Survey on Untethering of the Spinal Cord and Urological Manifestations among Spina Bifida Patients in Malaysia.

The incidence and severity of urinary tract infections (UTIs) due to spina bifida is poorly understood in Malaysia. Tethering of the spinal cord is a pathological fixation of the cord in the vertebral column that can result in neurogenic bladder dysfunction and other neurological problems. It occurs in patients with spina bifida, and the authors of this study sought to investigate the impact of untethering on the urological manifestations of children with a tethered cord, thereby consolidating a previously known understanding that untethering improves bladder and bowel function. Demographic and clinical data were collected via an online questionnaire and convenient sampling techniques were used. A total of 49 individuals affected by spina bifida participated in this study. UTIs were reported based on patients' observation of cloudy and smelly urine (67%) as well as urine validation (60%). UTI is defined as the combination of symptoms and factoring in urine culture results that eventually affects the UTI diagnosis in spina bifida individuals irrespective of CISC status. Furthermore, 18% of the respondents reported being prescribed antibiotics even though they had no history of UTI. Therefore, indiscriminate prescription of antibiotics by healthcare workers further compounds the severity of future UTIs. Employing CISC (73%) including stringent usage of sterile catheters (71%) did not prevent patients from getting UTI. Overall, 33% of our respondents reported manageable control of UTI (0-35 years of age). All individuals below the age of 5 (100%, n = 14) were seen to have improved urologically after the untethering surgery under the guidance of the Malaysia NTD support group. Improvement was scored and observed using KUB (Kidneys, Ureters and Bladder) ultrasound surveillance before untethering and continued thereafter. Spina bifida individuals may procure healthy bladder and bowel continence for the rest of their lives provided that neurosurgical and urological treatments were sought soon after birth and continues into adulthood.

Eph and Ephrin Variants in Malaysian Neural Tube Defect Families.

Neural tube defects (NTDs) are common birth defects with a complex genetic etiology. Mouse genetic models have indicated a number of candidate genes, of which functional mutations in some have been found in human NTDs, usually in a heterozygous state. This study focuses on Ephs-ephrins as candidate genes of interest owing to growing evidence of the role of this gene family during neural tube closure in mouse models. Eph-ephrin genes were analyzed in 31 Malaysian individuals comprising seven individuals with sporadic spina bifida, 13 parents, one twin-sibling and 10 unrelated controls. Whole exome sequencing analysis and bioinformatic analysis were performed to identify variants in 22 known Eph-ephrin genes. We reported that three out of seven spina bifida probands and three out of thirteen family members carried a variant in either EPHA2 (rs147977279), EPHB6 (rs780569137) or EFNB1 (rs772228172). Analysis of public databases shows that these variants are rare. In exome datasets of the probands and parents of the probands with Eph-ephrin variants, the genotypes of spina bifida-related genes were compared to investigate the probability of the gene-gene interaction in relation to environmental risk factors. We report the presence of Eph-ephrin gene variants that are prevalent in a small cohort of spina bifida patients in Malaysian families.

Asymptomatic neurotoxicity of amyloid ß-peptides (Aß1-42 and Aß25-35) on mouse embryonic stem cell-derived neural cells.

One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer's disease (AD), is to induce neurotoxicity by amyloid beta (Aß) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aß in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Aß peptides (Aß1-42 and Aß25-35). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies in the absence of leukemia inhibitory factor, followed by the addition of all-trans retinoic acid as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aß1-42 and Aß25-35 for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 µM Aß1-42 and 50 µM Aß25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aß peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aß peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies.

Genetic Diversity of Pediculus humanus capitis (Phthiraptera: Pediculidae) in Peninsular Malaysia and Molecular Detection of Its Potential Associated Pathogens.

Pediculosis capitis caused by Pediculus humanus capitis (De Geer) is endemic all over the world, and children are mostly affected, particularly those living in overcrowded institutions. Several studies have shown that P. h. capitis carried human pathogenic bacteria, suggesting the potential role of head lice in the transmission of pathogens to humans. In this study, we determined the genetic diversity of head lice collected from welfare homes sheltering underprivileged children by using DNA barcoding and demonstrated the presence of Acinetobacter spp., Serratia marcescens, and Staphylococcus aureus in head lice, which have never been investigated before in Malaysia. Cox1 DNA barcoding identified the head lice, P. h. capitis collected from welfare homes across two geographical areas of Peninsular Malaysia as belonging to clades A, B, and D. Acinetobacter bacteria: Acinetobacter guillouiae, Acinetobacter junii, Acinetobacter baumannii, and Acinetobacter nosocomialis were detected in head lice belonging to clades A and also D. In addition, DNA from S. marcescens and S. aureus were also detected in both clades A and D. To our knowledge, this is the first report on the genetic diversity of head lice in Malaysia through DNA barcoding, as well as the first to provide molecular evidence on the type of bacteria occurring in head lice in Malaysia. It is anticipated that the DNA barcoding technique used in this study will be able to provide rapid and accurate identification of arthropods, in particular, medically important ectoparasites.

Cranial neural tube defect after trimethoprim exposure.

