Displaying publications 1 - 20 of 44 in total

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  1. Kamal MA, Smith PF, Chaiyakunapruk N, Wu DBC, Pratoomsoot C, Lee KKC, et al.
    Br J Clin Pharmacol, 2017 07;83(7):1580-1594.
    PMID: 28176362 DOI: 10.1111/bcp.13229
    AIMS: A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios.

    METHODS: The pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration-time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R0 ), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case-fatality rates. Change in quality-adjusted life years was determined relative to base case.

    RESULTS: Oseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios.

    CONCLUSION: This methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework.

  2. Yu L, Abd Ghani MK, Aghemo A, Barh D, Bassetti M, Catena F, et al.
    Curr Med Chem, 2023;30(39):4390-4408.
    PMID: 36998130 DOI: 10.2174/0929867330666230330092725
    The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular disease, lung disease, and diabetes have particularly been high. A bibliometrics analysis on author's keywords was carried out, and searched for possible links between various coronavirus studies over the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition, malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to each other. Based on these findings, we hypothesized that the human immune system is a multilevel super complex system, which employs multiple strategies to contain microorganism infections and restore homeostasis. It was also found that the behavior of the immune system is not able to be described by a single immunological theory. However, one main strategy is "self-destroy and rebuild", which consists of a series of inflammatory responses: 1) active self-destruction of damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus, invading microorganisms' clearance could be only a passive bystander response to this destroy-rebuild process. Microbial infections could be self-limiting and promoted as an indispensable essential nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state in the patient may play an important role in the pathogenesis of COVID-19. Finally, a few possible coping strategies to mitigate COVID-19, including vaccination, are discussed.
  3. Allam VSRR, Paudel KR, Gupta G, Singh SK, Vishwas S, Gulati M, et al.
    Environ Sci Pollut Res Int, 2022 Sep;29(42):62733-62754.
    PMID: 35796922 DOI: 10.1007/s11356-022-21454-w
    Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.
  4. Tsagkaris C, Bilal M, Aktar I, Aboufandi Y, Tas A, Aborode AT, et al.
    Curr Alzheimer Res, 2022 Sep 08.
    PMID: 36089786 DOI: 10.2174/1567205019666220908084559
    The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), a respiratory pathogen with neuroinvasive potential. Neurological COVID-19 manifestations include loss of smell and taste, headache, dizziness, stroke, and potentially fatal encephalitis. Several studies found elevated proinflammatory cytokines such as TNF-α, IFN-γ, IL-6 IL-8, IL-10 IL-16, IL-17A, and IL-18 in severely and critically ill COVID-19 patients, which may persist even after apparent recovery from infection. Biomarker studies on CSF and plasma and serum from COVID-19 patients have also shown a high level of IL-6, intrathecal IgG, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and tau protein. Emerging evidence on the matter has established the concept of COVID-19 associated neuroinflammation, in the context of COVID-19 associated cytokine storm. While the short-term implications of this condition are extensively documented, its long-term implications are yet to be understood. The association of the aforementioned cytokines with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis, may increase COVID-19 patients' risk to develop neurodegenerative diseases. Analysis of proinflammatory cytokines and CSF biomarkers in patients with COVID-19 can contribute to the early detection of the disease's exacerbation, monitoring the neurological implications of the disease and devising risk scales, and identifying treatment targets.
  5. Arif NMNA, Roslan NS, Ismail SB, Nayak RD, Jamian MR, Mohamad Ali Roshidi AS, et al.
    PMID: 34444193 DOI: 10.3390/ijerph18168446
