Alternative and complementary medicine (CAM) is gaining the attention of the medical academic community due to increased public use and ongoing concern of efficacy, safety and quality of CAM treatments. The aim of this work was to review the scope of research that was performed in Israel during the past 10 years. We detected 91 works that focus on clinical research: RCT's, pilot studies, comparative studies, surveys of prevalence & patterns of use, and the attitudes of the medical establishment and of medical students. The results of this work indicate considerable progress in the research of CAM within medical establishments in Israel. We believe that future research will benefit from an upgrading of quality of research that will further focus on cost-effectiveness as well as on possible adverse effects of CAM. This goal can be achieved through appropriate research training of MD's and CAM therapists, and by governmental funding of the research.
The new discipline of whole systems research (WSR) targets the study of complex CAM therapies as system-level phenomena, as opposed to single-agent or uni-dimensional effects. This article describes the pre-defined goals, issues that were developed, and opportunities that were revealed in a workshop held in Vancouver BC, in which scientists, practitioners, and policy makers met to lay the foundations of WSR. Important issues were identified, such as treatment individualization, problems of diagnosis, patient-practitioner interaction, varying therapeutic contexts, and patient-determined outcome values. Research design issues that were addressed included a variety of challenges to the study of intact systems, in relation to both synergy and emergent behaviors, and the opportunities to innovate the conventional RCT. As the network of CAM scientists and practitioners engaged in WSR expands, a common nomenclature and body of techniques will help us to a better understanding of the ways in which whole systems affect healing.
Despite the popularity of complementary and alternative medicine among older persons, its use within this subpopulation is still not fully understood. This study aimed to explore the perceptions of older persons residing in communities in Ebonyi State as pertains the use of complementary and alternative medicine. Qualitative data collection was by focus group discussions (FGDs), in four communities, two urban and two rural, in Ebonyi state, Nigeria. A total of 12 FGDs involving 96 participants, each consisting of 8 males or females respectively were conducted using a synthesized FGD guide. A thematic analysis of data was performed with the aid of NVivo software. The Leventhal's self-regulatory model (SRM) was utilised as it provides a flexible framework for understanding the use of complementary and alternative medicine among older persons. Majority of the participants expressed belief in the inherent benefits of complementary and alternative medicine, which were categorized into medical and non-medical reasons. Febrile illness, including malaria, typhoid fever, and hepatitis; respiratory; haematological; and dermatological conditions were reported as the common health conditions for which participants used CAM. Additionally, participants mentioned using CAM for chronic conditions, such as diabetes mellitus, hypertension, and arthritis, as well as for general health promotion and wellbeing. Preference for CAM was influenced by belief in its effectiveness, perceived lower cost when compared to conventional treatments, delays in hospital diagnoses and treatments, and belief in the spiritual origins of diseases. Safety concerns regarding CAM use included a lack of information on dosing, directions for safe use, and potential side effects. The findings indicate a strong belief among participants in the benefits of complementary and alternative medicine which they believe offer both medical and non-medical advantages. However, despite these perceived benefits, safety concerns were also raised by some participants. Efforts to promote education and awareness about CAM, improve access to reliable information, and ensure the safe and effective use of CAM therapies are crucial for supporting the health and well-being of older persons who choose to incorporate CAM into their healthcare practices.
To map digital resources on traditional, complementary and integrative medicine, including databases, repositories, libraries and web portals providing access to traditional knowledge, research or policy information. We undertook a rapid review of publications related to digital resources on traditional medicine. We also surveyed specialists in traditional medicine for referrals to digital resources. We searched PubMed®, Embase, the Virtual Health Library of the Pan American Health Organization and Google. Eligible resources were digital platforms indexing traditional medicine knowledge, research or policy. From the publications identified, we retrieved relevant digital resources and extracted data on their scope, content and geographic distribution. From 102 studies, we identified 358 potentially relevant digital resources on traditional medicine across all regions of the World Health Organization (WHO). We included 125 of these resources in our inventory of traditional medicine digital resources. The Western Pacific Region accounted for 36% (45/125) of the resources, led by China with 34 resources, and the Americas accounted for 24% (30/125) of the resources, with 24 resources from the United States of America. Most