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Factors associated with prolonged cardiopulmonary resuscitation attempts in out-of-hospital cardiac arrest patients presenting to the emergency department

Embong H, Md Isa SA, Harunarashid H, Abd Samat AH

Australas Emerg Care, 2021 Jun;24(2):84-88.
PMID: 32847734 DOI: 10.1016/j.auec.2020.08.001

BACKGROUND: There is high variability among clinicians' decision of appropriate cardiopulmonary resuscitation (CPR) duration before deciding for termination of resuscitation. This study attempted to investigate factors associated with the decision to prolong resuscitation attempts in cardiac arrest patients treated in an emergencydepartment (ED).
METHODS: A retrospective study that evaluated two years of mortality registry starting in 2015 was conducted in the ED of University Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, Malaysia. Adult out-hospital cardiac arrest (OHCA) patients treated in the ED were included. Multivariate logistic regression analysis was utilized for the exploration of factors associated with prolonged CPR attempts (> 30min).
RESULTS: The median CPR duration was 24min (range 2-68min). Four variables were independently associated with prolonged CPR attempts: younger age (OR, 0.97; 95% CI, 0.95-0.99; p<0.001), pre-existing heart disease (OR, 1.97; 95% CI, 1.07-3.65; p=0.031), occurrence of transient return of spontaneous circulation (ROSC) (OR, 2.38; 95% CI, 1.05-5.36; p=0.037), and access to the ED by nonemergency medical services (EMS) transport (OR, 1.92; 95% CI, 1.09-3.37; p=0.024).
CONCLUSION: Patient-related and access-related factors were associated with prolonged CPR attempts among OHCA patients resuscitated in the ED.
Fulltext Probiotics for Alzheimer's Disease: A Systematic Review

Naomi R, Embong H, Othman F, Ghazi HF, Maruthey N, Bahari H

Nutrients, 2021 Dec 22;14(1).
PMID: 35010895 DOI: 10.3390/nu14010020

Alzheimer's disease (AD) is the most common form of neurodegenerative disorders affecting mostly the elderly. It is characterized by the presence of Aβ and neurofibrillary tangles (NFT), resulting in cognitive and memory impairment. Research shows that alteration in gut microbial diversity and defects in gut brain axis are linked to AD. Probiotics are known to be one of the best preventative measures against cognitive decline in AD. Numerous in vivo trials and recent clinical trials have proven the effectiveness of selected bacterial strains in slowing down the progression of AD. It is proven that probiotics modulate the inflammatory process, counteract with oxidative stress, and modify gut microbiota. Thus, this review summarizes the current evidence, diversity of bacterial strains, defects of gut brain axis in AD, harmful bacterial for AD, and the mechanism of action of probiotics in preventing AD. A literature search on selected databases such as PubMed, Semantic Scholar, Nature, and Springer link have identified potentially relevant articles to this topic. However, upon consideration of inclusion criteria and the limitation of publication year, only 22 articles have been selected to be further reviewed. The search query includes few sets of keywords as follows. (1) Probiotics OR gut microbiome OR microbes AND (2) Alzheimer OR cognitive OR aging OR dementia AND (3) clinical trial OR in vivo OR animal study. The results evidenced in this study help to clearly illustrate the relationship between probiotic supplementation and AD. Thus, this systematic review will help identify novel therapeutic strategies in the future as probiotics are free from triggering any adverse effects in human body.
Fulltext Early Intervention of Elateriospermum tapos Yoghurt in Obese Dams Mitigates Intergenerational Cognitive Deficits and Thigmotactic Behaviour in Male Offspring via the Modulation of Metabolic Profile

