Neuroinflammation in Bipolar Depression Benedetti, Francesco; Aggio, Veronica; Pratesi, Maria Luisa ...
Frontiers in psychiatry,
02/2020, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
Bipolar disorder (BD) is a leading cause of worldwide disability among mood disorders. Pathological mechanisms are still vastly unclear, and current treatments with conventional medications are often ...unsatisfactory in maintaining symptoms control and an adequate quality of life. Consequently, current research is focusing on shedding new light on disease pathogenesis, to improve therapeutic effectiveness. Recent evidence has suggested a prominent role of inflammation in mood disorders. Elevated levels of peripheral proinflammatory mediators have been reported in BD, as well as in other mood disorders, and people with systemic autoimmune diseases have an increased risk of developing BD. These immunological alterations are stable, and current medications are unable to alter peripheral concentrations even when clinical improvement is evident. These findings have also been replicated in the central nervous system (CNS) milieu, whereas genetic studies have shown that these immune alterations are not due to the disorder itself, being detectable before the illness onset. Moreover, these inflammatory modifications seem to be affected by and linked to other biomarkers of the disorder, such as alterations of white matter (WM) microstructure, metabolism, kynurenine pathway, and circadian rhythmicity. Finally, these immune variations seem to be useful as predictors of therapeutic responsiveness to medications, and in discriminating between clinically different outcomes. The objective of this review is to summarize available evidence on the connection between inflammation and BD, focusing on peripheral inflammatory markers and recent findings on their connection with other typical features of BD, to outline a general overview of the disorder. Moreover, it is meant to analyze the issues with data gathering and interpretation, given the partially contradictory and inconsistent nature of results.
Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. ...Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments.
The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of ...dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected by such diseases and on immune-active treatments have been analyzed. The aim is to better understand the relationship between SARS-CoV-2 infection/vaccines with dysimmune CNS diseases by describing 12 cases of multiple sclerosis/myelitis onset or reactivation after exposure to SARS-CoV-2 infection/vaccines and reviewing all published case reports or case series in which MS onset or reactivation was temporally associated with either COVID-19 (8 case reports, 3 case series) or anti-SARS-CoV-2 vaccines (13 case reports, 6 case series). All the cases share a temporal association between viral/vaccine exposure and symptoms onset. This finding, together with direct or immune-based mechanisms described both during COVID-19 and MS, claims in favor of a role for SARS-CoV-2 infection/vaccines in unmasking dysimmune CNS disorders. The most common clinical presentations involve the optic nerve, brainstem and spinal cord. The preferential tropism of the virus together with the presence of some host-related genetic/immune factors might predispose to the involvement of specific CNS districts.
Currently available data suggest that the union of a balanced diet and an overall healthy lifestyle may determine an amelioration in several clinical parameters and in the quality of life for ...patients with MS (pwMS). The study objective was to investigate the possible difference in MS severity in a group of Italian patients with MS based on their adherence to Mediterranean Diet (MedDiet). Eating habits were collected through a validated 110-items Food Frequency Questionnaire, the Medi-Lite score was used for adherence to MedDiet evaluation. MS severity was graded according to Herbert’s severity scale, based on the MSSS. 106 patients were classified in 3 groups according to their MedDiet adherence (low/medium/high). Higher adherence was associated with a 6.18 (95% CI: 1.44, 26.59) higher probability of having a mild-to-moderate MS. When studying the single constituents of the Medi-Lite score, none of them was individually associated with MS severity. It remains unclear whether effects of specific dietary components included in the MedDiet may impact the health status at disease onset or can slow down the symptoms due course of disease. Future studies are needed to reproduce our findings and should focus on answering the latter raised question.
Background:
It is postulated that the ability of dipeptidyl peptidase-4 inhibitors (DPP-4-i) to increase circulating endothelial progenitor cells (EPCs) may be at least partly mediated by active ...stromal cell–derived factor 1α (SDF-1α) (a pivotal mediator of stem cell mobilization from the bone marrow). As other DPP-4-i were demonstrated to increase EPC concentrations, in this study, we sought to investigate the ability of the DPP-4-i alogliptin in modifying EPCs and SDF-1α, in patients with good and poor diabetes control.
Methods:
Two groups of diabetic patients on metformin were divided by hemoglobin A1c (HbA1c): Group A—those with HbA1c ≤6.5% (28 patients) and Group B—those with HbA1c 7.5% to 8.5% (31 patients). Both groups received alogliptin 25 mg/daily for 4 months. At baseline and 4 months later, clinical, laboratory parameters, EPCs, and active SDF-1α were determined.
Results:
After 4-month treatment with alogliptin, either Group A or Group B showed reduced HbA1c levels and concomitant similar increase in EPCs and active SDF-1α.
Conclusions:
Alogliptin showed significant benefits in increasing EPCs and active SDF-1α either in good or poor diabetes control. The study demonstrated that similar to other DPP-4-i, also alogliptin is able to increase EPC concentrations, suggesting the existence of a class effect mediated by SDF-1α. The extent of increase in EPCs is independent from baseline diabetes control.