digital resources focused on pharmacological or clinical applications; only five addressed Indigenous medicine. Digital resources on traditional, complementary and integrative medicine are diverse but fragmented. Codified systems are predominant while Indigenous traditions are marginalized. WHO's Traditional Medicine Global Library offers an opportunity to correct these imbalances by creating an inclusive, ethically governed platform that safeguards knowledge systems and supports their equitable integration into global health. Identifier les ressources numériques sur la médecine traditionnelle, complémentaire et intégrative, y compris les bases de données, référentiels, bibliothèques et portails Web donnant accès à des connaissances traditionnelles, à des recherches ou à des informations en matière de politiques. Nous avons procédé à un examen rapide des publications liées aux ressources numériques sur la médecine traditionnelle. Nous avons également interrogé des spécialistes en médecine traditionnelle afin d’obtenir des références vers des ressources numériques. Nous avons effectué des recherches dans PubMed®, Embase, la bibliothèque virtuelle de santé de l’Organisation panaméricaine de la Santé et Google. Les ressources éligibles étaient des plateformes numériques répertoriant les connaissances, les recherches ou les politiques en matière de médecine traditionnelle. Les publications identifiées nous ont permis de récupérer les ressources numériques pertinentes et d’extraire des données sur leur portée, leurs contenus et leur répartition géographique. Dans 102 études, nous avons identifié 358 ressources numériques potentiellement pertinentes sur la médecine traditionnelle dans toutes les régions de l’Organisation mondiale de la Santé (OMS). Nous avons inclus 125 de ces ressources dans notre inventaire des ressources numériques sur la médecine traditionnelle. La région du Pacifique occidental représentait 36% (45/125) des ressources, la Chine arrivant en tête avec 34 ressources, et les Amériques représentaient 24% (30/125) des ressources, avec 24 ressources provenant des États-Unis d’Amérique. La plupart des ressources numériques étaient axées sur les applications pharmacologiques ou cliniques. Seules cinq d’entre elles traitaient de la médecine autochtone. Les ressources numériques sur la médecine traditionnelle, complémentaire et intégrative sont diverses, mais fragmentées. Les systèmes codifiés prédominent, tandis que les traditions autochtones sont marginalisées. La Bibliothèque mondiale de l’OMS sur la médecine traditionnelle offre la possibilité de corriger ces déséquilibres en créant une plateforme inclusive et régie par des principes éthiques qui préserve les systèmes de connaissances et soutient leur intégration équitable dans le système mondial de la santé. Cartografiar los recursos digitales sobre medicina tradicional, complementaria e integrativa, incluidas bases de datos, repositorios, bibliotecas y portales web que proporcionan acceso a conocimientos tradicionales, investigaciones o información normativa. Se realizó una revisión rápida de publicaciones relacionadas con recursos digitales sobre medicina tradicional. Asimismo, se consultó a especialistas en medicina tradicional para identificar recursos digitales pertinentes. Se realizaron búsquedas en PubMed®, Embase, la Biblioteca Virtual en Salud de la Organización Panamericana de la Salud y Google. Se consideraron elegibles las plataformas digitales que indexaban conocimientos, investigaciones o políticas sobre medicina tradicional. A partir de las publicaciones identificadas, se recuperaron recursos digitales pertinentes y se extrajeron datos sobre su alcance, contenido y distribución geográfica. A partir de 102 estudios, se identificaron 358 recursos digitales potencialmente pertinentes sobre medicina tradicional en todas las regiones de la Organización Mundial de la Salud (OMS). De estos, se incluyeron 125 recursos en el inventario de recursos digitales sobre medicina tradicional. La Región del Pacífico Occidental representó el 36% (45/125) de los recursos, encabezada por China con 34 recursos, mientras que la Región de las Américas representó el 24% (30/125), con 24 recursos procedentes de los Estados Unidos de América. La mayoría de los recursos digitales se centraban en aplicaciones farmacológicas o clínicas; solo cinco abordaban la medicina indígena. Los recursos digitales sobre medicina tradicional, complementaria e integrativa son diversos, pero fragmentados. Los sistemas codificados predominan, mientras que las tradiciones indígenas permanecen marginadas. La Biblioteca Mundial de Medicina Tradicional de la OMS ofrece una oportunidad para corregir estos desequilibrios mediante la creación de una plataforma inclusiva y regida por principios éticos que salvaguarde los sistemas de conocimiento y apoye su integración equitativa en la salud mundial. تحديد الموارد الرقمية المتعلقة بالطب التقليدي والتكميلي والتكاملي، بما في ذلك قواعد البيانات، والمستودعات، والمكتبات، والبوابات الإلكترونية التي تتيح الوصول إلى المعرفة التقليدية، أو الأبحاث، أو المعلومات المتعلقة بالسياسات. قمنا بإجراء مراجعة سريعة للمنشورات المتعلقة بالموارد الرقمية حول الطب التقليدي. كما قمنا باستطلاع آراء المتخصصين في الطب التقليدي للحصول على إحالات إلى الموارد الرقمية. قمنا بالبحث في قواعد بيانات ®PubMed وEmbase، والمكتبة الصحية الافتراضية لمنظمة الصحة للبلدان الأمريكية، وGoogle. كانت الموارد المؤهلة عبارة عن منصات رقمية تقوم بفهرسة المعرفة أو الأبحاث أو السياسات المتعلقة بالطب التقليدي. من المنشورات التي تم تحديدها، قمنا