Naomi R, Rusli RNM, Huat TS, Embong H, Bahari H, Kamaruzzaman MA

Nutrients, 2023 Mar 21;15(6).
PMID: 36986254 DOI: 10.3390/nu15061523

Maternal obesity is an intergenerational vicious cycle and one of the primary causes of cognitive deficits and high anxiety levels in offspring, which often manifest independently of sex. It is proven that curbing the intergenerational inheritance of obesity through early intervention during the gestation period has a positive outcome on the body composition, cognitive function, and anxiety level of the offspring. A recent discovery shows that the consumption of Elateriospermum tapos (E. tapos) seed extract modulates body mass and ameliorates stress hormones in obese dams, while a probiotic bacterial strain can cross the placenta and boost a child's memory. Thus, we speculate that probiotics are the best medium to integrate plant extract (E. tapos extract) to access the effect on the child's cognition. Thus, this study aimed to investigate the early intervention of E. tapos yoghurt in obese dams in the cognition and anxiety levels of male offspring. In this study, 40 female rats were fed with a high-fat diet (HFD) to induce obesity before pregnancy, while another 8 rats were fed with standard rat pellets for 16 weeks. Upon successful copulation, treatment was initiated for the obese dams up to the postnatal day (PND) 21. The groups included normal chow and saline (NS), HFD and saline (HS), HFD and yoghurt (HY), HFD and 5 mg/kg E. tapos yoghurt (HYT5), HFD and 50 mg/kg E. tapos yoghurt (HYT50), and HFD and 500 mg/kg E. tapos yoghurt (HYT500). All rats were euthanised on PND 21, and the body mass index (BMI), Lee index, and waist circumference were measured for the male offspring. Hippocampal-dependent memory tests and open field tests were conducted to access for cognition and anxiety status. Fasting blood glucose (FBG), total fat (%), insulin, leptin, lipid profile, and antioxidant parameter on serum and hypothalamus (FRAP and GSH) were accessed on PND 21. The result shows male offspring of 50 mg/kg-supplemented obese dams have comparable total fat (%), lipid profile, insulin level, FBG level, plasma insulin level, recognition index, low anxiety level, and improved hypothalamic FRAP and GSH levels to the normal group. In conclusion, this study highlights that the effect of early intervention of our novel formulation of E. tapos yoghurt in obese dams alleviates cognitive deficits and anxiety in male offspring by modulating metabolic profiles at the dose of 50 mg/kg.
Fulltext Elateriospermum tapos Yoghurt as a Therapeutic Intervention for Obesity-Associated Cognitive Impairments and Anxiety-like Behaviour in a High Fat Diet Maternal Obese Rat Model

Naomi R, Teoh SH, Rusli RNM, Embong H, Bahari H, Kumar J

Nutrients, 2023 May 15;15(10).
PMID: 37242195 DOI: 10.3390/nu15102312

Maternal obesity can be considered an intergenerational cycle and is also an important indicator of cognitive impairments. It is thought that using natural products is the best and safest way to combat maternal obesity and associated complications. Recent studies have shown that Elateriospermum tapos (E. tapos) contains bioactive compounds with anti-obesity effects, and yoghurt is a convenient medium for supplementing obese maternal rats with E. tapos extract. Thus, the aim of this study is to investigate the impact of E. tapos in yoghurt on maternally obese rats' cognitive function supplemented with a high-fat diet (HFD). In this study, 48 female Sprague-Dawley rats were used. The rats were fed HFD for a period of 16 weeks to induce obesity, after which they were allowed to mate. Upon confirmation of pregnancy, obese rats were given varying doses of E. tapos (5, 50, and 500 mg/kg) in yoghurt until postnatal (PND) day 21. On PND 21, the dams' body mass index (BMI), Lee index, abdominal circumference, oxidative status, and metabolic profile were measured. The behavioral tests (open field, place, and object recognition) were conducted on PND 21 to access memory. The results show that the 50 and 500 mg/kg E. tapos in yoghurt supplemented groups had similar BMI, Lee index, abdominal circumference, lipid profile, FBG, insulin, FRAP, and GSH levels, as well as a similar recognition index, in comparison with the control group supplemented with saline. In conclusion, the results of this study indicate that the newly formulated E. tapos in yogurt can act as an anti-obesity agent in maternal obesity, alleviate anxiety, and enhance hippocampal-dependent memory.
Fulltext The Role of Oxidative Stress and Inflammation in Obesity and Its Impact on Cognitive Impairments-A Narrative Review

Naomi R, Teoh SH, Embong H, Balan SS, Othman F, Bahari H, et al.

