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Background: Decision makers are increasingly tasked with reducing health care costs, but the public may be mistrustful of these efforts. Public deliberation helps gather input on these types of issues by convening a group of diverse individuals to learn about and discuss values-based dilemmas., Objective: To explore public perceptions of health care costs and how they intersect with medical mistrust., Design and Participants: This mixed-methods study analyzed data from a randomized controlled trial including four public deliberation groups (n = 96) and a control group (n = 348) comprising English-speaking adults aged 18 years and older. Data were collected in 2012 in four U.S. regions., Approach: We used data from four survey items to compare attitude shifts about costs among participants in deliberation groups to participants in the control group. We qualitatively analyzed deliberation transcripts to identify themes related to attitude shifts and to provide context for quantitative results about attitude shifts., Key Results: Deliberation participants were significantly more likely than control group participants to agree that doctors and patients should consider cost when making treatment decisions (β = 0.59; p < 0.01) and that people should consider the effect on group premiums when making treatment decisions (β = 0.48; p < 0.01). Qualitatively, participants mistrusted the health care system's profit motives (e.g., that systems prioritize making money over patient needs); however, after grappling with patient/doctor autonomy and learning about and examining their own views related to costs during the process of deliberation, they largely concluded that payers have the right to set some boundaries to curb costs., Conclusions: Individuals who are informed about costs may be receptive to boundaries that reduce societal health care costs, despite their mistrust of the health care system's profit motives, especially if decision makers communicate their rationale in a transparent manner. Future work should aim to develop transparent policies and practices that earn public trust.

Transforming growth factor (TGF-β) is associated with the progression of glioblastoma multiforme (GBM)-the most malignant of brain tumors. Since there is a structural homology between TGF-β and human chorionic gonadotropin (hCG) and as both TGF-β and hCG-β are known regulators of oxidative stress and survival responses in a variety of tumors, the role of TGF-β in the regulation of hCG-β and its consequences on redox modulation of glioblastoma cells was investigated. A heightened hCG-β level was observed in GBM tumors. TGF-β treatment increased hCG-β expression in glioma cell lines, and this heightened hCG-β was found to regulate redox homeostasis in TGF-β-treated glioma cells, as siRNA-mediated knockdown of hCG-β (i) elevated reactive oxygen species (ROS) generation, (ii) decreased thioredoxin Trx1 expression and thioredoxin reductase (TrxR) activity, and (iii) abrogated expression of TP53-induced glycolysis and apoptosis regulator (TIGAR). Silencing of hCG-β abrogated Smad2/3 levels, suggesting the existence of TGF-β-hCG-β cross-talk in glioma cells. siRNA-mediated inhibition of elevated TIGAR levels in TGF-β-treated glioma cells was accompanied by an increase in ROS levels. As a farnesyltransferase inhibitor, Manumycin is known to induce glioma cell apoptosis in a ROS-dependent manner, and we investigated whether Manumycin could induce apoptosis in TGF-β-treated cells with elevated hCG-β exhibiting ROS-scavenging property. Manumycin-induced apoptosis in TGF-β-treated cells was accompanied by elevated ROS levels and decreased expression of hCG-β, Trx1, Smad2/3, and TIGAR. These findings indicate the existence of a previously unknown TGF-β-hCG-β link that regulates redox homeostasis in glioma cells.

Purpose: This study aimed to investigate the frequency and characteristics of childhood-onset uveitis and evaluate the rate and specific causes of visual loss in this population., Methods: The data of 121 patients (179 eyes) with uveitis starting before ≤16 years and followed up for at least 6 months were retrospectively evaluated. Age at onset, sex, laterality, associated systemic disease, laboratory data, therapeutic strategies, surgeries, final visual acuity, and causes leading to visual acuity ≤20/200 were analyzed., Results: Childhood-onset uveitis made up 9.6% of our uveitis patients. The mean age at onset was 11.7 years (1-16) and the mean follow-up period was 38.5 months (6-148). Forty-three patients (35.5%) were female and 78 were male (64.5%). The disease was bilateral in 58 (47.9%) and unilateral in 63 (52.1%) patients. Uveitis was mostly (59.5%) seen between 12 and 16 years of age. Pars planitis, observed in 29 (24%) patients, was the leading cause of childhood-onset uveitis. Uveitis was idiopathic in 20 (16.5%) of patients. The most frequently associated diseases were Behcet's disease (BD) in 20 (16.5%), toxoplasmosis in 16 (13.2%), and juvenile idiopathic arthritis (JIA) in 8 (6.6%) patients. Anterior uveitis was observed in 38 (31.4%), intermediate uveitis in 31 (25.6%), posterior uveitis in 30 (24.8%), and panuveitis in 22 (18.2%) patients. The final visual acuity was ≤20/200 in 32/179 eyes (17.9%) of 27/121 patients (22.3%). The most often ocular complication leading to visual acuity ≤20/200 was optic atrophy and had been observed in 14 of 32 eyes (43.7%). Macular scar observed in five eyes (15.6%) was the second most often complication. Etiological distribution of 27 patients with visual acuity ≤20/200 was as follows: 12 had BD (44.4%), 5 had idiopathic uveitis (18.5%), 4 had pars planitis (14.8%), 3 had toxoplasmosis (11.1%), 2 had JIA (7.4%), and 1 had toxocara (3.7%)., Conclusions: Although rare, childhood-onset uveitis has a blinding potential and causes visual loss in up to 22.3% of the patients. In endemic areas like Turkey, BD may be the most common uveitis-associated systemic disease and the leading cause of visual loss in childhood uveitis as adulthood.

