The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Infrared spectroscopy has emerged as a powerful analytical technique with diverse applications in the pharmaceutical and bio-allied domains. This article provides an in-depth exploration of the method's utility in pharmaceutical applications, including identification, moisture content determination, and assay of pharmaceutical compounds. Additionally, it delves into the extensive role of infrared spectroscopy in bio-allied research, encompassing the investigation of structural arrangements, interactions, mobility, and dynamics of biomolecules. In the realm of pharmaceuticals, infrared spectroscopy stands as a reliable tool for the identification of compounds, ensuring the authenticity and quality control of drug formulations. The capacity to measure moisture content is crucial in ensuring the stability and efficacy of medicinal goods. Furthermore, the assay of pharmaceutical compounds by infrared spectroscopy offers a rapid and precise means of quantifying active ingredients, supporting the development and production of pharmaceutical formulations. In the bio-allied field, the versatility of infrared spectroscopy becomes evident in its contribution to understanding the intricate details of biomolecular structures and interactions. The method plays a pivotal role in investigating the structural arrangements of macromolecules, shedding light on the complexities of biological systems. Additionally, infrared spectroscopy facilitates the assessment of body fluids, enabling non-invasive diagnostics and monitoring of health conditions. The article also explores the application of infrared spectroscopy in the analysis of blood, providing valuable insights into hematological parameters and contributing to diagnostic methodologies. The method's wide-ranging influence on healthcare and forensic sciences is demonstrated by its promise in cancer detection, forensic investigations, and hematological illness monitoring.
Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. In 2023, there were an estimated 2·30 million (95% uncertainty interval [UI] 2·01 to 2·61) breast cancer incident cases, 764 000 deaths (672 000 to 854 000), and 24·1 million (21·3 to 27·5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44·2 per 100 000 person-years [31·2 to 58·4]), the age-standardised mortality rate (ASMR) was the highest (24·1 per 100 000 [16·8 to 31·9]). The highest ASIR was in the high-income group (75·7 per 100 000 [67·1 to 84·0]), and the lowest ASMR was in the upper-middle-income group (11·2 per 100 000 [10·2 to 12·3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147·2% (38·1 to 271·7), compared with a 1·2% (-11·5 to 17·2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29·9% (-33·6 to -25·9), but increased by 99·3% (12·5 to 202·9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28·3% (16·6 to 38·9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3·56 million (2·29 to 4·83), with 1·37 million (0·841 to 2·02) deaths. The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2·5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Gates Foundation, St Jude Children's Research Hospital.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. In 2023, approximately 1·3 billion (95% uncertainty interval [UI] 1·2 to 1·4) individuals were estimated to be living with MASLD (ie, 16·1% of the global population), with an age-standardised prevalence rate of 14 429·3 (95% UI 13 268·3 to 15 990·6) per 100 000 population, representing a percentage increase of 142·7% (95% UI 139·2 to 146·7) in crude numbers from 1990 (0·5 billion [0·5 to 0·6]) and of 28·6% (27·8 to 29·5) in the rate (11 217·2 [10 276·8 to 12 467·0] per 100 000 in 1990). An estimated 3·6 million (2·8 to 4·5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39·6 (31·2 to 49·9) per 100 000 population. Despite a 116·3% (93·3 to 139·4) increase in crude DALYs (from 1·7 million [1·3 to 2·1] in 1990), its age-standardised estimate remained consistent (1·8% [-8·6 to 12·8]) from 1990 (38·9 [30·1 to 49·8] per 100 000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29 246·1 [26 848·3 to 32 048·7] per 100 000) and Andean Latin America showed the highest DALY rate (152·3 [114·1 to 194·7] per 100 000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653·5 [7923·7 to 9592·8] per 100 000) and east Asia had the lowest DALY rate (16·3 [13·5 to 19·9] per 100 000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15 616·4 [14 349·2 to 17 263·3] per 100 000 people in 2023) than in females (13 245·2 [12 132·0 to 14 692·6] per 100 000 people), and peaked at age 80-84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35-39 years for males and age 55-59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2·2 [95% UI 1·6 to 3·1] per 100 000 people), followed by high BMI (1·4 [0·6 to 2·4] per 100 000 people) and smoking (1·0 [0·3 to 1·8] per 100 000 people). Our forecasting model estimates that 1·8 billion (95% UI 1·6 to 2·0) individuals are likely to have MASLD by 2050, representing a 42·0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15 774·9 (95% UI 14 613·9 to 17 336·2) per 100 000 people in 2050, representing an average annual percentage change of 0·3% (95% UI 0·3-0·3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. With a global prevalence of 16·1% and approximately 1·3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Gates Foundation.
