The EPMA journal最新文献

{"title":"Eye yoga for glaucoma: recovery of vascular dysregulation and visual field function-a randomized controlled trial.","authors":"Wanshu Zhou, Luisa Fricke, Bernhard A Sabel","doi":"10.1007/s13167-024-00389-x","DOIUrl":"10.1007/s13167-024-00389-x","url":null,"abstract":"<p><strong>Purpose: </strong>Because stress can aggravate vascular dysregulation (VD) in primary open-angle glaucoma (POAG), stress reduction by eye yoga (EY) was studied if this predictive, preventive, and personalized medical (3PM) approach could help normalize intraocular pressure (IOP), retinal vessel dynamics, and visual fields (VF).</p><p><strong>Patients and methods: </strong>POAG patients were randomized to an EY (<i>n</i> = 15) or control group (<i>n</i> = 12). EY was practiced daily for 1 h for 1 month at home using an iPod-audio guide while control patients read relaxing books daily.</p><p><strong>Results: </strong>After intervention, EY patients, but not controls, showed a 6.4% IOP reduction (<i>p</i> = 0.027) and had significant VF improvements (<i>p</i> < 0.001). After EY, pattern deviation recovered in VF regions where small microvessels showed reduced vasoconstriction (artery: <i>p</i> = 0.012; vein: <i>p</i> = 0.042) and improved mean artery diameter recovered significantly (<i>p</i> = 0.015). When pooling data of both groups, recovered VF regions, but not non-recovered fields, showed significantly larger arterial diameter gains (2.4 [- 0.3-5.3] MU) with no adverse events.</p><p><strong>Conclusions and 3pm recommendations: </strong>Because EY reduces vasoconstriction and improves VF function in POAG, we propose the \"eye ball retraction theory,\" whereby ocular muscle tension is induced by mental stress which is a contributing mechanism, or even the key mechanism, of POAG. Reducing stress by relaxation is therefore a remedy for it improves blood flow as the fundamental mechanism of vision recovery and restoration. VD reduction is therefore a valuable therapeutic target for glaucoma care and eye yoga home exercises are a safe and effective complementary 3PM method of POAG care.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00389-x.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 1","pages":"37-49"},"PeriodicalIF":6.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyridoxal 5'-phosphate and risk of stroke: triangulation of evidence from a nationally representative cohort and bidirectional Mendelian randomization analysis.","authors":"Mengqi Zhang, Jiani Zhong, Yanyi Peng, Lingjia Hao, Bo Xiao","doi":"10.1007/s13167-024-00392-2","DOIUrl":"10.1007/s13167-024-00392-2","url":null,"abstract":"<p><strong>Background: </strong>Stroke is a leading cause of mortality and disability worldwide. Identifying predictive biomarkers and modifiable risk factors is crucial for stroke prevention in the context of predictive, preventive, and personalized medicine (PPPM). We aimed to investigate the association of serum pyridoxal 5'-phosphate (PLP) levels with stroke prevalence in a nationally representative cohort and to assess the causal relationship using bidirectional Mendelian randomization (MR) analysis, with a focus on the implications for PPPM strategies in stroke management.</p><p><strong>Methods: </strong>We included 6839 participants aged ≥ 18 years from the National Health and Nutrition Examination Survey (NHANES) 2005-2013. Serum PLP levels were measured by high-performance liquid chromatography. Stroke prevalence was ascertained by self-report. We used generalized linear models, Kaplan-Meier curves, restricted cubic splines, stratified analysis, receiver operating characteristic (ROC) curves, and bidirectional two-sample MR to examine the association of PLP levels with stroke prevalence and assess the causal relationship.</p><p><strong>Results: </strong>In the fully adjusted model, participants with low serum PLP levels had significantly higher odds of stroke compared to those with high levels (odds ratio (OR) = 6.51e-01, 95% confidence interval (CI) 4.46e-01-9.50e-01, <i>P</i> = 2.74E-02). Kaplan-Meier curves showed significantly lower survival probability in the low PLP group (<i>P</i> < 0.05). The restricted cubic spline analysis revealed a non-linear association, with the highest stroke risk at lower PLP levels. The stratified analysis showed significant associations in several subgroups. The ROC analysis indicated good predictive performance of the fully adjusted model (area under the curve (AUC) > 0.7). The MR analysis supported a protective causal effect of PLP on stroke risk (OR = 0.7723581, 95% CI 0.6388086-0.9336201, <i>P</i> = 0.00345), while the reverse MR analysis did not suggest a causal effect of stroke on PLP levels.