Browse publications by year: 2021

  1. Keech AC, Oyama K, Sever PS, Tang M, Murphy SA, Hirayama A, et al.
    Circ J, 2021 Oct 25;85(11):2063-2070.
    PMID: 33980763 DOI: 10.1253/circj.CJ-20-1051
    BACKGROUND: There are concerns that Asian patients respond differently to some medications. This study evaluated the efficacy and safety of evolocumab among Asian vs. other subjects in the FOURIER trial, which randomized stable atherosclerosis patients to receive either evolocumab or placebo.Methods and Results:Effects of adding evolocumab vs. placebo to background statin therapy on low-density lipoprotein cholesterol (LDL-C) reductions, cardiovascular outcomes, and adverse events were compared among 27,564 participants with atherosclerotic disease, according to self-reported Asian (n=2,723) vs. other (n=24,841) races followed for a median of 2.2 years in the FOURIER trial. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. At randomization, Asians had slightly lower LDL-C (median 89 [IQR 78-104] mg/dL vs. 92 [80-109] mg/dL; P<0.001) and were much less likely to be on a high-intensity statin (33.3% vs. 73.3%; P<0.001). Evolocumab lowered LDL-C more in Asians than in others (66% vs. 58%; P<0.001). The effect of evolocumab on the primary endpoint was similar in Asians (HR, 0.79; 95% CI, 0.61-1.03) and others (HR, 0.86; 95% CI, 0.79-0.93; P interaction=0.55). There was no excess of serious adverse events with evolocumab among Asians over others.

    CONCLUSIONS: Use of evolocumab robustly lowers LDL-C and is equally efficacious in lowering the risk of cardiovascular events and safe in Asians as it is in others.

