improving reading recovery of a 64-year-old patient with pure alexia without agraphia following a stroke. His MRI revealed an area of infarct with microhemorrhages at the left occipitotemporal region. The patient was blinded to each therapy and underwent seven consecutive sessions of sham tDCS followed by seven consecutive sessions of real tDCS, coupled with 1-hour MOR therapy during each session. Western Aphasia Battery (WAB) was performed at baseline, before sham and real-tDCS, and 6 weeks after completing tDCS therapy. The patient showed improvement using both sham and real-tDCS with better reading comprehension, average reading time, and word per minute after real-tDCS. This study suggests that MOR, coupled with tDCS therapy may accelerate the reading recovery in patients with pure alexia.

Stroke care service in Malaysia is suboptimal despite the fact that it is one of the commonest cause of death. This is due to several limitations, including lack of resources and funding for the stroke care establishment and the management itself. Alternatively, other regions have come up with numerous ways to combat the difficulties in order to provide better stroke care services. We have identified the overwhelming benefits of creating stroke care units, thrombolysis services, and endovascular thrombectomy. For this reason, we designed a Regional Emergency Stroke Quick Response Network (RESQ) based on the needs of the current situation in Malaysia. With a standardised RESQ training, we hope to achieve close-knitted cooperation in between the emergency medical services, emergency department team and the RESQ, which subsequently will create an ideal improvised stroke care units.

Age-related macular degeneration (AMD), a leading cause of vision loss among elderly people is a progressive chronic disease of the central retina associated with environmental and genetic factors. Studies reported that gene polymorphism of various genes were analysed among AMD subjects from different populations with conflicting results. Among those, complement factor, vascular endothelial growth factor (VEGF), high temperature requirement A1 (HTRA1) and age-related maculopathy susceptibility 2 (ARMS2) genes were studied extensively among AMD subjects. In Malaysia the data on intravitreal ranibizumab drug therapy and the genetic association of gene polymorphisms among AMD remains unclear. The current study was initiated to determine the genetic association between the candidate gene polymorphisms in response to ranibizumab and also, the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy (PDT) among retinal eye disease patients from a tertiary care hospital. Upon ethical approval and consent, a total of 149 AMD and 152 controls were recruited for the prospective study. Moreover, a total number of 821 subjects were recruited for retrospective study using Electronic Medical Record database software from Hospital Selayang, Selangor. Genomic DNA and total RNA were extracted and the genotyping were analyzed using the conventional PCR and PCR-RFLP methods. The gene expression analysis was also performed for ARMS2 and HTRA1 genes. The statistical analysis was performed and all the data were analysed with the level of significance was set at P < 0.05. The mean age of AMD subjects were 68.6 ± 8.47 and 64.8 ± 10.21 years for the controls. Males were frequent in both AMD (64%) and controls (74%) compared to females. Among AMD, Chinese (57%) were high compared to Malays (34%) and Indians (9%), whereas in controls, Malays were high (42%) compared to Chinese (41%) and Indians (17%). From the retrospective analysis, ranibizumab was the most common

Age-related macular degeneration (AMD) is the most widely recognised cause of irreversible vision loss and previous studies have suggested that the advancement of wet AMD is influenced by both modifiable and non-modifiable elements. Single nucleotide polymorphism (SNPs) and copy number of variations (CNVs) have been associated with AMD in various populations, however the results are conflicting. Our aim is to determine the CNVs of Complement Factor H-Related genes among Malaysian subjects with wet AMD. 130 patients with wet AMD and 120 healthy controls were included in this research. DNA was extracted from all subjects and CNVs of CFH, CFHR1 and CFHR3 genes; determined using quantitative real-time PCR and were compared between the two groups. A consistent association was observed between CFH gene and wet AMD susceptibility (P < 0.05). The age-adjusted data suggests a possible increased risk of AMD disease (P < 0.05). No correlation was detected between CNVs and wet AMD for the remaining genes after we compared the frequencies of mean for that gene. An association was observed between CFH CNVs and wet AMD in the Malaysian population, however, strong evidence of a link with wet AMD was not found. Further investigative studies are needed using larger sample sizes to elucidate the role of CNVs in AMD pathogenesis.

Congenital heart disease (CHD) mainly is caused by the incomplete development of the heart during the first 6 weeks of pregnancy. Chromosomal and genetic abnormalities in the child and high levels of homocysteine in the blood are some of the risk factors related to CHD. Several studies in various populations have been done to determine the candidate genes in the predisposition to CHD with contradictory results, but there have been no studies that had been found in Malaysian CHD patients on homocysteine gene polymorphisms. Hence, this study was conducted to determine the allelic and genotypic analysis of the polymorphisms in candidate genes of the homocysteine enzymes; Methylenetetrahydrofolate Reductase (MTHFR), Cystathionine-b-synthase (CBS), Methionine Synthase (MTR) and Methionine Synthase Reductase (MTRR) genes. Based on the inclusion and exclusion criteria, buccal or blood samples were collected from 150 Malaysian non-syndromic CHD patients and 150 samples from healthy subjects as controls with no matching of age, genders and race between cases and controls. Genomic DNA was extracted from the samples using commercially available kits and the genotyping analysis for C677T MTHFR, A1298C MTHFR, A66G MTRR, A2756G MTR and 844ins68 CBS gene polymorphisms were analyzed using PCR-RFLP analysis. There was a significant difference observed in MTHFR A1298C gene polymorphism between cases and controls (P=0.008). However, there was no significant difference was observed for MTHFR C677T, MTRR A66G, MTR A2756G and CBS 844ins68 gene polymorphism. The association of MTHFR A1298C with the development of CHD in this study emphasis the role of MTHFR gene in the pathogenesis of non-syndromic CHD in Malaysian subjects.

Congenital heart disease (CHD) mainly is caused by the incomplete development of the heart during the first 6 weeks of pregnancy. Chromosomal and genetic abnormalities in the child and high levels of homocysteine in the blood are some of the risk factors related to CHD. Several studies in various populations have been done to determine the candidate genes in the predisposition to CHD with contradictory results, but there have been no studies that had been found in Malaysian CHD patients. Hence, this study was conducted to determine the allelic and genotypic analysis of the polymorphisms in candidate genes of the homocysteine enzymes which are the Methylenetetrahydrofolate Reductase (MTHFR), Cystathionine-b-synthase (CBS), Methionine Synthase (MTR) and Methionine Synthase Reductase (MTRR) genes. We conducted an unmatched cross-sectional study between CHD patients and healthy subjects to determine the association of these polymorphisms with CHD. Based on the inclusion and exclusion criteria, buccal or blood samples were collected from 150 Malaysian non-syndromic CHD patients and 150 samples from healthy subjects as controls with no matching of age, genders and race between cases and controls. Genomic DNA was extracted from the samples using commercially available kits and the genotyping analysis for C677T MTHFR, A1298C MTHFR, A66G MTRR, A2756G MTR and 844ins68 CBS gene polymorphisms are analyzed using the PCR-RFLP analysis. This study showed that there was a significant difference observed in the MTHFR A1298C gene polymorphisms between cases and controls with a significance value of P=0.008. When compared between genders and races, there was also a significant difference observed between males (P=0.003) and females (P=0.037) and among the Malay ethnics (P=0.023) of both CHD and control groups. On the other hand, no significant difference was observed for genotype frequencies between cases and controls of the MTHFR C677T, MTRR A66G, MTR A2756G and CBS 844ins68 gene pol