OBJECTIVES: The Neural Tube Defects Research Group of University of Malaya was approached to analyze a tablet named TELSE, which may have resulted in a baby born with central nervous system malformation at the University of Malaya Medical Centre. In this animal experimental study, we investigated the content of TELSE and exposure of its contents that resulted in failure of primary neurulation. RESULTS: Liquid Chromatography Tandem Mass spectrophotometry analysis of the TELSE tablet confirmed the presence of trimethoprim as the active compound. The TELSE tablet-treated females produced significant numbers of embryos with exencephaly (n = 8, 36.4%, *P < 0.0001), in all litters. The TELSE tablet-treated females subsequently given folic acid did not result in pregnancies despite there being evidence of possible resorption. Furthermore, after multiple rounds of mating which did not yield viable pregnancies, eventually, 2 embryos with exencephaly were harvested in a litter of 6 at 0.05% w/v pure trimethoprim once. The use of trimethoprim, a folic acid antagonist, peri-conceptionally increased the risk of exencephaly in the mouse.

Maternal intake of dietary virgin coconut oil modifies essential fatty acids and causes low body weight and spiky fur in mice.

BACKGROUND: Coconut oil is commonly used as herbal medicine worldwide. There is limited information regarding its effects on the developing embryo and infant growth. METHODS: We investigated the effect of virgin coconut oil post-natally and until 6 weeks old in mice (age of maturity). Females were fed with either standard, virgin olive oil or virgin coconut oil diets 1 month prior to copulation, during gestation and continued until weaning of pups. Subsequently, groups of pups borne of the respective diets were continuously fed the same diet as its mother from weaning until 6 weeks old. Profiles of the standard and coconut oil diets were analysed by gas chromatography flame ionization detector (GCFID). RESULTS: Analysis of the mean of the total weight gained/ loss over 6 weeks revealed that in the first 3 weeks, pups whose mothers were fed virgin coconut oil and virgin olive oil have a significantly lower body weight than that of standard diet pups. At 6 weeks of age, only virgin coconut oil fed pups exhibited significantly lower body weight. We report that virgin coconut oil modifies the fatty acid profiles of the standard diet by inducing high levels of medium chain fatty acids with low levels of essential fatty acids. Furthermore, pups borne by females fed with virgin coconut oil developed spiky fur. CONCLUSION: Our study has demonstrated that virgin coconut oil could affect infant growth and appearance via maternal intake; we suggest the use of virgin coconut oil as herbal medicine to be treated with caution.

Phosphorylated and Nonphosphorylated PfMAP2 Are Localized in the Nucleus, Dependent on the Stage of Plasmodium falciparum Asexual Maturation.

Plasmodium falciparum mitogen-activated protein (MAP) kinases, a family of enzymes central to signal transduction processes including inflammatory responses, are a promising target for antimalarial drug development. Our study shows for the first time that the P. falciparum specific MAP kinase 2 (PfMAP2) is colocalized in the nucleus of all of the asexual erythrocytic stages of P. falciparum and is particularly elevated in its phosphorylated form. It was also discovered that PfMAP2 is expressed in its highest quantity during the early trophozoite (ring form) stage and significantly reduced in the mature trophozoite and schizont stages. Although the phosphorylated form of the kinase is always more prevalent, its ratio relative to the nonphosphorylated form remained constant irrespective of the parasites' developmental stage. We have also shown that the TSH motif specifically renders PfMAP2 genetically divergent from the other plasmodial MAP kinase activation sites using Neighbour Joining analysis. Furthermore, TSH motif-specific designed antibody is crucial in determining the location of the expression of the PfMAP2 protein. However, by using immunoelectron microscopy, PPfMAP2 were detected ubiquitously in the parasitized erythrocytes. In summary, PfMAP2 may play a far more important role than previously thought and is a worthy candidate for research as an antimalarial.

First Case Report of Canthariasis in an Infant Caused by the Larvae of Lasioderma serricorne (Coleoptera: Anobiidae).

We report an unusual cause of gastrointestinal infection occurring in a 1-year-old infant patient who was brought to a public hospital in Kuala Lumpur, Malaysia. Larvae passed out in the patient's feces were confirmed by DNA barcoding as belonging to the species, Lasioderma serricorne (F.), known as the cigarette beetle. We postulate that the larvae were acquired from contaminated food and were responsible for gastrointestinal symptoms in the patient. To our knowledge, this the first report of human canthariasis caused by larvae of L. serricorne.

Intestinal Myiasis in a Malaysian Patient Caused by Larvae of Clogmia albipunctatus (Diptera: Psychodidae).

We report a case of human intestinal myiasis in a 41-yr-old female patient presented at a clinic in Seri Kembangan, Selangor, Malaysia. Larvae passed out in the patient's feces were sent to the Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. DNA barcoding confirmed the second case of intestinal myiasis in Malaysia involving the larvae of Clogmia albipunctatus (Duckhouse) (Diptera: Psychodidae). We review reported cases of myiasis and discuss the present case of intestinal myiasis in an urban patient.

The first Malay database toward the ethnic-specific target molecular variation.

BACKGROUND: The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). FINDINGS: Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). CONCLUSIONS: This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background.