Despite its ornamental value, Euphorbia fractiflexa (E. fractiflexa) is still little explored for pharmaceutical applications. Plant-based nanoparticles, especially nanocrystals (NCs), are of great interest due to their ability to improve drug delivery and combat antibiotic resistance. This study presents a novel nanotechnological approach by using E. fractiflexa, a plant native to Abu Arish in the Jazan province of Saudi Arabia, for the first time in pharmaceutical research. The natural occurrence and sustainability of E. fractiflexa in desert climates make it a viable green resource for the development of NCs. This study investigates the pharmaceutical potential of plant-derived nanoparticles, specifically NCs produced from the stem SAP of E. fractiflexa, a desert plant from Abu Arish, Saudi Arabia. The milky SAP from the stem of Euphorbia fractiflexa was collected and processed to produce NCs. The NCs were analyzed by dynamic light scattering (DLS) for their zeta potential, particle size and polydispersity index (PDI). Morphological analysis was performed using scanning electron microscopy (SEM). The antibacterial activity of the NCs was evaluated against Gram-positive and Gram-negative bacterial strains using the agar well diffusion method, with ciprofloxacin as a standard reference. A statistical analysis was performed to compare the antibacterial activity of the NCs with the standard. The NCs exhibited a zeta potential of - 7.62 ± 8.83 mV, indicating moderate stability, with particle sizes ranging from 100 to 200 nm, making them suitable for injectable applications. SEM revealed irregular, inhomogeneous crystal structures. The NCs showed significant antibacterial activity and inhibited both Gram-positive and Gram-negative bacteria with inhibition zones of 18 - 21.3 µm varied with individual bacteria. Although E. fractiflexa derived NCs exhibit slightly lower antibacterial efficacy than ciprofloxacin, their sustainability and natural origin make them promise. Further optimization of formulation methods is needed to optimize the injectable formulation for future antibacterial applications. This study highlights E. fractiflexa as a valuable natural resource for the development of innovative nanotechnology formulations. The prepared NCs showed significant antibacterial activity and suitable physicochemical properties for injectable drug delivery systems. These NCs are gaining increasing attention as they can improve drug delivery and combat antibiotic resistance through plant-based, environmentally friendly formulations. However, a notable limitation is their slightly lower efficacy compared to ciprofloxacin, indicating that the formulation needs to be further optimized to increase antibacterial efficacy. Overall, this work lays the foundation for the future development of nanomedicines based on E. fractiflexa and highlights the value of underutilized desert plants for pharmaceutical nanotechnology.
Enteric infectious diseases claim more than 1 million lives annually and are among the top ten causes of death in children younger than 5 years. Remarkable global investment has been dedicated to enteric infectious disease prevention and control; however, the shifting global health landscape is testing the continuance of progress. To evaluate the current status and guide future interventions, we present the latest epidemiological estimates of enteric infectious diseases from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 and assess progress towards the Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) mortality target of fewer than 20 deaths per 100 000 children younger than 5 years by 2025. We quantified the incidence, mortality, and disability-adjusted life-years (DALYs) of enteric infectious diseases by age, sex, and year across 204 countries and territories from 1990 to 2023. In GBD 2023, the following were considered under the category of enteric infectious diseases: diarrhoeal diseases, enteric fever (typhoid and paratyphoid), invasive non-typhoidal Salmonella spp (iNTS) infections, and other intestinal infectious diseases. We also examined 15 aetiologies contributing to diarrhoeal diseases. Incidence and prevalence were estimated with DisMod-MR (version 2.1), a Bayesian meta-regression tool, drawing on data from systematic reviews, population-based surveys, claims data, and hospital sources. Cause-specific mortality was modelled with Cause of Death Ensemble Modelling based on data from sources including vital registration, mortality surveillance, verbal autopsy, and minimally invasive tissue sampling. Years of life lost and years lived with disability were computed and