  2. Al-Abboodi AS, Al-Sheikh WM, Eid EEM, Azam F, Al-Qubaisi MS
    Saudi Pharm J, 2021 Mar;29(3):223-235.
    PMID: 33981171 DOI: 10.1016/j.jsps.2021.01.006
    The long-term objective of the present study was to prepare, physicochemically characterize and determine the anticancer of clausenidin/hydroxypropyl-β-cyclodextrin (Clu/HPβCD) inclusion complex. We used differential scanning calorimetry, X-ray diffractometer, fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometer and 13C and 1H nuclear magnetic resonance followed by in vitro anticancer assays. The orientation and intermolecular interactions of Clausenidin within cyclodextrin cavity were also ascertained by molecular docking simulation accomplished by AutoDock Vina. The guest molecule was welcomed by the hydrophobic cavity of the host molecule and sustained by hydrogen bond between host/guest molecules. The constant drug release with time, and increased solubility were found after successful complexation with HPβCD as confirmed by physicochemical characterizations. Clausenidin had greater cytotoxic effect on colon cancer HT29 cells when incorporated into HPβCD cavity than dissolved in DMSO. Also, from a comparison of cell viability between normal and cancer cells, a reduced side effect was observed. The Clu/HPβCD inclusion complex triggered reactive oxygen species-mediated cytotoxicity in HT29 cells. The inclusion complex-treated HT29 cells showed cell cycle arrest and death by apoptosis associated with caspases activation. The presence of HPβCD seems to aid the anticancer activity of clausenidin.
  3. Basri R, Issrani R, Hua Gan S, Prabhu N, Khursheed Alam M
    Saudi Pharm J, 2021 Mar;29(3):264-268.
    PMID: 33981175 DOI: 10.1016/j.jsps.2021.02.002
    Stroke is a key cerebrovascular disease that is related to high morbidity and mortality in the globe. The Kingdom of Saudi Arabia (KSA) is not an exception where stroke is fast developing into a serious challenge due to the high mortality rate. Additionally, stroke presents a tremendous economic burden and has a devastating effect on the quality of lives of individuals. The number of stroke cases are increasing yearly, thus posing a major challenge to the health care system. Therefore, it is crucial to implement primary and secondary prevention strategies in the KSA. Nevertheless, as compared with developed countries, information on the prevalence, socio-demographic properties and prevention of stroke remains scarce that could be attributed to the shortage of research conducted in this specified region. The review is written to address the various aspects of stroke in the KSA, based on current literatures search using PubMed, Scopus, Web of Science and Google Scholar databases, to identify studies published since inception to Dec 2020.
    MeSH terms: Delivery of Health Care; Humans; Morbidity; Saudi Arabia; Bibliometrics; Prevalence; Cost of Illness; Developed Countries; Stroke; PubMed; Secondary Prevention
  4. Sarker MMR, Khan F, Mohamed IN
    Front Pharmacol, 2021;12:610912.
    PMID: 33981215 DOI: 10.3389/fphar.2021.610912
    Dengue, a very widespread mosquito-borne infectious disease caused by Aedes aegypti virus, has been occurring during the monsoons every year. The prevalence and incidence of dengue fever and death due to its complications have been increased drastically in these recent years in Bangladesh, Philippines, Thailand, Brazil, and India. Recently, dengue had spread in an epidemic form in Bangladesh, Thailand, and Philippines. Although the infection affected a large number of people around the world, there is no established specific and effective treatment by synthetic medicines. In this subcontinent, Malaysia could effectively control its incidences and death of patients using alternative medication treatment mainly prepared from Carica papaya L. leaves along with proper care and hospitalization. Papaya leaves, their juice or extract, as well as their different forms of preparation have long been used traditionally for treating dengue fever and its complications to save patients' lives. Although it is recommended by traditional healers, and the general public use Papaya leaves juice or their other preparations in dengue fever, this treatment option is strictly denied by the physicians offering treatment in hospitals in Bangladesh as they do not believe in the effectiveness of papaya leaves, thus suggesting to patients that they should not use them. In Bangladesh, 1,01,354 dengue patients have been hospitalized, with 179 deaths in the year 2019 according to information from the Institute of Epidemiology, Disease Control, and Research as well as the Directorate General of Health Services of Bangladesh. Most of the patients died because of the falling down of platelets to dangerous levels and hemorrhage or serious bleeding. Therefore, this paper aims to critically review the scientific basis and effectiveness of Carica papaya L. leaves in treating dengue fever based on preclinical and clinical reports. Thrombocytopenia is one of the major conditions that is typical in cases of dengue infection. Besides, the infection and impairment of immunity are concerned with dengue patients. This review summarizes all the scientific reports on Carica papaya L. for its ability on three aspects of dengue: antiviral activities, prevention of thrombocytopenia and improvement of immunity during dengue fever.
    MeSH terms: Aedes; Animals; Antiviral Agents; Bangladesh; Blood Platelets; Brazil; Communicable Diseases; Dengue; Health Services; Hemorrhage; Hospitalization; Hospitals; Humans; Leukopenia; Malaysia; Philippines; Physicians; Plant Extracts; Thailand; Thrombocytopenia; Incidence; Prevalence; Plant Leaves; Carica; Epidemics
  5. Salehi B, Quispe C, Imran M, Ul-Haq I, Živković J, Abu-Reidah IM, et al.
    Front Pharmacol, 2021;12:625386.
    PMID: 33981219 DOI: 10.3389/fphar.2021.625386