باسترجاع الموارد الرقمية ذات الصلة، واستخرجنا بيانات عن نطاقها ومحتواها وتوزيعها الجغرافي. من بين 102 دراسة، قمنا بتحديد 358 موردًا رقميًا محتملًا ذي صلة بالطب التقليدي عبر جميع مناطق منظمة الصحة العالمية (WHO). أدرجنا 125 من هذه الموارد في قائمتنا للموارد الرقمية للطب التقليدي. استحوذت منطقة غرب المحيط الهادئ على %36 (45/125) من الموارد، بقيادة الصين في ظل وجود 34 موردًا، واستحوذت الأمريكتان على %24 (30/125) من الموارد، مع 24 موردًا من الولايات المتحدة الأمريكية. قامت معظم الموارد الرقمية بالتركيز على التطبيقات الدوائية أو الإكلينيكية؛ ولم تتناول سوى خمسة منها الطب التقليدي. الموارد الرقمية المتعلقة بالطب التقليدي والتكميلي والتكاملي متنوعة ولكنها مجزأة. وتسود الأنظمة المقننة بينما يتم تهميش التقاليد التقليدية. توفر المكتبة العالمية للطب التقليدي التابعة لمنظمة الصحة العالمية فرصة لتصحيح هذه الاختلالات، وذلك من خلال إنشاء منصة شاملة تخضع لقواعد أخلاقية تحمي أنظمة المعرفة، وتدعم دمجها بشكل منصف في الصحة العالمية. 旨在了解传统、补充和整合医学相关数字资源,包括提供传统知识、研究或政策信息访问权限的数据库、信息库、图书馆和门户网站。. 我们对涉及传统医学数字资源的出版物进行了速览综述。我们还面向传统医学领域的专家开展了调研活动,以了解其推荐使用的数字资源。我们搜索了 PubMed®、Embase、泛美卫生组织的虚拟健康图书馆和谷歌 (Google),然后将可检索到传统医学知识、研究或政策的数字平台纳入了适用数字资源的范畴。我们从已确定的出版物中检索到了相关数字资源并提取了有关此类资源范围、内容及地理分布情况的数据。. 基于 102 项研究,我们在世卫组织 (WHO) 所有区域内共找到了 358 个可能有关的传统医学数字资源。我们将其中 125 个资源列入了我们的传统医学数字资源清单中。在列入清单的这些资源中,西太平洋区域占 36% (45/125),其中又以中国(34 个资源)的占比最高;美洲区域占 24% (30/125),其中 24 个资源来自于美利坚合众国。大多数数字资源侧重于药理作用或临床应用;仅五个资源涉及土著医学。. 尽管传统、补充和整合医学相关数字资源种类繁多,但此类资源过于零散,未形成体系。编码化系统逐步占据主导地位,而土著传统则有向边缘化发展的趋势。世卫组织的传统医学全球图书馆创建了一个具有包容性且符合伦理规范的平台来保护知识系统和支持以公平合理的方式将此类知识系统整合到全球健康系统中,从而确保有机会纠正此类失衡现象。. Составить карту цифровых ресурсов по традиционной, комплементарной и интегративной медицине, в том числе баз данных, репозиториев, библиотек и веб-порталов, предоставляющих доступ к информации о традиционных знаниях, научных исследованиях или политике в данной области. Авторы выполнили краткий обзор публикаций, посвященных цифровым ресурсам по традиционной медицине. Были также опрошены специалисты по традиционной медицине, которые могли бы дать рекомендации по цифровым ресурсам. Поиск проводился по базам данных PubMed®, Embase, Виртуальной библиотеке здоровья Панамериканской организации здравоохранения, а также в Google. В рассмотрение включались цифровые платформы, индексирующие информацию по знаниям, соответствующим научным исследованиям и политике в области традиционной медицины. Из выявленных публикаций были извлечены соответствующие цифровые ресурсы и данные об их тематическом охвате, содержимом и географическом распределении. По данным 102 исследований было выявлено 358 потенциально релевантных цифровых ресурсов по традиционной медицине во всех регионах Всемирной организации здравоохранения (ВОЗ). 125 из них авторы включили в перечень цифровых ресурсов по традиционной медицине. На долю Западного Тихоокеанского региона пришлось 36% (45/125) ресурсов, во главе списка идет Китай с 34 ресурсами из них, а на долю Американского континента – 24% (30/125), где 24 ресурса представляли Соединенные Штаты Америки. Большинство цифровых ресурсов были посвящены вопросам фармакологии или клинического применения, и только пять освещали вопросы медицины коренных народов. Цифровые ресурсы по традиционной, комплементарной и интегративной медицине отличаются разнообразием, но в то же время и фрагментированностью. Преобладают кодифицированные системы, тогда как традиции коренных народов остаются на периферии. Глобальная библиотека ВОЗ по традиционной медицине предлагает возможность исправить этот дисбаланс, создав инклюзивную, управляемую на основе этических принципов платформу, которая защищает системы знаний и поддерживает их равноправное включение в систему мирового здравоохранения.
Recognizing and prioritizing the factors that influence the selection of treatment options is essential for effective health service planning and an appropriate health care delivery system. This study aimed to identify and prioritize the barriers and facilitators to the use of Traditional, Complementary, and Integrative Medicine (TCIM) in Iran. A two-phase, mixed-methods study was conducted. First, a two-round Delphi survey was conducted with a panel of 32 experts, including specialists in Persian medicine (PM) and health policymakers, to acheive consensus on a list of barriers and facilitators within the Iranian context. Subsequently, the Analytical Hierarchy Process (AHP) was applied with a 12-expert panel to determine the relative weight and priority of the agreed-upon criteria. The Delphi process yielded consensus on 18 facilitators and nine barriers. The facilitators were categorized into two main dimensions (Cultural and social facilitators, and Systemic facilitators) and six sub-dimensions. In comparison, the barriers formed four main dimensions (service delivery barriers, policy challenges, financial barriers, and knowledge and attitudinal barriers). Quantitative AHP results revealed that among facilitators, "effects of health professionals" (Final Weight: 0.29) was the most critical dimension, with "Recommendation and referral by conventional physicians (CPs)" (Final Weight: 0.18) as its top factor. Conversely, among barriers, "Policy Challenges" (Final Weight: 0.50) was the most significant dimension, substantially outweighing others. The findings highlight that the recommendation of TCIM by CPs are the strongest facilitator; yet, overarching policy challenges critically hamper its implementation. Addressing this disconnect requires integrated policy reforms and interdisciplinary collaboration to leverage TCIM within Iran's health care system effectively.
