Browse publications by year: 2024

  1. Mustufa C, Ghani HA, Nayak M, Khamis MF, Ariffin Z, Rahman NA
    J Pharm Bioallied Sci, 2024 Dec;16(Suppl 5):S4785-S4791.
    PMID: 40061676 DOI: 10.4103/jpbs.jpbs_1200_24
    BACKGROUND: This study aimed to translate and validate the rating-of-fatigue (ROF) scale in the Kannada language.

    METHODS: This current study involved two steps, where forward translation, backward translation, cross-cultural adaptation, and test of a pre-final version of the ROF scale were conducted in the first step. Content validity, face validity, and construct validity of the ROF scale were performed in five stages. This study enlisted the help of eight experts to create the ROF scale in the Kannada language. Moreover, 50 patients participated by responding to a variety of Likert scale and numeric scale questionnaires that surveyed the intention of measuring the ROF scale. The content validity and face validity were assessed by using the index prepared for the content validity and face validity, respectively, along with mean and standard deviation (SD). The correlation between the Kannada version of the ROF measure and a numerical rating scale-facial rating scale (NRS-FRS) was assessed by the Pearson's correlation coefficient (PCC). Moreover, a comparison of the mean value of ROF and NRS-FRS was performed by the paired t-test.

    RESULTS: The Kannada version of the ROF scale was prepared after getting consensus from all the experts. The fatigue questionnaire met a high level of expert content validity (0.93) and showed that most experts opined high relevance (1.00) for measuring dental fatigue. The fatigue questionnaire meets a high level of response in face validity (0.92) based on the face validity indices. PCC showed a high level of construct validity (r = 0.819) of the ROF scale. No significant difference (P = 0.858) was observed between ROF and NRS-FRS by the paired t-test.

    CONCLUSION: The Kannada version of the ROF scale is a valid tool to assess dental fatigue.

  2. Aljarousha M, Alghamdi WM, Attaallah S, Alhoot MA
    PMID: 40065803 DOI: 10.51329/mehdiophthal1510
    BACKGROUND: The Ocular Surface Disease Index (OSDI) questionnaire was first introduced and developed in 1997 by the Outcomes Research Group, and was adopted by Allergan, Inc. (Irvine, Goleta, CA). While several tools are available for evaluating dry eye syndrome (DES), the OSDI questionnaire is known to have high reliability and validity. Additionally, although more complex questionnaires are available, the goal of the OSDI is to ensure a rapid diagnosis of ocular surface disease. The OSDI consists of a 12-item questionnaire designed to assess the visual disability caused by DES. The OSDI score can range from 0 to 100, with higher scores indicating greater disability. This language-inclusive mini-review aimed to provide a comprehensive overview of previous studies that translated the OSDI into various languages and validated the translated versions.

    METHODS: OSDI validation studies were identified through a PubMed / MEDLINE and Google Scholar search spanning the 27 years since the establishment of the OSDI, using the broad term "Ocular Surface Disease Index-12 questions" and keywords that is "ocular surface disease index-12," "translation and validation," "transcultural validation," "development," "cross-cultural adaptation," and "reliability and validity." We included original studies that validated the translated version of the OSDI in various languages, presenting the key findings with a focus on reliability and repeatability outcomes.

    RESULTS: Thirteen full-text articles were thoroughly reviewed, including those identified through targeted keyword searches and the reference lists of these studies. The papers examined the translation of the English version of the OSDI-12 questionnaire into nine languages: Italian, Arabic, Chinese, Chilean Spanish, Japanese, Filipino, Farsi, Bahasa Melayu, and Brazilian Portuguese. Key details regarding the development, translation, and validation phases were summarized. Most of the included studies adhered to standard guidelines throughout the translation process to create a final version of the OSDI questionnaire. This was followed by clinical validation of the final translated version. The majority of the translated versions were assessed for internal consistency, reliability, test-retest repeatability, and discriminant validity.

    CONCLUSIONS: The original English version of the OSDI was translated into validated versions to achieve a final version in nine different languages. The majority of the translated versions demonstrated high reproducibility and reliability. The different language versions of the questionnaire removed language barriers in informing the eye-care community, evaluating DES, and assisting physicians in advising and managing their patients more suitably. Therefore, the validated versions of OSDI can be used as tools for clinical practice and DES research. Validating the OSDI questionnaire in various languages is essential to eliminate the language barrier in the assessment of dry eye disease.