combined to derive DALYs. For aetiology-specific estimation, population-attributable fractions (PAFs) for 15 pathogens were derived with a counterfactual framework. Point estimates and 95% uncertainty intervals (UIs) were generated from 250 draws from the posterior distribution. In 2023, enteric infectious diseases resulted in an estimated 1·27 million (95% UI 0·963-1·68) deaths globally, declining from 3·69 million (3·04-4·56) in 1990. The global age-standardised mortality rate (ASMR) decreased from 74·1 (62·0-92·9) per 100 000 population to 16·4 (12·6-21·3) per 100 000 population during the same period. Diarrhoeal diseases accounted for most deaths in 2023 (1·11 million [0·811-1·54]), followed by enteric fever and iNTS. South Asia and sub-Saharan Africa remained the most affected regions in 2023, with 599 000 (441 000-882 000) and 501 000 (373 000-648 000) deaths due to enteric infectious diseases, respectively, predominantly from diarrhoeal disease. Rotavirus was the leading cause of all-age diarrhoeal disease deaths (PAF 16·3% [12·0-21·5]), followed by norovirus (10·2% [2·4-17·0]) and Shigella spp (9·3% [5·4-15·2]). Among children younger than 5 years, PAFs of deaths due to diarrhoeal diseases were 40·2% (32·5-48·5) for rotavirus, 24·0% (15·1-36·7) for Shigella spp, and 23·4% (13·7-34·3) for adenovirus. Across 204 countries and territories, 141 met the GAPPD mortality target in 2023. The driving aetiologies among countries that did not meet the target in 2023 varied slightly by GBD super-region, but the highest or second-highest number of deaths in children younger than 5 years were consistently attributed to rotavirus. Astrovirus and sapovirus, newly included in GBD 2023, were responsible for 24 600 (6290-49 000) and 18 800 (4650-44 400) deaths, respectively, in 2023, mainly in children younger than 5 years. Our findings show that mortality and ASMRs of enteric infectious diseases declined substantially between 1990 and 2023. This decline is consistent with the expansion of public health measures and broader socioeconomic development. However, the burden in 2023 remains considerably high, with the highest mortality concentrated in sub-Saharan Africa and south Asia. Considering that more than a quarter of all countries had yet to meet the GAPPD mortality target in 2023, sustained efforts are needed to address the persistent burden in affected countries and to adapt to the changing global health landscape. Gates Foundation.
Self-medication is a common practice where individuals use medications without consulting a healthcare professional. While it offers convenience and cost-effectiveness, it also carries risks such as incorrect self-diagnosis, misuse of medications, and adverse drug reactions. Understanding self-medication behaviors is essential, particularly among healthcare students who may influence future patient care practices. This study aims to assess the knowledge, attitudes, and practices of self-medication among undergraduate students at Batterjee Medical College (BMC) in Jeddah, Saudi Arabia. The research also seeks to raise awareness about the potential risks of self-medication and highlight areas for future research on this subject. A cross-sectional descriptive study was conducted with 244 undergraduate students from nine academic programs at BMC. Students completed an online questionnaire adapted from a previously validated tool. The questionnaire assessed students' knowledge of self-medication, their attitudes towards its use, and their self-medication practices. Data were analyzed using IBM SPSS Statistics (Statistical Package for the Social Sciences) software, and P values of <0.05 were considered statistically significant. The majority of students demonstrated good knowledge of self-medication, with 76.3% able to describe its benefits and risks. Over 65% of students exhibited positive attitudes towards self-medication, considering it an acceptable practice for managing minor health issues. However, more than half (67%) reported practicing self-medication, with the most common reasons being convenience and cost-effectiveness. Reliance on informal sources of information, such as the internet and family members, was prevalent. This study highlights that self-medication is a common practice among healthcare students at BMC, driven by knowledge, convenience, and perceived need. While students are generally aware of the risks, there is a need for educational interventions to promote responsible self-medication and discourage over-reliance on informal information sources. Future research should explore interventions to reduce the potential harms of self-medication practices.