    Nigella is a small genus of the family Ranunculaceae, which includes some popular species due to their culinary and medicinal properties, especially in Eastern Europe, Middle East, Western, and Central Asia. Therefore, this review covers the traditional uses and phytochemical composition of Nigella and, in particular, Nigella sativa. The pharmacological studies reported in vitro, in vivo, and in humans have also been reviewed. One of the main strength of the use of Nigella is that the seeds are rich in the omega-6 fatty acid linoleic acid and provide an extra-source of dietary phytochemicals, including the bioactive thymoquinone, and characteristics saponins, alkaloids, and flavonoids. Among Nigella species, N. sativa L. is the most studied plant from the genus. Due to the phytochemical composition and pharmacological properties, the seed and seed oil from this plant can be considered as good candidates to formulate functional ingredients on the basis of folklore and scientific knowledge. Nonetheless, the main limations are that more studies, especially, clinical trials are required to standardize the results, e.g. to establish active molecules, dosage, chemical profile, long-term effects and impact of cooking/incorporation into foods.
  6. Yee CS, Okomoda VT, Hashim F, Waiho K, Sheikh Abdullah SR, Alamanjo C, et al.
    PeerJ, 2021;9:e11217.
    PMID: 33981498 DOI: 10.7717/peerj.11217
    This study investigated the effect of co-culturing microalgae with a floc-forming bacterium. Of the six microalgae isolated from a biofloc sample, only Thalassiosira weissflogii, Chlamydomonas sp. and Chlorella vulgaris were propagated successfully in Conway medium. Hence, these species were selected for the experiment comparing microalgae axenic culture and co-culture with the floc-forming bacterium, Bacillus infantis. Results obtained showed that the co-culture had higher microalgae biomass compared to the axenic culture. A similar trend was also observed concerning the lipid content of the microalgae-bacterium co-cultures. The cell number of B. infantis co-cultured with T. weissflogii increased during the exponential stage until the sixth day, but the other microalgae species experienced a significant early reduction in cell density of the bacteria at the exponential stage. This study represents the first attempt at co-culturing microalgae with B. infantis, a floc-forming bacterium, and observed increased biomass growth and lipid accumulation compared to the axenic culture.
    MeSH terms: Bacillus; Bacteria; Cell Count; Chlamydomonas; Lipids; Aquaculture; Biomass; Coculture Techniques; Chlorella vulgaris; Microalgae; Axenic Culture
  7. Tan YX, Cheong WL, Fong TS
    Cureus, 2021 Apr 09;13(4):e14388.
    PMID: 33981508 DOI: 10.7759/cureus.14388
    Lower back pain is a common presentation in clinical practice. Although most are musculoskeletal in nature, occult spine infection such as spondylodiscitis is commonly missed due to its insidious onset and non-specific symptoms. We report a case of a 63-year-old diabetic woman who presented to our institution's emergency department with altered mental status, nausea, and vomiting. She had a fall one month prior with persistent lower back-pain of increasing intensity. Initial laboratory data revealed an elevated leukocyte count with neutrophil predominance. Plain radiographs showed extensive gas shadows over the chest wall, abdomen, left thigh, and left knee. CT scan revealed L2 compression fracture with spondylodiscitis at L1/L2, left psoas abscess, and extensive subcutaneous emphysema. Open abscess drainage with extensive wound debridement was performed. Intra-operative pus, as well as blood cultures, yielded Escherichia coli. Unfortunately, the patient succumbed to the infection on the seventh day of admission secondary to multi-organ failure.
  8. Abdul Satar H, Yaakub A, Md Shukri N, Ahmad Tajudin LS
    Cureus, 2021 Apr 09;13(4):e14392.
    PMID: 33981511 DOI: 10.7759/cureus.14392
    Paediatric orbital cellulitis is a potential sight- and life-threatening condition. It is a serious infection in children that can result in significant complications, including blindness, cavernous sinus thrombosis, cerebral venous sinus thrombosis, meningitis, subdural empyema, and brain abscess. Of the patients with orbital cellulitis, 17% died from meningitis, and 20% of the survivors had permanent loss of vision. Therefore, the potential for sight- and life-threatening complications makes prompt diagnosis and early treatment very important. We report here a case of a two-year-old girl who presented with a three-day history of left periorbital swelling, preceded by left upper perioral swelling that extended upward to the left cheek and left lower lid and was associated with low-grade fever. The patient had been admitted and was treated as having left preseptal with facial cellulitis; the patient was started on intravenous amoxicillin/clavulanic acid (200 mg three times per day dose), and chloramphenicol ointment was applied to the periorbital area. On day 3, the condition worsened, and dental examination showed multiple dental caries, upper gum swelling and abscess, and mobility of teeth 61 and 62 (two baby teeth). Contrast-enhanced computed tomography (CECT) of the orbit, paranasal, and brain showed a left periosteal abscess collection extending to the inferomedial region of the orbit. Examination and tooth extraction were performed under general anesthesia. The intraoperative results showed the presence of a left upper gum abscess, which was possibly the primary source of infection. Clinical improvement was observed postoperatively. Orbital cellulitis can be a complication of a dental abscess. This case emphasizes the importance of primary tooth care in children. A lack of care can result in fatal complications.
    MeSH terms: Anesthesia, General; Blindness; Brain; Brain Abscess; Cheek; Child; Child, Preschool; Chloramphenicol; Dental Caries; Edema; Female; Humans; Infant; Meningitis; Ointments; Orbit; Empyema, Subdural; Tomography; Tooth Extraction; Tooth, Deciduous; Survivors; Amoxicillin-Potassium Clavulanate Combination; Cavernous Sinus Thrombosis; Orbital Cellulitis
  9. Abir T, Kalimullah NA, Osuagwu UL, Nur-A Yazdani DM, Husain T, Goson PC, et al.
    Ann Glob Health, 2021 04 26;87(1):43.
    PMID: 33981590 DOI: 10.5334/aogh.3269
    Background: Feelings of isolation, insecurity, and instability triggered by COVID-19 could have a long-term impact on the mental health status of individuals.

