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Ultrasound-guided combined supraclavicular brachial plexus and PECS II blocks for brachiobasilic fistula transposition surgery

Beh ZY, Lim SM, Lim WL, Ramli ARH

Indian J Anaesth, 2020 Dec;64(12):1079-1080.
PMID: 33542576 DOI: 10.4103/ija.IJA_535_20
Fulltext The effectiveness of surfactant replacement therapy for preterm infants with respiratory distress syndrome

Lim WL, Lim CT, Chye JK

Med J Malaysia, 1998 Dec;53(4):376-84.
PMID: 10971981

Thirty preterm infants weighing > or = 800 g with clinical and radiological evidence of respiratory distress syndrome (RDS) requiring mechanical ventilation with FiO2 of > or = 40% were given modified bovine surfactant (Survanta). They were compared with equal number of historical controls. Infants who received surfactant showed prompt and highly significant improvement in FiO2, mean airway pressure, arterial/alveolar oxygen tension ratio and ventilatory index. There was significant improvement in mortality rate (10% vs 33%; p = 0.03). Among the survivors, surfactant-treated infants required shorter duration of continuous positive airway pressure (CPAP) (3.4 vs 9.6 days; p = 0.04). For survivors with birthweight of > 1000 g, surfactant-treated infants required shorter duration of ventilatory support (intermittent positive pressure ventilation + CPAP) (7.5 vs 18.9 days, p = 0.02). Overall, surfactant-treated infants achieved full enteral feeds sooner (15.7 days vs 24.6 days; p = 0.03) and required shorter duration of total parenteral nutrition (13.9 days vs 25.6 days; p = 0.02). We concluded that surfactant replacement therapy was effective in the treatment of preterm infants with RDS.
Fulltext The Hippocampal Vulnerability to Herpes Simplex Virus Type I Infection: Relevance to Alzheimer's Disease and Memory Impairment

Yong SJ, Yong MH, Teoh SL, Soga T, Parhar I, Chew J, et al.

Front Cell Neurosci, 2021;15:695738.
PMID: 34483839 DOI: 10.3389/fncel.2021.695738

Herpes simplex virus type 1 (HSV-1) as a possible infectious etiology in Alzheimer's disease (AD) has been proposed since the 1980s. The accumulating research thus far continues to support the association and a possible causal role of HSV-1 in the development of AD. HSV-1 has been shown to induce neuropathological and behavioral changes of AD, such as amyloid-beta accumulation, tau hyperphosphorylation, as well as memory and learning impairments in experimental settings. However, a neuroanatomical standpoint of HSV-1 tropism in the brain has not been emphasized in detail. In this review, we propose that the hippocampal vulnerability to HSV-1 infection plays a part in the development of AD and amnestic mild cognitive impairment (aMCI). Henceforth, this review draws on human studies to bridge HSV-1 to hippocampal-related brain disorders, namely AD and aMCI/MCI. Next, experimental models and clinical observations supporting the neurotropism or predilection of HSV-1 to infect the hippocampus are examined. Following this, factors and mechanisms predisposing the hippocampus to HSV-1 infection are discussed. In brief, the hippocampus has high levels of viral cellular receptors, neural stem or progenitor cells (NSCs/NPCs), glucocorticoid receptors (GRs) and amyloid precursor protein (APP) that support HSV-1 infectivity, as well as inadequate antiviral immunity against HSV-1. Currently, the established diseases HSV-1 causes are mucocutaneous lesions and encephalitis; however, this review revises that HSV-1 may also induce and/or contribute to hippocampal-related brain disorders, especially AD and aMCI/MCI.
Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation

Tan SZK, Temel Y, Chan AY, Mok ATC, Perucho JAU, Blokland A, et al.

Brain Struct Funct, 2020 Sep;225(7):1957-1966.
PMID: 32594260 DOI: 10.1007/s00429-020-02102-w

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful as an unconditioned stimulus for modelling anticipatory fear and agoraphobia in a contextual fear conditioning paradigm. In this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then attempted to unravel some of the interactions with dopamine signalling using tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons. We showed that acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, while chronic administrations of both drugs were effective. We found that the dlPAG stimulation induced increase number of dopaminergic neurons in the ventral tegmental area (VTA) which was reversed in both chronic buspirone and escitalopram groups. We further found a strong positive correlation between the number of dopaminergic neurons and freezing in the VTA and showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta (SNpc) in escitalopram and buspirone groups, respectively. Overall, we showed that chronic treatment with an SSRI and a 5-HT1A agonist reduced anticipatory freezing behaviour which seems to be associated, through correlative studies, with a reversal of dlPAG stimulation induced increase in number of dopaminergic neurons in the VTA and/or SNpc.
Fulltext Quadratus Lumborum Block for Ovarian Cystectomy Surgery in a Patient With Severe Kyphoscoliosis

Beh ZY, Mok CS, Lim WL, Yip HW, Loh PS, Ramli MAS, et al.