  3. Hankoua BB, Diao M, Ligaba-Osena A, Garcia RA, Harun S, Ahlawat YK
    Front Plant Sci, 2024;15:1442324.
    PMID: 40066347 DOI: 10.3389/fpls.2024.1442324
    Cassava is a crucial source of daily calorie intake for millions of people in sub-Saharan Africa (SSA) but has an inferior protein content. Despite numerous attempts utilizing both traditional and biotechnological methods, efforts to address protein deficiency in cassava have yet to meet with much success. We aim to leverage modern biotechnologies to enhance cassava's nutritional value by creating bioengineered cassava cultivars with increased protein and starch content. In this study, we utilized Qui-Quine Starch (QQS), a novel orphan gene unique to Arabidopsis thaliana, to develop transgenic cassava plants with increased protein and starch accumulation in their tissues. A total of 10 independent transgenic cassava lines expressing QQS were successfully regenerated in this study, among which line R7 (F) demonstrated superior growth vigor. Quantitative RT-PCR verified the expression of the QQS gene in the transgenic lines. Data showed that QQS expression in cassava plants increased leaf protein content by 36% in line R''' (LA) L2 and root protein by 17% for the same line compared to their wild-type and empty vector (NPTII) control plants. Moreover, leaf-soluble total carbohydrates increased by 51.76% in line R (G) L2, and root-soluble total carbohydrates increased by 46.75% in line R7 (F). The novel function of QQS in increasing the starch content in the transgenic biomass is demonstrated. No significant change in the content of specific amino acids was observed among the lines and various plant parts. In addition, QQS expression revealed increased biomass, plant vigor, and early In vitro mini-tubers production for line R7 (F). Gene interaction study between AtQQS and 59 interacting partners generated 184 interactions or edges. These gene networks comprised several functional categories regulating the starch metabolic and auxin biosynthetic processes. The role of QQS in imparting starch and protein content of transgenic cassava plants is validated. The next logical step is the evaluation of biochemical profiles of cassava lines expressing QQS that reach maturity and the transferability of these findings to consumer-preferred cassava cultivars and local landraces grown in SSA. This study represents the first biotechnological report demonstrating a simultaneous increase of protein and starch content in bioengineered cassava.
  4. Davidson AL, Michailidou K, Parsons MT, Fortuno C, Bolla MK, Wang Q, et al.
    Am J Hum Genet, 2024 Sep 05;111(9):2059-2069.
    PMID: 39096911 DOI: 10.1016/j.ajhg.2024.07.004
    Co-observation of a gene variant with a pathogenic variant in another gene that explains the disease presentation has been designated as evidence against pathogenicity for commonly used variant classification guidelines. Multiple variant curation expert panels have specified, from consensus opinion, that this evidence type is not applicable for the classification of breast cancer predisposition gene variants. Statistical analysis of sequence data for 55,815 individuals diagnosed with breast cancer from the BRIDGES sequencing project was undertaken to formally assess the utility of co-observation data for germline variant classification. Our analysis included expected loss-of-function variants in 11 breast cancer predisposition genes and pathogenic missense variants in BRCA1, BRCA2, and TP53. We assessed whether co-observation of pathogenic variants in two different genes occurred more or less often than expected under the assumption of independence. Co-observation of pathogenic variants in each of BRCA1, BRCA2, and PALB2 with the remaining genes was less frequent than expected. This evidence for depletion remained after adjustment for age at diagnosis, study design (familial versus population-based), and country. Co-observation of a variant of uncertain significance in BRCA1, BRCA2, or PALB2 with a pathogenic variant in another breast cancer gene equated to supporting evidence against pathogenicity following criterion strength assignment based on the likelihood ratio and showed utility in reclassification of missense BRCA1 and BRCA2 variants identified in BRIDGES. Our approach has applicability for assessing the value of co-observation as a predictor of variant pathogenicity in other clinical contexts, including for gene-specific guidelines developed by ClinGen Variant Curation Expert Panels.
    MeSH terms: Adult; Female; Humans; Middle Aged; Tumor Suppressor Protein p53/genetics; BRCA1 Protein/genetics; Genetic Predisposition to Disease*; Mutation, Missense/genetics; BRCA2 Protein/genetics
  5. Biswas SK, Sumon MMH, Ahmed S, Ruma RA, Parvin A, Paul DK, et al.
    Phage (New Rochelle), 2024 Dec;5(4):186-202.
    PMID: 40045940 DOI: 10.1089/phage.2024.0005
    The escalating global threat of antibiotic resistance has prompted a critical need for innovative approaches to bacterial infection treatment. In terms of management, bacterial-associated disorders have reached a critical point in the world due to the advent of drug-resistant types of bacteria. Nonetheless, continued bacteriophage research presents a promising frontier in the battle against bacterial infections. In this study, we explored the effectiveness of bacteriophage therapy against antibiotic-resistant bacteria. According to our viewpoint, phage therapy could replace antibiotics in terms of safety, efficacy, and specificity. Furthermore, phage therapy offers versatility in administering single phage, phage products, or modified phage against various resistant bacteria. Moreover, Phage cocktails, with their synergistic combinations, showcase a holistic approach, mitigating the risk of resistance and expanding treatment possibilities. Similarly, the synergy between phages and antibiotics holds promise for overcoming antibiotic resistance and forging a path toward more effective and sustainable antimicrobial strategies. The review provides insights into the transformative impact of bacteriophage therapy on current bacterial infection treatment paradigms, its application with methodological challenges and limitations, as well as insights to scientists and policymakers on the best areas to study phages in order to combat antimicrobial resistance.
  6. GBD 2021 Forecasting Collaborators
    Lancet, 2024 May 18;403(10440):2204-2256.
    PMID: 38762325 DOI: 10.1016/S0140-6736(24)00685-8
    BACKGROUND: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050.