    Medical training is intensive and predisposes students to psychological distress and burnout. Unaddressed burnout in medical training may persist in the internship phase and impact the quality of patient care. While some associations have been established, the link between some individual factors and training characteristics with distress and burnout in medical training remained unclear. In this study, we aim to examine the prevalence of psychological distress and burnout, and its association with gender, training phase, funding status, cumulative grade points average (CGPA), and coping strategies among medical students. The study applied a multicenter cross-sectional study design and convenience sampling on medical students from two medical schools from Malaysia and India. We used a self-reporting instrument that includes demographic details, the 12-item General Health Questionnaire (GHQ), the Copenhagen Burnout Inventory (CBI), and the Brief Coping Orientation to Problems Experienced (Brief COPE). A total of 748 medical students participated in the study. The prevalence of psychological distress, personal-related, work-related, and patient-related burnout were 33.0%, 56.1%, 35.0%, and 26.2%, respectively. Being male, clinical year, self-funded, and having a CGPA of more than 3.50 predicted psychological distress and burnout with mixed results. Maladaptive coping mechanisms consistently predicted the risk of psychological distress and burnout by more than two times. The findings indicate that primary and secondary mental health interventions have a role in medical training. A systematic intervention should incorporate coping skills training alongside institutional-targeted intervention.
  6. Wu DBC, Chaiyakunapruk N, Pratoomsoot C, Lee KKC, Chong HY, Nelson RE, et al.
    Epidemiol Infect, 2018 03;146(4):496-507.
    PMID: 29446343 DOI: 10.1017/S0950268818000158
    Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients' quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
  7. Rasool M, Malik A, Qureshi MS, Manan A, Pushparaj PN, Asif M, et al.
    PMID: 24864161 DOI: 10.1155/2014/979730
    Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS). Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer's disease, Parkinson's disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.
  8. Rasool M, Iqbal J, Malik A, Ramzan HS, Qureshi MS, Asif M, et al.
    PMID: 24795768 DOI: 10.1155/2014/641597
    Oxidative stress, lipid peroxidation, and transaminase reactions are some of the mechanisms that can lead to liver dysfunction. A time-dependent study was designed to evaluate the ability of silymarin (SLN) and glycyrrhizin (GLN) in different dosage regimens to lessen oxidative stress in the rats with hepatic injury caused by the hepatotoxin carbon tetrachloride. Wistar male albino rats (n = 60) were randomly assigned to six groups. Group A served as a positive control while groups B, C, D, E, and F received a dose of CCl4 (50% solution of CCl4 in liquid paraffin, 2 mL/kg, intraperitoneally) twice a week to induce hepatic injury. Additionally, the animals received SLN and GLN in different doses for a period of six weeks. CCl4 was found to induce hepatic injury by significantly increasing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and thiobarbituric acid reactive substances while decreasing total protein and the activities of reduced glutathione, superoxide dismutase, and catalase. Treatment with various doses of SLN and GLN significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Our findings indicated that SLN and GLN have hepatoprotective effects against oxidative stress of the liver.
  9. Hassan M, Baig AA, Attique SA, Abbas S, Khan F, Zahid S, et al.
    Daru, 2021 Jun;29(1):73-84.
    PMID: 33537864 DOI: 10.1007/s40199-020-00384-3
    PURPOSE: To predict potential inhibitors of alpha-enolase to reduce plasminogen binding of Streptococcus pneumoniae (S. pneumoniae) that may lead as an orally active drug. S. pneumoniae remains dominant in causing invasive diseases. Fibrinolytic pathway is a critical factor of S. pneumoniae to invade and progression of disease in the host body. Besides the low mass on the cell surface, alpha-enolase possesses significant plasminogen binding among all exposed proteins.

