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Blow flies are the first insect group to colonize on a dead body and thus correct species identification is a crucial step in forensic investigations for estimating the minimum postmortem interval, as developmental times are species-specific. Due to the difficulty of traditional morphology-based identification such as the morphological similarity of closely related species and uncovered taxonomic keys for all developmental stages, DNA-based identification has been increasing in interest, especially in high biodiversity areas such as Thailand. In this study, the effectiveness of long mitochondrial cytochrome c oxidase subunit I and II (COI and COII) sequences (1247 and 635 bp, respectively) in identifying 16 species of forensically relevant blow flies in Thailand (Chrysomya bezziana, Chrysomya chani, Chrysomya megacephala, Chrysomya nigripes, Chrysomya pinguis, Chrysomya rufifacies, Chrysomya thanomthini, Chrysomya villeneuvi, Lucilia cuprina, Lucilia papuensis, Lucilia porphyrina, Lucilia sinensis, Hemipyrellia ligurriens, Hemipyrellia pulchra, Hypopygiopsis infumata, and Hypopygiopsis tumrasvini) was assessed using distance-based (Kimura two-parameter distances based on Best Match, Best Close Match, and All Species Barcodes criteria) and tree-based (grouping taxa by sequence similarity in the neighbor-joining tree) methods. Analyses of the obtained sequence data demonstrated that COI and COII genes were effective markers for accurate species identification of the Thai blow flies. This study has not only demonstrated the genetic diversity of Thai blow flies, but also provided a reliable DNA reference database for further use in forensic entomology within the country and other regions where these species exist.
Objective: Amyloid β (Aβ) depositions in plaques and cerebral amyloid angiopathy (CAA) represent common features of Alzheimer's disease (AD). Sequential deposition of post‐translationally modified Aβ in plaques characterizes distinct biochemical stages of Aβ maturation. However, the molecular composition of vascular Aβ deposits in CAA and its relation to plaques remain enigmatic.
Methods: Vascular and parenchymal deposits were immunohistochemically analyzed for pyroglutaminated and phosphorylated Aβ in the medial temporal and occipital lobe of 24 controls, 27 pathologically‐defined preclinical AD, and 20 symptomatic AD cases.
Results: Sequential deposition of Aβ in CAA resembled Aβ maturation in plaques and enabled the distinction of three biochemical stages of CAA. B‐CAA stage 1 was characterized by deposition of Aβ in the absence of pyroglutaminated AβN3pE and phosphorylated AβpS8. B‐CAA stage 2 showed additional AβN3pE and B‐CAA stage 3 additional AβpS8. Based on the Aβ maturation staging in CAA and plaques, three case groups for Aβ pathology could be distinguished: group 1 with advanced Aβ maturation in CAA; group 2 with equal Aβ maturation in CAA and plaques; group 3 with advanced Aβ maturation in plaques. All symptomatic AD cases presented with end‐stage plaque maturation, whereas CAA could exhibit immature Aβ deposits. Notably, Aβ pathology group 1 was associated with arterial hypertension, and group 2 with the development of dementia.
Interpretation: Balance of Aβ maturation in CAA and plaques defines distinct pathological subgroups of β‐amyloidosis. The association of CAA‐related Aβ maturation with cognitive decline, the individual contribution of CAA and plaque pathology to the development of dementia within the defined Aβ pathology subgroups, and the subgroup‐related association with arterial hypertension should be considered for differential diagnosis and therapeutic intervention.
Myomas, also known as fibroids, are a specific characteristic of the human species. No other primates develop fibroids. At a cellular level, myomas are benign hyperplastic lesions of uterine smooth muscle cells. There are interesting theoretical concepts that link the development of myomas in humans with the highly specific process of childbirth from an upright position and the resulting need for greatly increased “expulsive” forces during labor. Myomas might be the price our species pays for our bipedal and highly intelligent existence. Myomas affect, with some variability, all ethnic groups and approximately 50% of all women during their lifetime. While some remain asymptomatic, myomas can cause significant and sometimes life-threatening uterine bleeding, pain, infertility, and, in extreme cases, ureteral obstruction and death. Traditionally, over 50% of all hysterectomies were performed for fibroids, leading to a significant healthcare burden. In this article, we review the developments of the past 20 years with regard to multiple new treatment strategies that have evolved during this time.
Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data.
Methods: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections.
Results: If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0–30%), between 2016–2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15–56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population.
Conclusions: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden.
Lay summary: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.
Air pollution of particulate matter (PM) from traffic emissions has a significant impact on human health. Risk assessments for different traffic participants are often performed on the basis of data from local air quality monitoring stations. Numerous studies demonstrated the limitation of this approach. To assess the risk of PM exposure to a car driver more realistically, we measure the exposure to PM in a car cabin with a mobile aerosol spectrometer in Frankfurt am Main under different settings (local variations, opened versus a closed window) and compare it with data from stationary measurement. A video camera monitored the surroundings for potential PM source detection. In-cabin concentrations peaked at 508 µg m−3 for PM10, 133.9 µg m−3 for PM2.5, and 401.3 µg m−3 for coarse particles, and strongly depended on PM size and PM concentration in ambient air. The concentration of smaller particles showed low fluctuations, but the concentration of coarse particles showed high fluctuations with maximum values on busy roads. Several of these concentration peaks were assigned to the corresponding sources with characteristic particle size distribution profiles. The closure of the car window reduced the exposure to PM, and in particular to coarse particles. The mobile measured PM values differed significantly from stationary PM measures, although good correlations were computed for finer particles. Mobile rather than stationary measurements are essential to assess the risk of PM exposure for car passengers.
Obesity is considered as a type of chronic inflammation. It enhances the risk of developing cardiovascular disease, diabetes, and some cancers. The key players in the induction of inflammation in adipose tissue are macrophages. However the mechanism of macrophage activation in obese fat tissue is still not fully understood. Elevated level of saturated fatty acids in adipose tissue promotes inflammation and insulin resistance. Exposure of macrophages to saturated fatty acids stimulates pro-inflammatory c-Jun N-terminal kinase (JNK), nuclear factor kappa B (NF-kB) signaling, and production of pro-inflammatory cytokines, such as IL-6, IL-8, IL-1β, and TNFα. Palmitate is a major saturated free fatty acid released by adipocytes. It activates inflammatory pathways through Toll-like receptors (TLR) 2 and 4, provokes endoplasmic reticulum (ER) stress and increases levels of diacylglycerols (DAGs) and ceramides. Saturated fatty acids also affect cellular oxidative metabolism. Thus, mitochondrial fatty acid oxidation reduces ER-stress and expression of inflammatory cytokines in palmitate-treated macrophages. On the other hand mitochondrial reactive oxygen species (ROS) promote palmitate-mediated pro-inflammatory cytokine production. Recently, mitochondrial functions were linked to their morphology. Mitochondrial fission has been reported in β-cells and myocytes in response to high levels of glucose and free fatty acids, and was associated with disruption of mitochondrial functions, increased ROS level, and cell death. The aim of this study was to investigate the role of mitochondrial fragmentation in palmitate-induced inflammation in human macrophages. In our settings fatty acids, independently of their saturation, affected mitochondrial morphology. Mixtures of long chain saturated and unsaturated fatty acids as well as triglyceride-rich lipoprotein lipolysis products promoted mitochondrial fission. Mitochondrial fragmentation in palmitate-treated macrophages revealed a time- and concentration-dependent character, and was reversible upon palmitate removal. This observation, together with unaltered levels of mitochondrial protein and DNA content, and intact mitochondrial respiration, suggested that mitochondria were not damaged and were functionally active. Mechanistically, palmitate-induced mitochondrial fragmentation was not regulated by ER stress or loss of mitochondrial membrane potential. However, inhibition of palmitate incorporation into mitochondrial membrane phospholipids decreased mitochondrial fragmentation. Other approach to prevent mitochondrial fission was the inhibition of dynamin-related protein 1 (DRP1) activity, which drives mitochondrial fission by forming ring- like structures around mitochondria and constricting mitochondrial membranes. Palmitate altered mitochondrial membrane lipid composition and promoted DRP1-oligomerization. The inhibition of palmitate-induced mitochondrial fragmentation enhanced mitochondrial ROS production, c-Jun phosphorylation, and upregulated expression of pro-inflammatory cytokines. Taken together, these results suggest that mitochondrial fragmentation is a protective mechanism attenuating palmitate-induced inflammatory responses. Future experiments will be required to investigate the role of mitochondrial fragmentation in obesity-associated diseases in vivo.