    METHODS: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline.

    FINDINGS: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8-63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0-45·0] in 2050) and south Asia (31·7% [29·2-34·1] to 15·5% [13·7-17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4-40·3) to 41·1% (33·9-48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6-25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5-43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5-17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7-11·3) in the high-income super-region to 23·9% (20·7-27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5-6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2-26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [-0·6 to 3·6]).

    INTERPRETATION: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions.

    FUNDING: Bill & Melinda Gates Foundation.

    MeSH terms: Adult; Aged; Female; Forecasting*; Humans; Life Expectancy/trends; Male; Middle Aged; Mortality/trends; Risk Factors; Global Health*; Young Adult
  7. Almutairi W, Duane B
    Evid Based Dent, 2024 Sep;25(3):154-155.
    PMID: 38942941 DOI: 10.1038/s41432-024-01030-6
    DESIGN: The study was designed as a single-blinded, parallel, randomized controlled trial to compare the effectiveness of the Salvadora persica toothbrush (MTB), Salvadora persica chewing stick (MCS), and a standard toothbrush (STB) in controlling plaque and gingivitis. A total of 78 participants were randomly divided into three groups and instructed to use their assigned oral hygiene tool in a standardized manner for three.

    CASE SELECTION: Participants were non-dental students and staff of Universiti Kebangsaan Malaysia, Kuala Lumpur Campus, selected through convenience sampling. They met specific inclusion criteria, such as being systemically healthy, having ≥20 teeth, and having a Basic Periodontal Examination score of 0, 1, or 2, with no periodontal pockets greater than 5.5 mm.

    DATA ANALYSIS: Clinical outcomes were measured using the Plaque Index (PI) and Periodontal Inflamed Surface Area (PISA) at baseline, one-, and three-weeks post-intervention. Data analysis was performed using mixed-model analysis of variance for continuous variables and Fisher's exact test for categorical variables.

    RESULTS: All three groups showed significant improvements in plaque levels and severity of gingivitis from baseline to three weeks post-intervention. The MCS group demonstrated a significant improvement in mean PISA values of the anterior teeth compared to the MTB and STB groups. However, there was no significant difference in plaque level reduction or overall gingivitis severity among the three groups. This indicates that when used correctly, Salvadora persica toothbrushes and chewing sticks are as effective as standard toothbrushes in plaque control and gingival health.

    CONCLUSIONS: The study concludes that both Salvadora persica toothbrushes and chewing sticks can serve as effective alternatives to the standard toothbrush for plaque control and gingival health. This showcases the beneficial anti-plaque and anti-gingivitis properties of Salvadora persica. However, the effectiveness of these oral hygiene tools is contingent upon the correct usage techniques.

