Characteristics of Indonesian Stingless Bee Propolis and Study of Metabolomic Properties Based on Region and Species.

The chemical compounds found in propolis vary according to plant sources, species, and geographical regions. To date, Indonesian propolis has not yet become standardized in terms of its chemical constituents. Thus, this study aimed to identify the presence of marker compounds and determine whether different classes of Indonesian propolis exist. In this study, yields, total polyphenol content (TPC), total flavonoid content (TFC), and antioxidants were measured. Identification of chemical compounds was carried out with Fourier-transform infrared (FTIR) spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Metaboanalyst 6.0 was employed in conducting principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using the results of the FTIR and LC-MS/MS. The propolis with the highest TFC, TPC, and antioxidant activity was Geniotrigona thoracica from North Sumatra. The results of propolis compound mapping based on region with discriminant analysis revealed that types of propolis from Java have similar characteristics. Then, based on species, the types of propolis from Tetragonula laeviceps and Heterotrigona itama have special characteristics; the samples from these species can be grouped according to similar characteristics. In conclusion, 10 potential marker compounds were identified in Indonesian propolis, enabling regional and species-specific varieties of Indonesian propolis to be classified based on chemical composition mapping.

Amidine containing compounds: Antimicrobial activity and its potential in combating antimicrobial resistance.

Antimicrobial resistance (AMR) is a growing and concerning threat to global public health, necessitating innovative strategies to combat this crisis. Amidine-containing compounds have emerged as promising agents in the battle against AMR. This review gives a summary of recent advances from the past decade in studies of antimicrobial amidine-containing compounds with the aim to feature their structural diversity and the pharmacological relevance of the moiety to antimicrobial activity and their potential use in combating antimicrobial resistance, to the greatest extent possible. Highlighting is put on chemical structure of such compounds in relation to antimicrobial activities such as antibacterial, antifungal, and antiparasitic activities. Researchers commonly modify molecules containing amidine or incorporate amidine into existing antimicrobial agents to enhance their pharmacological attributes and combat antimicrobial resistance. This comprehensive review consolidates the current knowledge on amidine-containing compounds, elucidating their antimicrobial mechanisms and highlighting their promise in addressing the global AMR crisis. By offering a multidisciplinary perspective, we aim to inspire further research and innovation in this critical area of antimicrobial research.

Development and validation of the mobile adherence satisfaction scale (MASS) for medication adherence apps.

OBJECTIVE: To develop and validate the Mobile Adherence Satisfaction Scale (MASS) for assessing user satisfaction with mobile health applications aimed to improve medication adherence. METHODS: The study involved patients over 18 with asthma, hypertension, heart failure, or diabetes, who used the CareAide® app for six months. Scale development included a literature review, expert consultations, and patient interviews, initially identifying 129 items. These were refined to 27 using a two-round Delphi technique and grouped into six dimensions: user interface, perceived usability, system quality, service quality, feature satisfaction, and general satisfaction. A pilot study with 30 participants further refined the model, which was then validated with 135 participants using exploratory and confirmatory factor analyses in SPSS 29 and SmartPLS 4. Data were collected via self-administered questionnaires. RESULTS: A total of 135 complete questionnaires were analysed. Respondents had an average age of 66.7 years (SD = 11.6) with 42.2 % male (n = 57) and 57.8 % female (n = 78). After removal of an item due to cross loading, exploratory factor analysis resulted six dimensions and 26 items with Kaiser-Meyer-Olkin measure of 0.837 and Bartlett's Test of Sphericity (χ2(n = 325) = 2085.673, P < 0.001). The confirmatory factor analysis confirmed high reliability and validity: Cronbach's alpha values > 0.70 for each dimension and an overall alpha of 0.89, with Composite Reliability and Average Variance Extracted both >0.70 and >0.50, respectively, for each dimension. Structural model indicated a significant positive impact of user interface (ß = 0.226, P = 0.006) and feature satisfaction (ß = 0.230, P = 0.002) on general satisfaction, explaining 23.1 % of the variance (R2 = 0.231). CONCLUSION: The study developed and validated the MASS, a reliable tool for assessing user satisfaction with mHealth apps. User interface design and feature satisfaction are key for long-term engagement and consistent medication adherence.

Predictors of chronic kidney disease survival in type 2 diabetes: a 12-year retrospective cohort study utilizing estimated glomerular filtration rate.