    Objectives: The aim of this study was to examine the prevalence of mental health symptoms (anxiety, depression, and stress) in Bangladesh and the factors associated with these symptoms during the COVID-19 pandemic.

    Methods: From 1 to 30 April 2020, we used a validated self-administered questionnaire to conduct a cross-sectional study on 10,609 participants through an online survey platform. We assessed mental health status using the Depression, Anxiety, and Stress Scale (DASS-21). The total depression, anxiety, and stress subscale scores were divided into normal, mild, moderate, severe, and multinomial logistic regression was used to examine associated factors.

    Findings: The prevalence of depressive symptoms was 15%, 34%, and 15% for mild, moderate, and severe depressive symptoms, respectively. The prevalence of anxiety symptoms was 59% for severe anxiety symptoms, 14% for moderate anxiety symptoms, and 14% for mild anxiety symptoms, while the prevalence for stress levels were 16% for severe stress level, 22% for moderate stress level, and 13% for mild stress level. Multivariate analyses revealed that the most consistent factors associated with mild, moderate, and severe of the three mental health subscales (depression, anxiety, and stress) were respondents who lived in Dhaka and Rangpur division, females, those who self-quarantined in the previous seven days before the survey, and those respondents who experienced chills, breathing difficulty, dizziness, and sore throat.

    Conclusion: Our results showed that about 64%, 87%, and 61% of the respondents in Bangladesh reported high levels of depression, anxiety, and stress, respectively. There is a need for mental health support targeting women and those who self-quarantined or lived in Dhaka and Rangpur during the pandemic.