Antioxidants (Basel), 2023 May 10;12(5).
PMID: 37237937 DOI: 10.3390/antiox12051071

Obesity is a chronic low-grade inflammatory condition that induces the generation of oxidative stress and inflammation. This oxidative stress and inflammation stimulate brain atrophy and some morphological changes in the brain that eventually result in cognitive impairments. However, there is no exact study that has summarized the role of oxidative stress and inflammation in obesity and its impact on cognitive impairments. Thus, the objective of this review is to recapitulate the current role of oxidative stress and inflammation in cognitive decline based on in vivo evidence. A comprehensive search was performed in Nature, Medline and Ovid, ScienceDirect, and PubMed, and the search was limited to the past 10 years of publication. From the search, we identified 27 articles to be further reviewed. The outcome of this study indicates that a greater amount of fat stored in individual adipocytes in obesity induces the formation of reactive oxygen species and inflammation. This will lead to the generation of oxidative stress, which may cause morphological changes in the brain, suppress the endogenous antioxidant system, and promote neuroinflammation and, eventually, neuronal apoptosis. This will impair the normal function of the brain and specific regions that are involved in learning, as well as memory. This shows that obesity has a strong positive correlation with cognitive impairments. Hence, this review summarizes the mechanism of oxidative stress and inflammation that induce memory loss based on animal model evidence. In conclusion, this review may serve as an insight into therapeutic development focusing on oxidative stress and inflammatory pathways to manage an obesity-induced cognitive decline in the future.
Fulltext Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature

Phing AH, Makpol S, Nasaruddin ML, Wan Zaidi WA, Ahmad NS, Embong H

Int J Mol Sci, 2023 Mar 15;24(6).
PMID: 36982655 DOI: 10.3390/ijms24065580

Delirium, a common form of acute brain dysfunction, is associated with increased morbidity and mortality, especially in older patients. The underlying pathophysiology of delirium is not clearly understood, but acute systemic inflammation is known to drive delirium in cases of acute illnesses, such as sepsis, trauma, and surgery. Based on psychomotor presentations, delirium has three main subtypes, such as hypoactive, hyperactive, and mixed subtype. There are similarities in the initial presentation of delirium with depression and dementia, especially in the hypoactive subtype. Hence, patients with hypoactive delirium are frequently misdiagnosed. The altered kynurenine pathway (KP) is a promising molecular pathway implicated in the pathogenesis of delirium. The KP is highly regulated in the immune system and influences neurological functions. The activation of indoleamine 2,3-dioxygenase, and specific KP neuroactive metabolites, such as quinolinic acid and kynurenic acid, could play a role in the event of delirium. Here, we collectively describe the roles of the KP and speculate on its relevance in delirium.
Fulltext Lipopolysaccharide-Induced Delirium-like Behaviour in a Rat Model of Chronic Cerebral Hypoperfusion Is Associated with Increased Indoleamine 2,3-Dioxygenase Expression and Endotoxin Tolerance

Ang HP, Makpol S, Nasaruddin ML, Ahmad NS, Tan JK, Wan Zaidi WA, et al.