Development of T cells in the thymus is tightly controlled to continually produce functional, but not autoreactive, T cells. miRNAs provide a layer of post-transcriptional gene regulation to this process, but the role of many individual miRNAs in T-cell development remains unclear. miR-21 is prominently expressed in immature thymocytes followed by a steep decline in more mature cells. We hypothesized that such a dynamic expression was indicative of a regulatory function in intrathymic T-cell development. To test this hypothesis, we analyzed T-cell development in miR-21-deficient mice at steady state and under competitive conditions in mixed bone-marrow chimeras. We complemented analysis of knock-out animals by employing over-expression in vivo. Finally, we assessed miR-21 function in negative selection in vivo as well as differentiation in co-cultures. Together, these experiments revealed that miR-21 is largely dispensable for physiologic T-cell development. Given that miR-21 has been implicated in regulation of cellular stress responses, we assessed a potential role of miR-21 in endogenous regeneration of the thymus after sublethal irradiation. Again, miR-21 was completely dispensable in this process. We concluded that, despite prominent and highly dynamic expression in thymocytes, miR-21 expression was not required for physiologic T-cell development or endogenous regeneration.
Immune-modulating therapy is a promising therapy for patients with cholangiocarcinoma (CCA). Microsatellite instability (MSI) might be a favorable predictor for treatment response, but comprehensive data on the prevalence of MSI in CCA are missing. The aim of the current study was to determine the prevalence of MSI in a German tertiary care hospital. Formalin-fixed paraffin-embedded tissue samples, obtained in the study period from 2007 to 2015 from patients with CCA undergoing surgical resection with curative intention at Johann Wolfgang Goethe University hospital, were examined. All samples were investigated immunohistochemically for the presence of MSI (expression of MLH1, PMS2, MSH2, and MSH6) as well as by pentaplex polymerase chain reaction for five quasimonomorphic mononucleotide repeats (BAT-25, BAT-26, NR-21, NR-22, and NR-24). In total, 102 patients were included, presenting intrahepatic (n = 35, 34.3%), perihilar (n = 42, 41.2%), and distal CCA (n = 25, 24.5%). In the immunohistochemical analysis, no loss of expression of DNA repair enzymes was observed. In the PCR-based analysis, one out of 102 patients was found to be MSI-high and one out of 102 was found to be MSI-low. Thus, MSI seems to appear rarely in CCA in Germany. This should be considered when planning immune-modulating therapy trials for patients with CCA.
Acute graft-versus-host disease (GvHD) is still a major cause of treatment-related mortality after allogeneic stem cell transplantation. Allo-antigen recognition of donor T cells after transplantation account for the onset and persistence of this disease. MicroRNAs (miRNAs) are molecular regulators involved in numerous processes during T-cell development, homeostasis, and activation. Thus, miRNAs also contribute to pathological T-cell function during GvHD. Given their capacity of fine-tuning T-cell function, miRNAs have emerged as promising therapeutic targets to curtail acute GvHD, but simultaneously maintain T-cell-mediated graft-versus-tumor effects. Here, we review the role of key miRNAs contributing to the pathophysiology of GvHD. We focus on those miRNAs acting in T cells and for which a role in GvHD has been established in preclinical models. Finally, we provide an outlook for clinical application of this new therapeutic target for GvHD prevention and treatment.