    MeSH terms: Adult; Dental Plaque Index; Female; Humans; Malaysia; Male; Randomized Controlled Trials as Topic; Single-Blind Method; Salvadoraceae*; Young Adult
  8. Kamran S, Sinniah A, Chik Z, Nelli G, Alshawsh MA
    Biochem Biophys Res Commun, 2024 Nov 26;735:150677.
    PMID: 39265366 DOI: 10.1016/j.bbrc.2024.150677
    5-Fluorouracil (5-FU) is frequently used to treat colorectal cancer (CRC), but its clinical application is limited by its toxicity. Natural compounds have been combined with chemotherapeutic drugs to reduce chemotherapy-related toxicity. Diosmetin, a natural flavonoid, has demonstrated anticancer effects against CRC. This study investigated diosmetin's potential in combination with 5-FU using a murine model of HCT-116 colon cancer xenografts in nu/nu nude mice. HCT-116 cells were injected into the right flanks of mice, and once tumors reached a size of 50 mm3, the mice were treated with diosmetin (100 mg/kg), 5-FU (30 mg/kg), or a combination of both at two dose levels (100 + 30 mg/kg and 50 + 15 mg/kg) for 4 weeks. Blood and tumors were collected on the final day for further analysis. Mice treated with the higher combination dose exhibited the smallest tumor volume (330.91 ± 88.49 mm3). Biochemistry and histology analysis showed no toxicity or abnormalities in the liver, kidney, and heart with the combination therapy. Immunohistochemistry results revealed a notable reduction in the proliferation marker (Ki67) and inflammation marker (TLR4) in tumors from high-dose combination-treated mice. Moreover, immunofluorescence data indicated increased levels of apoptotic markers (Bax, Caspase-3, p53, p21) and downregulation of anti-apoptotic protein (Bcl-2) in the high-dose combination group. The findings suggest that 100 mg/kg of diosmetin combined with 30 mg/kg 5-FU significantly reduced tumor volume and had a less toxic effect on the heart compared to 5-FU monotherapy.
    MeSH terms: Animals; Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use; Antineoplastic Combined Chemotherapy Protocols/pharmacology; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Drug Synergism*; Humans; Mice, Nude*; Apoptosis/drug effects; Xenograft Model Antitumor Assays*; HCT116 Cells; Mice
  9. Zanti M, O'Mahony DG, Parsons MT, Dorling L, Dennis J, Boddicker NJ, et al.
    medRxiv, 2024 Sep 04.
    PMID: 39281752 DOI: 10.1101/2024.09.04.24313051
    Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS, and previous findings indicate that case-control likelihood ratios (LRs) outperform odds ratios for variant classification. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyzed germline sequencing data of BRCA1 and BRCA2 from 96,691 female breast cancer cases and 303,925 unaffected controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observed 11,227 BRCA1 and BRCA2 variants, with 6,921 being coding, covering 23.4% of BRCA1 and BRCA2 VUS in ClinVar and 19.2% of ClinVar curated (likely) benign or pathogenic variants. Case-control LR evidence was highly consistent with ClinVar assertions for (likely) benign or pathogenic variants; exhibiting 99.1% sensitivity and 95.4% specificity for BRCA1 and 92.2% sensitivity and 86.6% specificity for BRCA2. This approach provides case-control evidence for 785 unclassified variants, that can serve as a valuable element for clinical classification.
  10. Abdul Rahman FK, Binti Wan Puteh SE, Bin Zainuddin MA
    BMC Public Health, 2024 Nov 05;24(1):3055.
    PMID: 39501241 DOI: 10.1186/s12889-024-20545-2
    BACKGROUND: Dengue has emerged as a rapidly escalating health issue in low- and middle-income countries, with its burden and geographic spread increasing over the years. Malaysia, in particular, has witnessed a significant rise in dengue cases, accompanied by a spike in mortality rates. Several studies have identified various factors, primarily focusing on the 27 clinical aspects of severe dengue infection and the development of dengue-related fatalities. Expanding on this focus, this study aims to identify the demographic, clinical, and environmental factors contributing to dengue mortality, providing a more comprehensive understanding of the variables influencing dengue-related fatalities.

