Browse publications by year: 2021

  1. Mao D, Wunderlich J, Savkovic B, Jeffreys E, Nicholls N, Lee OW, et al.
    Sci Rep, 2021 Dec 14;11(1):24006.
    PMID: 34907273 DOI: 10.1038/s41598-021-03595-z
    Speech detection and discrimination ability are important measures of hearing ability that may inform crucial audiological intervention decisions for individuals with a hearing impairment. However, behavioral assessment of speech discrimination can be difficult and inaccurate in infants, prompting the need for an objective measure of speech detection and discrimination ability. In this study, the authors used functional near-infrared spectroscopy (fNIRS) as the objective measure. Twenty-three infants, 2 to 10 months of age participated, all of whom had passed newborn hearing screening or diagnostic audiology testing. They were presented with speech tokens at a comfortable listening level in a natural sleep state using a habituation/dishabituation paradigm. The authors hypothesized that fNIRS responses to speech token detection as well as speech token contrast discrimination could be measured in individual infants. The authors found significant fNIRS responses to speech detection in 87% of tested infants (false positive rate 0%), as well as to speech discrimination in 35% of tested infants (false positive rate 9%). The results show initial promise for the use of fNIRS as an objective clinical tool for measuring infant speech detection and discrimination ability; the authors highlight the further optimizations of test procedures and analysis techniques that would be required to improve accuracy and reliability to levels needed for clinical decision-making.
    MeSH terms: Acoustic Stimulation*; Female; Humans; Infant; Male; Speech/physiology*; Speech Perception/physiology*; Spectroscopy, Near-Infrared*
  2. Chai AWY, Tan AC, Cheong SC
    Sci Rep, 2021 12 14;11(1):23933.
    PMID: 34907286 DOI: 10.1038/s41598-021-03418-1
    Effective treatment options for head and neck squamous cell carcinoma (HNSCC) are currently lacking. We exploited the drug response and genomic data of the 28 HNSCC cell lines, screened with 4,518 compounds, from the PRISM repurposing dataset to uncover repurposing drug candidates for HNSCC. A total of 886 active compounds, comprising of 418 targeted cancer, 404 non-oncology, and 64 chemotherapy compounds were identified for HNSCC. Top classes of mechanism of action amongst targeted cancer compounds included PI3K/AKT/MTOR, EGFR, and HDAC inhibitors. We have shortlisted 36 compounds with enriched killing activities for repurposing in HNSCC. The integrative analysis confirmed that the average expression of EGFR ligands (AREG, EREG, HBEGF, TGFA, and EPGN) is associated with osimertinib sensitivity. Novel putative biomarkers of response including those involved in immune signalling and cell cycle were found to be associated with sensitivity and resistance to MEK inhibitors respectively. We have also developed an RShiny webpage facilitating interactive visualization to fuel further hypothesis generation for drug repurposing in HNSCC. Our study provides a rich reference database of HNSCC drug sensitivity profiles, affording an opportunity to explore potential biomarkers of response in prioritized drug candidates. Our approach could also reveal insights for drug repurposing in other cancers.
    MeSH terms: Antineoplastic Agents/therapeutic use*; Humans; Pharmacogenetics*; Databases, Factual*; Drug Repositioning*
  3. Saminathan M, Wan Mohamed WN, Md Noh ', Ibrahim NA, Fuat MA, Kumari Ramiah S, et al.
    PMID: 34907603 DOI: 10.1111/jpn.13670
    Ammoniation of oil palm frond (OPF) with non-protein nitrogen (N) sources has been shown to improve the nutritional value and digestibility of OPF in ruminants. This study evaluated the effect of treating OPF without (control) or with different urea levels (1%-5%) on chemical composition and in vitro gas production, digestibility and fermentation properties using goat rumen fluids. The results showed that the treated OPF with urea (1%-5%) had significantly lower (p 
  4. Fadhel Abbas Albaayit S, Khan MA, Abdullah R, Hezmee Mohd Noor M
    J Appl Biomed, 2021 Mar;19(1):40-47.
    PMID: 34907714 DOI: 10.32725/jab.2021.007
    CONTEXT: Clausena excavata Burm. f is a plant used in folklore medicine for the treatment of various ailments in South East Asia. The plant parts contain chemical components that are cytotoxic to many cancer cells.

