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Fulltext Prevalence and associated factors of stress, anxiety and depression among emergency medical officers in Malaysian hospitals

Yahaya SN, Wahab SFA, Yusoff MSB, Yasin MAM, Rahman MAA

World J Emerg Med, 2018;9(3):178-186.
PMID: 29796141 DOI: 10.5847/wjem.j.1920-8642.2018.03.003

BACKGROUND: Demanding profession has been associated with poor psychological health due to multiple factors such as overworking hours and night shifts. This study is to determine prevalence and associated factors of depression, anxiety and stress among medical officers working at emergency department in Malaysian hospitals.
METHODS: A cross-sectional study was conducted on 140 emergency department medical officers working at general hospitals from seven Malaysia regions. They were randomly selected and their depression, anxiety and stress level were measured by the 21-item Depression, Anxiety, Stress Scale.
RESULTS: The highest prevalence was anxiety (28.6%) followed by depression (10.7%) and stress (7.9%). Depression, anxiety and stress between seven hospitals were not significantly different (P>0.05). Male medical officers significantly experienced more anxiety symptoms than female medical officers (P=0.0022), however depression and stress symptoms between male and female medical officers were not significantly different (P>0.05). Depression, anxiety and stress were not associated with age, working experience, ethnicity, marital status, number of shifts and type of system adopted in different hospitals (P>0.05).
CONCLUSION: The prevalence of anxiety was high, whereas for depression and stress were considerably low. Gender was the only factor significantly associated with anxiety. Other factors were not associated with depression, anxiety and stress. Future research should aim to gain better understanding on unique factors that affect female and male medical officers' anxiety level in emergency setting, thus guide authorities to chart strategic plans to remedy this condition.
Fulltext Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside

Ayipo YO, Yahaya SN, Alananzeh WA, Babamale HF, Mordi MN

Infect Genet Evol, 2021 Sep;93:104944.
PMID: 34052418 DOI: 10.1016/j.meegid.2021.104944

Since the emergence of their primitive strains, the complexity surrounding their pathogenesis, constant genetic mutation and translation are contributing factors to the scarcity of a successful vaccine for coronaviruses till moment. Although, the recent announcement of vaccine breakthrough for COVID-19 renews the hope, however, there remains a major challenge of accessibility to urgently match the rapid global therapeutic demand for curtailing the pandemic, thereby creating an impetus for further search. The reassessment of results from a stream of experiments is of enormous importance in identifying bona fide lead-like candidates to fulfil this quest. This review comprehensively highlights the common pathomechanisms and pharmacological targets of HCoV-OC43, SARS-CoV-1, MERS-CoV and SARS-CoV-2, and potent therapeutic potentials from basic and clinical experimental investigations. The implicated targets for the prevention and treatment include the viral proteases (Mpro, PLpro, 3CLpro), viral structural proteins (S- and N-proteins), non-structural proteins (nsp 3, 8, 10, 14, 16), accessory protein (ns12.9), viroporins (3a, E, 8a), enzymes (RdRp, TMPRSS2, ADP-ribosyltransferase, MTase, 2'-O-MTase, TATase, furin, cathepsin, deamidated human triosephosphate isomerase), kinases (MAPK, ERK, PI3K, mTOR, AKT, Abl2), interleukin-6 receptor (IL-6R) and the human host receptor, ACE2. Notably among the 109 overviewed inhibitors include quercetin, eriodictyol, baicalin, luteolin, melatonin, resveratrol and berberine from natural products, GC373, NP164 and HR2P-M2 from peptides, 5F9, m336 and MERS-GD27 from specific human antibodies, imatinib, remdesivir, ivermectin, chloroquine, hydroxychloroquine, nafamostat, interferon-β and HCQ from repurposing libraries, some iron chelators and traditional medicines. This review represents a model for further translational studies for effective anti-CoV therapeutic designs.
Fulltext β-Carboline alkaloids induce structural plasticity and inhibition of SARS-CoV-2 nsp3 macrodomain more potently than remdesivir metabolite GS-441524: computational approach

Ayipo YO, Yahaya SN, Babamale HF, Ahmad I, Patel H, Mordi MN

Turk J Biol, 2021;45(4):503-517.
PMID: 34803450 DOI: 10.3906/biy-2106-64

The nsp3 macrodomain is implicated in the viral replication, pathogenesis and host immune responses through the removal of ADP-ribosylation sites during infections of coronaviruses including the SARS-CoV-2. It has ever been modulated by macromolecules including the ADP-ribose until Ni and co-workers recently reported its inhibition and plasticity enhancement unprecedentedly by remdesivir metabolite, GS-441524, creating an opportunity for investigating other biodiverse small molecules such as β-Carboline (βC) alkaloids. In this study, 1497 βC analogues from the HiT2LEAD chemical database were screened, using computational approaches of Glide XP docking, molecular dynamics simulation and pk-CSM ADMET predictions. Selectively, βC ligands, 129, 584, 1303 and 1323 demonstrated higher binding affinities to the receptor, indicated by XP docking scores of -10.72, -10.01, -9.63 and -9.48 kcal/mol respectively than remdesivir and GS-441524 with -4.68 and -9.41 kcal/mol respectively. Consistently, their binding free energies were -36.07, -23.77, -24.07 and -17.76 kcal/mol respectively, while remdesivir and GS-441524 showed -21.22 and -24.20 kcal/mol respectively. Interestingly, the selected βC ligands displayed better stability and flexibility for enhancing the plasticity of the receptor than GS-441524, especially 129 and 1303. Their predicted ADMET parameters favour druggability and low expressions for toxicity. Thus, they are recommended as promising adjuvant/standalone anti-SARS-CoV-2 candidates for further study.Key words: SARS-CoV-2, nsp3 macrodomain, ADP-ribose, β-carboline, bioinformatics, drug design.
Challenges of status epilepticus management in a resource-limited setting: A review

Lim KS, Fong SL, Yahaya SN, Thuy Le MA, Khosama H

IBRO Neurosci Rep, 2024 Dec;17:83-86.
PMID: 39026897 DOI: 10.1016/j.ibneur.2024.06.001

Status epilepticus (SE) is a life-threatening neurological condition with significant mortality. Rapid management is essential to minimize the mortality and disability of SE. Two recent trials provided evidence to guide SE management in early and established stages. The Rapid Anticonvulsant Medication Prior To Arrival Trial (RAMPART, 2011) showed that intramuscular midazolam is a better alternative for early convulsive SE in prehospital settings. The Established Status Epilepticus Treatment Trial (ESETT, 2020) supported the use of sodium valproate and levetiracetam as second-line treatment for its efficacy and shorter administration time. However, there are challenges to revising the status epilepticus management in resource-limited settings, in pre-hospital, first- and second-line treatment, as well as management of refractory and super-refractory SE. These challenges included restrictions or lack of training in the administration of benzodiazepine in the prehospital setting, limited availability and accessibility of newer antiseizure medications (ASMs) in emergency departments and smaller hospitals, and low clinicians' awareness of the latest evidence. A collaborative effort to educate, improve awareness, and make certain ASMs more readily available is recommended to achieve a better clinical outcome in SE.