    METHODS: In-silico based drug designing approach was implemented for evaluating potential inhibitors against alpha-enolase based on their binding affinities, energy score and pharmacokinetics. Lipinski's rule of five (LRo5) and Egan's (Brain Or IntestinaL EstimateD) BOILED-Egg methods were executed to predict the best ligand for biological systems.

    RESULTS: Molecular docking analysis revealed, Sodium (1,5-dihydroxy-2-oxopyrrolidin-3-yl)-hydroxy-dioxidophosphanium (SF-2312) as a promising inhibitor that fabricates finest attractive charges and conventional hydrogen bonds with S. pneumoniae alpha-enolase. Moreover, the pharmacokinetics of SF-2312 predict it as a therapeutic inhibitor for clinical trials. Like SF-2312, phosphono-acetohydroxamate (PhAH) also constructed adequate interactions at the active site of alpha-enolase, but it predicted less favourable than SF-2312 based on binding affinity.

    CONCLUSION: Briefly, SF-2312 and PhAH ligands could inhibit the role of alpha-enolase to restrain plasminogen binding, invasion and progression of S. pneumoniae. As per our investigation and analysis, SF-2312 is the most potent naturally existing inhibitor of S. pneumoniae alpha-enolase in current time.

  10. Aziz ZAA, Ahmad A, Setapar SHM, Karakucuk A, Azim MM, Lokhat D, et al.
    Curr Drug Metab, 2018;19(13):1100-1110.
    PMID: 30039757 DOI: 10.2174/1389200219666180723144850
    BACKGROUND: Essential oils are liquid extracts from aromatic plants, which have numerous applications in multiple industries. There are a variety of methods used for the extraction of essential oils, with each method exhibiting certain advantages and determining the biological and physicochemical properties of the extracted oils. Essential oils from different plant species contain more than 200 constituents which are comprised of volatile and non-volatile components. The application of essential oils as antimicrobial, anticancer, anti-inflammatory and anti-viral agents is due to their effective and efficient properties, inter alia.

    METHOD: Several advanced (supercritical fluid extraction, subcritical extraction liquid, solvent-free microwave extraction) and conventional (hydrodistillation, steam distillation, hydrodiffusion, solvent extraction) methods have been discussed for the extraction of essential oils. Advanced methods are considered as the most promising extraction techniques due to less extraction time, low energy consumption, low solvent used and less carbon dioxide emission.

    CONCLUSION: This manuscript reviewed the major research studies in the field and discussed several research findings on the chemical composition of essential oils, methods of oil extraction, and application of these oils in pharmaceutical and therapeutic fields. These essential oils can be used as anticancer, antimicrobial, antiviral, and as skin permeation enhancer agents.

  11. Masood W, Khan HA, Cheema HA, Shahid A, Bilal W, Kamal MA, et al.
    Inquiry, 2022;59:469580221139366.
    PMID: 36484333 DOI: 10.1177/00469580221139366
    While monkeypox virus (MPXV) remained endemic in central and western African countries, a sudden unusual spike of global cases among non-endemic countries is an enigma for scientists. With 257 cases reported as of 26th May 2021, a multi-country outbreak of monkeypox has been declared in countries including the UK, EU/EEA states, and North America. Even though the likelihood of transmissibility of MPXV is limited compared to COVID-19, yet a coordinated multidisciplinary effort is required to prevent any further global expansion. Few appropriate responsive approaches to contain the infection could be; limiting the contact with potential animal reservoirs, isolation of confirmed cases, using PPEs to prevent human-human transmission, awareness activities, and administration of pre and post prophylactic vaccination. In this review, we have discussed the previous and current outbreaks of MPXV along with the abrupt actions that are needed to address the situation.
  12. Kumar R, Khan FU, Sharma A, Siddiqui MH, Aziz IB, Kamal MA, et al.
    Environ Sci Pollut Res Int, 2021 Sep;28(34):47641-47650.
    PMID: 33895950 DOI: 10.1007/s11356-021-14028-9
    We are exposed to various chemical compounds present in the environment, cosmetics, and drugs almost every day. Mutagenicity is a valuable property that plays a significant role in establishing a chemical compound's safety. Exposure and handling of mutagenic chemicals in the environment pose a high health risk; therefore, identification and screening of these chemicals are essential. Considering the time constraints and the pressure to avoid laboratory animals' use, the shift to alternative methodologies that can establish a rapid and cost-effective detection without undue over-conservation seems critical. In this regard, computational detection and identification of the mutagens in environmental samples like drugs, pesticides, dyes, reagents, wastewater, cosmetics, and other substances is vital. From the last two decades, there have been numerous efforts to develop the prediction models for mutagenicity, and by far, machine learning methods have demonstrated some noteworthy performance and reliability. However, the accuracy of such prediction models has always been one of the major concerns for the researchers working in this area. The mutagenicity prediction models were developed using deep neural network (DNN), support vector machine, k-nearest neighbor, and random forest. The developed classifiers were based on 3039 compounds and validated on 1014 compounds; each of them encoded with 1597 molecular feature vectors. DNN-based prediction model yielded highest prediction accuracy of 92.95% and 83.81% with the training and test data, respectively. The area under the receiver's operating curve and precision-recall curve values were found to be 0.894 and 0.838, respectively. The DNN-based classifier not only fits the data with better performance as compared to traditional machine learning algorithms, viz., support vector machine, k-nearest neighbor, and random forest (with and without feature reduction) but also yields better performance metrics. In current work, we propose a DNN-based model to predict mutagenicity of compounds.
  13. Elsayed MEG, El-Abasiri RA, Marzo RR, Dardeer KT, Kamal MA, Abdelaziz H, et al.
    PLoS One, 2023;18(2):e0282264.
    PMID: 36848375 DOI: 10.1371/journal.pone.0282264
    BACKGROUND: Coronavirus disease-19 emerged in December 2019. Healthcare workers were exposed to this highly infectious virus during the pandemic and suffered several social and psychological consequences, such as anxiety, psychological distress, and burnout.