    OBJECTIVE: The study investigated the cytotoxic effects of ethyl acetate, methanol and chloroform C. excavata leaf extracts on the non-small-lung cancer, NCI-H460, cell line.

    METHODS: Based on the 3-(4,5-dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide (MTT) assay, among extracts, ethyl acetate C. excavata leaf extract (EACE) was the most potent anti-NCI-H460 cells, with IC50 value of 47.1 ± 6.1 μg/ml. The effects of EACE on NCI-H460 cells were also determined by clonogenic, 4', 6-diamidino-2-phenylindole (DAPI), and annexin-V-fluorescein isothiocyanate/propidium iodide-PI flow cytometric assays. Reactive oxygen species (ROS) production and apoptotic gene expressions was determined via flow cytometry and real-time quantitative PCR, respectively.

    RESULTS: EACE-treated NCI-H460 cells after 48 h underwent apoptosis as evident by loss of cell viability, cell shrinkage, and chromatin condensation. The results also showed EACE mediated increase in ROS production by the NCI-H460 cells. After 48 h treatment, EACE increased the pro-apoptotic BAX and decreased the anti-apoptotic Bcl-2, Survivin and c-Myc gene expressions.

    CONCLUSIONS: EACE is a potential anti-lung cancer by increasing cancer cell ROS production and apoptosis.

  5. Sharif Nia H, Chong PP, Yiong Huak C, Gorgulu O, Taghipour B, Sivarajan Froelicher E, et al.
    J Clin Nurs, 2021 Dec 15.
    PMID: 34908206 DOI: 10.1111/jocn.16166
    AIM: To investigate the accuracy, reliability and agreement between infrared forehead thermometers versus infrared tympanic thermometers temperature, a cross-sectional study was conducted in April 2020.

    METHODS: The forehead and tympanic temperatures of 615 subjects were measured simultaneously in three exposed SARS-COV-2 groups at one hospital in Iran, during April 2020. These comparisons were evaluated by Bland-Altman Plot, repeatability, Passing-Bablok regression and Lin's concordance correlation coefficient. The receiver operating characteristic (ROC) analysis was done to describe the discrimination accuracy of a diagnostic test. The study adhered to STROBE checklist for cross-sectional studies.

    RESULTS: A Bland-Altman plot indicated that the limits of agreement between the forehead and tympanic temperature were -0.259 to +0.19°C. Passing-Bablok regression analysis illustrated that the infrared forehead was not linearly related to tympanic temperatures (reference method), with a slope estimate that was significantly different from 1.00. The infrared forehead thermometer showed poor precision and lower accuracy than the tympanic. The forehead temperature readings had 60.0% sensitivity and 44.4% specificity (p > .05) to predict disease.

    CONCLUSION: According to the results of study, there is no evidence that the assessment of temperature by infrared forehead thermometer could discriminate between the two groups (positive and negative).