Int J Mol Sci, 2023 Jul 31;24(15).
PMID: 37569622 DOI: 10.3390/ijms241512248

Indoleamine 2,3-dioxygenase (IDO) and the tryptophan-kynurenine pathway (TRP-KP) are upregulated in ageing and could be implicated in the pathogenesis of delirium. This study evaluated the role of IDO/KP in lipopolysaccharide (LPS)-induced delirium in an animal model of chronic cerebral hypoperfusion (CCH), a proposed model for delirium. CCH was induced by a permanent bilateral common carotid artery ligation (BCCAL) in Sprague Dawley rats to trigger chronic neuroinflammation-induced neurodegeneration. Eight weeks after permanent BCCAL, the rats were treated with a single systemic LPS. The rats were divided into three groups: (1) post-BCCAL rats treated with intraperitoneal (i.p.) saline, (2) post-BCCAL rats treated with i.p. LPS 100 μg/kg, and (3) sham-operated rats treated with i.p. LPS 100 μg/kg. Each group consisted of 10 male rats. To elucidate the LPS-induced delirium-like behaviour, natural and learned behaviour changes were assessed by a buried food test (BFT), open field test (OFT), and Y-maze test at 0, 24-, 48-, and 72 h after LPS treatment. Serum was collected after each session of behavioural assessment. The rats were euthanised after the last serum collection, and the hippocampi and cerebral cortex were collected. The TRP-KP neuroactive metabolites were measured in both serum and brain tissues using ELISA. Our data show that LPS treatment in CCH rats was associated with acute, transient, and fluctuated deficits in natural and learned behaviour, consistent with features of delirium. These behaviour deficits were mild compared to the sham-operated rats, which exhibited robust behaviour impairments. Additionally, heightened hippocampal IDO expression in the LPS-treated CCH rats was associated with reduced serum KP activity together with a decrease in the hippocampal quinolinic acid (QA) expression compared to the sham-operated rats, suggested for the presence of endotoxin tolerance through the immunomodulatory activity of IDO in the brain. These data provide new insight into the underlying mechanisms of delirium, and future studies should further explore the role of IDO modulation and its therapeutic potential in delirium.
Fulltext Analyzing Active Compounds in Elateriospermum tapos Yogurt for Maternal Obesity: A Network Pharmacology and Molecular Docking Study

Naomi R, Teoh SH, Embong H, Balan SS, Othman F, Mamat-Hamidi K, et al.

Foods, 2023 Sep 26;12(19).
PMID: 37835227 DOI: 10.3390/foods12193575

Maternal obesity, characterized by an elevated body mass index (BMI) during pregnancy, is known to have adverse effects on the offspring. However, a recent study suggests that Elateriospermum tapos (E. tapos) yogurt may hold potential in mitigating excessive weight retention post-pregnancy. Thus, this study aims to employ network pharmacology to explore the pharmacological effects of the bioactive compounds present in E. tapos yogurt against maternal obesity. Initially, a screening process is conducted to identify the bioactive compounds in E. tapos yogurt, followed by the prediction of potential gene targets for these compounds using Swiss Target Prediction and the SuperPred databases. Maternal obesity-associated genes are sourced from the OMIM, DisGeNet, and GeneCards databases. The interaction between the identified compounds and maternal obesity genes is established via protein-protein interaction analysis, gene ontology examination, and KEGG pathway analysis. To validate the results, molecular docking studies are conducted using AutoDock Tools software. The findings reveal that out of the 64 compounds analyzed, three meet the screening criteria, resulting in a total of 380 potential gene targets. Among these targets, 240 are shared with maternal obesity-related genes. Further analysis demonstrates the favorable affinity of these active compounds with key targets, linking them to biological processes involving protein phosphorylation, inflammation, as well as the pathways related to lipid metabolism, atherosclerosis, and the other signaling pathways. In conclusion, this study provides valuable insights into the potential pharmacological effects of the bioactive compounds found in E. tapos yogurt against maternal obesity. These findings open avenues for further exploration and potential therapeutic interventions targeting maternal obesity.
Fulltext Comparison of clinical and laboratory characteristics between severe and non-severe dengue in paediatrics

Idrus NL, Md Jamal S, Abu Bakar A, Embong H, Ahmad NS

PLoS Negl Trop Dis, 2023 Dec;17(12):e0011839.
PMID: 38113250 DOI: 10.1371/journal.pntd.0011839