Community pharmacists act as a middleman among both patients and prescribing doctors. As such, they oversee making sure that patients receive the best possible pharmaceutical care for Metabolic syndrome (MetS). There is a dearth of adequate data on MetS awareness, attitudes, and treatment practices between community pharmacists within the UAE. To assess the attitudes of community pharmacies professionals across Abu Dhabi, Dubai, and the Northern Emirates toward managing and preventing MetS. This is a cross-sectional study design carried out between May 2023 and February 2024. Four final-year pharmacy students conducted in-person interviews among professionals working in community pharmacies and structured questionnaire was utilized for information collection. The questionnaire comprised Demographic information, attitudes and practices to Prevention and Management of Metabolic Syndrome. The total of 420 pharmacists were recruited for the study. The mean attitude score toward the prevention and treatment of metabolic syndrome was 75.8%, with a 95% confidence interval (CI) of [76.3, 81.4%]. The average practice score toward prevention and treatment of metabolic syndrome was 86.8% with a 95% CI of [85.3, 88.3%]. Supervising pharmacists were more likely to achieve a positive attitude score compared with assistant pharmacists (OR = 4.63; 95% CI: 2.32-9.21; p < 0.001). Pharmacists with more than 10 years of experience had higher odds of a positive attitude score compared with those with 1-5 years of practice (OR = 2.11; 95% CI: 1.11-3.99; p = 0.022). Good practice scores were significantly associated with working in chain pharmacies (OR = 1.69), holding senior professional positions (supervising pharmacist: OR = 8.39; chief pharmacist: OR = 5.90), having longer professional experience (6-10 years: OR = 5.08; >10 years: OR = 7.04), and receiving prior training on MetS (OR = 4.64; 95% CI: 2.52-8.55; p < 0.001). The findings show that the community pharmacists are cognizant about appropriate practices required for the treatment and management of MetS. It was inferred that the setting and quality (experience and training) of pharmacy professionals play vital roles in strengthening the attitude and practice of community pharmacists with regards to MetS.
The global incidence of endometrial cancer (EC) is increasing; however, current diagnostic and surveillance methodologies, which rely on invasive sampling and imaging, are insufficient for detecting early molecular alterations and accurately predicting treatment resistance and recurrence. Circulating microRNAs (c-miRNAs) are promising minimally invasive biomarkers that reflect tumor biology and disease dynamics. Nevertheless, their application in laboratory medicine is limited due to their low concentrations in circulation, the high degree of sequence homology among miRNA family members, interference from isomiRs, and preanalytical variability, all of which compromise reproducibility and inter-laboratory comparability. Electrochemical biosensing is an emerging analysis platform in clinical chemistry because of its ability to directly transduce signal changes as a result of hybridization, high turnaround, capability to operate using low sample volumes, and compatibility with automated and decentralized workflows. The nanostructuring of electrodes, engineering of probes, and integration of microfluidic systems have significantly enhanced the sensitivity of analytical processes and improved multiplexing capabilities. However, some of the critical barriers to translation, such as the absence of standardized calibration and normalization protocols, inadequate validation in clinically relevant matrices (plasma/serum) and a complete comparison of methods with established reference procedures, such as quantitative PCR and digital PCR, are still present. This review critically evaluates c-miRNA signatures and electrochemical biosensing platforms in laboratory medicine, examining validation, quality assurance, and regulatory processes for clinically actionable assays supporting early detection, risk stratification, therapy monitoring, and recurrence assessment. The future use of clinical methods will hinge on their reproducibility in actual matrices, their traceability to reference methods, and their accreditation.
Chemotherapy, the first approach in breast cancer management, is limited owing to systemic toxicity and drug resistance. For instance, 5-fluorouracil in recommended doses cause severe side effects, highlighting the urgent necessity of finding more effective and safer combinations. Hence, this study aims to develop biocompatible natural-based nanocarriers for the co-delivery of loratadine, an antihistaminic drug along with 5-fluorouracil in order to enhance the anticancer efficacy while reducing the required dose of 5-fluorouracil. In silico virtual screening was performed to examine the probable molecular interactions between loratadine or 5-fluorouracil, individually with two different polymers, chitosan and zein, to determine the most suitable carrier system. Zein exhibited superior binding affinity compared to chitosan. Nanoparticle optimization was conducted using a Box-Behnken design with zein, tannic acid, and either loratadine or 5-fluorouracil concentration as independent variables. The optimized formulations were characterized by dynamic light scattering, entrapment efficiency, morphology, in-vitro release, followed by cytotoxicity, apoptosis, and cell-cycle analyses in MCF-7 cells. The optimal formulation consisted of zein (50 mg), tannic acid (131.93 mg), and loratadine or 5-fluorouracil (5 mg). The optimized formulation of Loratadine loaded nanoparticles (NPs) showed a particle size of 197 nm, polydispersity index (PDI) of 0.153, zeta potential of -21.78 mV, and entrapment efficiency of 61.33%. Furthermore, the optimized 5-fluorouracil loaded nanoparticles exhibited a particle size of 231 nm, 0.170 for PDI, zeta potential of -24.01 mV, and EE of 74.91% for entrapment efficiency. The sustained drug release profile exhibited a controlled pattern over 24-48 h. Flow cytometry results showed that the mixed nanoparticles exhibited potent cytotoxicity equivalent to 5-fluorouracil loaded nanoparticles alone despite containing only half the 5-fluorouracil dose, confirming a potential synergistic effect. These findings confirmed the potential of drug-loaded nanoparticles as promising drug delivery systems for breast cancer management.