  6. Shah K, Sher M, Rabai'ah H, Ahmadian A, Salahshour S, Pansera BA
    Math Methods Appl Sci, 2021 Aug 22.
    PMID: 34908635 DOI: 10.1002/mma.7704
    In the current article, we aim to study in detail a novel coronavirus (2019-nCoV or COVID-19) mathematical model for different aspects under Caputo fractional derivative. First, from analysis point of view, existence is necessary to be investigated for any applied problem. Therefore, we used fixed point theorem's due to Banach's and Schaefer's to establish some sufficient results regarding existence and uniqueness of the solution to the proposed model. On the other hand, stability is important in respect of approximate solution, so we have developed condition sufficient for the stability of Ulam-Hyers and their different types for the considered system. In addition, the model has also been considered for semianalytical solution via Laplace Adomian decomposition method (LADM). On Matlab, by taking some real data about Pakistan, we graph the obtained results. In the last of the manuscript, a detail discussion and brief conclusion are provided.
  7. Nazri K, Lim SC, Gomes C
    F1000Res, 2021;10:921.
    PMID: 34909192 DOI: 10.12688/f1000research.73064.2
    Introduction: Malaysia is one of the countries with the highest lightning flash density globally. While sufficiency of lightning protection system is crucial to ensure human safety against lightning strikes, the public awareness towards lightning safety is also equally important in Malaysia. Hence, this study was conducted to understand the current lightning safety awareness level of the Malaysian population. Methods: An online questionnaire survey which consists of 22 scientific statements of lightning was first developed in Malay and English. The questionnaire allows the respondent to also check their own score upon completion of the questionnaire. It was then distributed to the public for data collection. The sample size comprised of both genders, all layers of society from various educational level and social background. Results: Overall, the awareness on lightning safety amongst Malaysian is at moderate level with an average score of slightly above 50%. Urbanites scored marginally better than their rural counterparts. One's education level does not dictate their awareness level of lightning safety. Discussion: In conclusion, the public in Malaysia needs to be better educated on lightning safety. Similar studies should be replicated in other countries experiencing similar levels of lightning activity to better understand the public's perception on lightning.
    MeSH terms: Female; Humans; Lightning*; Malaysia; Male; Surveys and Questionnaires; Rural Population
  8. Wu KL, Chua PT, Lee CL
    Gynecol Minim Invasive Ther, 2021 11 05;10(4):265-267.
    PMID: 34909388 DOI: 10.4103/GMIT.GMIT_27_20
    Deep infiltrating endometriosis (DIE) is a common finding in patients diagnosed with adenomyosis. Women commonly present with severe, incapacitating dysmenorrhea. We report a case of severe dysmenorrhea and lower abdominal tightness for 4 years, diagnosed with posterior adenomyosis. The patient underwent surgery and DIE involving the rectosigmoid and coexisting uterocervical adenomyosis infiltrating bowel muscularis successfully diagnosed and treated using laparoscopic "shaving" technique. Dysmenorrhea significantly resolved after surgery. Laparoscopic surgical "shaving" technique for external adenomyosis infiltrating Rectosigmoid muscularis is feasible, where uterine preservation is desired.
  9. Jiee SF, Jantim A, Mohamed AF, Emiral ME
    J Prev Med Hyg, 2021 Sep;62(3):E605-E612.
    PMID: 34909486 DOI: 10.15167/2421-4248/jpmh2021.62.3.2031
    Introduction: COVID-19 pandemic has placed the entire world, including Malaysia in a state of fear. The rising burden on healthcare facilities has put healthcare workers consistently at risk of healthcare-associated infection. We sought to identify determinants of preventive practice against COVID-19 at work among primary healthcare professionals in Sabah, Malaysia.

    Method: This was a cross-sectional study involving healthcare workers of the Penampang and Putatan districts of Sabah, Malaysia. A total of 167 health professionals from primary healthcare settings took part in this study via a self-administered questionnaire from November 2020 until January 2021. Independent t-test and Analysis of Variance were used to determine differences in preventive practice for categorical independent variables. Pearson product-moment correlation was applied to assess the relationship between Job Satisfaction, burnout, and preventive practice. Subsequently, predictors of preventive practice at work among healthcare workers in Sabah were identified through Binomial Logistic Regression.

    Results: The prevalence of good preventive practice among health professionals at work was 71.3%. There was no difference in preventive practice between professions. Almost all participants reported having good personal protective equipment compliance and hand hygiene practice at work. Marital status (AOR = 4.170, 95% CI = 1.787, 9.733; p = 0.001), average sleep hours (AOR = 1.775, 95% CI = 1.144, 2.754; p = 0.01), and pandemic-related burnout (AOR = 0.905, 95% CI = 0.847, 0.967; p = 0.003) were identified as significant predictors of preventive practice at primary healthcare facilities.

    Conclusions: The outcome of this study is beneficial to the healthcare organization. It can serve as a useful guide to tackle issues related to poor preventive practice against COVID-19 at work for health professionals.