Cureus, 2024 Jan;16(1):e51513.
PMID: 38318594 DOI: 10.7759/cureus.51513

Quadratus lumborum block (QLB) has been described as a regional analgesic technique in various abdominal surgeries. We present a case report of a high-risk patient who underwent ovarian cystectomy with QLB and deep sedation after failed neuraxial anesthesia. A 29-year-old female patient with comorbidities osteogenesis imperfecta, severe kyphoscoliosis with restrictive lung disease, and cervical syringomyelia with cranio-cervical junction stenosis (C2/C3). The patient had large ovarian cysts with associated dyspnea. She accepted surgery-an open bilateral ovarian cystectomy-despite being advised that general anesthesia would be high-risk. Regional anesthetic options were limited and challenging, given her anatomy and difficulty in positioning. Neuraxial anesthesia was attempted but was unsuccessful. The patient safely underwent surgery (lower midline laparotomy) using QLB. This clinically challenging case demonstrates the feasibility of QLB as the mainstay multimodal anesthetic approach (without general and neuraxial anesthesia) for abdominal surgery under exceptional circumstances.
Pyogenic meningitis in hospitalized children in Kelantan, Malaysia

Choo KE, Ariffin WA, Ahmad T, Lim WL, Gururaj AK

Ann Trop Paediatr, 1990 Mar;10(1):89-98.
PMID: 1694651

A 2.5-year retrospective study of pyogenic meningitis in hospitalized children in Kelantan was carried out with regard to aetiology, clinical features, investigation, treatment and outcome. There were 58 children with 43 cases (74.1%) occurring below the age of 1 year. Frequent presenting symptoms included fever (98.3%), fits (77.6%), anorexia (39.7%), vomiting (34.5%) and drowsiness (12.1%). On admission, 37 (63.7%) had neck stiffness, 10 (17.2%) had Kernig's sign and 32 (55.2%) had coma. CSF cultures were positive for Haemophilus influenzae in 29 (50%), Streptococcus pneumonia in 13 (22.4%) and Neisseria meningitidis in 3 (5.2%). The antibiotic sensitivity profiles showed that the three main organisms were 100% sensitive to Chloramphenicol, Streptococcus pneumoniae was 100% sensitive to penicillin, Neisseria meningitidis was 100% sensitive to penicillin and ampicillin, and Haemophilus influenzae was 90% sensitive to penicillin and ampicillin. The total hospital mortality was 18.9%. All but two of the eleven deaths occurred in children younger than 1 year. Nineteen of the 35 (54.3%) survivors attended for at least one follow-up after discharge from hospital. Of these 19 children, 47.4% had neurological sequelae.
Fulltext Pluripotent Human embryonic stem cell derived neural lineages for in vitro modelling of enterovirus 71 infection and therapy

Yap MS, Tang YQ, Yeo Y, Lim WL, Lim LW, Tan KO, et al.

Virol J, 2016 Jan 06;13:5.
PMID: 26738773 DOI: 10.1186/s12985-015-0454-6

The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials.
Plant Polyphenols as Neuroprotective Agents in Parkinson's Disease Targeting Oxidative Stress

Hor SL, Teoh SL, Lim WL

Curr Drug Targets, 2020;21(5):458-476.
PMID: 31625473 DOI: 10.2174/1389450120666191017120505

Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the human midbrain. Various ongoing research studies are competing to understand the pathology of PD and elucidate the mechanisms underlying neurodegeneration. Current pharmacological treatments primarily focused on improving dopamine metabolism in PD patients, despite the side effects of long-term usage. In recent years, it is recognized that oxidative stress-mediated pathways lead to neurodegeneration in the brain, which is associated with the pathophysiology of PD. The importance of oxidative stress is often less emphasized when developing potential therapeutic approaches. Natural plant antioxidants have been shown to mediate the oxidative stress-induced effects in PD, which has gained considerable attention in both in vitro and in vivo studies. Yet, clinical trials on natural polyphenol compounds are limited, restricting the potential use of these compounds as an alternative treatment for PD. Therefore, this review provides an understanding of the oxidative stress-induced effects in PD by elucidating the underlying events contributing to oxidative stress and explore the potential use of polyphenols in improving the oxidative status in PD. Preclinical findings have supported the potential of polyphenols in providing neuroprotection against oxidative stress-induced toxicity in PD. However, limiting factors, such as safety and bioavailability of polyphenols, warrant further investigations so as to make them the potential target for clinical applications in the treatment and management of PD.
Fulltext Physicochemical Properties and Biocompatibility of Electrospun Polycaprolactone/Gelatin Nanofibers