Healthcare professionals (HCP) encounter a multitude of challenges regarding the utilisation of medicines, vaccines, and alternative therapies in pregnant and breastfeeding women (PBW). The objective of this study was to explore the experiences, beliefs, and attitudes of HCP toward prescribing medicines, vaccines, and alternative therapies during pregnancy and breastfeeding in Catalonia, Spain. This study employed a qualitative methodology, guided by a gender-based perspective. Three discussion groups were conducted, with the participation of 21 HCP during February 2024. Sampling was intentional, purposive designed to ensure discourse diversity. Recruitment was conducted through key contacts in public primary healthcare centres, sexual and reproductive health care centres, hospital settings in Catalonia, using snowball techniques. The data were analysed using thematic analysis. The challenges encountered by HCP who provide care to PBW are numerous and vary depending on the healthcare speciality area. Family physicians and nurses identified a lack of training in obstetrics as a factor contributing to difficulties in prescribing medicines. Midwives emphasised the importance of monitoring and follow-up during pregnancy, especially in cases where an adaptation of medication is required, while gynaecologists drew attention to the challenges posed by an increase in medication avoidance. HCP expressed concerns about the safety of the COVID-19 vaccine, as opposed to the greater safety of evidence of pertussis and influenza vaccines. The use of alternative therapies may lead to potential complications during consultations, as some users do not disclose their use. This study underscores the challenges encountered by HCP in drug prescriptions, complementary medicine, and vaccination during pregnancy and breastfeeding, considering HCP differences between specialities. Additionally, the study emphasises the difficulties associated with dual follow-up cases and the significance of establishing trusting relationships with users and shared decision-making processes or a good medication adherence. HCP have participated sharing their experience in prescribing medication and recommendations on vaccines and alternative medicine. The results of this study can be used to effect change in the practice of HCP.
Medical assistance in dying (MAiD) became a legal end-of-life option on December 10, 2015, in Québec, and on June 17, 2016, in the rest of Canada. Since its legalization, there has been a steady increase in the number of MAiD requests and provisions. Across permissive jurisdictions, Québec now has the highest rate of assisted death. Despite the growing use of MAiD, research examining the factors driving this increase remains limited and fragmented. Existing studies offer partial and sometimes contradictory explanations, with little integration of legal, institutional, societal, and individual dimensions. Further research is needed to better understand the determinants of MAiD requests and practices, particularly in the Canadian and Québec contexts. This research aims to understand the factors influencing changes in MAiD requests and administrations in Québec by examining laws, practices, societal perspectives, organization of care and services, and individual characteristics of those requesting MAiD, as well as their interrelationships. We present the protocol developed by the Consortium interdisciplinaire de recherche sur l'aide médicale à mourir, an interdisciplinary research consortium, including an international advisory committee, set up for this research. The design of this protocol is multimethods and convergent mixed methods, including (1) an international cross-thematical approach with 4 main research methods (a scoping review, key informant interviews, focus groups with health care professionals, and a population-based survey) chosen to partially answer research questions across the entire study and to compare with other jurisdictions and (2) 11 theme-specific methods (including community forums, media coverage analysis, comparative legal analyses, case studies of triads, individual interviews, and system mapping) to enrich and complement findings from the cross-thematical approach. When this 3-year funded study started in July 2024, several research methods not requiring ethics committee approval (because no human participants were involved) were initiated, including scoping and systematic reviews, media coverage analysis, and comparative legal analyses. By August 2025, interviews with key informants were completed, and analyses took place in September. Concurrently, other subteams started data collection (focus groups December 2025) or are getting ready to seek ethics approval for their protocols and data collection processes involving human participants: case studies of triads, individual interviews, and community forums. Findings from the international cross-thematical approach and theme-specific methods will provide a comprehensive understanding of the factors influencing the use of MAiD in Québec. This study has strengths, including the use of a specific theoretical framework, a variety of complementary methods, and an integrated knowledge mobilization strategy. As for its limitations, we foresee challenges with the comparison of jurisdictions in terms of language, culture, and legal systems, as well as access to data about MAiD cases, since reporting systems may differ between jurisdictions. DERR1-10.2196/83549.
While numerous scholars have studied Hippocrates' philosophy, ideas, and oaths, there has been limited research on his pharmacological theories especially combined with clinical medication. This paper extracts and reconstructs a pharmacological system from the extensive corpus of Hippocrates, dividing it into two parts: the first is the philosophical theory of medicine, exploring the natural properties of all things and humans, producing the Four Humors Theory; the second is clinical pharmacology, discussing how to maintain balance to preserve or restore health. The system comprises two major inferences: first, the four elemental qualities form the foundational logic of natural philosophy and the pharmacological essence of medical philosophy; second, the system guides the complementary "regimen therapy" and the "evacuation therapy" based on the underlying logic of the four elemental qualities. Through theoretical construction and practical validation, this reflects ancient Greece's exploration of the relationship between pharmacal practice and medical philosophy during the classical era.
The predictive value of lipoprotein(a) (Lp[a]), high-sensitivity C-reactive protein (hsCRP), and remnant cholesterol (RC) beyond low-density lipoprotein cholesterol (LDL-C) varies across cardiovascular disease (CVD) outcomes. This analysis evaluates the extent to which concentrations of these non-LDL-C biomarkers improve MI-specific risk prediction in a primary prevention population. We analyzed 306,183 UK Biobank participants free of cardiovascular disease at baseline with available Lp(a), RC, and hsCRP measurements. RC was calculated as total cholesterol minus LDL-C minus high-density lipoprotein cholesterol (HDLC). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression across biomarker quintiles and cumulative biomarker burden. The primary endpoint was first MI. Over 15 years of follow-up, 10,824 MI events occurred. In fully adjusted models comparing quintile 5 with quintile 1, HRs (95% CI) were 1.09 (1.08-1.11) for Lp(a), 1.14 (1.13-1.16) for RC, and 1.08 (1.06-1.10) for hsCRP. Per-SD increases were associated with higher MI risk for RC 1.22 (1.20-1.25), Lp(a) 1.16 (1.13-1.18), and hsCRP 1.13 (1.10-1.15). The risk of MI increased stepwise with cumulative biomarker burden; compared with individuals with no biomarker in the top quintile, HRs (95% CI) were 1.45 (1.39-1.51), 2.14 (2.02-2.26), and 2.83 (2.48-3.24) for those with one, two, or all three elevated biomarkers, respectively. Lp(a), RC, and hsCRP each provide independent and complementary information for MI risk. Their combined elevation identifies individuals at higher MI risk, suggesting selective testing of all three biomarkers in primary prevention.