  10. Yeo E, Yew Chieng CJ, Choudhury H, Pandey M, Gorain B
    PMID: 34909654 DOI: 10.1016/j.crphar.2021.100019
    The present research had been attempted to formulate and characterize tocotrienols-rich naringenin nanoemulgel for topical application in chronic wound conditions associated with diabetes. In due course, different phases of the nanoemulsion were chosen based on the solubility study, where combination of Capryol 90 and tocotrienols, Solutol HS15, and Transcutol P were selected as oil, surfactant, and cosurfactant, respectively. The nanoemulsions were formulated using the spontaneous emulsification method. Subsequently, Carbopols were incorporated to develop corresponding nanoemulgels of the optimized nanoemulsions. Thermodynamically stable optimized nanoemulgels were evaluated for their globule size, polydispersity index (PDI), surface charge, viscosity, mucoadhesive property, spreadability, in vitro release and release mechanism. Further, increasing polymer concentration in the nanoemulgels was reflected with the increased mucoadhesive property with corresponding decrease in the release rate of the drug. The optimized nanoemulgel (NG1) consisted of uniform dispersion (PDI, 0.452 ​± ​0.03) of the nanometric globules (145.58 ​± ​12.5) of the dispersed phase, and negative surface charge (-21.1 ​± ​3.32 ​mV) with viscosity 297,600 ​cP and good spreadability. In vitro release of naringenin in phosphate buffer saline revealed a sustained release profile up to a maximum of 74.62 ​± ​4.54% from the formulated nanoemulgel (NG1) within the time-frame of 24 ​h. Alternatively, the release from the nanoemulsion was much higher (89.17 ​± ​2.87%), which might be due to lack of polymer coating on the dispersed oil droplets. Moreover, the in vitro release kinetics from the nanoemulgel followed the first-order release and Higuchi model with non-Fickian diffusion. Therefore, encouraging results in this research is evident in bringing a promising future in wound management, particularly associated with diabetes complications.
  11. Santosa A, Rosengren A, Ramasundarahettige C, Rangarajan S, Chifamba J, Lear SA, et al.
    JAMA Netw Open, 2021 12 01;4(12):e2138920.
    PMID: 34910150 DOI: 10.1001/jamanetworkopen.2021.38920
    Importance: Stress may increase the risk of cardiovascular disease (CVD). Most studies on stress and CVD have been conducted in high-income Western countries, but whether stress is associated with CVD in other settings has been less well studied.

    Objective: To investigate the association of a composite measure of psychosocial stress and the development of CVD events and mortality in a large prospective study involving populations from 21 high-, middle-, and low-income countries across 5 continents.

    Design, Setting, and Participants: This population-based cohort study used data from the Prospective Urban Rural Epidemiology study, collected between January 2003 and March 2021. Participants included individuals aged 35 to 70 years living in 21 low-, middle-, and high-income countries. Data were analyzed from April 8 to June 15, 2021.

    Exposures: All participants were assessed on a composite measure of psychosocial stress assessed at study entry using brief questionnaires concerning stress at work and home, major life events, and financial stress.

    Main Outcomes and Measures: The outcomes of interest were stroke, major coronary heart disease (CHD), CVD, and all-cause mortality.

    Results: A total of 118 706 participants (mean [SD] age 50.4 [9.6] years; 69 842 [58.8%] women and 48 864 [41.2%] men) without prior CVD and with complete baseline and follow-up data were included. Of these, 8699 participants (7.3%) reported high stress, 21 797 participants (18.4%) reported moderate stress, 34 958 participants (29.4%) reported low stress, and 53 252 participants (44.8%) reported no stress. High stress, compared with no stress, was more likely with younger age (mean [SD] age, 48.9 [8.9] years vs 51.1 [9.8] years), abdominal obesity (2981 participants [34.3%] vs 10 599 participants [19.9%]), current smoking (2319 participants [26.7%] vs 10 477 participants [19.7%]) and former smoking (1571 participants [18.1%] vs 3978 participants [7.5%]), alcohol use (4222 participants [48.5%] vs 13 222 participants [24.8%]), and family history of CVD (5435 participants [62.5%] vs 20 255 participants [38.0%]). During a median (IQR) follow-up of 10.2 (8.6-11.9) years, a total of 7248 deaths occurred. During the course of follow-up, there were 5934 CVD events, 4107 CHD events, and 2880 stroke events. Compared with no stress and after adjustment for age, sex, education, marital status, location, abdominal obesity, hypertension, smoking, diabetes, and family history of CVD, as the level of stress increased, there were increases in risk of death (low stress: hazard ratio [HR], 1.09 [95% CI, 1.03-1.16]; high stress: 1.17 [95% CI, 1.06-1.29]) and CHD (low stress: HR, 1.09 [95% CI, 1.01-1.18]; high stress: HR, 1.24 [95% CI, 1.08-1.42]). High stress, but not low or moderate stress, was associated with CVD (HR, 1.22 [95% CI, 1.08-1.37]) and stroke (HR, 1.30 [95% CI, 1.09-1.56]) after adjustment.

