Mathematical generation of data-driven hippocampal CA1 pyramidal neurons and interneurons copies via A-GLIF models for large-scale networks covering the experimental variability range.

Efficient and accurate large-scale networks are a fundamental tool in modeling brain areas, to advance our understanding of neuronal dynamics. However, their implementation faces two key issues: computational efficiency and heterogeneity. Computational efficiency is achieved using simplified neurons, whereas there are no practical solutions available to solve the problem of reproducing in a large-scale network the experimentally observed heterogeneity of the intrinsic properties of neurons. This is important, because the use of identical nodes in a network can generate artifacts which can hinder an adequate representation of the properties of a real network. To this aim, we introduce a mathematical procedure to generate an arbitrary large number of copies of simplified hippocampal CA1 pyramidal neurons and interneurons models, which exhibit the full range of firing dynamics observed in these cells - including adapting, non-adapting and bursting. For this purpose, we rely on a recently published adaptive generalized leaky integrate-and-fire (A-GLIF) modeling approach, leveraging on its ability to reproduce the rich set of electrophysiological behaviors of these types of neurons under a variety of different stimulation currents. The generation procedure is based on a perturbation of model's parameters related to the initial data, firing block, and internal dynamics, and suitably validated against experimental data to ensure that the firing dynamics of any given cell copy remains within the experimental range. A classification procedure confirmed that the firing behavior of most of the pyramidal/interneuron copies was consistent with the experimental data. This approach allows to obtain heterogeneous copies with mathematically controlled firing properties. A full set of heterogeneous neurons composing the CA1 region of a rat hippocampus (approximately 1.2 million neurons), are provided in a database freely available in the live paper section of the EBRAINS platform. By adapting the underlying A-GLIF framework, it will be possible to extend the numerical approach presented here to create, in a mathematically controlled manner, an arbitrarily large number of non-identical copies of cell populations with firing properties related to other brain areas.

Cell-based therapies for the surgical treatment of periodontal intrabony defects: a systematic review.

OBJECTIVE: The aim of the study is to investigate the efficacy of cell-based therapy in the surgical treatment of periodontal intrabony defects. MATERIALS AND METHODS: PRISMA guidelines were followed, and the study protocol was regis-tered in PROSPERO. Electronic and hand searches were carried out on electronic databases and major international journals of periodontology. All randomized clinical trials (RCTs) comparing cell-based therapies com-bined with surgery to surgery alone for the treatment of periodontal intrabony defects were considered. Quality assessment was performed using the Cochrane Risk of Bias Tool for randomized clinical trials (RoB 2). Quantitative evaluation of data was performed by meta-analysis. RESULTS: Five hundred twenty-eight records were initially screened and 5 RCTs fulfilling the eligibility criteria were included. Periodontal ligament stem cells, dental pulp stem cells, periosteum-derived stem cells, gingival fibroblasts and their associated stem cells were used in combination with different surgical techniques to treat intrabony periodontal defects. Meta-analysis showed a statistically signif-icant effect in favor of cell-based groups for clinical attachment level gain (p=0.004), with a difference in means of 1.7 mm (95% CI 0.5; 2.9). This was replicated for intrabony defect depth reduction (p=0.006), with a difference in means of 1.3 (95% CI 0.4; 2.3). CONCLUSIONS: Cell-based therapies have been positively applied for the surgical treatment of intrabony periodontal defects with promising results. However, the results obtained should be interpreted with caution due to the low number of available RCTs, the study design heterogeneity, and the limited extension of the follow-up.

Henoch-Schönlein purpura in a patient with bowel bypass syndrome.

Henoch-Schönlein purpura (HSP) is a common vasculitis being characterized by the classic tetrad of nonthrombocytopenic palpable purpura, arthritis or arthralgias, gastrointestinal and renal involvement. Antigen-antibody (IgA) complexes activate the alternative complement pathway, resulting in inflammation and small vessels vasculitis. We present the case of a 53 years old Italian woman with HSP who was previously hospitalized for purpura skin lesions of the lower legs and diarrhea; a skin biopsy showed a leukocytoclastic vasculitis with perivascular accumulation of neutrophils and mononuclear cells. She was treated with immunosuppressive therapy. After 8 months she was hospitalized again for a recurrent episode of purpura skin lesions of the lower legs. At age 49 she was affected by obesity (BMI = 41.6 Kg/m2), treated via a bilio-pancreatic diversion that led, within a year, to a BMI reduction (25 Kg/m2). We suppose that bariatric surgery played a role on the development of autoimmune phenomena and that the formation of immunecomplexes is secondary to the excess of intestinal bacterial antigens. A cyclic therapy with Paromomicine 500 mg twice daily and Metronidazole 250 mg twice daily was performed with a clear up of the clinical picture. In medical literature are described numerous complications which include arthritis, erythema nodosum-like lesions, eruptions and other skin manifestations in patients who have undergone jejunocolic bypass. This case report describes for the first time the presence of HSP in a patient with bowel bypass syndrome and it is also able to demonstrate the relationship between the intestinal bacterial overgrowth and the systemic autoimmune system.