The deer ked (Lipoptena cervi) is distributed in Europe, North America, and Siberia and mainly infests cervids as roe deer, fallow deer, and moose. From a one health perspective, deer keds occasionally bite other animals or humans and are a potential vector for Bartonella schoenbuchensis. This bacterium belongs to a lineage of ruminant-associated Bartonella spp. and is suspected to cause dermatitis and febrile diseases in humans. In this study, we analyzed the microbiome from 130 deer keds collected from roe deer, fallow deer and humans in the federal states of Hesse, Baden-Wuerttemberg, and Brandenburg, Germany. Endosymbiontic Arsenophonus spp. and Bartonella spp. represented the biggest portion (~90%) of the microbiome. Most Bartonella spp. (n = 93) were confirmed to represent B. schoenbuchensis. In deer keds collected from humans, no Bartonella spp. were detected. Furthermore, Acinetobacter spp. were present in four samples, one of those was confirmed to represent A. baumannii. These data suggest that deer keds harbor only a very narrow spectrum of bacteria which are potentially pathogenic for animals of humans.
Introduction: The clinical management of breech presentations at term is still a controversially discussed issue among clinicians. Clear predictive criteria for planned vaginal breech deliveries are desperately needed to prevent adverse fetal and maternal outcomes and to reduce elective cesarean section rates. The green-top guideline considers an estimated birth weight of 3.8 kg or more an indication to plan a cesarean section despite the lack of respective evidence.
Objective: To compare maternal and neonatal outcome of vaginal intended breech deliveries of births with children with a birth weight of 2.5 kg– 3.79 kg and children with a birth weight of 3.8 kg and more.
Design: Prospective cohort study.
Sample: All vaginal intended deliveries out of a breech position of newborns weighing between 2.5 kg and 4.5 kg at the Obstetrics department at Goethe University Hospital Frankfurt from January 2004 until December 2016
Methods: Neonatal and maternal outcome of a light weight group (LWG) (< 3.8 kg) was compared to and a high weight group (HWG) (≥ 3.8 kg) using Pearson’s Chi Square test and Fishers exact test. A logistic regression analysis was performed to detect an association between cesarean section rates, fetal outcome and the birth weight.
Results: No difference in neonatal morbidity was detected between the HWG (1.8%, n = 166) and the LWG (2.6%, n = 888). Cesarean section rate was significantly higher in the HWG with 45.2% in comparison to 28.8% in the LWG with an odds ratio of 1.57 (95% CI 1.29–1.91, p<0.0001). In vaginal deliveries, a high birth weight was not associated with an increased risk of maternal birth injuries (LWG in vaginal deliveries: 74.3%, HWG in vaginal deliveries: 73.6%; p = 0.887; OR = 1.9 (95% CI 0.9–1.1))
Conclusion: A fetal weight above 3.79 kg does not predict increased maternal or infant morbidity after delivery from breech presentation at term. Neither the literature nor our analyses document evidence for threshold of estimated birth weight that is associated with maternal and/or infant morbidity. However, patients should be informed about an increased likelihood of cesarean sections during labor when attempting vaginal birth from breech position at term in order to reach an informed shared decision concerning the birth strategy. Further investigations in multi center settings are needed to advance international guidelines on vaginal breech deliveries in the context of estimated birth weight and its impact on perinatal outcome.
GTP cyclohydrolase (GCH1) governs de novo synthesis of the enzyme cofactor, tetrahydrobiopterin (BH4), which is essential for biogenic amine production, bioactive lipid metabolism and redox coupling of nitric oxide synthases. Overproduction of BH4 via upregulation of GCH1 in sensory neurons is associated with nociceptive hypersensitivity in rodents, and neuron‐specific GCH1 deletion normalizes nociception. The translational relevance is revealed by protective polymorphisms of GCH1 in humans, which are associated with a reduced chronic pain. Because myeloid cells constitute a major non‐neuronal source of BH4 that may contribute to BH4‐dependent phenotypes, we studied here the contribution of myeloid‐derived BH4 to pain and itch in lysozyme M Cre‐mediated GCH1 knockout (LysM‐GCH1−/−) and overexpressing mice (LysM‐GCH1‐HA). Unexpectedly, knockout or overexpression in myeloid cells had no effect on nociceptive behaviour, but LysM‐driven GCH1 knockout reduced, and its overexpression increased the scratching response in Compound 48/80 and hydroxychloroquine‐evoked itch models, which involve histamine and non‐histamine dependent signalling pathways. Mechanistically, GCH1 overexpression increased BH4, nitric oxide and hydrogen peroxide, and these changes were associated with increased release of histamine and serotonin and degranulation of mast cells. LysM‐driven GCH1 knockout had opposite effects, and pharmacologic inhibition of GCH1 provided even stronger itch suppression. Inversely, intradermal BH4 provoked scratching behaviour in vivo and BH4 evoked an influx of calcium in sensory neurons. Together, these loss‐ and gain‐of‐function experiments suggest that itch in mice is contributed by BH4 release plus BH4‐driven mediator release from myeloid immune cells, which leads to activation of itch‐responsive sensory neurons.