    Conclusions and Relevance: This cohort study found that higher psychosocial stress, measured as a composite score of self-perceived stress, life events, and financial stress, was significantly associated with mortality as well as with CVD, CHD, and stroke events.

    MeSH terms: Adult; Aged; Cardiovascular Diseases/etiology*; Cardiovascular Diseases/epidemiology; Cardiovascular Diseases/psychology*; Developing Countries*; Female; Follow-Up Studies; Humans; Life Change Events; Male; Middle Aged; Prospective Studies; Socioeconomic Factors; Stress, Psychological/complications*; Global Health; Proportional Hazards Models; Developed Countries*; Social Determinants of Health*
  12. Montero-Odasso MM, Kamkar N, Pieruccini-Faria F, Osman A, Sarquis-Adamson Y, Close J, et al.
    JAMA Netw Open, 2021 Dec 01;4(12):e2138911.
    PMID: 34910151 DOI: 10.1001/jamanetworkopen.2021.38911
    IMPORTANCE: With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for individuals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking.

    OBJECTIVES: To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps.

    EVIDENCE REVIEW: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence- and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic.

    FINDINGS: Of 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although individual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (≥11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations.

    CONCLUSIONS AND RELEVANCE: This systematic review found that current clinical practice guidelines on fall prevention and management for older adults showed a high degree of agreement in several areas in which strong recommendations were made, whereas other topic areas did not achieve this level of consensus or coverage. Future guidelines should address clinical applicability of their recommendations and include perspectives of patients and other stakeholders.

