The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation.

Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.

Correction: Depression, mitochondrial bioenergetics, and electroconvulsive therapy: a new approach towards personalized medicine in psychiatric treatment - a short review and current perspective.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Depression, mitochondrial bioenergetics, and electroconvulsive therapy: a new approach towards personalized medicine in psychiatric treatment - a short review and current perspective.

Major depressive disorder (MDD) is a globally occurring phenomenon and developed into a severe socio-economic challenge. Despite decades of research, the underlying pathophysiological processes of MDD remain incompletely resolved. Like other mental disorders, MDD is hypothesized to mainly affect the central nervous system (CNS). An increasing body of research indicates MDD to also change somatic functioning, which impairs the physiological performance of the whole organism. As a consequence, a paradigm shift seems reasonable towards a systemic view of how MDD affects the body. The same applies to treatment strategies, which mainly focus on the CNS. One new approach highlights changes in the bioenergetic supply and intracellular network dynamics of mitochondria for the pathophysiological understanding of MDD. Mitochondria, organelles of mostly all eukaryotic cells, use carbon compounds to provide biochemical energy in terms of adenosine triphosphate (ATP). ATP is the bioenergetic currency and the main driver for enzymatic activity in all cells and tissues. Clinical symptoms of MDD including fatigue, difficulties concentrating, and lack of motivation were reported to be associated with impaired mitochondrial ATP production and changes in the density of the mitochondrial network. Additionally, the severity of these symptoms correlates negatively with mitochondrial functioning. Psychotherapy, antidepressant medication, and electroconvulsive therapy (ECT), a method used to treat severe and treatment-resistant forms of MDD, achieve robust antidepressant effects. The biological mechanisms beyond the treatment response to antidepressant strategies are partially understood. Here, mitochondrial functioning is discussed as a promising new biomarker for diagnosis and treatment effects in MDD.

Effectiveness of a guided online mindfulness-focused intervention in a student population: Study protocol for a randomised control trial.

BACKGROUND: Previous studies show that university students experience higher psychological stress than the general population, resulting in increased vulnerability for mental disorders for the student population. Online mindfulness interventions will be delivered to students as a potentially promising and more flexible approach compared to face-to-face interventions with the aim of improving their mental health. This study purposes to investigate the effectiveness of a guided online mindfulness-focused intervention for university students by using both self-reported and psychobiological measures. METHODS AND ANALYSES: In this multicentre, two-armed randomised controlled trial with a parallel design, a guided version of the online mindfulness-focused intervention 'StudiCare Mindfulness' will be compared with a waitlist control group. In total, 120 participants will be recruited at different universities (of Applied Sciences) in (Neu-) Ulm. Data will be assessed prior to randomisation, after eight weeks (post-intervention) and six months after randomisation (follow-up). The primary outcome measure is mindfulness. The secondary outcome measures include depression, anxiety and stress levels, well-being, interoceptive sensibility, emotion regulation and alexithymia. Psychobiological parameters comprise interoceptive accuracy, hair cortisol and FKBP5 genotype. Sociodemographic variables, treatment expectations, side and adverse side effects, as well as intervention satisfaction and adherence will be assessed. All data analyses will be conducted according to the intention-to-treat principle. ETHICS AND DISSEMINATION: All study procedures have been approved by the Ethics Committee of Ulm University (application No. 48/18). The findings will be disseminated widely through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: DRKS00014701.