Mannan-induced Nos2 in macrophages enhances IL-17–driven psoriatic arthritis by innate lymphocytes
(2018)
Previous identification of the inducible nitric oxide synthase (NOS2) gene as a risk allele for psoriasis (Ps) and psoriatic arthritis (PsA) suggests a possible pathogenic role of nitric oxide (NO). Using a mouse model of mannan-induced Ps and PsA (MIP), where macrophages play a regulatory role by releasing reactive oxygen species (ROS), we found that NO was detectable before disease onset in mice, independent of a functional nicotinamide adenine dinucleotide phosphate oxidase 2 complex. MIP was suppressed by either deletion of Nos2 or inhibition of NO synthases with NG-nitro-L-arginine methyl ester, demonstrating that Nos2-derived NO is pathogenic. NOS2 expression was also up-regulated in lipopolysaccharide- and interferon-γ–stimulated monocyte subsets from patients with PsA compared to healthy controls. Nos2-dependent interleukin-1α (IL-1α) release from skin macrophages was essential for arthritis development by promoting IL-17 production of innate lymphoid cells. We conclude that Nos2-derived NO by tissue macrophages promotes MIP, in contrast to the protective effect by ROS.
Background. The placement of an implant in a previously infected site is an important etiologic factor contributing to implant failure. The aim of this case report is to present the management of retrograde peri-implantitis (RPI) in a first maxillary molar site, 2 years after the implant placement. The RPI was treated using an air-abrasive device, Er,Cr:YSGG laser, and guided bone regeneration (GBR).
Case Description. A 65-year-old Caucasian male presented with a draining fistula associated with an implant at tooth #3. Tooth #3 revealed periapical radiolucency two years before the implant placement. Tooth #3 was extracted, and a ridge preservation procedure was performed followed by implant rehabilitation. A periapical radiograph (PA) showed lack of bone density around the implant apex. The site was decontaminated with an air-abrasive device and Er,Cr:YSGG laser, and GBR was performed. The patient was seen every two weeks until suture removal, followed by monthly visits for 12 months. The periapical X-rays, from 6 to 13 months postoperatively, showed increased bone density around the implant apex, with no signs of residual clinical or radiographic pathology and probing depths ≤4 mm.
Conclusions. The etiology of RPI in this case was the placement of an implant in a previously infected site. The use of an air-abrasive device, Er,Cr:YSGG, and GBR was utilized to treat this case of RPI. The site was monitored for 13 months, and increased radiographic bone density was noted.
Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown great results in numerous clinical trials and have improved the clinical outcome for patients with hormone-receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer significantly. To date, three CDK4/6 inhibitors are approved by the US Food and Drug Administration (FDA): palbociclib, ribociclib and abemaciclib; the first two compounds are aproved by the European Medicines Agency (EMA) as well. In combination with endocrine therapy, all of them led to significantly improved progression-free survival compared with endocrine therapy alone. The aim of this article is to give an overview of the efficacy data and to describe the CDK4/6 inhibitor-based treatment-associated adverse events, including hematological and nonhematological adverse events. In addition, it describes the corrrect approach to patient monitoring and adverse event mangement and summarizes the current recommendations for dose reductions and dose interruptions regarding the key adverse events, such as neutropenia, diarrhea, QTc prolongation and hepatobiliary toxicity. Accurate patient monitoring and management of the side effects is crucial, as several clinical trials in early breast cancer are in progress and may lead to an additional approval in the neo-/adjuvant setting.
Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. In this study, we aimed to further characterize the role of macrophage-derived EVs in immune responses against hepatitis C virus (HCV) and the potential of polyunsaturated fatty acids (PUFAs) to modulate this modality of innate immunity. To this end, EVs were isolated from interferon-stimulated macrophage cultures or from serum of patients with acute or chronic hepatitis C. EVs were characterized by electron microscopy, flow cytometry, RNA-sequencing, and Western blot analysis. The effect of EVs on replication of HCV was assessed in coculture models. Functional analyses were performed to assess the impact of PUFAs on EV-mediated antiviral immunity. We found that macrophages secreted various cytokines shortly after stimulation with type I and II IFN, which orchestrated a fast but short-lasting antiviral state. This rapid innate immune answer was followed by the production of macrophage-derived EVs, which induced a late, but long-lasting inhibitory effect on HCV replication. Of note, exposure of macrophages to PUFAs, which are important regulators of immune responses, dampened EV-mediated antiviral immune responses. Finally, EVs from patients with hepatitis C exhibited long-lasting antiviral activities during IFN therapy as well. The antiviral effect of EVs from Caucasian and Japanese patients differed, which may be explained by different nutritional uptake of PUFAs. In conclusion, our data indicate that macrophage-derived EVs mediate long-lasting inhibitory effects on HCV replication, which may bridge the time until efficient adaptive immune responses are established, and which can be blunted by PUFAs.
Background: Prevention of persistent pain following breast cancer surgery, via early identification of patients at high risk, is a clinical need. Supervised machine-learning was used to identify parameters that predict persistence of significant pain.
Methods: Over 500 demographic, clinical and psychological parameters were acquired up to 6 months after surgery from 1,000 women (aged 28–75 years) who were treated for breast cancer. Pain was assessed using an 11-point numerical rating scale before surgery and at months 1, 6, 12, 24, and 36. The ratings at months 12, 24, and 36 were used to allocate patents to either "persisting pain" or "non-persisting pain" groups. Unsupervised machine learning was applied to map the parameters to these diagnoses.
Results: A symbolic rule-based classifier tool was created that comprised 21 single or aggregated parameters, including demographic features, psychological and pain-related parameters, forming a questionnaire with "yes/no" items (decision rules). If at least 10 of the 21 rules applied, persisting pain was predicted at a cross-validated accuracy of 86% and a negative predictive value of approximately 95%.
Conclusions: The present machine-learned analysis showed that, even with a large set of parameters acquired from a large cohort, early identification of these patients is only partly successful. This indicates that more parameters are needed for accurate prediction of persisting pain. However, with the current parameters it is possible, with a certainty of almost 95%, to exclude the possibility of persistent pain developing in a woman being treated for breast cancer.
Based on increasing evidence suggesting that MS pathology involves alterations in bioactive lipid metabolism, the present analysis was aimed at generating a complex serum lipid-biomarker. Using unsupervised machine-learning, implemented as emergent self-organizing maps of neuronal networks, swarm intelligence and Minimum Curvilinear Embedding, a cluster structure was found in the input data space comprising serum concentrations of d = 43 different lipid-markers of various classes. The structure coincided largely with the clinical diagnosis, indicating that the data provide a basis for the creation of a biomarker (classifier). This was subsequently assessed using supervised machine-learning, implemented as random forests and computed ABC analysis-based feature selection. Bayesian statistics-based biomarker creation was used to map the diagnostic classes of either MS patients (n = 102) or healthy subjects (n = 301). Eight lipid-markers passed the feature selection and comprised GluCerC16, LPA20:4, HETE15S, LacCerC24:1, C16Sphinganine, biopterin and the endocannabinoids PEA and OEA. A complex classifier or biomarker was developed that predicted MS at a sensitivity, specificity and accuracy of approximately 95% in training and test data sets, respectively. The present successful application of serum lipid marker concentrations to MS data is encouraging for further efforts to establish an MS biomarker based on serum lipidomics.