    MeSH terms: Accidental Falls/prevention & control*; Aged; Aged, 80 and over; Combined Modality Therapy; Environment Design; Health Promotion/methods; Health Promotion/standards; Health Services for the Aged/standards*; Humans; Middle Aged; Osteoporosis/complications; Osteoporosis/therapy; Wounds and Injuries/etiology; Wounds and Injuries/therapy; Practice Guidelines as Topic; Physical Therapy Modalities/standards; Consensus
  13. Zulkefli NJ, Teh CSJ, Mariappan V, Ngoi ST, Vadivelu J, Ponnampalavanar S, et al.
    PLoS One, 2021;16(12):e0261382.
    PMID: 34910764 DOI: 10.1371/journal.pone.0261382
    Burkholderia pseudomallei (B. pseudomallei) is an intracellular pathogen that causes melioidosis, a life-threatening infection in humans. The bacterium is able to form small colony variants (SCVs) as part of the adaptive features in response to environmental stress. In this study, we characterize the genomic characteristics, antimicrobial resistance (AMR), and metabolic phenotypes of B. pseudomallei SCV and wild type (WT) strains. Whole-genome sequence analysis was performed to characterize the genomic features of two SCVs (CS and OS) and their respective parental WT strains (CB and OB). Phylogenetic relationship between the four draft genomes in this study and 19 publicly available genomes from various countries was determined. The four draft genomes showed a close phylogenetic relationship with other genomes from Southeast Asia. Broth microdilution and phenotype microarray were conducted to determine the AMR profiles and metabolic features (carbon utilization, osmolytes sensitivity, and pH conditions) of all strains. The SCV strains exhibited identical AMR phenotype with their parental WT strains. A limited number of AMR-conferring genes were identified in the B. pseudomallei genomes. The SCVs and their respective parental WT strains generally shared similar carbon-utilization profiles, except for D,L-carnitine (CS), g-hydroxybutyric acid (OS), and succinamic acid (OS) which were utilized by the SCVs only. No difference was observed in the osmolytes sensitivity of all strains. In comparison, WT strains were more resistant to alkaline condition, while SCVs showed variable growth responses at higher acidity. Overall, the genomes of the colony morphology variants of B. pseudomallei were largely identical, and the phenotypic variations observed among the different morphotypes were strain-specific.
  14. Lau YS, Tan LK, Chan CK, Chee KH, Liew YM
    Phys Med Biol, 2021 Dec 31;66(24).
    PMID: 34911053 DOI: 10.1088/1361-6560/ac4348
    Percutaneous coronary intervention (PCI) with stent placement is a treatment effective for coronary artery diseases. Intravascular optical coherence tomography (OCT) with high resolution is used clinically to visualize stent deployment and restenosis, facilitating PCI operation and for complication inspection. Automated stent struts segmentation in OCT images is necessary as each pullback of OCT images could contain thousands of stent struts. In this paper, a deep learning framework is proposed and demonstrated for the automated segmentation of two major clinical stent types: metal stents and bioresorbable vascular scaffolds (BVS). U-Net, the current most prominent deep learning network in biomedical segmentation, was implemented for segmentation with cropped input. The architectures of MobileNetV2 and DenseNet121 were also adapted into U-Net for improvement in speed and accuracy. The results suggested that the proposed automated algorithm's segmentation performance approaches the level of independent human obsevers and is feasible for both types of stents despite their distinct appearance. U-Net with DenseNet121 encoder (U-Dense) performed best with Dice's coefficient of 0.86 for BVS segmentation, and precision/recall of 0.92/0.92 for metal stent segmentation under optimal crop window size of 256.
  15. de Leon J, Schoretsanitis G, Smith RL, Molden E, Solismaa A, Seppälä N, et al.
    Pharmacopsychiatry, 2021 Dec 15.
    PMID: 34911124 DOI: 10.1055/a-1625-6388
    This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
  16. Wazid SW, Yunus RM, Mohd Hairi NN, Choo WY
    J Elder Abuse Negl, 2021 10 20;33(5):368-384.
    PMID: 34670476 DOI: 10.1080/08946566.2021.1990815
    Among the challenges in systematic inquiry into elder abuse and neglect (EAN) is the lack of standardized tool of measurement. Existing literature demonstrates diverse tools being used, with the Conflict Tactics Scale (CTS) and its versions being the most common. The Malaysian Elder Mistreatment Project (MAESTRO) utilized the Modified CTS developed and used by the National Study of Elder Abuse and Neglect in Ireland (NSEA-I). This article aimed to validate this Malay version of the modified CTS for use in the Malaysian context and by Malay-speaking populations across Southeast Asia while highlighting the various practical and methodological challenges encountered along the process. Data were collected from 1927 older respondents who lived in Kuala Pilah district. Preliminary data screening led to the dropping of 10 items due to 0 variance. Further four items were deleted during CFA due to low loading. The indicators of neglect factor were made into a composite factor due to high collinearity. The final scale had acceptable reliability and validity. This tool is likely to assist in assessing and detecting EAN more quickly and conveniently. It will also assist future researches of EAN in taking into account the issues that arise in the measurement of EAN.
    MeSH terms: Aged; Humans; Malaysia; Risk Factors; Reproducibility of Results
  17. Setiawan HW, Pratiwi IN, Nimah L, Pawanis Z, Bakhtiar A, Fauzinigtyas R, et al.
    Inquiry, 2021 12 10;58:469580211060291.
    PMID: 34879719 DOI: 10.1177/00469580211060291