Lim WL, Chowdhury SR, Ng MH, Law JX

Int J Environ Res Public Health, 2021 04 29;18(9).
PMID: 33947053 DOI: 10.3390/ijerph18094764

Tissue-engineered substitutes have shown great promise as a potential replacement for current tissue grafts to treat tendon/ligament injury. Herein, we have fabricated aligned polycaprolactone (PCL) and gelatin (GT) nanofibers and further evaluated their physicochemical properties and biocompatibility. PCL and GT were mixed at a ratio of 100:0, 70:30, 50:50, 30:70, 0:100, and electrospun to generate aligned nanofibers. The PCL/GT nanofibers were assessed to determine the diameter, alignment, water contact angle, degradation, and surface chemical analysis. The effects on cells were evaluated through Wharton's jelly-derived mesenchymal stem cell (WJ-MSC) viability, alignment and tenogenic differentiation. The PCL/GT nanofibers were aligned and had a mean fiber diameter within 200-800 nm. Increasing the GT concentration reduced the water contact angle of the nanofibers. GT nanofibers alone degraded fastest, observed only within 2 days. Chemical composition analysis confirmed the presence of PCL and GT in the nanofibers. The WJ-MSCs were aligned and remained viable after 7 days with the PCL/GT nanofibers. Additionally, the PCL/GT nanofibers supported tenogenic differentiation of WJ-MSCs. The fabricated PCL/GT nanofibers have a diameter that closely resembles the native tissue's collagen fibrils and have good biocompatibility. Thus, our study demonstrated the suitability of PCL/GT nanofibers for tendon/ligament tissue engineering applications.
Fulltext Perioperative death in Malaysia: the transition phase from a developing nation to a developed one

Kandasami P, Inbasegaran K, Lim WL

Med J Malaysia, 2003 Aug;58(3):413-9.
PMID: 14750382

This paper examines the surgical pathology associated with perioperative deaths in a country that is undergoing the transition from a developing to a developed nation status. The data from an ongoing nation-wide perioperative mortality study was prospectively collected for the period July 1996 to December 1997 and analyzed. The surgical pathology related to perioperative deaths in Malaysia is different from other developing and developed countries. While death from trauma and the late presentation of surgical conditions are similar to developing countries, infective gastrointestinal conditions were rarely encountered. Diseases associated with advanced age such as colorectal cancer, peptic ulcer, urological diseases and vascular conditions are beginning to emerge. As the country races towards a developed nation status, increasing life expectancy and changing life-styles are expected to influence the disease pattern. The planning of surgical facilities and manpower development must recognize the changes taking place.
Neuroprotective Effects of Lactoferrin in Alzheimer's and Parkinson's Diseases: A Narrative Review

Yong SJ, Veerakumarasivam A, Lim WL, Chew J

ACS Chem Neurosci, 2023 Mar 30.
PMID: 36995304 DOI: 10.1021/acschemneuro.2c00679

Recent advancements in lactoferrin research have uncovered that lactoferrin does function not only as an antimicrobial protein but also as an immunomodulatory, anticancer, and neuroprotective agent. Focusing on neuroprotection, this literature review delineates how lactoferrin interacts in the brain, specifically its neuroprotective effects and mechanisms against Alzheimer's and Parkinson's diseases (AD and PD), the two most common neurodegenerative diseases. The neuroprotective pathways involving surface receptors (heparan sulfate proteoglycan (HSPG) and lactoferrin receptor (LfR)), signaling pathways (extracellular regulated protein kinase-cAMP response element-binding protein (ERK-CREB) and phosphoinositide 3-kinase/Akt (PI3K/Akt)), and effector proteins (A disintegrin and metalloprotease10 (ADAM10) and hypoxia-inducible factor 1α (HIF-1α)) in cortical/hippocampal and dopaminergic neurons are described. These cellular effects of lactoferrin are likely responsible for attenuating cognitive and motor deficits, amyloid-β and α-synuclein accumulation, and neurodegeneration in animal and cellular models of AD and PD. This review also discusses the inconsistent findings related to the neuroprotective effects of lactoferrin against AD. Overall, this review contributes to the existing literature by clarifying the potential neuroprotective effects and mechanisms of lactoferrin in the context of AD and PD neuropathology.
Fulltext Neural Differentiation of Human Pluripotent Stem Cells for Nontherapeutic Applications: Toxicology, Pharmacology, and In Vitro Disease Modeling

Yap MS, Nathan KR, Yeo Y, Lim LW, Poh CL, Richards M, et al.