</p><p><strong>Conclusions: </strong>Low serum PLP levels are significantly associated with higher stroke prevalence in a nationally representative the United States (US) sample. Integration of observational and genetic evidence supports a protective causal role of PLP in stroke risk. Serum PLP may serve as a promising predictive biomarker for stroke risk assessment and a potential target for personalized nutritional interventions in stroke prevention, in line with PPPM strategies. Our findings highlight the importance of maintaining optimal vitamin B6 status for effective PPPM-guided stroke prevention and management.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00392-2.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 1","pages":"95-111"},"PeriodicalIF":6.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering key roles of B cells in prognostication and tailored therapeutic strategies for lung adenocarcinoma: a multi-omics and machine learning approach towards predictive, preventive, and personalized treatment strategies.","authors":"Jinjin Zhang, Dingtao Hu, Pu Fang, Min Qi, Gengyun Sun","doi":"10.1007/s13167-024-00390-4","DOIUrl":"10.1007/s13167-024-00390-4","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) remains a significant global health challenge, with an urgent need for innovative predictive, preventive, and personalized medicine (PPPM) strategies to improve patient outcomes. This study leveraged multi-omics and machine learning approaches to uncover the prognostic roles of B cells in LUAD, thereby reinforcing the PPPM approach.</p><p><strong>Methods: </strong>We integrated multi-omics data, including bulk RNA, ATAC-seq, single-cell RNA, and spatial transcriptomics sequencing, to characterize the B cell landscape in LUAD within the PPPM framework. Subsequently, we developed an integrative machine learning program that generated the Scissor+ related B cell score (SRBS). This score was validated in the training and validation sets, and its prognostic value was assessed along with clinical features to develop predictive nomograms. This study further assessed the role of SRBS and SRBS genes in response to immunotherapy and identified personalized drug targets for distinct risk subgroups, with gene expression verified experimentally to ensure tailored medical interventions.</p><p><strong>Results: </strong>Our analysis identified 79 Scissor+ B cell genes linked to LUAD prognosis, supporting the predictive aspect of PPPM. The SRBS model, which utilizes multiple machine learning algorithms, performed excellently in predicting prognosis and clinical transformation, embodying the preventive and personalized aspects of PPPM. Multifactorial analysis confirmed that SRBS was an independent prognostic factor. We observed varying biological functions and immune cell infiltration in the tumor immune microenvironment (TIME) between the high- and low-SRBS groups, underscoring personalized treatment approaches. Notably, patients with elevated SRBS may exhibit resistance to immunotherapy but show increased sensitivity to chemotherapy and targeted therapies. Additionally, we found that LDHA, as an SRBS gene with significant clinical implications, may regulate the sensitivity of LUAD cells to cisplatin.</p><p><strong>Conclusion: </strong>This study presents a B cell-associated gene signature that serves as a prognostic marker to facilitate personalized treatment for patients with LUAD, adhering to the principles of PPPM.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00390-4.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 1","pages":"127-163"},"PeriodicalIF":6.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactobacillaceae-mediated eye-brain-gut axis regulates high myopia-related anxiety: from the perspective of predictive, preventive, and personalized medicine.","authors":"Yuze Mi, Ke Chen, Shaokai Lin, Luyao Tong, Jiawei Zhou, Minghui Wan","doi":"10.1007/s13167-024-00387-z","DOIUrl":"10.1007/s13167-024-00387-z","url":null,"abstract":"<p><strong>Background: </strong>High myopia has become a major cause of blindness worldwide and can contribute to emotional deficits through its impact on the central nervous system. The potential crosstalk with gut microbiome positions high myopia as a valuable model for studying the eye-brain-gut axis, highlighting the intricate interplay between visual health, neurological function, and the gut microbiome. Understanding these connections is crucial from a predictive, preventive, and personalized medicine (PPPM) perspective, as it may reveal novel intervention targets for managing both visual and mental health.