    COVID-19 pandemic raises various challenges faced by health workers in hospitals. This study explored strategies for overcoming challenges in caring for COVID-19 patients at hospitals in Indonesia based on healthcare workers' experience. In-depth interviews were employed with 28 healthcare workers (physicians and nurses) who were purposively sampled. Data were collected via phone and analysed using the Colaizzi method. Five following challenges were found: difficulties in working with personal protective equipment (PPE), offline training for handling Covid and using PPE not being implemented evenly for all health workers, physical and psychological fatigue, difficulties in carrying out health education and assessment towards patients and families, and limited resources to cope with the COVID-19 pandemic. Meanwhile, some barriers require support from the government, public and hospital managers. The information gained from research on the strategies for caring for COVID-19 patients can contribute to better preparedness for hospitals and health workers facing the COVID-19 pandemic.
    MeSH terms: Health Personnel; Humans; Indonesia; Pandemics
  18. Sajid MR, Almehmadi BA, Sami W, Alzahrani MK, Muhammad N, Chesneau C, et al.
    PMID: 34886312 DOI: 10.3390/ijerph182312586
    Criticism of the implementation of existing risk prediction models (RPMs) for cardiovascular diseases (CVDs) in new populations motivates researchers to develop regional models. The predominant usage of laboratory features in these RPMs is also causing reproducibility issues in low-middle-income countries (LMICs). Further, conventional logistic regression analysis (LRA) does not consider non-linear associations and interaction terms in developing these RPMs, which might oversimplify the phenomenon. This study aims to develop alternative machine learning (ML)-based RPMs that may perform better at predicting CVD status using nonlaboratory features in comparison to conventional RPMs. The data was based on a case-control study conducted at the Punjab Institute of Cardiology, Pakistan. Data from 460 subjects, aged between 30 and 76 years, with (1:1) gender-based matching, was collected. We tested various ML models to identify the best model/models considering LRA as a baseline RPM. An artificial neural network and a linear support vector machine outperformed the conventional RPM in the majority of performance matrices. The predictive accuracies of the best performed ML-based RPMs were between 80.86 and 81.09% and were found to be higher than 79.56% for the baseline RPM. The discriminating capabilities of the ML-based RPMs were also comparable to baseline RPMs. Further, ML-based RPMs identified substantially different orders of features as compared to baseline RPM. This study concludes that nonlaboratory feature-based RPMs can be a good choice for early risk assessment of CVDs in LMICs. ML-based RPMs can identify better order of features as compared to the conventional approach, which subsequently provided models with improved prognostic capabilities.
    MeSH terms: Machine Learning; Adult; Aged; Humans; Middle Aged; Reproducibility of Results; Case-Control Studies; Risk Assessment
  19. Pung CYY, Tan ST, Tan SS, Tan CX
    PMID: 34886546 DOI: 10.3390/ijerph182312820
    The outbreak of Coronavirus Disease-2019 (COVID-19) has upended education systems. The pandemic switched traditional face-to-face classes to online classes. Poor eating behaviors in undergraduate students' lives may affect the well-being of their later stages of life. This study aimed to investigate the eating behaviors among online learning undergraduates during the COVID-19 pandemic. A total of 122 students were recruited. The results revealed more than half of the respondents (52.46%) skipped meals. Breakfast (46.72%) was the most skipped meal. The majority of the respondents (94.26%) snacked between meals. Biscuits (88.52%), bread (84.43%), and fruits (80.33%) were the most common snacked foods. Meal skipping was found to be associated with gender (χ2 = 6.83, p < 0.05). In the future, more health interventions program aimed to promote healthy eating behaviors among undergraduates are highly warranted.
  20. Draman MS, Grennan-Jones F, Taylor P, Muller I, Evans S, Haridas A, et al.
    Curr Issues Mol Biol, 2021 Oct 27;43(3):1794-1804.
    PMID: 34889904 DOI: 10.3390/cimb43030126
    Thyroid stimulating antibodies (TSAB) cause Graves' disease and contribute to Graves' Orbitopathy (GO) pathogenesis. We hypothesise that the presence of TSH binding proteins (truncated TSHR variants (TSHRv)) and/or nonclassical ligands such as thyrostimulin (α2β5) might provide a mechanism to protect against or exacerbate GO. We analysed primary human orbital preadipocyte-fibroblasts (OF) from GO patients and people free of GO (non-GO). Transcript (QPCR) and protein (western blot) expression levels of TSHRv were measured through an adipogenesis differentiation process. Cyclic-AMP production by TSHR activation was studied using luciferase-reporter and RIA assays. After differentiation, TSHRv levels in OF from GO were significantly higher than non-GO (p = 0.039), and confirmed in ex vivo analysis of orbital adipose samples. TSHRv western blot revealed a positive signal at 46 kDa in cell lysates and culture media (CM) from non-GO and GO-OF. Cyclic-AMP decreased from basal levels when OF were stimulated with TSH or Monoclonal TSAB (M22) before differentiation protocol, but increased in differentiated cells, and was inversely correlated with the TSHRv:TSHR ratio (Spearman correlation: TSH r = -0.55, p = 0.23, M22 r = 0.87, p = 0.03). In the bioassay, TSH/M22 induced luciferase-light was lower in CM from differentiated GO-OF than non-GO, suggesting that secreted TSHRv had neutralised their effects. α2 transcripts were present but reduced during adipogenesis (p < 0.005) with no difference observed between non-GO and GO. β5 transcripts were at the limit of detection. Our work demonstrated that TSHRv transcripts are expressed as protein, are more abundant in GO than non-GO OF and have the capacity to regulate signalling via the TSHR.
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