    METHODS: This study utilized a 1:2 case-control design, analyzing data from the E-dengue system database and medical records from January 2015 to December 2022, involving 219 participants (73 dengue fatalities as cases and 146 recovered patients as controls). Dengue deaths were confirmed by the Penang State Mortality Review Committee, and controls were randomly selected from laboratory-confirmed dengue cases. Statistical analyses were performed using SPSS software, including descriptive statistics, chi-square tests, and multivariable logistic regression to identify predictors of dengue mortality, with variables included in the multivariable model if p 

    MeSH terms: Adolescent; Adult; Aged; Child; Female; Humans; Malaysia/epidemiology; Male; Middle Aged; Risk Factors; Urbanization; Case-Control Studies; Young Adult
  11. Das A, Nyahatkar S, Sonar S, Kalele K, Subramaniyan V
    J Liq Biopsy, 2024 Dec;6:100166.
    PMID: 40027309 DOI: 10.1016/j.jlb.2024.100166
    Liquid biopsy has emerged as one of the non-invasive diagnostic strategies for cancer, offering significant advantages over traditional tissue biopsies. Exosomes the nanoscale extracellular vesicles, have significantly been in the spotlight of research and investigation as highly informative biomarkers in liquid biopsy. These vesicles, which are secreted by a variety of cells, including tumor cells, contain useful information on the molecular characteristics of the parent cell and could be used as a mirror into the processes underlying cancer biology. The analysis of the biomolecular exosomal cargo, including proteins, nucleic acids, and lipids, has shown great promise for the development of sensitive and specific liquid biopsy-based biomarkers for cancer detection, monitoring, and prognosis. This review discusses the role of exosomes in the liver cancer development and metastatic process, including their ability to transfer oncogenic material and facilitate tumor progression. It also explores the application of exosomes as a tool for early cancer detection, monitoring disease status, and predicting prognosis, with a specific focus on liver cancer. Exosomes hold great promise as a minimally invasive liquid biopsy approach that could revolutionize the way we diagnose and manage this deadly disease.
  12. Patil N, Patil K, Jain M, Mohammed A, Yadav A, Dhanda PS, et al.
    J Alzheimers Dis Rep, 2024;8(1):1339-1360.
    PMID: 40034365 DOI: 10.1177/25424823241284464
    BACKGROUND: Alzheimer's disease (AD) is a prevalent, incurable, and chronic neurodegenerative condition characterized by the accumulation of amyloid-β protein (Aβ), disrupting various bodily systems. Despite the lack of a cure, phenolic compounds like cannabidiol (CBD), a non-psychoactive component of cannabis, have emerged as potential therapeutic agents for AD.

    OBJECTIVE: This systematic review explores the impact of different types of cannabidiol on AD, unveiling their neuroprotective mechanisms.

    METHODS: The research used PubMed, Scopus, and Web of Science databases with keywords like "Alzheimer's disease" and "Cannabidiol." Studies were evaluated based on title, abstract, and relevance to treating AD with CBD. No restrictions on research type or publication year. Excluded were hypothesis papers, reviews, books, unavailable articles, etc.

    RESULTS: Microsoft Excel identified 551 articles, with 92 included in the study, but only 22 were thoroughly evaluated. In-vivo and in-silico studies indicate that CBD may disrupt Aβ42, reduce pro-inflammatory molecule release, prevent reactive oxygen species formation, inhibit lipid oxidation, and counteract Aβ-induced increases in intracellular calcium, thereby protecting neurons from apoptosis.

    CONCLUSIONS: In summary, the study indicates that CBD and its analogs reduce the production of Aβ42. Overall, these findings support the potential of CBD in alleviating the underlying pathology and symptoms associated with AD, underscoring the crucial need for further rigorous scientific investigation to elucidate the therapeutic applications and mechanisms of CBD in AD.

  13. Mohammed Yousuf Abdi S, Azizan KA, Syed Abdullah SS, Samsu ZA
    Metabolomics, 2024 Dec 30;21(1):14.
    PMID: 39738744 DOI: 10.1007/s11306-024-02205-z
    INTRODUCTION: Burkholderia thailandensis E264 is a non-pathogenic soil bacterium that produces rhamnolipids (RLs), which are utilised in various fields. Although studies have illustrated changes in RLs congeners in response to environmental factors, studies on the influence of temperature on the RLs congeners produced by B. thailandensis E264 are scarce.

