A co-ultramicronized palmitoylethanolamide/luteolin composite mitigates clinical score and disease-relevant molecular markers in a mouse model of experimental autoimmune encephalomyelitis

Background: Persistent and/or recurrent inflammatory processes are the main factor leading to multiple sclerosis (MS) lesions. The composite ultramicronized palmitoylethanolamide, an endogenous N-acylethanolamine, combined with the flavonoid luteolin, PEALut, have been found to exert neuroprotective activities in experimental models of spinal and brain injury and Alzheimer disease, as well as a clinical improvement in human stroke patients. Furthermore, PEALut enhances the expression of different myelin proteins in oligodendrocyte progenitor cells suggesting that this composite might have protective effects in MS experimental models. Methods: The mouse model of experimental autoimmune encephalomyelitis (EAE) based on active immunization with a fragment of myelin oligodendrocyte glycoprotein (MOG35-55) was used. The daily assessment of clinical score and the expression of serum amyloid A (SAA1), proinflammatory cytokines TNF-\u3b1, IL-1\u3b2, IFN-\u3b3, and NLRP3 inflammasome, as well as TLR2, Fpr2, CD137, CD3-\u3b3, and TCR-\u3b6 chain, heterodimers that form T cell surface glycoprotein (TCR), and cannabinoid receptors CB1, CB2, and MBP, were evaluated in the brainstem and cerebellum at different postimmunization days (PIDs). Results: Vehicle-MOG35-55-immunized (MOG35-55) mice developed ascending paralysis which peaked several days later and persisted until the end of the experiment. PEALut, given intraperitoneally daily starting on day 11 post-immunization, dose-dependently improved clinical score over the range 0.1-5 mg/kg. The mRNA expression of SAA1, TNF-\u3b1, IL-1\u3b2, IFN-\u3b3, and NLRP3 were significantly increased in MOG35-55 mice at 14 PID. In MOG35-55 mice treated with 5 mg /kg PEALut, the increase of SAA1, TNF- \u3b1, IL-1\u3b2, and IFN-\u3b3transcripts at 14 PID was statistically downregulated as compared to vehicle-MOG35-55 mice (p < 0.05). The expression of TLR2, Fpr2, CD137, CD3-\u3b3, TCR-\u3b6 chain, and CB2 receptors showed a significant upregulation in vehicle-MOG35-55 mice at 14 PID. Instead, CB1 and MBP transcripts have not changed in expression at any time. In MOG/PEALut-treated mice, TLR2, Fpr2, CD137, CD3-\u3b3, TCR-\u3b6 chain, and CB2 mRNAs were significantly downregulated as compared to vehicle MOG35-55 mice. Conclusions: The present results demonstrate that the intraperitoneal administration of the composite PEALut significantly reduces the development of clinical signs in the MOG35-55 model of EAE. The dose-dependent improvement of clinical score induced by PEALut was associated with a reduction in transcript expression of the acute-phase protein SAA1, TNF-\u3b1, IL-1\u3b2, IFN-\u3b3, and NLRP3 proinflammatory proteins and TLR2, Fpr2, CD137, CD3-\u3b3, TCR-\u3b6 chain, and CB2 receptors

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

PIV measurements over a double bladed Darrieus-type vertical axis wind turbine: A validation benchmark

Vertical axis wind turbines (VAWTs) are very attractive for in-home power generation since they can be adopted even at low wind speeds and highly variable wind direction. Even if significant experimental research activity has been carried out to improve VAWTs performance, the ability to accurately reproduce flow field characteristics around turbine blades by CFD (computational fluid dynamics) techniques represents a powerful approach to further enhance wind turbines performance. Thanks to CFD, in fact, it is possible to reproduce flow characteristics with a detail level impossible to achieve by experiments. Nevertheless, in order to appropriately analyze the flow structure by CFD application, an accurate validation is essential, and high-quality measurements of some main flow characteristics are required. In recent publications the authors investigated, both experimentally and numerically, the performance of an innovative double bladed Darrieus-type VAWT, with the aim to define an optimal configuration also focusing on self-starting ability of the prototype by employing CFD technique. Nevertheless, comparison between experiments and numerical results was made only in terms of power and torque coefficient. To overcome such limitation, in this paper the authors propose an experimental benchmark case for CFD results validation, describing detailed flow field in correspondence of one pair of blades of the innovative Darrieus-type VAWT in static conditions. Measurements were performed employing Particle Image Velocimetry (PIV) technique on a scaled model of the turbine blades realized by 3D printing. An uncertainty analysis was also performed which showed a high accuracy of the obtained experimental results. The measurements of the main flow characteristics (bi-dimensional velocity components) were then used for a test case CFD validation of two different turbulence model