    OBJECTIVES: To assess the psychological distress, anxiety, depression, coping strategies, risk perception, and attitude toward interprofessional teamwork among Egyptian healthcare workers during the COVID-19 pandemic.

    METHODS: We conducted a cross-sectional online survey which consisted of five sections. The primary outcomes were anxiety (GAD-7), depression (PHQ-9), risk perception towards COVID-19, interprofessional teamwork attitude, and coping strategies during the Coronavirus disease-19 pandemic. The web-based questionnaire was distributed to Egyptian healthcare workers from the 20th of April 2020 to the 20th of May 2020. A snowball sampling method was used. Regression analysis was conducted to test the relationship between the socioeconomic characteristics and the previously mentioned outcomes.

    RESULTS: A total of 403 participants responded to the online questionnaire. The majority were females (70.5%) and within the age group of 26-40 years (77.7%), with 2-5 years of work experience (43.2%). Most participants were pharmacists (33%) and physicians (22.1%). Eighty-two participants (21%) reported moderate to severe anxiety, and 79 participants reported (19.4%) moderate to severe depressive symptoms. In the univariate model, the marital status was associated with depression (OR 0.47, 95% CI 0.28-0.78), anxiety (OR 0.52, 95% CI 0.32-0.85), and an attitude toward interprofessional teamwork (β = -1.96 95% CI -2.72 to -1.2). Providing direct care to the patients was associated with lower anxiety symptoms (AOR 0.256, 95% CI 0.094-0.697). More severe anxiety and depressive symptoms were associated with difficulties in everyday life and the professional work environment (AOR 4.246 and 3.3, P = 0.003 and 0.01, respectively). Availability of mental health facilities at the workplace was associated with a lower risk perception towards COVID-19 (β = -0.79, 95% CI -1.24 to -0.34) and a more positive attitude towards teamwork (β = 2.77 95% CI 1.38-4.15).

    CONCLUSIONS: According to our results, the COVID-19 pandemic was associated with mild anxiety and depression among healthcare workers in Egypt, especially pharmacists and physicians. We recommend more research targeting the mental health of healthcare workers in Egypt. If proven cost-effective and needed, wide-scale mental health screening and public health campaigns can facilitate effective prevention and treatment strategies. In addition, the availability of mental health facilities at the workplace could alleviate some of the risk perception associated with health emergencies and improve interprofessional teamwork.