    OBJECTIVE: It was hypothesised that RL congeners will be distributed differently at different temperature, which caused the produced RL to have different properties. This brought about the idea of a tailored production of RL for specific application through temperature control. Thus, this study aimed to investigate the distribution of RLs congeners by B. thailandensis E264 in response to different temperatures.

    METHODOLOGY: B. thailandensis E264 was grown at three different temperatures (25 °C, 30 °C, and 37 °C) for nine days and subjected to metabolomic analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS).

    RESULTS: The findings indicated that temperature significantly affected the metabolomic distribution of B. thailandensis E264, with mono-rhamno-mono-lipid and mono-rhamno-di-lipid being the predominant metabolites at 37 °C and 30 °C, with relative abundances of 64.1% and 65.3%, respectively. In comparison, di-rhamno-di-lipid was detected at 25 °C with an overall relative abundance of 77.7%.

    CONCLUSION: This investigation showed that changing the cultivation temperature of the non-pathogenic B. thailandensis E264 produces diverse rhamnolipid congeners, which could enable the targeted synthesis of specific RLs for various applications and increase the market value of biosurfactants.

    MeSH terms: Chromatography, Liquid/methods; Mass Spectrometry/methods; Temperature*
  14. Aqilah Zahirah Norazmi N, Hafizah Mukhtar N, Ravindar L, Suhaily Saaidin A, Huda Abd Karim N, Hamizah Ali A, et al.
    Bioorg Chem, 2024 Aug;149:107510.
    PMID: 38833991 DOI: 10.1016/j.bioorg.2024.107510
    In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into biologically active scaffolds has been hailed as an appealing strategy in medicinal chemistry. The conjugation to organometallic fragments can be achieved by an appropriate linker or by directly coordinating the existing drugs to a metal. The success of Ferroquine (FQ, SR97193), an effective chloroquine-ferrocene conjugate currently undergoing the patient-exploratory phase as a combination therapy with the novel triaminopyrimidine ZY-19489 for malaria, has sparked intense interest in organometallic compound drug discovery. We present the evolution of organometallic antimalarial agents over the last decade, focusing on the parent moiety's class and the type of organometallics involved. Four main organometallic antimalarial compounds have been chosen based on conjugated organic moieties: existing antimalarial drugs, other clinical drugs, hybrid drugs, and promising scaffolds of thiosemicarbazones, benzimidazoles, and chalcones, in particular. The presented insights contribute to the ongoing discourse on organometallic compound drug development for malaria diseases.
    MeSH terms: Animals; Humans; Malaria/drug therapy; Plasmodium falciparum/drug effects; Structure-Activity Relationship; Molecular Structure; Parasitic Sensitivity Tests
  15. Almatar ERE, Alsharidah S, Bourusly M, Ahmed RL, Alabdulhadi MA
    Int Med Case Rep J, 2024;17:1013-1018.
    PMID: 40017997 DOI: 10.2147/IMCRJ.S496062
    Guillain-Barré syndrome (GBS) is a rare complication in children with acute lymphoblastic leukemia (ALL). This case report explores the presentation and management of GBS in a 16-year-old male with a history of ALL, who developed GBS during maintenance therapy. The patient exhibited progressive symmetrical weakness, sensory loss, and autonomic dysfunction. Diagnostic workup, including nerve conduction studies and lumbar puncture, confirmed the diagnosis of GBS. Differentiating GBS from vincristine-induced neuropathy, a common challenge in this population, was crucial for appropriate management. The patient responded well to intravenous immunoglobulin and supportive care. This case highlights the importance of considering GBS in the differential diagnosis of neurological complications in children with ALL and emphasizes the need for prompt diagnosis and treatment.
  16. Loganathan T, Zaini AZ, Kunpeuk W, Suphanchaimat R, Yi H, Farwin A, et al.
    BMJ Public Health, 2024 Dec;2(2):e000923.
    PMID: 40018641 DOI: 10.1136/bmjph-2024-000923
    INTRODUCTION: The COVID-19 pandemic adversely impacted migrants in Malaysia, raising concerns about the effectiveness of public health measures. This study aims to investigate challenges faced by migrant populations in complying with public health measures during the pandemic.

