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Abstract Objective Post‐traumatic epilepsy (PTE) is an acquired epilepsy that develops in the months or years following a traumatic brain injury (TBI) and can lead to substantial personal, financial, and societal burden. To date, PTE is rarely curable; current treatments are partially effective and often accompanied by adverse side effects. While research on PTE has expanded significantly in the last several years, there remain numerous challenges to identifying effective prevention and treatment strategies. In this paper, we describe advances from the CURE Epilepsy PTE Initiative, including its implementation and the emphasis on team science. Methods The CURE Epilepsy PTE Initiative funded six research teams to link preclinical and clinical studies to engage in the validation of experimental models, characterization of pathophysiology and biological pathways, and identification of risk factors associated with PTE. Three teams had projects with both a preclinical and a clinical component; these teams focused on: targeting the epileptogenic effects of subarachnoid blood, exploring the neuropathological mechanisms of epileptogenesis, and defining the role of extracellular matrix injury. Two teams undertook entirely preclinical projects: exploring the role of vascular injury, gliosis, and neurogenesis as drivers for PTE, and identifying genetic, proteomic, metabolomic, and microRNA biosignatures to improve the prediction of PTE. One team's project was entirely clinical and investigated genetic and protein biomarkers to improve the prediction of PTE. Results In addition to scientific discoveries including characterization of a variety of animal models and progress towards the understanding of biological underpinnings and biomarkers for PTE, significant programmatic and personnel‐related processes were incorporated, including standardized, rigorous policies and procedures to ensure quality and accountability between and within groups. Significance We propose CURE Epilepsy's team science approach as an effective way to bring together a diverse set of investigators to explore biological mechanisms that may lead to cures for the epilepsies.

Introduction. Fibromyalgia syndrome (FS) comprises general body pain, sleep disturbances, and fatigue. Vitamin B12 (VB), vitamin D (VD), and iron deficiencies lead to similar complaints. First, this study aimed to evaluate the VB, VD, and ferritin levels of patients with FS. Second, it aimed to investigate whether there was a relationship between these parameters and FS severity.

Morphea, or localized scleroderma, is a chronic inflammatory condition that unequivocally affects the dermis and subcutaneous connective tissue. It undeniably causes significant disfigurement in approximately half of patients, profoundly impacting their self-esteem. The available treatment options include corticosteroids (taken orally or administered subcutaneously), phototherapy, CO 2 fractional laser treatment, and biologically mediated medications. It is crucial to note that using fillers as adjuvant therapy for inflammatory diseases indisputably raises concerns due to the potential to trigger inflammation and lead to disease reactivation. In one case, a 24-year-old patient with morphea on her face underwent a combined approach involving plastic surgery, dermatology, and regenerative aesthetics treatment with lipo-filling initially by an expert plastic surgeon. Then, after reviewing the literature and consensus from the dermatologist, aesthetics physician, and alternative medicine expert, it was decided to use calcium hydroxylapatite-carboxymethylcellulose (Radiesse, Merz Pharmaceuticals GmbH, Frankfurt, Germany) in the affected area. After a year of follow-up, there was a significant improvement in the appearance of her face and skin, as confirmed by a 10-point improvement on an activity measuring scale. Additional research will solidify whether calcium hydroxylapatite (CaHA) is the optimal injectable for treating dermal autoimmune diseases. Our initial approach demonstrates significant promise for regenerative biostimulation. Through collaboration, we have effectively integrated plastic surgery techniques, fillers, dermatologists, and alternative medicine perspectives to treat inflammatory diseases, providing a comprehensive and robust exploration of morphea treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Carolina Schneider and Luis A. Parra Hernandez declare(s) personal fees from Merz Aesthetics. Received speaker honorariums from Merz Aesthetics, which owns the licenses for Radiesse. These honorariums were received before the publication of this paper and were unrelated to this case report. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Schneider et al.)

Objectives: This study aimed to investigate the potential roles of proprotein convertase subtilisin/ kexin type 9 (PCSK9) and apelin in the etiology of fibromyalgia syndrome (FS)., Patients and Methods: The retrospective study was conducted between May 2022 and February 2023. Fifty-eight female FS patients (mean age: 45.2±9.9 years; range, 25 to 66 years) and 30 age- and body mass index-matched control subjects (mean age: 43.1±9.9 years; range, 26 to 67 years) were included in the study. Apelin and PCSK9 levels of all individuals were measured using appropriate methods., Results: The levels of PCSK9 (173.2±62.2 vs. 75.1±44.1, p<0.001) and apelin (354.6±195.5 vs. 229.0±83.2, p<0.001) were significantly higher in patients with FS compared to the control group. A positive correlation was found between PCSK9 and apelin levels and various measures, including the Fibromyalgia Impact Questionnaire (FIQ), Symptom Severity Scale (SSS), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Inventory (BDI). Additionally, there was a positive correlation between apelin levels and FIQ, SSS, PSQI, Beck Anxiety Inventory, and BDI scores. The optimal cutoff value for PCSK9 in predicting FS was 110.0 ng/mL, with a sensitivity of 84.5% and specificity of 83.9% (area under the curve [AUC]=0.920, 95% confidence interval [CI]: 0.852-0.987, p<0.001). For apelin, the optimal cutoff value for predicting FS was 258.8 ng/L, with a sensitivity of 63.8% and specificity of 64.5% (AUC=0.732, 95% CI: 0.623-0.840, p<0.001)., Conclusion: Our findings suggest that PCSK9 may play a role in FS etiology and potentially contribute to oxidative stress. Increased apelin levels may be a compensatory response to high oxidative stress, possibly leading to hyperalgesia. Both PCSK9 and apelin can be predictive markers for FS., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2024, Turkish League Against Rheumatism.)

