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The etiology of CNS diseases including multiple sclerosis, Parkinson’s disease and amyotrophic lateral sclerosis remains elusive despite decades of research resulting in treatments with only symptomatic effects. In this study, we provide evidence that a metabolic shift from glucose to lipid is a key mechanism in neurodegeneration. We show that, by downregulating the metabolism of lipids through the key molecule carnitine palmitoyl transferase 1 (CPT1), it is possible to reverse or slowdown disease progression in experimental models of autoimmune encephalomyelitis-, SOD1G93A and rotenone models, mimicking these CNS diseases in humans. The effect was seen both when applying a CPT1 blocker or by using a Cpt1a P479L mutant mouse strain. Furthermore, we show that diet, epigenetics, and microbiota are key elements in this metabolic shift. Finally, we present a systemic model for understanding the complex etiology of neurodegeneration and how different regulatory systems are interconnected through a central metabolic pathway that becomes deregulated under specific conditions.

Autologus augmentation of wound remodeling with platelet concentrate is a burgeoning field with promising results. We hypothesized that the addition of filtered platelet concentrate (fPC) to an acellular biologic graft would improve crural healing and tissue integrity in hiatal hernia repair. Sixteen healthy Yorkshire female pigs were divided into three groups: hiatus repair (HR) (n = 7), HR with biologic graft (HRM; n = 8, and HR with biologic graft and fPC (fPC; n = 9). Surgeries were performed by a single surgeon. Animals were euthanized at 8 weeks, and the distal esophagus with hiatus was harvested en-block. Tissue was graded by a histopathologist on collagen deposition, vascularization, and inflammation at the graft–hiatal interface. Tensile strength testing was performed using the Teststar IIs (MTS), coupled with a strain extensometer (Epsilon). Samples of equal dimensions were preloaded to 1 N and deformed at a constant rate of 0.2 mm/s. Statistical analysis was performed via Kruskal–Wallis one-way analysis of variance. Aspirate analysis revealed a mean platelet count of 3 million platelets/1 mL of aspirate. Animals in the fPC group had significantly increased mean chronic inflammation (3.1 ± 1.1 vs. 1.8 ± 1.6, 1.2 ± 1.2, p = 0.04) compared to HR alone and HR + biologic graft. Vascular deposition did not differ between groups (p = 0.8). A trend toward increased collagen deposition was demonstrated for the fPC group (1.4 ± 1.1 vs. 2.0 ± 0.6 in HR group and 3.0 ± 1.2 in HRM group, p = 0.06). There was a statistically significant increase in tensile strength, yield force, and Young’s modulus in the fPC group compared with HR and HR + biologic mesh (p

Multiple sclerosis is a complex neurodegenerative disease, thought to arise through autoimmunity against antigens of the central nervous system. The autoimmunity hypothesis fails to explain why genetic and environmental risk factors linked to the disease in one population tend to be unimportant in other populations. Despite great advances in documenting the cell and molecular mechanisms underlying MS pathophysiology, the autoimmunity framework has also been unable to develop a comprehensive explanation of the etiology of the disease. I propose a new framework for understanding MS as a dysfunction of the metabolism of lipids. Specifically, the homeostasis of lipid metabolism collapses during acute-phase inflammatory response triggered by a pathogen, trauma, or stress, starting a feedback loop of increased oxidative stress, inflammatory response, and proliferation of cytoxic foam cells that cross the blood brain barrier and both catabolize myelin and prevent remyelination. Understanding MS as a chronic metabolic disorder illuminates four aspects of disease onset and progression: 1) its pathophysiology; 2) genetic susceptibility; 3) environmental and pathogen triggers; and 4) the skewed sex ratio of patients. It also suggests new avenues for treatment.

Disease detection in historical samples currently relies on DNA extraction and amplification, or immunoassays. These techniques only establish pathogen presence rather than active disease. We report the first use of shotgun proteomics to detect the protein expression profile of buccal swabs and cloth samples from two 500-year-old Andean mummies. The profile of one of the mummies is consistent with immune system response to severe pulmonary bacterial infection at the time of death. Presence of a probably pathogenic Mycobacterium sp. in one buccal swab was confirmed by DNA amplification, sequencing, and phylogenetic analyses. Our study provides positive evidence of active pathogenic infection in an ancient sample for the first time. The protocol introduced here is less susceptible to contamination than DNA-based or immunoassay-based studies. In scarce forensic samples, shotgun proteomics narrows the range of pathogens to detect using DNA assays, reducing cost. This analytical technique can be broadly applied for detecting infection in ancient samples to answer questions on the historical ecology of specific pathogens, as well as in medico-legal cases when active pathogenic infection is suspected.