    METHODS: We conducted 29 in-depth interviews with stakeholders between April 2022 and February 2023. Thematic analysis was conducted, and results were organised by major COVID-19 public health measures: (1) movement restrictions, (2) non-pharmaceutical interventions, (3) COVID-19 screening and testing and (4) quarantine, isolation and hospitalisations.

    RESULTS: Migrants encountered difficulties complying with the movement control orders due to livelihood crises and a lack of understanding of regulations. Financial constraints hindered migrants' ability to purchase quality face masks, and they lacked the comprehension of the importance of non-pharmaceutical interventions for disease prevention. In the absence of government intervention, non-governmental organisations and international organisations played an important role in providing essential food aid, health information, face masks and hygiene products, and other services to migrants. Despite encouragement to seek testing and treatment, migrants were deterred by fear of immigration enforcement and unaffordable fees. Overcrowded living conditions made physical distancing, isolation and quarantine challenging. Many avoided government-designated quarantine centres due to financial constraints and fear of arrest. Delayed medical treatment may have resulted in high COVID-19 mortality among migrants.

    CONCLUSIONS: The COVID-19 pandemic highlighted significant health disparities experienced by migrants in Malaysia, including the double health and livelihood crises, and limited access to essential health information, resources, healthcare and social protection. Urgent reforms are needed to ensure migrant-inclusive health policies, enhance outbreak preparedness and prevent unnecessary suffering and deaths among migrants during both pandemic and non-pandemic periods.

  17. Ghadah Abdulrahman AQ, Endytiastuti E, Ardhani R, Sutardjo Rus Sudarso I, Pidhatika B, Fauzi MB, et al.
    F1000Res, 2024;13:1258.
    PMID: 40012745 DOI: 10.12688/f1000research.156336.2
    INTRODUCTION: Calcium hydroxide (Ca(OH) 2) is the material of choice for pulp therapy. However, Ca(OH) 2 has drawbacks such as toxicity, poor sealing, and tunnel defect formation. Alternative materials have been developed to provide more biocompatible materials with better dentin formation ability. The objective of this study was to evaluate the effect of composites containing gelatin (G), chitosan (CH), tetraethyl orthosilicate (TEOS), and Ca(OH) 2, namely G-CH-TEOS-Ca (OH) 2 (Extended data) on inflammation of the dental pulp (expression of COX-2, PGP 9.5, TNF-α, and neutrophil number).

    MATERIALS AND METHODS: A total of 16 Wistar rat models of acute pulp injury were prepared and divided into two groups, treatment and control, 8 with each. In the treatment group, we applied a pulp-capping material using G-CH-TEOS-Ca (OH) 2 and Ca(OH) 2. On the 1 st and 3 rd days, rats were sacrificed. Tissue samples from 4 rats in each group were processed for histological preparation. COX-2, PGP 9.5, and TNF-α were observed using immunohistochemical (IHC) staining, and neutrophil numbers were observed using hematoxylin-eosin staining. Image analysis of COX-2, PGP 9.5, and TNF-α expression was performed using ImageJ software.

    RESULTS: The results showed a decrease in COX-2 expression, but not significantly while PGP 9.5 and TNF-α expression were significantly higher than those in the control group. Neutrophil numbers were lower in the treatment group than in the control group, but the difference was not statistically significant.

    CONCLUSION: The G-CH-TEOS-Ca (OH) 2 composite material may have potential as an exposed pulp medicament by reducing inflammation (COX-2 expression and number of neutrophils) and increasing the regeneration factor (TNF-α expression) and nerve (PGP 9.5 expression).

    MeSH terms: Animals; Male; Rats, Wistar*; Ubiquitin Thiolesterase/metabolism; Rats
  18. Mohammed AJ, Yimer N, Jesse FFA, Jaafar WNFW, Husna A
    J Adv Vet Anim Res, 2024 Dec;11(4):944-953.
    PMID: 40013277 DOI: 10.5455/javar.2024.k844
    OBJECTIVES: The current study aimed to investigate the prophylactic potential of EBN compared to EDTA in mitigating Cd's toxic effects on pregnancy rates and embryonic development in rats.