Predicting the course of kidney disease in individuals with both type 1 and type 2 diabetes mellitus (DM) is a significant clinical and policy challenge. In several regions, DM is now the leading cause of end-stage renal disease. The aim of this study to identify both modifiable and non-modifiable risk factors, along with clinical markers and coexisting conditions, that increase the likelihood of stage 3-5 chronic kidney disease (CKD) development in individuals with type 2 DM in the United Arab Emirates (UAE). This was a single-center retrospective cohort study based on data derived from electronic medical records of UAE patients with DM who were registered at outpatient clinics at Tawam Hospital in Al Ain, UAE, between January 2011 and December 2021. Type 2 DM patients aged ≥ 18 years who had serum HbA1c levels ≥ 6.5% were included in the study. Patients with type 1 DM, who had undergone permanent renal replacement therapy, who had under 1 year of follow-up, or who had missing or incomplete data were excluded from the study. Factors associated with diabetic patients developing stage 3-5 CKD were identified through Cox regression analysis and a fine and gray competing risk model to account for competing events that could potentially hinder the development of CKD. A total of 1003 patients were recruited for the study. The mean age of the study cohort at baseline was 70.6 ± 28.2 years. Several factors were found to increase the risk of developing stage 3-5 CKD: advancing age (HR 1.005, 95% CI 1.002-1.009, p = 0.026), a history of hypertension (HR 1.69, 95% CI 1.032-2.8, p = 0.037), a history of heart disease (HR 1.49, 95% CI 1.16-1.92, p = 0.002), elevated levels of serum creatinine (HR 1.006, 95% CI 1.002-1.010, p = 0.003), decreased levels of estimated glomerular filtration rate (eGFR) (HR 0.943, 95% CI, 0.938-0.947; p < 0.001), and the use of beta-blockers (HR 139, 95% CI 112-173, p = 0.003). Implementing preventative measures, initiating early interventions, and developing personalized care plans tailored to address specific risk factors are imperative for reducing the impact of CKD. Additionally, the unforeseen findings related to eGFR highlight the ongoing need for research to deepen our understanding of the complexities of kidney disease.

Prevalence of Stroke-Associated Pneumonia and Its Predictors Among Hyperglycaemia Patients During Acute Ischemic Stroke.

BACKGROUND: Hyperglycaemia (HG) during an acute ischemic stroke (AIS) is not only associated with unfavourable functional outcomes but also associated with stroke-associated pneumonia (SAP). This study aimed to determine the prevalence of SAP among Malaysian patients with AIS and the predictors of SAP among patients with HG during AIS. METHODS: This is a retrospective cross-sectional study that included patients with AIS admitted to Hospital Sultanah Nur Zahirah, Malaysia from 2017 to 2020. SAP was defined as infection with pneumonia during the first seven days after IS. HG was defined as a blood glucose level > 7.8 mmol/L within 72 h after admission. Patients with SAP were divided into two groups according to HG status. Multivariate logistic regression analysis was performed using SPSS software, version 22 (IBM Corp., Armonk, NY) to identify SAP predictors among patients with HG. Kaplan-Meier log-rank test was used to compare the survival rate from unfavourable functional outcomes between hyperglycaemic patients with and without SAP. RESULTS: Among 412 patients with AIS, 69 (16.74%) had SAP. The prevalence of SAP among patients with HG and normoglycemia during AIS was 20.98%, and 10.65%, respectively. Age above 60 years, leucocytosis, and National Institute of Health Stroke Scale (NIHSS) > 14 on admission were independent predictors of SAP with aOR of 2.08 (95% CI;1.01-4.30), 2.83 (95% CI; 1.41-5.67), and 3.67 (95% CI; 1.53-8.80), respectively. No significant difference in unfavourable functional outcomes survival was found among patients with and without SAP (p = 0.653). CONCLUSION: This study demonstrated the prevalence of SAP was higher among patients with HG compared to normoglycemia during AIS. The patient being old, leucocytosis and severe stroke upon admission predict the occurrence of SAP among patients with HG during AIS.

The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing.