This review aims to comprehensively discuss the emerging role of artificial intelligence (AI) and three-dimensional (3D) printing in the design and development of personalized polymeric nanocomposite-based drug delivery systems. The focus is on how integrating these technologies enhances the precision, efficacy, and customization of pharmacotherapy compared with conventional formulations. An extensive literature survey was conducted using databases such as PubMed, Scopus, Web of Science, and ScienceDirect, focusing on publications from the past decade. Peerreviewed studies, reviews, and reports on polymeric nanocomposites, AI-based formulation design, and 3D-printed drug delivery systems were critically analyzed. The collected data were synthesized to elucidate design principles, fabrication methods, and the synergistic application of AI and 3D printing in personalized medicine. Polymeric nanocomposites have demonstrated superior performance in targeted and controlled drug release due to their adaptable physicochemical properties and biocompatibility. The application of AI enables predictive modeling, optimization of formulation parameters, and patient stratification through data-driven algorithms. Concurrently, 3D printing enables the fabrication of patient-specific dosage forms and implants with programmable drug-release profiles. Together, these technologies enable the development of individualized therapeutic systems that enhance treatment outcomes and minimize adverse effects. This synergistic incorporation of AI and additive manufacturing tackles some of the main obstacles in precision medicine by diminishing trial-and-error in formulation, enhancing reproducibility, and promoting better outcomes during treatment. Such multidisciplinary applications are most promising in cancer, diabetes, neurodegenerative, infectious, and cardiovascular diseases. The integration of AI and 3D printing represents a transformative advancement in personalized nanocomposite drug delivery. These interdisciplinary approaches collectively enable precise control over drug release kinetics, dosage customization, and formulation design. Future developments focusing on regulatory standardization, ethical data use, and large-scale clinical translation will further accelerate the adoption of AI- and 3D-printing-assisted personalized drug delivery systems in clinical practice. While these technologies hold great potential for personalized and precise therapeutics, their clinical translation remains challenged by regulatory validation, manufacturing reproducibility, and data transparency requirements.
Nephrolithiasis is a common urological condition characterized by kidney stone formation and complex metabolic imbalances. Uromodulin (Tamm-Horsfall protein, THP) is the principal urinary glycoprotein and a promising risk-stratifying biomarker and long-term follow-up marker for nephrolithiasis. This review examines the dual action of THP in stone disease. The normal glycosylated form of THP can inhibit the formation of calcium oxalate crystals, whereas structurally modified or hypoglycosylated THP can promote crystal adhesion and aggregation. We provide a critical comparison between conventional immunoassays and emerging THP biosensors with respect to analytical performance, selectivity, and preanalytical requirements for the measurement of urine with reasonable reliability. Electrochemical and optical biosensors, as well as nanomaterials, are increasingly being used in biosensors, with graphene, gold nanoparticles (AuNPs), and tantalum oxide. Non-Faradaic impedance (Ta2O5-passivated interdigitated electrodes) has been demonstrated to detect a 0.5 ng/mL LOD in artificial urine, and printed impedance sensors and AuNP-based lateral-flow formats have a typical LOD of 25 to 80 ng/mL and have been demonstrated using minimally processed urine (e.g., centrifugation and/or dilution), instead of crude samples. Since urinary THP is usually in the mg L-1 range, sub-ng/mL sensitivity cannot be understood in standard terms of detectability, but in terms of special use-cases (e.g., highly diluted samples, low-THP phenotypes, or quantitative low-end monitoring), it can be detected. In conclusion, we examined several significant limitations to translation, including biological variability (such as hydration status, infection, and circadian variations), the influence of the matrix, the lack of calibration and traceability, and the imperative for prospective clinical validation. Although microfluidics and digital presentation facilitate point-of-care tracking, the integration of AI/ML is not yet prevalent.