    MATERIALS AND METHODS: Ninety-eight female rats (Sprague Dawley) were divided into donor and recipient groups, with donors further divided into seven subgroups, including negative control, Cd-exposed, EBN-treated, and EDTA-treated groups. Embryos from donors were transferred to recipient rats, with EBN and Cd administered for 4 weeks and EDTA given only in the last 5 days for the donor group.

    RESULTS: Results showed significant differences in pregnancy rates and blastocyst quality. EBN at 120 mg/kg BW led to higher blastocyst production and better quality compared to Cd-exposed groups. The highest pregnancy rates in recipient groups correlated with the highest blastocyst scores from donors.

    CONCLUSION: EBN at 120 mg/kg demonstrated significant protection against Cd toxicity and its effect on pregnancy rates, embryo production, quality, and pre- and post-embryo transfer, surpassing the effects of both 90 mg/kg EBN and EDTA. This study provides empirical evidence in support of the conventional belief in the positive impact of EBN on female reproduction.

  19. Ab Rajab NS, Yasin MAM, Ghazali WSW, Talib NA, Taib WRW, Sulong S
    Yale J Biol Med, 2024 Sep;97(3):281-295.
    PMID: 39351328 DOI: 10.59249/FBOT5313
    Background: The link between rheumatoid arthritis (RA) and schizophrenia (SZ) has long been a hot topic of deliberation among scientists from various fields. Especially when it comes to genetics, the connection between RA and SZ is still up for discussion, as can be observed in this study. The HLA genes are the most disputed in identifying a connection between the two diseases, but a more thorough investigation of other genes that may be ignored could yield something even more interesting. Thus, finding the genes responsible for this long-sought relationship will necessitate looking for them. Materials and Methods: Shared and overlapped associated genes involved between SZ and RA were extracted from four databases. The overlapping genes were examined using Database for Annotation, Visualization and Integrated Discovery (DAVID) and InnateDB to search the pertinent genes that concatenate between these two disorders. Results: A total of 91 overlapped genes were discovered, and that 13 genes, divided into two clusters, showed a similarity in function, suggesting that they may serve as an important meeting point. FCGR2A, IL18R, BTNL2, AGER, and CTLA4 are five non-HLA genes related to the immune system, which could lead to new discoveries about the connection between these two disorders. Conclusion: An in-depth investigation of these functionally comparable non-HLA genes that overlap could reveal new interesting information in both diseases. Understanding the molecular and immune-related aspects of RA and SZ may shed light on their etiology and inform future research on targeted treatment strategies.
    MeSH terms: HLA Antigens/genetics; Humans; Genetic Predisposition to Disease; Databases, Genetic; Butyrophilins/genetics
  20. Abdul Rahman A, Mohd Isa IL, Tofail SAM, Bartlomiej L, Rodriguez BJ, Biggs MJ, et al.
    ACS Appl Bio Mater, 2024 Jun 17;7(6):4102-4115.
    PMID: 38758756 DOI: 10.1021/acsabm.4c00431
    The diatom's frustule, characterized by its rugged and porous exterior, exhibits a remarkable biomimetic morphology attributable to its highly ordered pores, extensive surface area, and unique architecture. Despite these advantages, the toxicity and nonbiodegradable nature of silica-based organisms pose a significant challenge when attempting to utilize these organisms as nanotopographically functionalized microparticles in the realm of biomedicine. In this study, we addressed this limitation by modulating the chemical composition of diatom microparticles by modulating the active silica metabolic uptake mechanism while maintaining their intricate three-dimensional architecture through calcium incorporation into living diatoms. Here, the diatom Thalassiosira weissflogii was chemically modified to replace its silica composition with a biodegradable calcium template, while simultaneously preserving the unique three-dimensional (3D) frustule structure with hierarchical patterns of pores and nanoscale architectural features, which was evident by the deposition of calcium as calcium carbonate. Calcium hydroxide is incorporated into the exoskeleton through the active mechanism of calcium uptake via a carbon-concentrating mechanism, without altering the microstructure. Our findings suggest that calcium-modified diatoms hold potential as a nature-inspired delivery system for immunotherapy through antibody-specific binding.
    MeSH terms: Materials Testing*; Particle Size*; Silicon Dioxide/chemistry; Surface Properties; Porosity; Drug Delivery Systems
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