    MeSH terms: Adolescent; Adult; Aged; Anxiety/epidemiology; Bangladesh/epidemiology; Mental Disorders/epidemiology*; Cross-Sectional Studies; Depression/epidemiology; Humans; Middle Aged; Psychiatric Status Rating Scales; Surveys and Questionnaires; Stress, Psychological/epidemiology; Prevalence; Pandemics
  10. Hayat K, Arshed M, Fiaz I, Afreen U, Khan FU, Khan TA, et al.
    Front Public Health, 2021;9:603602.
    PMID: 33981657 DOI: 10.3389/fpubh.2021.603602
    Background: The novel coronavirus (COVID-19) pandemic has significantly increased the rate of mortality and morbidity worldwide due to its rapid transmission rate. The mental health status of individuals could have a negative impact attributed to this global situation. Therefore, this study was intended to explore the symptoms of depression and anxiety among healthcare workers (HCWs) of Pakistan during the ongoing COVID-19 pandemic. Methods: A cross-sectional survey was undertaken by administering a web-based questionnaire between May and June 2020. Two tools, including the Patient Health Questionnaire (PHQ9) and Generalized Anxiety Disorder-7 (GAD-7), were employed to measure anxiety and depression symptoms among HCWs. The data analyses were carried out using descriptive statistics, Man Whitney, and Kruskal Wallis tests. Results: Of 1094 HCWs who participated in this online survey, 742 (67.8%) were physicians, followed by nurses (n = 277, 25.3%) and pharmacists (n = 75, 6.9%). The survey respondents had a median depression and anxiety score of 5.00 (7.00-3.00) and 8.00 (11.00-5.00), respectively. A considerable number of HCWs (82.2%) utilized online psychological resources to deal with their psychological distress. Female HCWs, nurses, frontline HCWs, and HCWs aged 30-49 years were more likely to suffer from depression and anxiety (p < 0.05). Conclusion: During the recent ongoing pandemic of COVID-19, there is a mild level of symptoms of depression and anxiety among HCWs. Our findings call for urgent psychological interventions for vulnerable groups of Pakistani HCWs.
    MeSH terms: Adult; Aged; Anxiety; Anxiety Disorders; Biometry; Cross-Sectional Studies; Depression; Female; Health Status; Humans; Male; Middle Aged; Morbidity; Pakistan; Pharmacists; Physicians; Surveys and Questionnaires; Coronavirus; Internet; Pandemics
  11. Nagendrababu V, Murray PE, Ordinola-Zapata R, Peters OA, Rôças IN, Siqueira JF, et al.
    Int Endod J, 2021 Sep;54(9):1491-1515.
    PMID: 33982298 DOI: 10.1111/iej.13565
    Guidance to authors is needed to prevent their waste of talent, time and resources in writing manuscripts that will never be published in the highest-quality journals. Laboratory studies are probably the most common type of endodontic research projects because they make up the majority of manuscripts submitted for publication. Unfortunately, most of these manuscripts fail the peer-review process, primarily due to critical flaws in the reporting of the methods and results. Here, in order to guide authors, the Preferred Reporting Items for study Designs in Endodontology (PRIDE) team developed new reporting guidelines for laboratory-based studies: the Preferred Reporting Items for Laboratory studies in Endodontology (PRILE) 2021 guidelines. The PRILE 2021 guidelines were developed exclusively for the area of Endodontology by integrating and adapting the modified CONSORT checklist of items for reporting in vitro studies of dental materials and the Clinical and Laboratory Images in Publications (CLIP) principles. The process of developing the PRILE 2021 guidelines followed the recommendations of the Guidance for Developers of Health Research Reporting Guidelines. The aim of the current document is to provide authors with an explanation for each of the items in the PRILE 2021 checklist and flowchart with examples from the literature, and to provide advice from peer-reviewers and editors about how to solve each problem in manuscripts prior to their peer-review. The Preferred Reporting Items for study Designs in Endodontology (PRIDE) website (http://pride-endodonticguidelines.org/prile/) provides a link to the PRILE 2021 explanation and elaboration document as well as to the checklist and flowchart.
    MeSH terms: Endodontics*; Laboratories*; Research Design; Checklist; Research Report
  12. Huaraca Huasco W, Riutta T, Girardin CAJ, Hancco Pacha F, Puma Vilca BL, Moore S, et al.
    Glob Chang Biol, 2021 08;27(15):3657-3680.
    PMID: 33982340 DOI: 10.1111/gcb.15677
    Fine roots constitute a significant component of the net primary productivity (NPP) of forest ecosystems but are much less studied than aboveground NPP. Comparisons across sites and regions are also hampered by inconsistent methodologies, especially in tropical areas. Here, we present a novel dataset of fine root biomass, productivity, residence time, and allocation in tropical old-growth rainforest sites worldwide, measured using consistent methods, and examine how these variables are related to consistently determined soil and climatic characteristics. Our pantropical dataset spans intensive monitoring plots in lowland (wet, semi-deciduous, and deciduous) and montane tropical forests in South America, Africa, and Southeast Asia (n = 47). Large spatial variation in fine root dynamics was observed across montane and lowland forest types. In lowland forests, we found a strong positive linear relationship between fine root productivity and sand content, this relationship was even stronger when we considered the fractional allocation of total NPP to fine roots, demonstrating that understanding allocation adds explanatory power to understanding fine root productivity and total NPP. Fine root residence time was a function of multiple factors: soil sand content, soil pH, and maximum water deficit, with longest residence times in acidic, sandy, and water-stressed soils. In tropical montane forests, on the other hand, a different set of relationships prevailed, highlighting the very different nature of montane and lowland forest biomes. Root productivity was a strong positive linear function of mean annual temperature, root residence time was a strong positive function of soil nitrogen content in montane forests, and lastly decreasing soil P content increased allocation of productivity to fine roots. In contrast to the lowlands, environmental conditions were a better predictor for fine root productivity than for fractional allocation of total NPP to fine roots, suggesting that root productivity is a particularly strong driver of NPP allocation in tropical mountain regions.
    MeSH terms: Africa; Soil; South America; Trees; Tropical Climate; Ecosystem*; Plant Roots; Biomass; Forests; Rainforest*
  13. Kul E, Abdulrahim R, Bayındır F, Matori KA, Gül P
    Dent Med Probl, 2021 5 14;58(2):187-191.
    PMID: 33982454 DOI: 10.17219/dmp/126745
    BACKGROUND: If a temporary restoration is in the esthetic area and needs to be worn for a long time, the color stability of temporary materials becomes an important factor.

    OBJECTIVES: The aim of this in vitro study was to evaluate the long-term effects of various staining solutions on the color stability of different temporary materials produced with the computer-aided design and computer-aided manufacturing (CAD/CAM) technology.

    MATERIAL AND METHODS: In the study, the following materials were used: VITA CAD-Temp® (group 1); Ceramill® Temp (group 2); and Telio® CAD (group 3). Forty disk-shaped specimens (10 mm in diameter, 2 mm in thickness) of each material (N = 120) were produced with a CAD/CAM system. Staining solutions - of tea (A), of coffee (B) and cola (C) - and distilled water (D, control) were used, and color was evaluated before and after storing the samples in the solutions. Measurements were taken with a spectrophotometer and the color parameters (L*, a*, b*, and ΔE) were calculated according to the Commission internationale de l'éclairage system (CIELab). The results were evaluated with the two-way analysis of variance (ANOVA) and Tukey's tests (α = 0.05).