</p><p><strong>Working hypothesis and methodology: </strong>In our study, we hypothesized that visual stimuli associated with high myopia may lead to gut microecological dysregulation, potentially triggering mood disorders such as anxiety and depression. To test this hypothesis, we assessed genetic associations between high myopia (<i>N</i> = 50,372) and depression (<i>N</i> = 674,452) as well as anxiety (<i>N</i> = 21,761) using inverse variance weighted as the primary analytical method. We also investigated the potential mediating role of the gut microbiome (<i>N</i> = 18,340). The findings were validated in an independent cohort and summarized through meta-analysis.</p><p><strong>Results: </strong>A genetic causal relationship between high myopia and anxiety was found (odds ratio [OR] = 8.76; 95% confidence interval [CI], 2.69-28.54; <i>p</i> = 3.16 × 10^-4), with 20.3% of the effect mediated by the gut microbiome <i>family Lactobacillaceae</i> (<i>β</i> = 0.517; 95% CI, 0.104-1.090; <i>p</i> = 0.037). The analysis also showed a suggestive causal relationship between high myopia and depression (OR = 1.25; 95% CI, 1.00-1.57; <i>p</i> = 0.048).</p><p><strong>Conclusions: </strong>Our study shows that high myopia causes anxiety via the <i>Lactobacillaceae</i> family of the gut microbiome, supporting the eye-brain-gut axis concept. This underscores the need to shift from reactive to predictive, preventive, and personalized medicine (PPPM). Targeting <i>Lactobacillaceae</i> offers novel insights for early intervention and personalized treatment of high myopia-related anxiety and sheds light on interventions for other vision-related brain disorders.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00387-z.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"15 4","pages":"573-585"},"PeriodicalIF":6.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacoproteomics reveals energy metabolism pathways as therapeutic targets of ivermectin in ovarian cancer toward 3P medical approaches.","authors":"Zhijun Li, Na Li, Marie Louise Ndzie Noah, Qianwen Shao, Xianquan Zhan","doi":"10.1007/s13167-024-00385-1","DOIUrl":"10.1007/s13167-024-00385-1","url":null,"abstract":"<p><strong>Objective: </strong>Ovarian cancer is the malignant tumor with the highest mortality rate in the female reproductive system, enormous socio-economic burden, and limited effective drug therapy. There is an urgent need to find novel effective drugs for ovarian cancer therapy. Our previous in vitro studies demonstrate that ivermectin effectively inhibits ovarian cancer cells and affects energy metabolism pathways. This study aims to clarify in vivo mechanisms and therapeutic targets of ivermectin in the treatment of ovarian cancer to establish predictive biomarkers, guide personalized treatments, and improve preventive strategies in the framework of 3P medicine.</p><p><strong>Methods: </strong>A TOV-21G tumor-bearing mouse model was constructed based on histopathological data and biochemical parameters. TMT-based proteomic analysis was performed on tumor tissues from the different treatment groups. All significantly differentially abundant proteins were characterized by hierarchical clustering, Gene Ontology (GO) enrichment analyses, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In addition, the data were integrated and analyzed with the proteomic data of clinical ovarian cancer tissues from our previous study and the proteomic data of ivermectin intervention in ovarian cancer cells to identify key regulators of ivermectin.</p><p><strong>Results: </strong>Ivermectin (10 mg/kg) had a significant anti-ovarian cancer effect in mice, with a tumor inhibitory rate of 61.5%. Molecular changes in tumor tissue of ivermectin-treated mice were established, and protein-protein interaction (PPI) analysis showed that the main differential pathway networks included the TCA cycle, propanoate metabolism, 2-0xocarboxyacid metabolism, and other pathways. Integrating our previous clinical ovarian cancer tissue and cell experimental data, this study found that ivermectin significantly interfered with the energy metabolic pathways of ovarian cancer, including glycolysis, TCA cycle, oxidative phosphorylation, and other related pathways.