BACKGROUND: In the Asian population, the presence of the CYP2C19 loss-of-function (LOF) allele is a known genetic variation. This allele is associated with a reduced capacity to metabolize clopidogrel into its active forms through the CYP2C19 enzyme, resulting in diminished platelet inhibition and an elevated risk of recurrent cardiovascular events. Regulatory authorities have recommended an alternative P2Y12 inhibitor, ticagrelor, for individuals carrying the LOF allele. Consequently, this study seeks to assess the impact of the CYP2C19 genotype on the Platelet reactivity index (PRI) using a rapid genetic testing approach in Asian patients with chronic coronary syndromes (CCS) who undergo percutaneous coronary intervention (PCI). METHODS: This prospective study employed a parallel design, single-center design, and randomized approach. Genotyping for the CYP2C19*2 and *3 polymorphisms was conducted using the Nested Allele-Specific Multiplex PCR (NASM-PCR) technique. Patients meeting the inclusion criteria underwent genotyping for CYP2C19 polymorphisms. Following PCI, patients were randomly assigned to receive either ticagrelor or clopidogrel. PRI assessments were performed four hours after loading dose administration. The trial was registered with ClinicalTrials.gov under the identifier NCT05516784. RESULTS: Among the 94 patients recruited for the study, 40 (42.55%) were identified as carriers of the LOF allele for CYP2C19*2 and *3 (*1/*2, *2/*2, *1/*3). Out of the 84 patients evaluated for PRI (44 receiving clopidogrel and 40 receiving ticagrelor), 21 (47.7%) of the clopidogrel group and 39 (97.5%) of the ticagrelor group exhibited a favorable response to antiplatelet therapy (PRI < 50). Patients treated with ticagrelor demonstrated superior antiplatelet responses compared to those receiving clopidogrel, regardless of LOF carrier status (P = 0.005 and < 0.001 for non-LOF and LOF carriers, respectively). CONCLUSION: NASM-PCR as a rapid genetic test holds promise for personalizing antiplatelet therapy in Asian CCS patients.

Mesenchymal stem cell-derived extracellular vesicles for metabolic syndrome therapy: Assessing efficacy with nuclear magnetic resonance spectroscopy.

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities. The prevalence of MetS has surged, transforming it into a pressing public health concern that could potentially affect around 20%-25% of the global population. As MetS continues its ascent, diverse interventions, pharmacological, nonpharmacological and combined have been deployed. Yet, a comprehensive remedy that fully eradicates MetS symptoms remains elusive, compounded by the risks of polypharmacy's emergence. Acknowledging the imperative to grasp MetS's intricate pathologies, deeper insights for future research and therapy optimisation become paramount. Conventional treatments often target specific syndrome elements. However, a novel approach emerges in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) therapy, promising a holistic shift. MSC-EVs, tiny membranous vesicles secreted by mesenchymal stem cells, have garnered immense attention for their multifaceted bioactivity and regenerative potential. Their ability to modulate inflammation, enhance tissue repair and regulate metabolic pathways has prompted researchers to explore their therapeutic application in MetS. This review primarily aims to provide an overview of how MSC-EVs therapy can improve metabolic parameters in subjects with MetS disease and also introduce the usefulness of NMR spectroscopy in assessing the efficacy of MSC-EVs therapy for treating MetS.

Determinants of Inadequate Empiric Antimicrobial Therapy in ICU Sepsis Patients in Al-Madinah Al-Munawwarah, Saudi Arabia: A Comparison of Artificial Neural Network and Regression Analysis.

In the management of sepsis, providing adequate empiric antimicrobial therapy is one of the most important pillars of sepsis management. Therefore, it is important to evaluate the adequacy of empiric antimicrobial therapy (EAMT) in sepsis patients admitted to intensive care units (ICU) and to identify the determinants of inadequate EAMT. The aim of this study was to evaluate the adequacy of empiric antimicrobial therapy in patients admitted to the ICU with sepsis or septic shock, and the determinants of inadequate EAMT. The data of patients admitted to the ICU units due to sepsis or septic shock in two tertiary healthcare facilities in Al-Madinah Al-Munawwarah were retrospectively reviewed. The current study used logistic regression analysis and artificial neural network (ANN) analysis to identify determinants of inadequate empiric antimicrobial therapy, and evaluated the performance of these two approaches in predicting the inadequacy of EAMT. The findings of this study showed that fifty-three per cent of patients received inadequate EAMT. Determinants for inadequate EAMT were APACHE II score, multidrug-resistance organism (MDRO) infections, surgical history (lower limb amputation), and comorbidity (coronary artery disease). ANN performed as well as or better than logistic regression in predicating inadequate EAMT, as the receiver operating characteristic area under the curve (ROC-AUC) of the ANN model was higher when compared with the logistic regression model (LRM): 0.895 vs. 0.854. In addition, the ANN model performed better than LRM in predicting inadequate EAMT in terms of classification accuracy. In addition, ANN analysis revealed that the most important determinants of EAMT adequacy were the APACHE II score and MDRO. In conclusion, more than half of the patients received inadequate EAMT. Determinants of inadequate EAMT were APACHE II score, MDRO infections, comorbidity, and surgical history. This provides valuable inputs to improve the prescription of empiric antimicrobials in Saudi Arabia going forward. In addition, our study demonstrated the potential utility of applying artificial neural network analysis in the prediction of outcomes in healthcare research.