Stem Cells Int, 2015;2015:105172.
PMID: 26089911 DOI: 10.1155/2015/105172

Human pluripotent stem cells (hPSCs) derived from either blastocyst stage embryos (hESCs) or reprogrammed somatic cells (iPSCs) can provide an abundant source of human neuronal lineages that were previously sourced from human cadavers, abortuses, and discarded surgical waste. In addition to the well-known potential therapeutic application of these cells in regenerative medicine, these are also various promising nontherapeutic applications in toxicological and pharmacological screening of neuroactive compounds, as well as for in vitro modeling of neurodegenerative and neurodevelopmental disorders. Compared to alternative research models based on laboratory animals and immortalized cancer-derived human neural cell lines, neuronal cells differentiated from hPSCs possess the advantages of species specificity together with genetic and physiological normality, which could more closely recapitulate in vivo conditions within the human central nervous system. This review critically examines the various potential nontherapeutic applications of hPSC-derived neuronal lineages and gives a brief overview of differentiation protocols utilized to generate these cells from hESCs and iPSCs.
Modeling Parkinson's Disease in Zebrafish

Najib NHM, Nies YH, Abd Halim SAS, Yahaya MF, Das S, Lim WL, et al.

CNS Neurol Disord Drug Targets, 2020;19(5):386-399.
PMID: 32640968 DOI: 10.2174/1871527319666200708124117

Parkinson's Disease (PD) is one of the most common neurodegenerative disorders that affects the motor system, and includes cardinal motor symptoms such as resting tremor, cogwheel rigidity, bradykinesia and postural instability. Its prevalence is increasing worldwide due to the increase in life span. Although, two centuries since the first description of the disease, no proper cure with regard to treatment strategies and control of symptoms could be reached. One of the major challenges faced by the researchers is to have a suitable research model. Rodents are the most common PD models used, but no single model can replicate the true nature of PD. In this review, we aim to discuss another animal model, the zebrafish (Danio rerio), which is gaining popularity. Zebrafish brain has all the major structures found in the mammalian brain, with neurotransmitter systems, and it also possesses a functional blood-brain barrier similar to humans. From the perspective of PD research, the zebrafish possesses the ventral diencephalon, which is thought to be homologous to the mammalian substantia nigra. We summarize the various zebrafish models available to study PD, namely chemical-induced and genetic models. The zebrafish can complement the use of other animal models for the mechanistic study of PD and help in the screening of new potential therapeutic compounds.
Microarray-based analysis of differential gene expression profile in rotenone-induced Parkinson's disease zebrafish model

Nies YH, Yahaya MF, Lim WL, Teoh SL

CNS Neurol Disord Drug Targets, 2023 Jun 08.
PMID: 37291778 DOI: 10.2174/1871527322666230608122552

BACKGROUND & OBJECTIVES: Despite much clinical and laboratory research that has been performed to explore the mechanisms of Parkinson's disease (PD), its pathogenesis remains elusive to date. Therefore, this study aimed to identify possible regulators of neurodegeneration by performing microarray analysis of the zebrafish PD model's brain following rotenone exposure.
METHODS: A total of 36 adult zebrafish were divided into two groups: control (n = 17) and rotenone-treated (n = 19). Fish were treated with rotenone water (5 µg/L water) for 28 days and subjected to locomotor behavior analysis. Total RNA was extracted from the brain tissue after rotenone treatment. The cDNA synthesized was subjected to microarray analysis and subsequently validated by qPCR.
RESULTS: Administration of rotenone has significantly reduced locomotor activity in zebrafish (p < 0.05), dysregulated dopamine-related gene expression (dat, th1, and th2, p < 0.001), and reduced dopamine level in the brain (p < 0.001). In the rotenone-treated group, genes involved in cytotoxic T lymphocytes (gzm3, cd8a, p < 0.001) and T cell receptor signaling (themis, lck, p < 0.001) were upregulated significantly. Additionally, gene expression involved in microgliosis regulation (tyrobp, p < 0.001), cellular response to IL-1 (ccl34b4, il2rb, p < 0.05), and regulation of apoptotic process (dedd1, p < 0.001) were also upregulated significantly.
CONCLUSION: The mechanisms of T cell receptor signaling, microgliosis regulation, cellular response to IL-1, and apoptotic signaling pathways have potentially contributed to PD development in rotenone-treated zebrafish.
Fulltext MicroRNA Dysregulation in Parkinson's Disease: A Narrative Review