</p><p><strong>Conclusions: </strong>This study evaluated the anti-ovarian cancer effect in vitro and in vivo, and its specific regulatory effect on energy metabolism. The expressions of drug target molecules in the energy metabolism pathway of ovarian cancer will be used to guide the diagnosis and prevention of ovarian cancer. The significant efficacy of ivermectin will be applied to the treatment of ovarian cancer and personalized medication. This has guiding significance for the clinical diagnosis, treatment, personalized medication, and prognosis evaluation of ovarian cancer.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00385-1.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"15 4","pages":"711-737"},"PeriodicalIF":6.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-based holistic 3PM approach as the 'game-changer' for individualised rehabilitation-the proof-of-principle model by treated breast cancer survivors.","authors":"Martin Pesta, Barbara Mrazova, Marko Kapalla, Vlastimil Kulda, Eleni Gkika, Olga Golubnitschaja","doi":"10.1007/s13167-024-00386-0","DOIUrl":"10.1007/s13167-024-00386-0","url":null,"abstract":"<p><p>Breast cancer belongs to the most commonly diagnosed malignancies worldwide, with its increasing incidence paralleled by advances in early diagnostics and effective treatments resulting in significantly improved survival rates. However, breast cancer survivors often experience significantly reduced quality of life linked to the long-term health burden as a consequence of aggressive oncological treatments applied. Their most frequently recorded complains include chronic fatigue, reduced physical activity, disordered sleep, chronification of pain, and severe mental health impairments-all per evidence are associated with compromised mitochondrial health and impaired homeostasis. Self-report of a breast cancer survivor is included in this article to illustrate currently uncovered patient needs. This article highlights mechanisms behind the suboptimal health of breast cancer survivors associated with mitochondrial damage, and introduces a novel, mitochondria-based holistic approach addressing rehabilitation concepts for breast cancer survivors following advanced principles of predictive, preventive and personalised medicine (3PM). By operating via mitochondrial function, the proposed holistic approach triggers systemic effects at molecular, sub/cellular and organismal levels positively affecting energy metabolism, repair mechanisms as well as physical and mental health creating, therefore, highly effective rehabilitation algorithms tailored to an individualised patient profile. The proposed methodology integrates mitochondrial health assessments utilising mitochondrial homeostasis biomarkers in tear fluid as a non-invasive diagnostic tool, tailored nutraceuticals and lifestyle adjustments. The introduced approach aligns with advanced principles of 3PM, offering a holistic and proactive framework for managing persistent post-treatment symptoms of suboptimal health in the cohort of cancer survivors. Furthermore, presented approach is also applicable to pre-habilitation programmes considering needs of other patient cohorts affected by chronic diseases such as CVD and orthopaedic disorders with planned major surgical incisions, who require individually adapted pre- and rehabilitation programmes. Implementing such innovative pre- and rehabilitation strategies may lead to a full recovery, sustainable health conditions and, therefore, facilitating patients' comeback to normal daily activities, family and professional life. Contextually, presented approach is considered a 'proof-of-principle' model for the 3PM-related paradigm shift from reactive medicine to a cost-effective holistic health management in both primary and secondary care benefiting a large spectrum of affected patient cohorts, individuals in suboptimal health conditions as well as society at large.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"15 4","pages":"559-571"},"PeriodicalIF":6.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in the metabolic score for insulin resistance index for risk prediction of stroke in middle-aged and older Chinese population.","authors":"Tingting Wang, Zhiheng Yi, Yuhan Tan, Yangshen Huang, Tengli Li, Shan Gao, Yaoling Wu, Weiduan Zhuang, Shaowei Guo","doi":"10.1007/s13167-024-00388-y","DOIUrl":"10.1007/s13167-024-00388-y","url":null,"abstract":"<p><strong>Background: </strong>As a major noncommunicable disease, stroke poses a major threat to public health. In the context of predictive, preventative, and personalised medicine (PPPM/3PM), early identification of high-risk individuals is crucial for targeted prevention and personalised treatment for stroke. This study aimed to investigate the association between changes in the Metabolic Score for Insulin Resistance Index (METS-IR) and incident stroke. From the perspective of PPPM/3PM, we hypothesised that monitoring dynamic changes of the METs-IR levels and targeting cumulative METs-IR index contribute to risk prediction, targeted prevention, and personalised management of stroke.