The SARS-CoV-2 virus emerged towards the end of 2019 and caused a major worldwide pandemic lasting at least 2 years, causing a disease called COVID-19. SARS-CoV-2 caused a severe infection with direct cellular toxicity, stimulation of cytokine release, increased oxidative stress, disruption of endothelial structure, and thromboinflammation, as well as angiotensin-converting enzyme 2 (ACE2) down-regulation-mediated renin-angiotensin system (RAS) activation. In addition to glucosuria and natriuresis, sodium-glucose transport protein 2 (SGLT2) inhibitors (SGLT2i) cause weight loss, a decrease in glucose levels with an insulin-independent mechanism, an increase in erythropoietin levels and erythropoiesis, an increase in autophagy and lysosomal degradation, Na + /H + -changer inhibition, prevention of ischemia/reperfusion injury, oxidative stress and they have many positive effects such as reducing inflammation and improving vascular function. There was great anticipation for SGLT2i in treating patients with diabetes with COVID-19, but current data suggest they are not very effective. Moreover, there has been great confusion in the literature about the effects of SGLT2i on COVID-19 patients with diabetes . Various factors, including increased SGLT1 activity, lack of angiotensin receptor blocker co-administration, the potential for ketoacidosis, kidney injury, and disruptions in fluid and electrolyte levels, may have hindered SGLT2i's effectiveness against COVID-19. In addition, the duration of use of SGLT2i and their impact on erythropoiesis, blood viscosity, cholesterol levels, and vitamin D levels may also have played a role in their failure to treat the virus. This article aims to uncover the reasons for the confusion in the literature and to unravel why SGLT2i failed to succeed in COVID-19 based on some solid evidence as well as speculative and personal perspectives., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease involving several articular and extra-articular structures. Despite the important progresses recently made in all of the aspects of this disease, its management is still burdened by unresolved issues. The aim of this exercise was to provide a set of statements that may be helpful for the management of PsA., Methods: A group of 38 Italian rheumatologists with recognized expertise in PsA selected and addressed the following four topics: "early PsA," "axial-PsA," "extra-articular manifestations and comorbidities," "therapeutic goals." Relevant articles from the literature (2016-2022) were selected by the experts based on a PubMed search. A number of statements for each topic were elaborated., Results: Ninety-four articles were selected and evaluated, 68 out of the 1,114 yielded by the literature search and 26 added by the Authors. Each of the four topic was subdivided in themes as follows: transition from psoriasis to PsA, imaging vs. CASPAR criteria in early diagnosis, early treatment for "early PsA"; axial-PsA vs. axialspondyloarthritis, diagnosis, clinical evaluation, treatment, standard radiography vs. magnetic resonance imaging for "axial PsA"; influence of inflammatory bowel disease on the therapeutic choice, cardiovascular comorbidity, bone damage, risk of infection for "comorbidities and extra-articular manifestations"; target and tools, treat-to-target strategy, role of imaging for "therapeutic goals." The final document consisted of 49 statements., Discussion: The final product of this exercise is a set of statements concerning the main issues of PsA management offering an expert opinion for some unmet needs of this complex disease., Competing Interests: SD’A received consulting and speaking fees from AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer and UCB. MB had the following financing relationships with subjects with commercial interests in the health sector: BMS, Janseen, Novartis, Lilly, Abbvie, Pfizer, and Galapagos. LD received consultation honoraria from Abbvie, Amgen, Astra-Zeneca, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, Swedish Orphan Biovitrium (SOBI), Takeda, and Vifor Pharmaceuticals. The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unrestricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Kiniksa, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI. CD has received consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos, Sparrow and Sanofi; grant support from AbbVie and Novartis. FF received consulting/speaker fee or research support from AbbVie, Amgen, Alfa-Sigma, Biogen, Bristol-Myers Squibb, Eli-Lilly, Galapagos, Janssen, Lilly, Novartis, and Pfizer. MGa received consulting and speaking fees from Abbvie, Pfizer, Novartis, Galapagos, Janssen, MSD, Lilly, Astra Zeneca. RGe received consulting and speaking fees from AbbVie, Alfasigma, BMS, MSD, Pfizer, Roche. MGo received consulting and speaking fees from AbbVie, Amgen, Lilly, Novartis, Pfizer. EG received consulting/speaker fee or research support from AbbVie, Eli-Lilly, Galapagos, Janssen, Novartis, and Pfizer. FI received honoraria or consulting fees from Abbvie, Eli-Lilly, Galapagos, Janssen, and Pfizer. BL received speaker fee or research support from AbbVie, Eli-Lilly, Janssen, Novartis, Pfizer, and Bristol. CM received speaker’s bureau or grants from Abbvie, Amgem, BMS, Galapagos, Lilly, Novartis, and Pfizer. RR received consulting/speaker fee or research support from AbbVie, Novartis, Janssen, Eli-Lilly, Amgen, and Pfizer. MR received advisory board honoraria, consultancy fees and/or speaker fees from Abbvie, BMS, Eli-Lilly, Galapagos, Menarini, Novartis, Pfizer, Sandoz, Theramex, UCB. MS received consulting/speaker fees or research support from Bristol-Myers Squibb, Janssen, Eli-Lilly, Pfizer, Galapagos, and Boehringer-Ingheleim. CSe received consulting/speaker fee or research support from AbbVie, Amgen, Alfa-Sigma, Biogen, Eli-Lilly, EUSA-Recordati, Galapagos, Janssen, Novartis, Pfizer, SOBI. AM received consulting/speaker fee from Abbvie, Eli-Lilly, Janssen, Novartis, and UCB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 D’Angelo, Atzeni, Benucci, Bianchi, Cantini, Caporali, Carlino, Caso, Cauli, Ciccia, D’Agostino, Dagna, Dejaco, Epis, Ferrucci, Franceschini, Fusaro, Gabini, Gerli, Giacomelli, Govoni, Gremese, Guggino, Iagnocco, Iannone, Laganà, Lubrano, Montecucco, Peluso, Ramonda, Rossini, Salvarani, Sebastiani, Sebastiani, Selmi, Tirri and Marchesoni.)

