The Integration of Decision Analysis Techniques in High-Throughput Clinical Analyzers

From the early 1990s, the introduction of high-throughput clinical analyzers has significantly changed the workflow of In-Vitro-Diagnostics (IVD) tests. These high-tech instruments have helped and keep helping clinical laboratories both to increase quality diagnostic responses and to get more for every dollar they spend. Nevertheless, IVD industrial research has been up to now largely hardware-driven with the introduction in the market of many sophisticated technologies. The software component, models and decision support systems in particular, has lagged behind. To reach the full potential of diagnostic automation, it must be addressed the challenge of making the most intelligent use of the hardware that is deployed. Focusing on time efficiency, the authors have devised an operations research-based method for a class of high-throughput clinical analyzers. To demonstrate the validity of the research, the proposed method has been coded and integrated into the Laboratory Information System of the Laboratorio di Analisi Cliniche Dr. P. Pignatelli, one of the most important clinical laboratories in Southern Italy. Siemens Immulite ®; 2000 has been the reference case. The enhanced operating planning procedure provides a monetary benefit of 52,000 USD/year per instruments and a trade-off between clinical benefits and operating costs equivalent to the one provided by the current hardware-driven research at Siemens. Despite the proposed approach has the potential to determine guidelines for enhancing a wide range of current high-throughput clinical analyzers, we have to register a failure in trying to convince technology providers to invest in embedding such new models in their hardware. Some possible causes for such failure are highlighted, trying to find possible improvements for future developments

Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions

Brain injury induces a peripheral acute cytokine response that directs the transmigration of leukocytes into the brain. Because this brain-to-peripheral immune communication affects patient recovery, understanding its regulation is important. Using a mouse model of inflammatory brain injury, we set out to find a soluble mediator for this phenomenon. We found that extracellular vesicles (EVs) shed from astrocytes in response to intracerebral injection of interleukin-1β (IL-1β) rapidly entered into peripheral circulation and promoted the transmigration of leukocytes through modulation of the peripheral acute cytokine response. Bioinformatic analysis of the protein and microRNA cargo of EVs identified peroxisome proliferator–activated receptor α (PPARα) as a primary molecular target of astrocyte-shed EVs. We confirmed in mice that astrocytic EVs promoted the transmigration of leukocytes into the brain by inhibiting PPARα, resulting in the increase of nuclear factor κB (NF-κB) activity that triggered the production of cytokines in liver. These findings expand our understanding of the mechanisms regulating communication between the brain and peripheral immune system and identify astrocytic EVs as a molecular regulator of the immunological response to inflammatory brain damage

Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions

Brain injury induces a peripheral acute cytokine response that directs the transmigration of leukocytes into the brain. Because this brain-to-peripheral immune communication affects patient recovery, understanding its regulation is important. Using a mouse model of inflammatory brain injury, we set out to find a soluble mediator for this phenomenon. We found that extracellular vesicles (EVs) shed from astrocytes in response to intracerebral injection of interleukin-1β (IL-1β) rapidly entered into peripheral circulation and promoted the transmigration of leukocytes through modulation of the peripheral acute cytokine response. Bioinformatic analysis of the protein and microRNA cargo of EVs identified peroxisome proliferator–activated receptor α (PPARα) as a primary molecular target of astrocyte-shed EVs. We confirmed in mice that astrocytic EVs promoted the transmigration of leukocytes into the brain by inhibiting PPARα, resulting in the increase of nuclear factor κB (NF-κB) activity that triggered the production of cytokines in liver. These findings expand our understanding of the mechanisms regulating communication between the brain and peripheral immune system and identify astrocytic EVs as a molecular regulator of the immunological response to inflammatory brain damage

Bungaku zasshi "Waroni" ni okeru chiiki shugiteki kito no seisei to tenkai : bungaku seido fukei hyosho shakai gengoteki jokyo (honbun)

The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory IL-10–expressing human CD4+CD25+ T cells and IL-10+FoxP3+ Tregs in mice. Finally, microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10+ Tregs compared with mice “humanized” with microbiota from healthy controls. This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a treatment for MS