</p><p><strong>Methods: </strong>All data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), a nationwide prospective cohort study. The individuals were categorised into four subgroups based on the quartiles (Q) of the cumulative METS-IR index as a reflection of changes in the METS-IR values from 2012 to 2015. Logistic regression was employed to examine the association between cumulative METS-IR index and stroke incidence. Additionally, restricted cubic spline regression analysis was used to assess potential linearity.</p><p><strong>Results: </strong>Among the 4288 participants, 275 (6.4%) experienced a stroke. The risk of stroke events increased with higher cumulative METS-IR index levels. Compared with the lowest quartile (Q1), the OR of having a stroke was 1.20 (0.81, 1.78) for Q2, 1.51 (1.04, 2.21) for Q3 and 2.17 (1.52, 3.10) for the highest quartile (Q4). After adjusting for multiple potential confounders, Q4 (OR: 1.57, 95% CI: 1.04, 2.35) remained significantly associated with stroke. The association between the cumulative METS-IR index and stroke incidence was linear in males, females, and the overall population (all <i>P</i> values for nonlinearity > 0.05).</p><p><strong>Conclusions: </strong>A higher cumulative METS-IR index was associated with an increased risk of incident stroke among middle-aged and older Chinese individuals. In the context of PPPM/3PM, incorporating metabolic health into stroke risk assessment advances the prediction, prevention and personalised management of stroke.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00388-y.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"15 4","pages":"599-610"},"PeriodicalIF":6.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain chronification risk assessment: advanced phenotyping and scoring for prediction and treatments tailored to individualized patient profile.","authors":"Igor Martuliak, Olga Golubnitschaja, Lubos Chvala, Marko Kapalla, Miroslav Ferencik, Michala Bubeliny, Michal Venglarcik, Ladislav Kocan","doi":"10.1007/s13167-024-00383-3","DOIUrl":"10.1007/s13167-024-00383-3","url":null,"abstract":"<p><p>Acute pain is a physiologic, protective life-important warning neurological signal indicating multi-level tissue modulations caused by a broad spectrum of health adverse events such as stress overload, mechanical trauma, ischemia-reperfusion, sterile and infection-triggered inflammation, single- and multi-organ damage, acute and chronic wounds, tissue remodeling and degeneration, amongst others. On the other hand, pain chronification results in a pathologic transformation from the protective pain signaling into persistent debilitative medical condition with severe consequences including but not restricted to phenotype-specific behavioral patterns, reduced quality of life, and cognitive and mood disorders. Who is predisposed to an increased vs. decreased pain sensitivity and to the pain chronification? The motivation of personalized medicine that \"same size does not fit all\" is getting obvious also for an advanced approach in algesiology. Consequently, an in-depth patient stratification is essential for the paradigm change in overall pain management from currently applied reactive medical services to the cost-effective predictive, preventive, and personalized medicine (PPPM/3PM) in primary (reversible damage to health and targeted protection against health-to-disease transition) and secondary (personalized protection against disease progression) care. To this end, specifically innovative concepts of phenotyping elaborated in this study play a crucial role in patient stratification for predicting pain-associated outcomes, evidence-based targeted prevention of the pain chronification, and creation of treatment algorithms tailored to individualized patient profiles.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00383-3.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"15 4","pages":"739-750"},"PeriodicalIF":6.