The global incidence and mortality of cancer continue to increase, and various chemotherapeutic agents, while highly effective, are associated with serious side effects like immunosuppression, metabolic dysfunction, and drug resistance. As a complementary or alternative approach, traditional Chinese medicine (TCM), which is known for its multi-target mechanisms and low toxicity, has garnered increasing attention in cancer research. Magnolia officinalis (M. officinalis) is a member of the Magnoliaceae family, and dried bark from its stems, roots, and branches is its primary medicinal part. According to TCM theory, M. officinalis may resolve dampness, eliminate phlegm, promote qi circulation, and relieve stagnation, and it has been widely applied in the treatment of gastrointestinal disorders. Modern pharmacological studies have identified bioactive compounds, including lignans, volatile oils, alkaloids, and polysaccharides, in M. officinalis, but the mechanisms underlying these pharmacological effects are still unclear and their clinical applications are limited by the lack of robust clinical evidence. We conducted a systematic review of both contemporary research databases (e.g., PubMed, CNKI, ScienceDirect, and other Chinese medical databases) and classic TCM literature to compile the bioactive components of M. officinalis, their pharmacological mechanisms in oncology, and recent preclinical progress. We also discuss the prospects and challenges of developing M. officinalis as an anticancer agent to provide a theoretical basis for its future development and clinical application.
Recent advances in biological therapies, small molecules and allergen-specific immunotherapy are reshaping the management of immunoallergic diseases, progressively shifting therapeutic goals from short-term disease control toward the possibility of achieving sustained clinical remission. Despite increasing evidence across multiple conditions, a universally accepted and disease-transversal definition of clinical remission (CR) remains lacking. In this review we propose a comprehensive framework for defining clinical remission across a broad spectrum of immune-mediated diseases traditionally managed in Allergy and Clinical Immunology practice, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, chronic urticaria, atopic dermatitis, mastocytosis, food allergy, and eosinophilic esophagitis. Clinical remission is defined as a sustained state of absence of clinically relevant disease manifestations, independently of underlying biological activity; suppression of inflammatory pathways and normalization of biomarkers define biological remission, which may coexist with, but is not required for, clinical remission. We introduce the 3D-CR model, a pragmatic, disease-adaptable framework integrating 3 complementary domains - clinical, biological, and functional - to characterize remission states as complete, partial, or absent. Building on this model, we propose the Allergic Disease Remission Score (ADReS) as a modular tool designed to support standardized assessment, longitudinal follow-up, and cross-disease comparison in clinical trials and real-world settings. These tools are intended as conceptual and research instruments rather than prescriptive algorithms for individual therapeutic decision-making. Finally, we outline a World Allergy Organization call to action advocating for a harmonized global approach to defining, measuring, and implementing clinical remission as a meaningful treatment target. Establishing standardized remission endpoints has the potential to improve patient outcomes, facilitate precision medicine strategies, enhance comparability across studies, and reduce heterogeneity in clinical research and practice worldwide.
The rapid expansion of data-driven technologies, particularly machine learning (ML) and artificial intelligence (AI), has substantially influenced biomedical research and drug discovery. In neuropharmacology, the availability of large-scale genomic, proteomic, chemical, and clinical datasets has stimulated the adoption of AI-based approaches to address persistent challenges in neurological drug development, including high attrition rates and the scarcity of disease-modifying therapies. Unlike prior reviews that broadly discuss AI applications in drug discovery or neurology, this narrative review focuses specifically on neuropharmacology, with an emphasis on translational relevance, disease-oriented examples, and real-world constraints. We critically examine the application of AI and ML across key stages of the neuropharmacological drug discovery pipeline, including target identification, drug-target interaction prediction, lead optimization, toxicity assessment, and early-stage clinical translation. Particular attention is given to concrete case studies in neurodegenerative and neurological disorders, illustrating where AI has meaningfully enhanced discovery efficiency and where its anticipated "revolutionary" impact has not yet been realized. In parallel, we analyze the biological, technical, and regulatory barriers that limit the clinical success of AI-driven strategies, including data bias, limited model interpretability, incomplete understanding of brain biology, and translational bottlenecks. By integrating case-based evidence with a critical analytical perspective, this review delineates both the opportunities and limitations of AI in neuropharmacology. We argue that AI is most effective when deployed as a complementary tool alongside mechanistic neuroscience and clinical expertise, rather than as a standalone solution. As AI methodologies continue to mature, their careful, transparent, and ethically governed integration into neuropharmacological research may advance precision medicine and help bridge persistent gaps in the treatment of neurological disorders.