Non-dimensional numerical analysis of coupled Metal Hydride-Phase Change Material hydrogen storage system

Efficient storage solutions that decouple energy use and production are pivotal for the green energy transition, due to the non-controllable operation of solar and wind power. In this scenario, hydrogen, and in particular metal hydride storage, has shown excellent potential. In this paper we develop a mathematical model to characterize the operation of several cylindrical Metal Hydride-Phase Change Material tank layouts and to determine the improved configuration in terms of charge/discharge time and power. We use non-dimensional parameters to guide the design of a hybrid metal hydride-phase change material hydrogen storage system. We introduce a critical value for the state of charge of the storage system, equal to φc∗=0.15, above which heat exchange dominates the process efficiency. Results show that, when varying the canister main aspect ratio between 5 and 100, the equivalent inlet/outlet power increases by a factor ≈10. The ratio of the thermal conductivities is found to have a significant impact in the desorption phase, where the equivalent power increases by a factor ≈4 when raising the ratio from 0.1 to 0.8. Finally, we evaluate three case studies by introducing three different improved configurations and comparing them with the baseline design. A LaNi5/LiNO3−3H2O system for the storage of 1kWh of H2 exhibits 5.65kW and 0.83kW of average power in absorption and desorption, respectively. Such an improved configuration is 93% faster in charge/discharge process with respect to the baseline design. A coupled Mg2NiH4 - NaNO3 exhibits 2.93 kW and 0.30 kW of average power in absorption and desorption, respectively. This configuration is 81% faster than the baseline design. A coupled Mg2NiH4 - KNO3 exhibits 1.66 kW and 0.56 kW of average power in absorption and desorption, while the cycle time is reduced from 1220 min to 147 min (−88%)

Optimized modeling and design of a pcm-enhanced h2 storage

Thermal and mechanical energy storage is pivotal for the effective exploitation of renewable energy sources, thus fostering the transition to a sustainable economy. Hydrogen-based systems are among the most promising solutions for electrical energy storage. However, several technical and economic barriers (e.g., high costs, low energy and power density, advanced material requirements) still hinder the diffusion of such solutions. Similarly, the realization of latent heat storages through phase change materials is particularly attractive because it provides high energy density in addition to allowing for the storage of the heat of fusion at a (nearly) constant temperature. In this paper, we posit the challenge to couple a metal hydride H-2 canister with a latent heat storage, in order to improve the overall power density and realize a passive control of the system temperature. A highly flexible numerical solver based on a hybrid Lattice Boltzmann Phase-Field (LB-PF) algorithm is developed to assist the design of the hybrid PCM-MH tank by studying the melting and solidification processes of paraffin-like materials. The present approach is used to model the storage of the heat released by the hydride during the H-2 loading process in a phase change material (PCM). The results in terms of Nusselt numbers are used to design an enhanced metal-hydride storage for H-2-based energy systems, relevant for a reliable and cost-effective "Hydrogen Economy". The application of the developed numerical model to the case study demonstrates the feasibility of the posited design. Specifically, the phase change material application significantly increases the heat flux at the metal hydride surface, thus improving the overall system power density

Sequelae of conflict-related sexual violence on survivors: the perspective of two systematic reviews

BACKGROUND: Conflict-related sexual violence (CRSV) is a form of gender-based violence and a violation of human rights. We conducted two systematic reviews (1) to analyze the qualitative evidence reported in peer reviewed scientific literature published in the last ten years and focusing on the negative consequences of conflict-related sexual violence on survivors’ physical, psychological, and social dimensions of health and (2) to summarize the knowledge on the forensic medical examination (FME) of victims of CRSV in the same study period. METHODS: A literature search was conducted on January 13, 2023, and on April 3rd, 2023, on three different databases. The search strings combined blocks of terms related to sexual violence and conflict, and in the second review FME. Information regarding the main characteristics and design of the study, survivors and their experience, CRSV, and FME was collected. In the first review, the negative consequences on the physical, psychological, and social dimension of victims were extracted following the Biopsychosocial model of health, while in the second information pertained the different phases of FME. RESULTS: Considering CRSV, 23 articles met inclusion criteria, with 18 of them reporting negative repercussions on physical health, all of them highlighting adverse psychological outcomes, and 21 disclosing unfavorable social consequences. The outcomes described in more studies were sexual and reproductive health issues, manifestations of symptoms attributable to post-traumatic stress disorder, and stigma. Barriers to access to care were emerging findings. Our analysis highlighted that CRSV takes place in an enabling environment. The level and the modalities of violence, employed by a variety of stakeholders, created a chain of brutality in conflict-affected settings, on the move, and in the host countries. Concerning the second review, 17 articles met inclusion criteria. The majority underlined physical (e.g., nonsexual) sequelae and were conducted in the host country of survivors who fled from conflict. Physician’s opinion on the consistency of the findings and protection outcomes were rarely reported. CONCLUSION: The first review highlighted the importance of qualitative evidence in understanding the negative outcomes of conflict-related sexual violence on survivors. Conflict-related sexual violence is a sexual and reproductive health issue and a violation of human rights. Sexuality education is needed, challenging gender norms and roles and encompassing gender-based violence. Gender-inclusive protocols and services need to be implemented to address the specific needs of all victims. Governments should translate health policies into concrete action targeting survivors. The second review emphasized the limited attention given in literature to FME of CRSV and to CRSV-specific lesions, as well as the need for specialized training and expertise for professionals in this field