    RESULTS: Clinically perceivable (ΔE00 > 0.8) and statistically significant (p < 0.001) color differences were detected in all specimens. The highest ΔE00 value was found in the Ceramill Temp specimens. In addition, the highest ΔE00 values were noted for the specimens stored in cola and the coffee solution for all groups. The lowest ΔE00 value was observed for the groups stored in the tea solution.

    CONCLUSIONS: Clinically perceivable color changes were observed in all the specimens kept in the solutions. Color changes were greater for cola and coffee as compared to tea.

    MeSH terms: Color; Esthetics, Dental*; Humans; Materials Testing; Surface Properties; Computer-Aided Design*
  14. Verma RK, Pandey M, Chawla P, Choudhury H, Mayuren J, Bhattamisra SK, et al.
    PMID: 33982657 DOI: 10.2174/1871527320666210512014505
    BACKGROUND: The complication of Alzheimer's disease (AD) has made the development of its therapeutic a challenging task. Even after decades of research, we have achieved no more than a few years of symptomatic relief. The inability to diagnose the disease early is the foremost hurdle behind its treatment. Several studies have aimed to identify potential biomarkers that can be detected in body fluids (CSF, blood, urine, etc) or assessed by neuroimaging (i.e., PET and MRI). However, the clinical implementation of these biomarkers is incomplete as they cannot be validated.

    METHOD: To overcome the limitation, the use of artificial intelligence along with technical tools has been extensively investigated for AD diagnosis. For developing a promising artificial intelligence strategy that can diagnose AD early, it is critical to supervise neuropsychological outcomes and imaging-based readouts with a proper clinical review.

    CONCLUSION: Profound knowledge, a large data pool, and detailed investigations are required for the successful implementation of this tool. This review will enlighten various aspects of early diagnosis of AD using artificial intelligence.

    MeSH terms: Alzheimer Disease; Artificial Intelligence; Body Fluids; Magnetic Resonance Imaging; Biomarkers; Early Diagnosis; Positron-Emission Tomography; Neuroimaging
  15. Singh B, Maiti GP, Zhou X, Fazel-Najafabadi M, Bae SC, Sun C, et al.
    Arthritis Rheumatol, 2021 Dec;73(12):2303-2313.
    PMID: 33982894 DOI: 10.1002/art.41799
    OBJECTIVE: In a recent genome-wide association study, a significant genetic association between rs34330 of CDKN1B and risk of systemic lupus erythematosus (SLE) in Han Chinese was identified. This study was undertaken to validate the reported association and elucidate the biochemical mechanisms underlying the effect of the variant.

    METHODS: We performed an allelic association analysis in patients with SLE, followed by a meta-analysis assessing genome-wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE-relevant cell lines were applied to determine the functional consequences of rs34330.

    RESULTS: We replicated a genetic association between SLE and rs34330 (meta-analysis P = 5.29 × 10-22 , odds ratio 0.84 [95% confidence interval 0.81-0.87]). Follow-up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation-real-time quantitative polymerase chain reaction, we demonstrated substantial allele-specific promoter and enhancer activity, and allele-specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC-binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF-1]). Chromosome conformation capture revealed long-range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. Finally, CRISPR/dead CRISPR-associated protein 9-based epigenetic activation/silencing confirmed these results. Gene-edited cell lines also showed higher levels of proliferation and apoptosis.

    CONCLUSION: Collectively, these findings suggest a mechanism whereby the rs34330 risk allele (C) influences the presence of histone marks, RNA Pol II, and IRF-1 transcription factor to regulate expression of several target genes linked to proliferation and apoptosis. This process could potentially underlie the association of rs34330 with SLE.