Sound source localization is a fundamental ability for living organisms and essential for human daily functioning. Sound localization heavily relies on binaural auditory input. Unilateral auditory impairment not only disrupts sound localization but also alters cortical activation patterns. However, current understanding of these adaptive cortical changes remains limited, with a lack of multidimensional and systematic research. Here, we employed multimodal neuroimaging-functional near-infrared spectroscopy (fNIRS) and pupillometry-to investigate the physiological mechanisms of sound localization from complementary perspectives. We recruited 33 normal-hearing participants, 12 with right single-sided deafness (RSSD), and 8 with left single-sided deafness (LSSD). All participants completed a sound localization task with seven azimuths (±90°, ±60°, ±30°, 0°) in the frontal hemifield. Our results revealed symmetric activation patterns in higher-order auditory cortices within the auditory dorsal stream and distinct cognitive processing for left vs. right hemispheres during sound localization. Following unilateral auditory deprivation, we observed distinct patterns of cortical reorganization that differed by deprivation side. Specifically, RSSD was associated with maintained spatial gradient encoding but required prefrontal compensation, whereas LSSD showed sacrificed spatial resolution for hemispheric processing efficiency. These findings offer novel insights into brain adaptation to unilateral auditory deprivation and provide a foundation for future research and clinical applications.
Inflammatory bowel disease (IBD) is a chronic, relapsing condition associated with diagnostic delays, disease misclassification, and variable treatment response. Conventional diagnostic and monitoring tools remain limited in capturing the biological complexity of IBD, prompting growing interest in metabolomics as a complementary approach. This systematic review aimed to examine the role of metabolomics in enhancing the diagnosis and management of IBD across adult and pediatric populations. Systematic review. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. PubMed, Web of Science Core Collection, ScienceDirect, Cochrane Library, and Google Scholar were searched from inception to identify eligible studies. Observational studies and clinical trials assessing metabolomics in IBD diagnosis or management were included. Methodological quality was appraised using the Newcastle-Ottawa Scale, RoB 2, and ROBINS-I. Due to substantial heterogeneity, a narrative synthesis was performed. Fourteen studies involving approximately 3700 participants met the inclusion criteria. Metabolomic analyses of serum, feces, urine, and plasma consistently identified disease-associated metabolic perturbations, particularly in amino acids, bile acids, lipids, and short-chain fatty acids. Only two studies reported formal diagnostic performance, with sensitivity and specificity exceeding 80% for distinguishing IBD subtypes. Several studies demonstrated metabolomic changes associated with treatment response and remission; however, outcome definitions varied widely across studies. Metabolomics shows significant potential to enhance IBD diagnosis and management, particularly for disease differentiation and treatment monitoring. Nonetheless, clinical translation is constrained by methodological heterogeneity and limited diagnostic validation. Future research should prioritize standardized protocols and robust diagnostic accuracy studies. This review explores metabolomics’ role in enhancing IBD diagnosis and management for both adults and children. The systematic review followed PRISMA 2020 guidelines, searching PubMed, Web of Science, Cochrane Library, ScienceDirect, and Google Scholar. Two reviewers independently screened studies and assessed risk of bias using Cochrane’s RoB 2, ROBINS-I, and NOS. A narrative synthesis was conducted due to study heterogeneity. Out of 2,630 records screened, 14 studies met eligibility criteria. These included ten observational studies, one case-control, one longitudinal observational, one RCT, and one nonrandomized trial. Six observational studies were of high quality. Metabolomics shows potential for enhancing IBD diagnosis and treatment, but high heterogeneity and a lack of diagnostic accuracy studies limit practical insights. The identified biomarkers/metabolites are consistent with previous studies, showing metabolomics’ potential in diagnosing and treating IBD in both pediatric and adult populations. Recent observational studies report sensitivity and specificity, indicating progress. Comprehensive diagnostic protocols should be developed based on previously identified biomarkers/metabolites before conducting rigorous diagnostic accuracy studies to evaluate their accuracy and improve clinical application of research findings.
Cardiovascular disease (CVD) is a leading cause of diabetes-related mortality in Mexico. Although diabetes subgroups capture underlying disease heterogeneity, their association and utility for risk prediction for fatal CVD in Mexican adults remain unclear. Here, we aimed to assess the risk of fatal CVD risk and their complementary role for fatal CVD risk prediction across diabetes subgroups in Mexican adults. We included adults with diabetes from the Mexico City Prospective Study (MCPS). Participants were classified into mild obesity-related (MOD), severe insulin-deficient (SIDD), severe insulin-resistant (SIRD), and mild age-related (MARD) diabetes using a self-normalizing neural network algorithm. Fatal CVD was defined as death from ischemic heart disease or stroke (ICD-10 I20-I25, I60-I69). SCORE2-Diabetes was internally recalibrated for fatal CVD outcomes only for use within MCPS, as this does not represent a formal validation of the original composite endpoint. Cause-specific Cox proportional hazards and Fine & Gray competing risk regression models were used to estimate subgroup-specific risk, and sequential models evaluated the incremental predictive value of diabetes subgroups combined with SCORE2-Diabetes and traditional risk factors. We analyzed data from 24,943 adults living with diabetes (mean age 58 ± 12, 67% female, no ethnicity data available). Over a median follow-up of 19.3 years (IQR 12.7-20.6), 2218 fatal CVD events (8.9%) were recorded. SIDD was the most prevalent subgroup (50.0%), followed by SIRD (14.1%), MARD (17.7%), and MOD (18.3%). SIDD and MARD showed the highest adjusted risk of fatal CVD (HR 1.58 [95% CI 1.38-1.81] and 1.35 [1.13-1.60]), whereas MOD and SIRD had lower risk, even when considering competing causes of non-CVD deaths. Recalibrated SCORE2-Diabetes demonstrated adequate discrimination overall (c-statistic 0.748, 95% CI 0.734-0.762) and for most diabetes subgroups but underperformed in MARD, with internal recalibration for fatal CVD outcomes improving risk assessment. The combination of diabetes subgroups and SCORE2-Diabetes modestly improved prediction for fatal CVD outcomes. Diabetes subgroups show heterogeneity in fatal CVD risk in Mexican adults. SIDD and MARD identify high-risk individuals and integration subgroup classification with SCORE2-Diabetes is complementary for fatal CVD risk prediction. This research was supported by a grant provided by the Bernard Lown Scholars in Cardiovascular Health Program grant number BLSCHP-2403. La enfermedad cardiovascular (ECV) es una de las principales causas de mortalidad relacionada con la diabetes en México. Si bien los subgrupos de diabetes reflejan la heterogeneidad subyacente de la enfermedad, su asociación y utilidad para la predicción del riesgo de ECV fatal en adultos mexicanos aún no están claras. El objetivo de este estudio fue evaluar el riesgo de ECV fatal y el papel complementario en la predicción de dicho riesgo para los diferentes subgrupos de diabetes en adultos mexicanos. Se incluyeron adultos con diabetes del Estudio Prospectivo de la Ciudad de México (MCPS). Los participantes se clasificaron en diabetes relacionada con obesidad leve (MOD), diabetes con deficiencia grave de insulina (SIDD), diabetes con resistencia grave a la insulina (SIRD) y diabetes leve relacionada con la edad (MARD) mediante un algoritmo de redes neuronales auto-normalizables. ECV fatal se definió como muerte por cardiopatía isquémica o accidente cerebrovascular (CIE-10 I20–I25, I60–I69). SCORE2-Diabetes se recalibró internamente para los desenlaces de ECV fatales únicamente para su uso dentro de MCPS, ya que esto no representa una validación formal del desenlace de compuesto del modelo original. Se utilizaron modelos de regresión de riesgos proporcionales de Cox específicos para cada causa y modelos de regresión de riesgos competitivos de Fine & Gray para estimar el riesgo específico de cada subgrupo. Modelos secuenciales evaluaron el valor predictivo incremental de los subgrupos de diabetes combinados con SCORE2-Diabetes y factores de riesgo tradicionales. Analizamos datos de 24,943 adultos con diabetes (edad media 58 ± 12 años, 67% mujeres, sin datos de etnicidad disponibles). Durante una mediana de seguimiento de 19.3 años (RIC 12.7–20.6), se registraron 2218 eventos cardiovasculares fatales (8.9%). El subgrupo más prevalente fue SIDD (50.0%), seguido de SIRD (14.1%), MARD (17.7%) y MOD (18.3%). SIDD y MARD mostraron el mayor riesgo ajustado de ECV fatal (HR 1.58 [IC95%: 1.38–1.81] y 1.35 [1.13–1.60]), mientras que MOD y SIRD presentaron un riesgo menor, incluso considerando causas competitivas de muerte no relacionadas a ECV. SCORE2-Diabetes recalibrado demostró una discriminación adecuada en general (estadístico-c 0.748, IC95%: 0.734–0.762) y para la mayoría de los subgrupos de diabetes, pero tuvo un rendimiento inferior en MARD. La recalibración interna de SCORE2-Diabetes para desenlaces de ECV fatal mejoró la evaluación del riesgo. La combinación de subgrupos de diabetes y SCORE2-Diabetes mejoró modestamente la predicción de desenlaces fatales de ECV. Los subgrupos de diabetes muestran heterogeneidad en el riesgo de ECV fatal en adultos mexicanos. SIDD y MARD identifican individuos de alto riesgo y la integración de la clasificación de subgrupos de diabetes con SCORE2-Diabetes es complementaria para la predicción del riesgo de ECV fatal. Este proyecyo fue financiado por el Bernard Lown Scholars in Cardiovascular Health Program, número de financiamiento BLSCHP-2403.
Visual impairment affects over 2.2 billion people worldwide and the major causes include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. For research in these areas, although animal models offer a more physiologically complex system than in vitro approaches, their use raises ethical considerations, and species-specific differences such as variations in protein sequences and signaling pathways. This can limit the direct translatability of the outcomes. Traditional 2-D cell cultures, in contrast, lack the multicellular organization and dynamic microenvironment necessary to replicate human retinal complexity. Retinal organoids (ROs), three-dimensional tissue constructs derived from pluripotent stem cells, have emerged as a promising model due to their human origin and complex cellular interactions that cannot be achieved in conventional 2-D/3-D co-culture models. In this review, we provide a brief overview of the evolution from 2-D to 3-D retinal models, highlight the structural and functional features of ROs including the presence of layered retinal architecture, photoreceptor outer segment formation, and light-responsive electrophysiological activity and summarize their applications in disease modeling, drug discovery, and gene and cell therapy. ROs represent a significant advancement over traditional models by enabling the recapitulation of human-specific retinal development, facilitating the study of patient-derived disease phenotypes, and providing a platform for personalized therapeutic screening. Their development has deepened understanding of pathological mechanisms in conditions such as retinitis pigmentosa and AMD, while enabling preclinical testing of targeted interventions like CRISPR-based gene editing and photoreceptor cell replacement. Nonetheless, challenges remain in fully replicating retinal vascularization, long-term functional maturation, and synaptic connectivity, underscoring the need for continued refinement and integration with complementary model systems.