Prevalence of psilocybin use in vaping and associated factors: a study among amphetamine-type stimulants (ATS) use disorder in Malaysia.

BACKGROUND: The emergence of New Psychoactive Substances (NPS), including synthetic psilocybin, has raised concern among health experts due to the numerous health and socioeconomic consequences. The current trend is shifting to the hazardous use of synthetic psilocybin in vaping, and little is known about the prevalence of use, specifically among amphetamine-type stimulants (ATS) users. METHODS: Interviewer-administered questionnaires were conducted in drug detention centers between March and October 2022. The study was conducted using ASSIST 3.0 and obtained information on the respondents' socio-demographic characteristics and clinical profiles. N = 355 ATS users were enrolled in this study. RESULTS: The results show a high prevalence of psilocybin vaping among ATS users (182/355, 53.1%). Most of the respondents were males (85.1%) and unmarried (69.3%), with a mean age of 29.2 (SD = 7.3). Across all respondents, five factors were associated with psilocybin vaping: tobacco smoking, aOR =5.790 (95% CI: 1.723, 8.183); cannabis uses, aOR= 9.152 (95% CI: 2.693, 10.396); and alcohol use, aOR= 3.137 (95% CI: 1.461, 5.817). Respondents of the Malay race had higher odds of being involved in psilocybin vaping compared to other races, with aOR= 1.638 (0.043, 2.459). Meanwhile, a reduction in age by 1.9 will increase the likelihood of involvement in psilocybin vaping with aOR = 1.897 (95% CI: 0.857, 1.938). CONCLUSION: Psilocybin in vaping is growing among ATS users and across all populations. Unfortunately, knowledge regarding the long-term effects on health is limited. Further studies should highlight the harmful effects of psilocybin and the potential risk of psilocybin vaping among the younger population.

Chronic obstructive pulmonary disease and emerging ER stress-related therapeutic targets.

COPD pathogenesis is frequently associated with endoplasmic reticulum stress (ER stress) progression. Targeting the major unfolded protein response (UPR) branches in the ER stress pathway may provide pharmacotherapeutic selection strategies for treating COPD and enable relief from its symptoms. In this study, we aimed to systematically review the potential role of the ER stress inhibitors of major UPR branches (IRE1, PERK, and ATF6) in COPD-related studies and determine the current stage of knowledge in this field. The systematic review was carried out adhering to the PRISMA checklist based on published studies obtained from specific keyword searches of three databases, namely PubMed, ScienceDirect and Springer Database. The search was limited to the year 2000-2022 which includes all in vitro studies, in vivo studies and clinical trials related to the application of ER stress inhibitors toward COPD-induced models and disease. The risk of bias was evaluated using the QUIN, SYRCLE, revised Cochrane risk of bias tool for randomized trials (RoB 2.0) and NIH tool respectively. A total of 7828 articles were screened from three databases and a final total of 37 studies were included in the review. The ER stress and UPR pathways are potentially useful to prevent COPD progression and attenuate the exacerbation of COPD and related symptoms. Interestingly, the off-target effects from inhibition of the UPR pathway may be desirable or undesirable depending on context and therapeutic applications. Targeting the UPR pathway could have complex consequences as the production of ER molecules involved in folding may be impaired which could continuously provoke misfolding of proteins. Although several emerging compounds were noted to be potentially useful for targeted therapy against COPD, clinical studies have yet to be thoroughly explored.