    MeSH terms: Alleles; Humans; Lupus Erythematosus, Systemic/genetics*; Promoter Regions, Genetic; Apoptosis/genetics*; Computational Biology; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide*; Cell Proliferation/genetics*; Cyclin-Dependent Kinase Inhibitor p27/genetics*; Genome-Wide Association Study
  16. Naheed N, Maher S, Saleem F, Khan A, Wadood A, Rasheed S, et al.
    Drug Dev Res, 2021 12;82(8):1169-1181.
    PMID: 33983647 DOI: 10.1002/ddr.21831
    Urease plays a significant role in the pathogenesis of urolithiasis pyelonephritis, urinary catheter encrustation, hepatic coma, hepatic encephalopathy, and peptic acid duodenal ulcers. Salvinia molesta was explored to identify new bioactive compounds with particular emphasis on urease inhibitors. The aqueous methanol extract was fractionated using solvents of increasing polarity. A series of column chromatography and later HPLC were performed on butanol extract. The structures of the resulting pure compounds were resolved using NMR (1D and 2D), infrared, and mass spectroscopy. The novel isolate was evaluated for antioxidant activity (using DPPH, superoxide anion radical scavenging, oxidative burst, and Fe+2 chelation assays), anti-glycation behavior, anticancer activity, carbonic anhydrase inhibition, phosphodiesterase inhibition, and urease inhibition. One new glucopyranose derivative 6'-O-(3,4-dihydroxybenzoyl)-4'-O-(4-hydroxybenzoyl)-α/β-D-glucopyranoside (1) and four known glycosides were identified. Glycoside 1 demonstrated promising antioxidant potential with IC50 values of 48.2 ± 0.3, 60.3 ± 0.6, and 42.1 ± 1.8 μM against DPPH, superoxide radical, and oxidative burst, respectively. Its IC50 in the Jack bean urease inhibition assay was 99.1 ± 0.8 μM. The mechanism-based kinetic studies presented that compound 1 is a mixed-type inhibitor of urease with a Ki value of 91.8 ± 0.1 μM. Finally, molecular dynamic simulations exploring the binding mode of compound 1 with urease provided quantitative agreement between estimated binding free energies and the experimental results. The studies corroborate the use of compound 1 as a lead for QSAR studies as an antioxidant and urease inhibitor. Moreover, it needs to be further evaluated through the animal model, that is, in vivo or tissue culture-based ex-vivo studies, to establish their therapeutic potential against oxidative stress phosphodiesterase-II and urease-induced pathologies.
  17. Md Yusop AH, Alsakkaf A, Noordin MA, Idris H, Nur H, Szali Januddi F
    J Biomed Mater Res B Appl Biomater, 2021 12;109(12):2184-2198.
    PMID: 33983686 DOI: 10.1002/jbm.b.34866
    This work is dedicated to the investigation of drug-release control by a direct effect of degradation from biodegradable metallic surfaces. Degradation behaviors characterized by surface morphology, immersion, and electrochemical techniques demonstrated that curcumin-coated zinc (c-Zn) had a higher degradation rate compared to curcumin-coated Fe (c-Fe). High anodic dissolution rate due to the higher degradation rate and widely extended groove-like degradation structure of c-Zn propelled a higher curcumin release. On the other hand, a slower curcumin release rate shown by c-Fe scaffolds is ascribed to its lower anodic dissolution and to its pitting degradation regime with relatively smaller pits. These findings illuminate the remarkable advantage of different degradation behaviors of degradable metallic surfaces in directly controlling the drug release without the need for external electrical stimulus.
  18. Raman S, Shafie AA, Abraham MT, Shim CK, Maling TH, Rajendran S, et al.
    PLoS One, 2021;16(5):e0251760.
    PMID: 33984051 DOI: 10.1371/journal.pone.0251760
    Oral cancer has been recognized as a significant challenge to healthcare. In Malaysia, numerous patients frequently present with later stages of cancers to the highly subsidized public healthcare facilities. Such a trend contributes to a substantial social and economic burden. This study aims to determine the cost of treating oral potentially malignant disorders (OPMD) and oral cancer from a public healthcare provider's perspective. Medical records from two tertiary public hospitals were systematically abstracted to identify events and resources consumed retrospectively from August 2019 to January 2020. The cost accrued was used to estimate annual initial and maintenance costs via two different methods- inverse probability weighting (IPW) and unweighted average. A total of 86 OPMD and 148 oral cancer cases were included. The initial phase mean unadjusted cost was USD 2,861 (SD = 2,548) in OPMD and USD 38,762 (SD = 12,770) for the treatment of cancer. Further annual estimate of initial phase cost based on IPW method for OPMD, early and late-stage cancer