BACKGROUND: The timely identification of severe dengue in peadiatric patients is of utmost importance, as any delay in diagnosis could lead to an irreversible state of shock potentially leading to fatal consequences. The primary aim of our study was to characterize dengue severity in paediatric patients based on initial symptoms, signs, and laboratory investigation of their presentation in the emergency department.
METHODOLOGY: We conducted a retrospective data retrieval from the medical records of 254 paediatric patients who had been diagnosed with confirmed cases of dengue fever. The clinical characteristics were compared between severe and non-severe dengue. Multiple logistic regression analysis was utilised to elucidate the variables that exhibited associations with severe dengue.
RESULTS: A total of 254 paediatric patients were included, among whom 15.4% (n = 39) were diagnosed with severe dengue. Multiple logistic regression analysis identified lethargy, systolic blood pressure (SBP) below 90 mmHg, capillary refilled time (CRT) longer than 2 seconds, ascites, and hepatomegaly were independently associated with severe dengue.
CONCLUSION: In paediatric patients, severe dengue is associated with specific clinical indicators, including lethargy, low systolic blood pressure, prolonged capillary refill time (CRT), and the presence of ascites and hepatomegaly. Identifying these clinical features early is crucial for primary care physicians, as it enables accurate diagnosis and timely intervention to manage severe dengue effectively.
Fulltext Phytochemical Analysis and Toxicity Assessment of Bouea Macrophylla Yoghurt

Rusli RNM, Naomi R, Yazid MD, Embong H, Perumal K, Othman F, et al.

Toxins (Basel), 2023 Feb 03;15(2).
PMID: 36828439 DOI: 10.3390/toxins15020125

The Bouea macrophylla fruit is native to Malaysia and is known for its many beneficial effects on one's health. Probiotics are well-known for their roles as anti-inflammatory, antioxidant, and anti-tumour properties due to their widespread use. As a result, the purpose of this study was to incorporate the ethanolic extract of Bouea macrophylla into yoghurt and then assess the rodents for any toxicological effects. According to the findings of the nutritional analysis, each 100 mL serving of the newly formulated yoghurt contains 3.29 g of fat, 5.79 g of carbohydrates, 2.92 g of total protein, and 2.72 g of sugar. The ability of the newly developed yoghurt to stimulate the growth of Lactobacilli was demonstrated by the fact that the peak intensity of Lactobacillus species was measured at 1.2 × 106 CFU/g while the titratable acidity of the lactic acid was measured at 0.599 CFU/g. In order to carry out the toxicological evaluation, forty-eight male Sprague Dawley (SD) rats were utilized. Oral administration of single doses of 2000 mg/kg over the course of 14 days was used for the study of acute toxicity. Subacute toxicity was studied by giving animals Bouea macrophylla yoghurt (BMY) at repeated doses of 50, 250, 500, and 1000 mg/kg/day over a period of 28 days, while the control group was given normal saline. The results of the acute toxicity test revealed that rats treated with increasing doses up to a maximum of 2000 mg/kg exhibited no signs of toxicity. After an additional 14 days without treatment, acute toxicity of a single dose (2000 mg/kg) of BMY did not show any treatment-related toxicity in any of the rats that were observed. According to the data from the subacute toxicity study, there were no differences between the treated groups and the control groups in terms of food and water intake, body weight, plasma biochemistry (AST, ALT, ALP, and creatinine), haematological products, or organ weights. The architecture of the liver, heart, and kidney were all found to be normal upon histological examination. This indicates that oral consumption of BMY did not result in any negative effects being manifested in the rodents.
Fulltext The role of Elateriospermum tapos yoghurt in mitigating high-fat dietary cause of maternal obesity-an experimental study

Naomi R, Rusli RNM, Othman F, Balan SS, Abidin AZ, Embong H, et al.

Front Endocrinol (Lausanne), 2023;14:1131830.
PMID: 37415666 DOI: 10.3389/fendo.2023.1131830