Users' load aggregation, control of smart appliances, and exploitation of thermal inertia of buildings are among key elements to improve the energy demand of buildings, toward the goals of near zero ...energy buildings. In this paper, we investigated a case study of an existing residential and commercial building with a microgrid and advanced technical and control systems. We have developed a model to simulate loads and the effects of control systems. The results show how increasing the extent of the microgrid and control strategies improves the load profile and energy consumption, also preserving the users' habits and comfort. Via these elements, the concept of near zero energy building can further advance toward a "near zero power building" or "zero-kilometer energy building."
We show convergence of the gradients of the Schrödinger potentials to the (uniquely determined) gradient of Kantorovich potentials in the small-time limit under general assumptions on the marginals, ...which allow for unbounded densities and supports. Furthermore, we provide novel quantitative stability estimates for the optimal values and optimal couplings for the Schrödinger problem (SP), that we express in terms of a negative order weighted homogeneous Sobolev norm. The latter encodes the linearized behavior of the 2-Wasserstein distance between the marginals. The proofs of both results highlight for the first time the relevance of gradient bounds for Schrödinger potentials, that we establish here in full generality, in the analysis of the short-time behavior of Schrödinger bridges. Finally, we discuss how our results translate into the framework of quadratic Entropic Optimal Transport, that is a version of SP more suitable for applications in machine learning and data science.
Smart Tunnel and Dynamic Risk Analysis Focaracci, Alessandro; Greco, Giacomo; Martirano, Luigi
IEEE transactions on industry applications,
05/2020, Letnik:
56, Številka:
3
Journal Article
Recenzirano
The article proposes an innovative system of supervision and data acquisition, oriented to fire safety through a dynamic risk analysis, called supervisory control and dynamic risk analysis (SCADRA). ...SCADRA achieves operation and management benefits for safety, functionality, and energy optimization, by means of dynamic control and monitoring measures. A "Smart Tunnel" can be defined as a model where technical systems are designed and installed in an advanced way, by using digital components and sensors. SCADRA has been developed to offer a complete tool (human machine interface) for real-time monitoring of tunnel safety by tunnel operators, integrated with the innovative dynamic risk analysis. SCADRA offers compensatory and/or supplementary safety measures for emergency management and supports fire rescue teams that are operating in tunnel in which some requirements could not be realized.
The paper presents a feasible model of architecture for the technical building systems (TBS) particularly suitable for nearly zero energy buildings (NZEBs). The suggested model aggregates the users ...around an electric node in order to reach up the threshold value of electric power, and to get a more virtuous and flexible cumulative load profile. Present proposal is a full electric common smart micro grid with a single point of connection, with heating and domestic hot water generated by a centralized electric heat pump system. The renewable energy is provided by a photovoltaic field connected to the common grid. A building automation control system operates those electric TBS modulating the global load for a building demand response (DR). The effectiveness of the proposed model consists of exploiting thermal inertia as an energy storage, by forcing both local and central set points of heating and air conditioning systems. The control is based on the integrated and common operation of all users and all systems of the building as one unique "large user." The integrated management of the grid is operated to control the whole electric demand exploiting the self-consumption, avoiding peaks, and maintaining a flat load profile. The suggested microgrid model allows concretely the possibility to realize a building DR with benefits for the end-users in a consumer view point. A study of the effect of these control opportunities on whole electric demand is done by simulation on a case study.
We investigated the effect of alogliptin and gliclazide on endothelial progenitor cells (EPCs) in type 2 diabetes.
Eighty patients with type 2 diabetes and HbA1c between 7.5% and 8.5% were randomized ...to receive either alogliptin (25 mg/daily) or gliclazide extended-release (30 mg/daily for HbA1c 7.5-8.0% and 60 mg/daily for HbA1c 8.0-8.5%) in combination with metformin for 4 months. At baseline and 4 months, clinical and laboratory parameters of EPCs were determined.
After 4 months of treatment, alogliptin and gliclazide resulted in a similar significant reduction in HbA1c (%) (8.0±0.3 vs. 7.1±0.2, and 8.0±0.3 vs. 7.0±0.2, respectively; P<0.05) and a similar and significant increase in EPC count (cells/10
WBC) (CD45
CD133
KDR
: 2.2±1.2 vs. 3.7±1.6, CD45
CD34
KDR
: 3.3±1
8 vs. 4.9±1.8; P<0.05 for alogliptin; CD45
CD133
KDR
: 2.3±1.3 vs. 3
6±1.5, CD45
CD34
KDR
: 3.1±1.3 vs. 4
6±1.7; P<0.05 for gliclazide).
Both alogliptin and gliclazide demonstrated a beneficial effect in increasing EPCs in poorly controlled type 2 diabetes. As alogliptin and gliclazide exhibit different mechanisms of action, the observed increase in EPCs seems to be due to their glucose-lowering effect.
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