was USD 3,561 (SD = 4,154), USD 32,530 (SD = 12,658) and USD 44,304 (SD = 16,240) respectively. Overall cost of late-stage cancer was significantly higher than early-stage by USD 11,740; 95% CI [6,853 to 16,695]; p< 0.001. Higher surgical care and personnel cost predominantly contributed to the larger expenditure. In contrast, no significant difference was identified between both cancer stages in the maintenance phase, USD 700; 95% CI [-1,142 to 2,541]; p = 0.457. A crude comparison of IPW estimate with unweighted average displayed a significant difference in the initial phase, with the latter being continuously higher across all groups. IPW method was shown to be able to use data more efficiently by adjusting cost according to survival and follow-up. While cost is not a primary consideration in treatment recommendations, our analysis demonstrates the potential economic benefit of investing in preventive medicine and early detection.
    MeSH terms: Delivery of Health Care; Health Expenditures; Follow-Up Studies; Health Personnel; Health Resources; Health Services; Hospitals, Public; Humans; Maintenance; Malaysia; Medical Records; Mouth Neoplasms; Probability; Retrospective Studies; Cost of Illness; Early Detection of Cancer
  19. Lim LWK, Chung HH, Lau MML, Aziz F, Gan HM
    Gene, 2021 Jul 30;791:145708.
    PMID: 33984441 DOI: 10.1016/j.gene.2021.145708
    The true mahseer (Tor spp.) is one of the highest valued fish in the world due to its high nutritional value and great unique taste. Nevertheless, its morphological characterization and single mitochondrial gene phylogeny in the past had yet to resolve the ambiguity in its taxonomical classification. In this study, we sequenced and assembled 11 complete mahseer mitogenomes collected from Java of Indonesia, Pahang and Terengganu of Peninsular Malaysia as well as Sarawak of East Malaysia. The mitogenome evolutionary relationships among closely related Tor spp. samples were investigated based on maximum likelihood phylogenetic tree construction. Compared to the commonly used COX1 gene fragment, the complete COX1, Cytb, ND2, ND4 and ND5 genes appear to be better phylogenetic markers for genetic differentiation at the population level. In addition, a total of six population-specific mitolineage haplotypes were identified among the mahseer samples analyzed, which this offers hints towards its taxonomical landscape.
    MeSH terms: Animals; Base Sequence/genetics; Cyprinidae/classification*; Cyprinidae/genetics*; DNA, Mitochondrial/genetics; Haplotypes/genetics; Indonesia; Malaysia; Mitochondria/genetics; Phylogeny; Biomarkers; Sequence Analysis, DNA/methods; Genes, Mitochondrial/genetics; Genome, Mitochondrial/genetics*
  20. Prodan Z, Mroczek T, Sivalingam S, Bennink G, Asch FM, Cox M, et al.
    PMID: 33984478 DOI: 10.1053/j.semtcvs.2021.03.036
    Valved allografts and xenografts for reconstruction of the right ventricular outflow tract (RVOT) lack durability and do not grow. We report the first clinical use of a completely bioabsorbable valved conduit (Xeltis pulmonary valve - XPV) in children. Twelve children (six male), median age five (two to twelve) years and median weight 17 (10 to 43) kg, underwent RVOT reconstruction with the XPV. Diagnoses were: pulmonary atresia with ventricular septal defect (VSD) (n=4), tetralogy of Fallot (n=4), common arterial trunk (n=3), and transposition of the great arteries with VSD and pulmonary stenosis (n=1). All had had previous surgery, including prior RVOT conduit implantation in six. Two diameters of conduit 16mm (n=5) and 18mm (n=7) were used. At 24 months none of the patients has required surgical re-intervention, 9 of the 12 are in NYHA functional class I and three patients in NYHA class II. None of the conduits has shown evidence of progressive stenosis, dilation or aneurysm formation. Residual peak gradient of >40 mm Hg was observed in three patients, caused by kinking of the conduit at implantation in 1 and distal stenosis in the peripheral pulmonary arteries in 2 patients. Five patients developed severe pulmonary valve insufficiency (PI); the most common mechanism was prolapse of at least one of the valve leaflets. The XPV conduit is a promising innovation for RVOT reconstruction. Progressive PI requires however an improved design (geometry, thickness) of the valve leaflets.
    MeSH terms: Aneurysm; Child; Child, Preschool; Constriction, Pathologic; Dilatation; Heart Defects, Congenital; Humans; Male; Prolapse; Pulmonary Artery; Pulmonary Valve; Pulmonary Valve Insufficiency; Pulmonary Valve Stenosis; Tetralogy of Fallot; Transposition of Great Vessels; Truncus Arteriosus; Pulmonary Atresia; Absorbable Implants; Allografts; Heterografts
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