Nies YH, Mohamad Najib NH, Lim WL, Kamaruzzaman MA, Yahaya MF, Teoh SL

Front Neurosci, 2021;15:660379.
PMID: 33994934 DOI: 10.3389/fnins.2021.660379

Parkinson's disease (PD) is a severely debilitating neurodegenerative disease, affecting the motor system, leading to resting tremor, cogwheel rigidity, bradykinesia, walking and gait difficulties, and postural instability. The severe loss of dopaminergic neurons in the substantia nigra pars compacta causes striatal dopamine deficiency and the presence of Lewy bodies indicates a pathological hallmark of PD. Although the current treatment of PD aims to preserve dopaminergic neurons or to replace dopamine depletion in the brain, it is notable that complete recovery from the disease is yet to be achieved. Given the complexity and multisystem effects of PD, the underlying mechanisms of PD pathogenesis are yet to be elucidated. The advancement of medical technologies has given some insights in understanding the mechanism and potential treatment of PD with a special interest in the role of microRNAs (miRNAs) to unravel the pathophysiology of PD. In PD patients, it was found that striatal brain tissue and dopaminergic neurons from the substantia nigra demonstrated dysregulated miRNAs expression profiles. Hence, dysregulation of miRNAs may contribute to the pathogenesis of PD through modulation of PD-associated gene and protein expression. This review will discuss recent findings on PD-associated miRNAs dysregulation, from the regulation of PD-associated genes, dopaminergic neuron survival, α-synuclein-induced inflammation and circulating miRNAs. The next section of this review also provides an update on the potential uses of miRNAs as diagnostic biomarkers and therapeutic tools for PD.
Maternal dexamethasone exposure inhibits the gonadotropin-releasing hormone neuronal movement in the preoptic area of rat offspring

Lim WL, Soga T, Parhar IS

Dev Neurosci, 2014;36(2):95-107.
PMID: 24713635 DOI: 10.1159/000360416

Migration and final positioning of gonadotropin-releasing hormone (GnRH) neurons in the preoptic area (POA) is critical for reproduction. It is known that maternal dexamethasone (DEX) exposure impairs reproductive function and behaviour in the offspring. However, it is still not known whether maternal DEX exposure affects the postnatal GnRH neurons in the offspring. This study determined the neuronal movement of enhanced green fluorescent protein (EGFP)-tagged GnRH neurons in slice culture of postnatal day 0 (P0), P5 and P50-60 transgenic male rats. Effect of maternal DEX treatment on EGFP-GnRH neuronal movement and F-actin distribution on GnRH neurons at P0 stage were studied. Time-lapse analysis of P0 and P5 EGFP-GnRH neurons displayed active cellular movement within the POA compared to young adult P50-60 stages, suggesting possible fine-tuning movement for positioning of early postnatal GnRH neurons. The DEX-treated EGFP-GnRH neurons demonstrated decreased motility in the POA and reduced F-actin distribution in the GnRH neurons at 60 h culture compared to the vehicle-treated. These results suggest that the P0 GnRH neuronal movement in the POA is altered by maternal DEX exposure, which possibly disrupts the fine-tuning process for positioning and development of early postnatal GnRH neurons in the brain, potentially linked to reproductive dysfunction in adulthood.
Fulltext Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring

Lim WL, Soga T, Parhar IS

Cell Tissue Res, 2014 Feb;355(2):409-23.
PMID: 24374911 DOI: 10.1007/s00441-013-1765-9

The migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the preoptic area (POA) from embryonic day 13 is important for successful reproduction during adulthood. Whether maternal glucocorticoid exposure alters GnRH neuronal morphology and number in the offspring is unknown. This study determines the effect of maternal dexamethasone (DEX) exposure on enhanced green fluorescent protein (EGFP) driven by GnRH promoter neurons (TG-GnRH) in transgenic rats dual-labelled with GnRH immunofluorescence (IF-GnRH). The TG-GnRH neurons were examined in intact male and female rats at different postnatal ages, as a marker for GnRH promoter activity. Pregnant females were subcutaneously injected with DEX (0.1 mg/kg) or vehicle daily during gestation days 13-20 to examine the number of GnRH neurons in P0 male offspring. The total number of TG-GnRH neurons and TG-GnRH/IF-GnRH neuronal ratio increased from P0 and P5 stages to P47-52 stages, suggesting temporal regulation of GnRH promoter activity during postnatal development in intact rats. In DEX-treated P0 males, the number of IF-GnRH neurons decreased within the medial septum, organum vasculosom of the lamina terminalis (OVLT) and anterior hypothalamus. The percentage of TG-GnRH neurons with branched dendritic structures decreased in the OVLT of DEX-P0 males. These results suggest that maternal DEX exposure affects the number and dendritic development of early postnatal GnRH neurons in the OVLT/POA, which may lead to altered reproductive functions in adults.
Fulltext Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

Lim WL, Idris MM, Kevin FS, Soga T, Parhar IS

Front Endocrinol (Lausanne), 2016;7:117.
PMID: 27630615 DOI: 10.3389/fendo.2016.00117

Maternal dexamethasone [(DEX); a glucocorticoid receptor agonist] exposure delays pubertal onset and alters reproductive behavior in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring's reproductive function by disrupting the gonadotropin-releasing hormone (GnRH) neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of GnRH promoter. Pregnant females were administered with DEX (0.1 mg/kg) or vehicle (VEH, water) daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0) males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT) was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the postsynaptic marker molecule, postsynaptic density 95, was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.
Fulltext Kisspeptin Activates Ankrd 26 Gene Expression in Migrating Embryonic GnRH Neurons

Soga T, Lim WL, Khoo AS, Parhar IS

Front Endocrinol (Lausanne), 2016;7:15.
PMID: 26973595 DOI: 10.3389/fendo.2016.00015

Kisspeptin, a newly discovered neuropeptide, regulates gonadotropin-releasing hormone (GnRH). Kisspeptins are a large RF-amide family of peptides. The kisspeptin coded by KiSS-1 gene is a 145-amino acid protein that is cleaved to C-terminal peptide kisspeptin-10. G-protein-coupled receptor 54 (GPR54) has been identified as a kisspeptin receptor, and it is expressed in GnRH neurons and in a variety of cancer cells. In this study, enhanced green fluorescent protein (EGFP) labeled GnRH cells with migratory properties, which express GPR54, served as a model to study the effects of kisspeptin on cell migration. We monitored EGFP-GnRH neuronal migration in brain slide culture of embryonic day 14 transgenic rat by live cell imaging system and studied the effects of kisspeptin-10 (1 nM) treatment for 36 h on GnRH migration. Furthermore, to determine kisspeptin-induced molecular pathways related with apoptosis and cytoskeletal changes during neuronal migration, we studied the expression levels of candidate genes in laser-captured EGFP-GnRH neurons by real-time PCR. We found that there was no change in the expression level of genes related to cell proliferation and apoptosis. The expression of ankyrin repeat domain-containing protein (ankrd) 26 in EGFP-GnRH neurons was upregulated by the exposure to kisspeptin. These studies suggest that ankrd 26 gene plays an unidentified role in regulating neuronal movement mediated by kisspeptin-GPR54 signaling, which could be a potential pathway to suppress cell migration.
Job insecurity and psychological distress during the COVID-19 outbreak: The moderating role of perceived supervisor support among hotel employees in Malaysia

Appannan JS, Maheswaran L, Raimee N, Lim WL, Amran FH

Work, 2022;73(4):1135-1145.
PMID: 36057808 DOI: 10.3233/WOR-211467

BACKGROUND: Millions of employees were laid off during the COVID-19 pandemic. The hospitality industry has been gravely hit by this crisis.
OBJECTIVE: Drawing from the theory of conservation of resources (COR), our study aims to examine possible factors that influence turnover intention among hotel employees.
METHODS: The hypotheses were tested on 141 hotel employees from Klang Valley, Malaysia. Data were collected by means of questionnaires, purposive sampling was employed, and PLS-SEM was used in performing the data analyses.
RESULTS: Job insecurity and psychological distress were found to be the potent antecedent of turnover intention. In contrast, the role of perceived supervisor support did not significantly moderate the effects of both job insecurity and psychological distress on the quitting intention.
CONCLUSION: Re-looking at existing policies and leadership styles may be fruitful in ensuring the sustainability path of an organization. This is pivotal in growing back the entire hospitality industry that has gravely affected by COVID-19.

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