To assess hospital pharmacy practices in the United Arab Emirates, in the context of medication dispensing, administration, and technological integration. Data were collected through an anonymous cross-sectional survey of hospital pharmacists. Information on hospital demographics, pharmacy staffing, and medication dispensing and administration practices was obtained. The use of key technologies, including electronic health records, barcode medication administration systems, automated dispensing cabinets, robotic dispensing units, and smart infusion pumps, was explored. Processes such as order verification, double-checking, sterile compounding, and telepharmacy services were also assessed. Descriptive statistics were applied, and associations were tested. Sixty-four pharmacists responded to achieve 85.3% response rate. The primary method for medication dose distribution in participating hospitals was centralized and manual (e.g. unit-dose distribution) (56.3%). The majority of participants (60.9%) declared they double checked medication orders entry, 84.9% double checked before dispensing, and 46.9% used automated dispensing systems. Nearly half reported regular pharmacist checks post-technician fill. Most hospitals (81.3%) ensured 24/7 pharmacist availability. Basic data analytics were used by 54.7% of hospitals, with only (10.9%) employing advanced analytics. Machine-readable coding was used extensively mainly during dispensing. Sterile compounding was commonly performed manually (54.7%). About half of the hospitals adopted telehealth (57.8%). Larger hospitals adopted more advanced technologies. This study was the first to offer a comprehensive evaluation of medication dispensing and administration practices in UAE hospitals. More technological advancements could be adopted to ensure safe and efficient medication use systems are in place. The study provided valuable insights into system design, resource allocation, and health professional training needs required for improvement.
Gallbladder cancer is a biliary malignancy characterized by a high mortality rate, primarily due to the limitations of current serum biomarkers and imaging techniques in detecting the disease at an early stage. Circulating microRNAs (miRNAs) in serum, plasma, and bile are stable, less invasive biomarkers that are indicative of the biology of gallbladder cancer and have the potential for diagnostics through liquid biopsy. This review critically evaluates miRNA-based electrochemical biosensors that have been developed to detect gallbladder cancer, including their analytical performance, sensitivity, specificity, and detection limits in clinically relevant matrices, preanalytical variables, and analytical and clinical validation in clinical laboratories. We provide a brief overview of the relevant miRNA signatures in disease, their specificity to gallbladder cancer over other malignancies and inflammatory responses, comment on the approaches to transduction and nanomaterial-engineered interfaces in the detection of sensitive miRNAs in human biofluids, and critique the performance of biosensors in relation to the conventional molecular procedures, such as RT-qPCR and droplet digital PCR (ddPCR). In routine applications, particular emphasis is placed on specificity, detection limits in clinically relevant matrices, robustness, and sources of both analytical and biological variability. This encompasses the complex composition of bile, which includes bile salts, proteins, and pH changes that can pose challenges such as electrode fouling. We also describe how these biosensors are integrated into central laboratories and point-of-care procedures to diagnose, differentiate between malignant and inflammatory biliary lesions, assess risks, and treat gallbladder cancer. The review provides a conceptual framework of translation that reinforces the purpose and reasoning behind the implementation of electrochemical biosensors in clinical oncology by bridging miRNA pathobiology with miRNA electrochemical biosensors assay engineering and laboratory medicine issues to guide the design and implementation of miRNA electrochemical biosensors as a clinical diagnostic tool.
Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0-19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000-489 000), 144 000 deaths (131 000-162 000), and 11·7 million (10·7-13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5-36·1) globally, from 197 000 (173 000-218 000) in 1990, but increased in the WHO African region by 55·6% (25·5-92·4), from 31 500 (24 900-38 500) to 49 000 (42 600-58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5-26·5) in GBD 2017 to 10·5% (8·1-13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2-52·0) of global childhood cancer deaths in 2023. Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.
The review specifically examines the pivotal role of HDAC6 in the pathophysiological pathway of Amyotrophic Lateral Sclerosis (ALS), an escalating neurodegenerative ailment marked by the discerning damage to motor neurons. Several lines of evidence implicate inadequate proteostasis in significantly influencing neuronal degeneration. The accumulation of misfolded proteins and proteotoxicity are highlighted as significant factors in ALS pathophysiology. Key pathological hallmarks include ubiquitin-positive inclusions, disrupted RNA metabolism, cytoskeletal perturbations, and compromised axonal transport systems. HDAC6 dysregulation disrupts axonal transport, impairing mitochondrial function and increasing oxidative stress, leading to rapid motor neuron damage and cell death. The enzyme's aberrant deacetylation of α-tubulin destabilizes microtubules and impairs intracellular trafficking. Despite HDAC6's participation in these unfavorable processes, it also exerts neuroprotective properties. It deacetylates tubulin, promoting efficient axonal transport and autophagic clearance. HDAC6 helps form aggresomes and stress granules, which are essential for cellular defence against proteotoxic stress. Through its zinc finger ubiquitin-binding domain, HDAC6 interacts with polyubiquitinated proteins, facilitating their autophagic degradation. HDAC6 inhibition can boost autophagic flux and reduce protein aggregation, while its activation may amplify the protective effects. This dichotomous behaviour of HDAC6 may pose an obstacle to the design of targeted therapy. Illuminating the complex mechanisms through which HDAC6 influences neurodegeneration and neuroprotection is important before constructing effective treatments for ALS. The review provides a clear understanding of the complex role of HDAC6 in ALS pathogenesis and highlights potential strategies to improve the prognosis of people affected by this neurological illness.