  14. Kamal MA, Perveen K, Khan F, Sayyed RZ, Hock OG, Bhatt SC, et al.
    Front Microbiol, 2023;14:1228117.
    PMID: 37601347 DOI: 10.3389/fmicb.2023.1228117
    Heavy metal pollution of soil is a major concern due to its non-biodegradable nature, bioaccumulation, and persistence in the environment. To explore the probable function of EDTA in ameliorating heavy metal toxicity and achieve the sustainable development goal (SDG), Brassica juncea L. seedlings were treated with different concentrations of EDTA (0, 1.0, 2.0, 3.0, and 4.0 mM Kg-1) in heavy metal-polluted soil. Plant samples were collected 60 days after sowing; photosynthetic pigments, H2O2, monoaldehyde (MDA), antioxidant enzymes, and ascorbic acid content, as well as plant biomass, were estimated in plants. Soil and plant samples were also examined for the concentrations of Cd, Cr, Pb, and Hg. Moreover, values of the phytoremediation factor were utilized to assess the accumulation capacity of heavy metals by B. juncea under EDTA treatments. In the absence of EDTA, B. juncea seedlings accrued heavy metals in their roots and shoots in a concentration-dependent manner. However, the highest biomass of plants (roots and shoots) was recorded with the application of 2 mM kg-1 EDTA. Moreover, high levels (above 3 mM kg-1) of EDTA concentration have reduced the biomass of plants (roots and shoots), photosynthetic area, and chlorophyll content. The effect of EDTA levels on photosynthetic pigments (chlorophyll a and b) revealed that with an increment in EDTA concentration, accumulation of heavy metals was also increased in the plant, subsequently decreasing the chlorophyll a and b concentration in the plant. TLF was found to be in the order Pb> Hg> Zn> and >Ni, while TF was found to be in the order Hg>Zn>Ni>Pb, and the best dose was 3 mM kg-1 EDTA for Hg and 4 mM kg-1 for Pb, Ni, and Zn. Furthermore, hyperaccumulation of heavy metals enhanced the generation of hydrogen peroxide (H2O2), superoxide anions (O2•-), and lipid peroxidation. It also interrupts mechanisms of the antioxidant defense system. Furthermore, heavy metal stress reduced plant growth, biomass, and chlorophyll (chl) content. These findings suggest that the exogenous addition of EDTA to the heavy metal-treated seedlings increases the bioavailability of heavy metals for phytoextraction and decreases heavy metal-induced oxidative injuries by restricting heavy metal uptake and components of their antioxidant defense systems.
  15. Ahmad AA, Ubaidah Mustapa Kamal MA, Ruslan SR, Abdullah S, Ahmad AR
    J Shoulder Elbow Surg, 2020 Nov;29(11):2319-2325.
    PMID: 32499198 DOI: 10.1016/j.jse.2020.03.003
    BACKGROUND: Fixation of clavicle fractures has now become a more popular option as it provides better outcome compared with conservative management. Wide-awake local anesthesia no tourniquet (WALANT) has been effectively used in plating of distal radius and olecranon fractures. This paper expands the usage of WALANT into the shoulder girdle, namely plating of the clavicle that has not been described. The operation is typically performed under general anesthesia.

    METHODS: We report a case series of 16 patients who successfully underwent fixation of the clavicle under the wide-awake technique. The clavicle fractures were grouped under the AO Fracture Classification. The WALANT solution comprised 1% lidocaine, 1:100,000 epinephrine, and 10:1 sodium bicarbonate. A total of 40 mL was injected in each patient with 10 mL subcutaneously along the clavicle followed by 30 mL subperiosteally at multiple intervals and directions.

    RESULTS: The Numerical Pain Rating Score was 0 during WALANT injection and during surgery except for 2 patients with Numerical Pain Rating Scores of 1 and 2, respectively, during reduction.

    CONCLUSION: We conclude that clavicle plating under WALANT is a good alternative option of anesthesia.

  16. Liu S, Dang M, Lei Y, Ahmad SS, Khalid M, Kamal MA, et al.
    Curr Pharm Des, 2020;26(37):4808-4814.
    PMID: 32264807 DOI: 10.2174/1381612826666200407161842
    BACKGROUND: Alzheimer's disease (AD) is the most well-known reason for disability in persons aged greater than 65 years worldwide. AD influences the part of the brain that controls cognitive and non-cognitive functions.

    OBJECTIVE: The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology.

    METHODS: We performed a docking-based virtual screening utilizing the 3D structure of AChE and BuChE to search for potential inhibitors for AD. In this work, a screened inhibitor Ajmalicine similarity search was carried out against a natural products database (Super Natural II). Lipinski rule of five was carried out and docking studies were performed between ligands and enzyme using 'Autodock4.2'.

    RESULTS: Two phytochemical compounds SN00288228 and SN00226692 were predicted for the inhibition of AChE and BuChE, respectively. The docking results revealed Ajmalicine, a prominent natural alkaloid, showing promising inhibitory potential against AChE and BuChE with the binding energy of -9.02 and -8.89 kcal/mole, respectively. However, SN00288228- AChE, and SN00226692-BuChE were found to have binding energy -9.88 and -9.54 kcal/mole, respectively. These selected phytochemical compounds showed better interactions in comparison to Ajmalicine with the target molecule.

    CONCLUSION: The current study verifies that SN00288228 and SN00226692 are more capable inhibitors of human AChE and BuChE as compared to Ajmalicine with reference to ΔG values.