Maternal obesity is the key predictor for childhood obesity and neurodevelopmental delay in the offspring. Medicinal plants are considered to be the safe and best option, and at the same time, probiotic consumption during pregnancy provides beneficial effects for both the mother and the child. Current research has shown that Elateriospermum tapos (E. tapos) yoghurt is safe to consume and consists of many bioactive compounds that can exert an anti-obesity effect. Thus, this study has been designed to study the role of E. tapos yoghurt in mitigating maternal obesity. In this study, a total of 48 female Sprague Dawley (SD) rats were assigned to six groups, with eight rats per group, and obesity was induced over 16 weeks with a high-fat diet (HFD) pellet. On the 17th week, the rats were allowed to mate and pregnancy was confirmed through vaginal smear. The obese induced group was further divided into negative and positive control groups, followed by E. tapos yoghurt treatment groups with three different concentrations (5, 50, and 500 mg/kg). The changes in body weight, calorie intake, lipid profile, liver profile, renal profile, and histopathological analysis were measured on postnatal day (PND) 21. The results show that the group with the highest concentration of E. tapos yoghurt (HYT500) supplementation shows gradual reduction in body weight and calorie intake on PND 21 and modulates the lipid level, liver, and renal enzymes to a normal level similar to the normal group. In histological analysis, HYT500 reverses the damage caused by HFD in liver and colon, and reverses the adipocytes' hypertrophy in retroperitoneal white adipose tissue and visceral fat. In conclusion, supplementation of E. tapos yoghurt during the gestational period up to weaning is effective in the gradual weight loss of maternal obese dams from the 500-mg/kg-supplemented group in this study.
Fulltext Phytochemical component and toxicological evaluation of purple sweet potato leaf extract in male Sprague-Dawley rats

Hisamuddin ASB, Naomi R, Bin Manan KA, Bahari H, Yazid MD, Othman F, et al.

Front Pharmacol, 2023;14:1132087.
PMID: 37077809 DOI: 10.3389/fphar.2023.1132087

This study assessed the toxicity of lutein-rich purple sweet potato leaf (PSPL) extract in male Sprague-Dawley rats. Methods and study design: A total of 54 adult male Sprague-Dawley rats were used. For the acute toxicity study, three rats in the acute control group were fed 2,000 mg/kg of PSPL for 14 days. The subacute toxicity study included six rats each in four groups administered 50, 250, 500, or 1,000 mg/kg for 28 days and observed for further 14 days without treatment in the subacute control and subacute satellite groups. Changes in body weight; blood biochemistry; hematological parameters; relative organ weight; and histological sections of the heart, kidney, liver, pancreas, aorta, and retina were observed for signs of toxicity. Results: The gradual increase in weekly body weight, normal level full blood count, normal liver and kidney profile, relative organ weight, and histological sections of all stained organ tissue in the treated group compared with the acute, subacute, and satellite control groups demonstrated the absence of signs of toxicity. Conclusion: Lutein-rich PSPL extract shows no signs of toxicity up to 2,000 mg/kg/day.
Fulltext The role of lutein-rich purple sweet potato leaf extract on the amelioration of diabetic retinopathy in streptozotocin-induced Sprague-Dawley rats

Hisamuddin ASB, Naomi R, Manan KAB, Bahari H, Othman F, Embong H, et al.

Front Pharmacol, 2023;14:1175907.
PMID: 37274105 DOI: 10.3389/fphar.2023.1175907

The objective of this study is to access the effect of purple sweet potato leaf (PSPL) extract on diabetic retinopathy (DR) of streptozotocin (STZ)-induced male Sprague-Dawley (SD) rats. In this study, rats were injected intraperitoneally with a single dose of 60 mg/kg STZ, and diabetes was confirmed on day 7. Rats were further divided into a few groups, which were then orally administered with one of the following treatments: 25 mg/kg of gliclazide (D25G), 200 mg/kg of PSPL extract (DT 200), and 400 mg/kg of PSPL extract (DT 400). However, the normal control (NS) and control group for diabetic (DNS) were given normal saline (NS) for 12 weeks. The results show that the treated group demonstrated a reduction in serum oral glucose tolerance test (OGTT) levels of DT 200 and DT 400, and an increase in the serum and retinal insulin levels, and restored oxidative stress markers in serum and retina on week 12. The PSPL extract exhibited protective effects in maintaining the kidney, liver, retina, and pancreas architecture in 400 mg/kg compared to the 200 mg/kg treated group and D25G, thereby restoring fully transparent lenses in diabetes-induced rats. In conclusion, 400 mg/kg PSPL is the most effective dose for the amelioration of STZ-induced DR pathology in male SD rats.

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