Meningitis remains the leading infectious cause of neurological disabilities globally, disproportionately affecting children younger than 5 years and populations in the African meningitis belt. Whereas previous global estimates focused on ten pathogen categories, this study presents the most comprehensive analysis to date, assessing the meningitis burden attributable to 17 causative pathogens based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework. GBD is a systematic, scientific effort aimed at quantifying the comparative magnitude of health loss caused by diseases, injuries, and risk factors across age groups, sexes, and geographical locations over time. We estimated meningitis mortality using the Cause of Death Ensemble model (CODEm) and morbidity using DisMod-MR 2.1, incorporating data from vital registration, verbal autopsy, surveillance, hospital data, and systematic reviews. Aetiology-specific estimates were generated with pathogen-linked case-fatality ratios and splined binomial regression models. Risk factor attribution was based on established risk-outcome pairs and population attributable fractions. In 2023, there were 259 000 (95% uncertainty interval 202 000-335 000) global deaths and 2·54 million (2·20-2·93) incident cases of meningitis. Children younger than 5 years accounted for more than a third of deaths (86 600 [53 300-149 000]). Streptococcus pneumoniae, Neisseria meningitidis, non-polio enteroviruses, and other viruses were the leading causes of death, while non-polio enteroviruses caused the most cases. The four WHO-defined preventable meningitis pathogens of interest (S pneumoniae, N meningitidis, Haemophilus influenzae, and Group B streptococcus) contributed to 98 700 deaths (77 000-127 000) and 594 000 cases (514 000-686 000). Low birthweight, short gestation, and household air pollution were the top risk factors for meningitis-related mortality. Although mortality and incidence have declined significantly since 1990, progress is insufficient to meet WHO 2030 targets. Despite marked progress in reducing bacterial meningitis via global vaccination campaigns, a substantial meningitis burden persists, attributable both to common pathogens such as S pneumoniae and N meningitidis and to emerging non-bacterial pathogens such as Candida spp and drug-resistant fungi. Achieving WHO goals will require sustained investment in surveillance, vaccination, maternal screening, and health-system strengthening, especially in high-burden settings. Gates Foundation, Wellcome Trust, and UK Department of Health and Social Care.
Chronic respiratory diseases are an important global issue, particularly in Asia, where burden patterns vary widely across countries. With more than half the world's population living in Asia, understanding the national and regional burden of chronic respiratory diseases is essential; however, research on this area remains inadequate. We aimed to investigate the burden of chronic respiratory diseases in Asia at national and regional levels, and to identify key risk factors. The Global Burden of Diseases, Injuries, and Risk Factors Study 2023 provides estimates for assessing the burden of chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease (ILD), and pulmonary sarcoidosis. We focused on 34 countries in Asia, encompassing the high-income Asia Pacific region and central, east, south, and southeast Asia. Estimates for age-standardised prevalence and disability-adjusted life-year (DALY) rates per 100 000 population, including 95% uncertainty intervals (UIs), were extracted by location, sex, year, and Socio-demographic Index (SDI). The average annual percentage change was calculated and presented as a percentage with 95% CIs. Estimates of modifiable attributable risk factors for DALYs and mortality were also included. In Asia, the age-standardised prevalence and DALY rates for chronic respiratory diseases generally declined from 1990 to 2023; however, the trend varied substantially by disease and country. In 2023, the age-standardised prevalence rate of COPD was highest in south Asia (3044·18 [95% UI 2748·67-3303·04] per 100 000 population), while the age-standardised asthma prevalence rate was highest in the high-income Asia Pacific region (4870·24 [4046·70-5962·78] per 100 000 population) and southeast Asia (4778·18 [3970·25-5735·61] per 100 000 population). Despite southeast Asia and the high-income Asia Pacific region having a similar age-standardised asthma prevalence rate, southeast Asia had a higher age-standardised DALY rate (508·67 [95% UI 394·89-669·92] per 100 000 population) compared with the high-income Asia Pacific region (204·40 [129·23-290·41] per 100 000 population). A decrease in the age-standardised DALY rate for chronic respiratory diseases was observed with increasing SDI, contrasting with its prevalence patterns. Age-standardised DALY rates of COPD decreased in all Asian countries except for Georgia (average annual percentage change 1·37 [95% CI 1·26-1·48]) and Kazakhstan (0·73 [0·55-0·93]), and age-standardised DALY rates of asthma decreased in all countries. Smoking and ambient particulate matter pollution were identified as leading attributable risk factors for chronic respiratory diseases across Asia. Household air pollution from solid fuels was a regionally pronounced risk factor for chronic respiratory diseases, particularly in south Asia (age-standardised DALY rate 657·58 [95% UI 485·04-880·45] per 100 000 population). Although smoking was a major risk factor in males, ambient particulate matter pollution and secondhand smoke emerged as important attributable risk factors for chronic respiratory diseases in females. Countries with lower SDI had markedly higher DALY rates, highlighting the need to address socioeconomic and health-care inequities. Household air pollution from solid fuels continues to impose a substantial but preventable burden in south Asia, calling for clean energy adoption and improved ventilation. Gates Foundation.