  17. Islam MA, Kundu S, Alam SS, Hossan T, Kamal MA, Hassan R
    PLoS One, 2021;16(4):e0249788.
    PMID: 33822812 DOI: 10.1371/journal.pone.0249788
    BACKGROUND: Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 started to spread globally since December 2019 from Wuhan, China. Fever has been observed as one of the most common clinical manifestations, although the prevalence and characteristics of fever in adult and paediatric COVID-19 patients is inconclusive. We aimed to conduct a systematic review and meta-analysis to estimate the overall pooled prevalence of fever and chills in addition to fever characteristics (low, medium, and high temperature) in both adult and paediatric COVID-19 patients.

    METHODS: The protocol of this systematic review and meta-analysis was registered with PROSPERO (CRD42020176327). PubMed, Scopus, ScienceDirect and Google Scholar databases were searched between 1st December 2019 and 3rd April 2020 without language restrictions. Both adult (≥18 years) and paediatric (<18 years) COVID-19 patients were considered eligible. We used random-effects model for the meta-analysis to obtain the pooled prevalence and risk ratio (RR) with 95% confidence intervals (CIs). Quality assessment of included studies was performed using the Joanna Briggs Institute critical appraisal tools. Heterogeneity was assessed using the I² statistic and Cochran's Q test. Robustness of the pooled estimates was checked by different subgroups and sensitivity analyses.

    RESULTS: We identified 2055 studies, of which 197 studies (n = 24266) were included in the systematic review and 167 studies with 17142 adults and 373 paediatrics were included in the meta-analysis. Overall, the pooled prevalence of fever in adult and paediatric COVID-19 patients were 79.43% [95% CI: 77.05-81.80, I2 = 95%] and 45.86% [95% CI: 35.24-56.48, I2 = 78%], respectively. Besides, 14.45% [95% CI: 10.59-18.32, I2 = 88%] of the adult COVID-19 patients were accompanied with chills. In adult COVID-19 patients, the prevalence of medium-grade fever (44.33%) was higher compared to low- (38.16%) and high-grade fever (14.71%). In addition, the risk of both low (RR: 2.34, 95% CI: 1.69-3.22, p<0.00001, I2 = 84%) and medium grade fever (RR: 2.79, 95% CI: 2.21-3.51, p<0.00001, I2 = 75%) were significantly higher compared to high-grade fever, however, there was no significant difference between low- and medium-grade fever (RR: 1.17, 95% CI: 0.94-1.44, p = 0.16, I2 = 87%). 88.8% of the included studies were of high-quality. The sensitivity analyses indicated that our findings of fever prevalence for both adult and paediatric patients are reliable and robust.

    CONCLUSIONS: The prevalence of fever in adult COVID-19 patients was high, however, 54.14% of paediatric COVID-19 patients did not exhibit fever as an initial clinical feature. Prevalence and risk of low and medium-grade fevers were higher compared to high-grade fever.

  18. Islam MA, Alam SS, Kundu S, Hossan T, Kamal MA, Cavestro C
    Front Neurol, 2020;11:562634.
    PMID: 33329305 DOI: 10.3389/fneur.2020.562634
    Background: Coronavirus disease 2019 (COVID-19) started to spread globally since December 2019 from Wuhan, China. Headache has been observed as one of the clinical manifestations in COVID-19 patients. We aimed to conduct a comprehensive systematic review and meta-analysis to estimate the overall pooled prevalence of headache in COVID-19 patients. Methods: PubMed, Scopus, ScienceDirect, and Google Scholar databases were searched to identify studies published between December 2019 and March 2020. Adult (≥18 years) COVID-19 patients were considered eligible. We used random-effects model to estimate the pooled prevalence with 95% confidence intervals (CIs). Quality assessment was done using the Joanna Briggs Institute critical appraisal tools. This study is registered with PROSPERO (CRD42020182529). Results: We identified 2,055 studies, of which 86 studies (n = 14,275, 49.4% female) were included in the meta-analysis. Overall, the pooled prevalence of headache in COVID-19 patients was 10.1% [95% CI: 8.76-11.49]. There was no significant difference of headache prevalence in severe or critical vs. non-severe (RR: 1.05, p = 0.78), survived (recovered or discharged) vs. non-survived (RR: 1.36, p = 0.23), and ICU vs. non-ICU (RR: 1.06, p = 0.87) COVID-19 patients. We detected 64.0, 34.9, and 1.1% of the included studies as high, moderate, and low quality, respectively. Conclusions: From the first 4-month data of the outbreak, headache was detected in 10.1% of the adult COVID-19 patients.
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