The liver has many significant functions, such as detoxification, the urea cycle, gluconeogenesis, and protein synthesis. Systemic diseases, hypoxia, infections, drugs, and toxins can easily affect the liver, which is extremely sensitive to injury. Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage. The primary regulator of intracellular pH in the liver is the Na + /H + exchanger (NHE). Physiologically, NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline. Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensin-converting enzyme 2. In severe cases of coronavirus disease 2019, high angi-otensin II levels may cause NHE overstimulation and lipid accumulation in the liver. NHE overstimulation can lead to hepatocyte death. NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver. Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation, the virus may indirectly cause an increase in fibrinogen and D-dimer levels. NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release. Also, NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver. Increasing NHE3 activity leads to Na + loading, which impairs the containment and fluidity of bile acid. NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid, thus triggering systemic damage. Unlike other tissues, tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine. Thus, increased luminal Na + leads to diarrhea and cytokine release. Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver., Competing Interests: Conflict-of-interest statement: MCC and EC declare that they have no conflict of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The release of cytokines and chemokines such as IL-1β, IL-2, IL-6, IL-7, IL-10, TNF-α, IFN-γ, CCL2, CCL3, and CXCL10 is increased in critically ill patients with COVID-19. Excessive cytokine release during COVID-19 is related to increased morbidity and mortality. Several mechanisms are put forward for cytokine release syndrome during COVID-19. Here we have mentioned novel pathways. SARS-CoV-2 increases angiotensin II levels by rendering ACE2 nonfunctional. Angiotensin II causes cytokine release via AT 1 and AT 2 receptors. Moreover, angiotensin II potently stimulates the Na+/H+ exchanger (NHE). It is a pump found in the membranes of many cells that pumps Na+ inward and H+ outward. NHE has nine isoforms. NHE1 is the most common isoform found in endothelial cells and many cells. NHE is involved in keeping the intracellular pH within physiological limits. When the intracellular pH is acidic, NHE is activated, bringing the intracellular pH to physiological levels, ending its activity. Sustained NHE activity is highly pathological and causes many problems. Prolonged NHE activation in COVID-19 may cause a decrease in intracellular pH through H+ ion accumulation in the extracellular area and subsequent redox reactions. The activation reduces the intracellular K+ concentration and leads to Na+ and Ca 2+ overload. Increased ROS can cause intense cytokine release by stimulating NF-κB and NLRP3 inflammasomes. Cytokines also cause overstimulation of NHE. As the intracellular pH decreases, SARS-CoV-2 rapidly infects new cells, increasing the viral load. This vicious circle increases morbidity and mortality in patients with COVID-19. On the other hand, SARS-CoV-2 interaction with NHE3 in intestinal tissue is different from other tissues. SARS-CoV-2 can trigger CRS via NHE3 inhibition by disrupting the intestinal microbiota. This review aimed to help develop new treatment models against SARS-CoV-2- induced CRS by revealing the possible effects of SARS-CoV-2 on the NHE., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)