The global increase in antimicrobial resistance presents a significant public health challenge and calls for the discovery of new antimicrobial agents with innovative mechanisms of action. Spirocyclic compounds, characterized by two or more rings connected via a single shared atom, have attracted interest due to their rigid three-dimensional structures and promising pharmacological activities. This review aims to summarize research published between 2019 and 2025 on the antibacterial potential of natural, semisynthetic, and synthetic spirocyclic compounds, emphasizing their activity against Gram-positive, Gramnegative, and resistant bacterial strains. It also highlights promising therapeutic scaffolds and explores Structure- Activity Relationships (SAR) where available. Relevant literature was gathered from peer-reviewed scientific databases. Studies reporting antibacterial evaluations of spirocyclic derivatives were included. Reported compounds were classified based on their core scaffold type, and their antibacterial activities, synergistic effects with standard antibiotics, and insights from computational docking were examined. Several spirocyclic scaffolds demonstrated antibacterial potential, including spiro β-lactams, spiro chromanes, spiro thiazolidines, and especially spiro oxindoles, which were the most extensively studied (44 research articles). Many compounds showed notable antibacterial activity against drug-resistant strains, and synergistic effects were observed when combined with conventional antibiotics. One spiro pyrimidinetrione derivative was approved recently by the US FDA, indicating translational potential. Molecular docking studies supported mechanistic understanding by predicting possible bacterial targets. Due to their wide applications across various scaffolds, spiro frameworks could be a valuable strategy in defeating bacteria. This architecture offers structurally unique compounds by expanding the threedimensional chemical space that may address antimicrobial resistance. Further exploration through Mechanistic validations and systematic structure-activity relationships studies is required to fully understand the potential of spiro compounds. Spirocyclic compounds are a valuable class of antibacterial agents owing to their structural diversity and efficacy. This review offers insights into their therapeutic potential and provides a foundation for future drug development targeting antimicrobial resistance.
This in vitro study aimed to develop a novel choline-based ionic liquid-incorporated silicone denture base soft liners (SDBSLs) with improved antifungal potential and compliance in standard properties. Choline borate (CB) ionic liquid was synthesized, characterized, and blended with a silicone liner (Molloplast-B) in concentrations of 1%, 2%, and 5% w/w to form the experimental group, CB, with three subgroups (CB1%, CB2%, and CB5%, respectively). Commercial silicone liners served as the negative control, while silicone liners blended with the antifungal drug itraconazole (1.25% wt/wt) were the positive control. The antifungal potential against Candida albicans was evaluated via a direct-contact assay, with growth inhibition quantified by measuring the culture turbidity (OD600). The tear strength was determined using the type A test and the Shore A hardness was measured using a durometer. A physical parameter, percent mass change (%), was tested using the immersion method (at 1 week and 6 weeks). The Alamar Blue assay was performed to assess the biocompatibility of the samples. Data were statistically analyzed using SPSS 25, with p = <0.001. The results showed that CB1% had the most significant inhibitory effect on C. albicans growth (83.71%). The drug- incorporated liners gained the most weight (5.00 ± 0.11%). The liners in CB5% were the toughest, with a tear strength of 5.31 ± 1.84 kN/m. The liners in the negative control group (Molloplast-B) were the softest (Shore A = 60.16 ± 1.07), followed by those in CB5% (51.33 ± 1.40). The biocompatibility of the ionic liquid-modified samples was better than that of the positive controls. The novel choline borate in silicone liners enhanced the antifungal potential and met the standard criteria of physical and mechanical compliance.