Gastrointestinal cancers represent a major global health burden and are associated with high morbidity and mortality worldwide. Despite advances in conventional therapies, treatment outcomes remain limited due to therapy resistance, toxicity, and poor long-term efficacy, highlighting the need for novel and complementary therapeutic strategies. Magnolol, a biphenolic lignan isolated from Magnolia officinalis, has attracted considerable attention due to its reported anticancer activity in multiple gastrointestinal malignancies. This review systematically summarizes current preclinical evidence on the anticancer effects of magnolol in oral, esophageal, gastric, colorectal, pancreatic, and liver cancers. Available studies demonstrate that magnolol inhibits cancer cell proliferation, migration, invasion, angiogenesis, and epithelial-mesenchymal transition, while inducing cell cycle arrest and apoptosis. These effects are mediated through modulation of key cancer-associated signaling pathways, including PI3K/Akt/NF-κB, MAPK/JNK, ERK, TGF-β/Smad, and caspase-dependent apoptotic pathways. The review further highlights recent insights into the structure-activity relationship of magnolol and its semi-synthetic derivatives, emphasizing how targeted chemical modifications influence anticancer potency and mechanistic specificity. In addition, challenges related to magnolol's poor aqueous solubility, rapid metabolism, and limited bioavailability are discussed, with particular focus on nanotechnology-based delivery systems developed to improve its pharmacokinetic profile and therapeutic performance. This current review provides an integrated overview of magnolol's molecular mechanisms, chemical optimization strategies, and translational limitations in gastrointestinal cancer therapy, and outlines future research directions necessary to support its progression toward clinical application.
Sickle cell disease (SCD) is a severe, inherited hemoglobin disorder characterized by chronic hemolysis, vaso-occlusive crises (VOCs), and systemic inflammation. Hydroxyurea is the standard conventional pharmacotherapy for SCD, but it has certain limitations, necessitating the need to explore other safe and effective treatment options for SCD. Ayurveda interventions offer a potential therapeutic approach complementary to conventional medicine for SCD management, with anti-inflammatory, immunomodulatory, and hematopoietic properties. This randomized controlled trial will evaluate the efficacy and safety of an Ayurvedic therapeutic regimen as an adjunct to hydroxyurea in SCD management, assessing its impact on hematological parameters, inflammatory biomarkers, VOC frequency, and overall quality of life. A PROBE (Prospective, Randomized, Open-Label, Blinded End Point) study will be conducted on individuals of any gender aged 18 years or older and diagnosed with SCD (with hemoglobin S levels more than 60% and a history of at least 1 VOC per year over the past 3 y). Individuals with acute VOC or any severe infection requiring hospitalization, a history of significant comorbidities, or hematopoietic stem cell transplantation will not be considered. The study will be conducted at the All India Institute of Medical Sciences, Bhopal, India. A total of 100 participants will undergo random assignment in a 1:1 ratio to receive either an Ayurveda regimen (Dadimadi Ghrita, Punarnavadi Mandura, and Vasaguduchyadi Kwatha) as an add-on to hydroxyurea or hydroxyurea alone for 8 months. The primary outcome will be a change in hemoglobin electrophoresis parameters (hemoglobin S, fetal hemoglobin, and adult hemoglobin) and the frequency of VOC episodes over 8 months. The secondary outcome measures include changes in the levels of proinflammatory markers (interleukin-6, interleukin-8, C-reactive protein, and transforming growth factor-β) and lactate dehydrogenase, frequency of hospitalization for VOCs and blood transfusions, and health-related quality of life (Short Form-8 Health Survey questionnaire). Safety will be evaluated by recording the incidence of adverse events and changes in liver and kidney function tests from baseline. The recruitment of study participants was initiated on November 1, 2023. By the second week of February 2025, 83 participants had been enrolled in the study. The final study is expected to be complete by December 31, 2025. We will start the analysis of the study outcomes in February 2026, and the publication of the final results is expected by August 2026. This randomized controlled trial protocol outlines a rigorous study design aimed to explore the potential benefits of an integrated therapeutic regimen comprising Ayurveda interventions and standard conventional care in the long-term management of SCD through validated clinical and laboratory parameters. The outcomes of this study can address the needs and challenges associated with SCD management and inform future management protocols.
Humanised, respectful maternity care improves birth outcomes, enhances maternal satisfaction, and reduces the risk of trauma and unnecessary intervention. Integrative maternity care-incorporating evidence-based traditional, complementary and integrative medicines (TCIM) such as acupressure and massage-can support this approach. However, an evidence-practice gap remains, particularly in low- and middle-income countries (LMICs), where integrative modalities are rarely incorporated into provider education or evaluated for contextual appropriateness. To evaluate the implementation, acceptability and feasibility of an 'Acupressure for childbirth' training program at Edna Adan Hospital in Somaliland, Africa; and determine conditions for which these techniques were most useful. Participants completed training and evaluation of skills, and provided responses to surveys pre-training, immediately post-training, and six-months post-training. The 56 participants included midwives, nurses, doulas, students, educators and physicians. Significant improvements in knowledge and skills were observed post-training (p < 0.01) and sustained at six-months (p < 0.05). Participants reported high satisfaction and regular clinical use, most commonly for labour preparation and pain management. In a context of high prevalence of female genital mutilation (FGM), participants reported particular benefit for heightened anxiety, fear and pain, noting increased comfort, relaxation and emotional reassurance during labour. Techniques were observed as easy to integrate into routine care and positively received by women and support people. This evaluation demonstrates that maternity care provider training in acupressure and massage is feasible, acceptable and appropriate within a low-resource maternity setting. Integrative, non-invasive techniques may provide valuable physical and psychosocial support, highlighting the importance of contextual fit and strengthening humanised maternity care.