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian randomization reveals predictive, preventive, and personalized insights into inflammatory bowel disease: the role of gut microbiome and circulating inflammatory proteins.","authors":"Wuqing Zhao, Shixiao Li, Qianqian Li, Qiang Li, Ya Zheng, Hong Lu","doi":"10.1007/s13167-024-00384-2","DOIUrl":"10.1007/s13167-024-00384-2","url":null,"abstract":"<p><strong>Background: </strong>A chronic illness with increasing global frequency, inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), profoundly affects patients' quality of life and healthcare systems. IBD pathogenesis consists of changes in gut microbiota, immune system dysregulation, and genetic predisposition. Although emerging data suggests that gut microbiota and circulating inflammatory proteins play critical roles in IBD, their utility as biomarkers for predictive, preventive, and personalized medicine (PPPM) remains incompletely understood.</p><p><strong>Working hypothesis and methods: </strong>We hypothesized that specific gut microbiota and inflammatory proteins causally influence IBD risk and mediate pathways between gut microbiota and IBD development. We employed Mendelian randomization (MR) using genome-wide association studies (GWAS) to explore these causal relationships, including further analyses on UC and CD subtypes.</p><p><strong>Results: </strong>We identified eight gut microbiota species linked to IBD, with four protective and four increasing risk. Nine inflammatory proteins were also associated, six increasing risk and three protective. MMP-10 and IL-10Rα mediated the effects of Clostridiaceae1 on IBD risk. For UC, five microbiota species were protective, five were risk factors, and two proteins increased risk while three were protective. IL-10Rα mediated the effects of Clostridiaceae1 on UC risk. For CD, eight microbiota species were protective, four increased risk, and nine proteins were implicated. However, no mediation pathways were supported by multivariable MR.</p><p><strong>Conclusions: </strong>This study highlights specific gut microbiota and inflammatory proteins that may serve as therapeutic targets for PPPM in IBD, UC, and CD. These findings offer new insights into IBD pathogenesis and suggest potential avenues for improved prevention, early detection, and personalized treatment strategies.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00384-2.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"15 4","pages":"693-709"},"PeriodicalIF":6.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Observational and genetic associations between cardiorespiratory fitness and age-related diseases: longitudinal analyses in the UK Biobank study.","authors":"Huimin Lu, Haotian Wang, Cancan Li, Xiaoni Meng, Deqiang Zheng, Lijuan Wu, Youxin Wang","doi":"10.1007/s13167-024-00382-4","DOIUrl":"10.1007/s13167-024-00382-4","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have indicated that increased cardiorespiratory fitness is associated with a decreased risk of cardiovascular disease (CVD), Alzheimer's disease (AD), and Parkinson's disease (PD). However, the causal mechanisms remain unclear. The objective of this study was to assess the role of fitness in the early detection and reduction of disease risk within the framework of predictive, preventive, and personalized medicine (PPPM/3PM).</p><p><strong>Methods: </strong>The associations of fitness with CVD, AD, and PD were explored in a large cohort of up to 502,486 individuals between the ages of 40 and 69 years from the UK Biobank. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CVD, AD, and PD among participants who completed a submaximal fitness test. Causality relationships were assessed via two-sample Mendelian randomization (MR).</p><p><strong>Results: </strong>After a median of 11 years of follow-up, each 3.5 ml of O₂⋅min^-1⋅kg^-1 increase in total body mass (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviations (SDs)) was associated with decreased risks of CVD (20.0%, 95% CI 17.6-22.3%), AD (31.9%, 95% CI 26.7-33.6%), and PD (21.2%, 95% CI 11.2-31.8%). After adjusting for obesity, the observational associations were attenuated. According to the MR analyses, fitness was associated with PD (OR _<i>IVW</i> 0.937, 95% CI 0.897-0.978) and small vessel stroke (OR _<i>IVW</i> 0.964, 95% CI 0.933-0.995).</p><p><strong>Conclusion: </strong>Our results indicate that fitness has an effect on age-related diseases. Protective associations of higher fitness levels with the risk of CVD, AD, and PD were validated in this cohort study. These findings might be valuable for predicting, preventing, and reducing disease morbidity and mortality through primary prevention and healthcare in the context of PPPM.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00382-4.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"15 4","pages":"629-641"},"PeriodicalIF":6.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}