Negative consequences of conflict-related sexual violence on survivors: a systematic review of qualitative evidence

BackgroundConflicts exacerbate dynamics of power and inequalities through violence normalization, which acts as a facilitator for conflict-related sexual violence. Literature addressing its negative outcomes on survivors is scant. The aim of this systematic review was to analyze the qualitative evidence reported in scientific literature and focusing on the negative consequences of conflict-related sexual violence on victims' physical, psychological, and social dimensions of health in a gender-inclusive and disaggregated form.MethodsA literature search was conducted on January 13, 2023 on Pubmed, Scopus, and PsychArticles. The search strings combined two blocks of terms related to sexual violence and conflict. A time filter was applied, limiting the search to studies published in the last ten years. Information regarding the main characteristics and design of the study, survivors and their experience, and about conflict-related sexual violence was collected. The negative consequences of conflict-related sexual violence on the physical, psychological, and social dimension of victims were extracted according to the Biopsychosocial model of health. The review followed the Joanna Briggs Institute methodology for systematic reviews and relied on the Preferred Reporting Items for Systematic reviews and Meta-Analyses.ResultsAfter full text review, 23 articles met the inclusion criteria, with 18 of them reporting negative repercussions on physical health, all of them highlighting adverse psychological outcomes, and 21 disclosing unfavorable social consequences. The negative outcomes described in multiple studies were sexual and reproductive health issues, the most mentioned being pregnancy, manifestations of symptoms attributable to post-traumatic stress disorder, and stigma. A number of barriers to access to care were presented as emerging findings.ConclusionsThis review provided an analysis of the negative consequences of conflict-related sexual violence on survivors, thus highlighting the importance of qualitative evidence in understanding these outcomes and addressing barriers to access to care. Conflict-related sexual violence is a sexual and reproductive health issue. Sexuality education is needed at individual, community, and provider level, challenging gender norms and roles and encompassing gender-based violence. Gender-inclusive protocols and services need to be implemented to address the specific needs of all victims. Governments should advocate for SRHRs and translate health policies into services targeting survivors of CRSV

Expression and Differential Responsiveness of Central Nervous System Glial Cell Populations to the Acute Phase Protein Serum Amyloid A

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves hepatic production of acute-phase proteins, including serum amyloid A (SAA). Extrahepatically, SAA immunoreactivity is found in axonal myelin sheaths of cortex in Alzheimer's disease and multiple sclerosis (MS), although its cellular origin is unclear. We examined the responses of cultured rat cortical astrocytes, microglia and oligodendrocyte precursor cells (OPCs) to master pro-inflammatory cytokine tumour necrosis factor (TNF)-\u3b1 and lipopolysaccaride (LPS). TNF-\u3b1 time-dependently increased Saa1 (but not Saa3) mRNA expression in purified microglia, enriched astrocytes, and OPCs (as did LPS for microglia and astrocytes). Astrocytes depleted of microglia were markedly less responsive to TNF-\u3b1 and LPS, even after re-addition of microglia. Microglia and enriched astrocytes showed complementary Saa1 expression profiles following TNF-\u3b1 or LPS challenge, being higher in microglia with TNF-\u3b1 and higher in astrocytes with LPS. Recombinant human apo-SAA stimulated production of both inflammatory mediators and its own mRNA in microglia and enriched, but not microglia-depleted astrocytes. Co-ultramicronized palmitoylethanolamide/luteolin, an established anti-inflammatory/neuroprotective agent, reduced Saa1 expression in OPCs subjected to TNF-\u3b1 treatment. These last data, together with past findings suggest that co-ultramicronized palmitoylethanolamide/luteolin may be a novel approach in the treatment of inflammatory demyelinating disorders like MS