Background: Studies are exploring ways to improve medication adherence, with sentiment analysis (SA) being an underutilized innovation in pharmacy. This technique uses artificial intelligence (AI) and natural language processing to assess text for underlying feelings and emotions., Aim: This study aimed to evaluate the use of two SA models, Valence Aware Dictionary for Sentiment Reasoning (VADER) and Emotion English DistilRoBERTa-base (DistilRoBERTa), for the identification of patients' sentiments and emotions towards their pharmacotherapy., Method: A dataset containing 320,095 anonymized patients' reports of experiences with their medication was used. VADER assessed sentiment polarity on a scale from - 1 (negative) to + 1 (positive). DistilRoBERTa classified emotions into seven categories: anger, disgust, fear, joy, neutral, sadness, and surprise. Performance metrics for the models were obtained using the sklearn.metrics module of scikit-learn in Python., Results: VADER demonstrated an overall accuracy of 0.70. For negative sentiments, it achieved a precision of 0.68, recall of 0.80, and an F1-score of 0.73, while for positive sentiments, it had a precision of 0.73, recall of 0.59, and an F1-score of 0.65. The AUC for the ROC curve was 0.90. DistilRoBERTa analysis showed that higher ratings for medication effectiveness, ease of use, and satisfaction corresponded with more positive emotional responses. These results were consistent with VADER's sentiment analysis, confirming the reliability of both models., Conclusion: VADER and DistilRoBERTa effectively analyzed patients' sentiments towards pharmacotherapy, providing valuable information. These findings encourage studies of SA in clinical pharmacy practice, paving the way for more personalized and effective patient care strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: The existence of glioma stem cells (GSCs) in cancer is related to glioma radiotherapy resistance. In this research, the effect of protein arginine methyltransferase 1 (PRMT1) on the radiosensitivity of glioma stem cell (GSC)-like cells, as well as its underlying mechanism, was investigated., Methods: GSCs-like cells were analyzed and identified by flow cytometry. The self-renewal capability was evaluated by sphere-forming assay. The PRMT1 expression level in glioblastoma were analyzed using the Gene Expression Profiling Interactive Analysis database. The mRNA and protein were scrutinized by RT-qPCR and western blot, respectively. The radiosensitivity was evaluated by clonogenic survival assay. Ferroptosis was evaluated by detecting the levels of reactive oxygen species, malondialdehyde, Fe 2+ , glutathione, and 4-hydroxynonenal., Results: U87 and SHG44 cells with GSC-like phenotype (GSC-U87 and GSC-SHG44) displayed strong expression of CD133 and nestin versus the glioma cells. GSC-U87 and GSC-SHG44 possess the self-renewal capability. The level of PRMT1 was higher in glioblastoma tumor tissues than in the normal paracancer tissues. Knockdown of PRMT1 enhanced the radiotherapy sensitivity of GSCs-like cells, which was evidenced by reduced survival fraction in GSC-U87 and GSC-SHG44 underwent sh-PRMT1 transfection. But, this effect was attenuated by Fer-1 (a ferroptosis inhibitor) treatment, accompanied by the abatement of ferroptosis., Conclusion: PRMT1 promoted radiotherapy resistance in GSCs-like cells by inhibiting ferroptosis., (© 2024. The Author(s) under exclusive licence to Japan Radiological Society.)

Objectives: We aimed to present the demographic, clinical, laboratory, and treatment data of children with non-infectious uveitis and to evaluate the risk factors for the development of complications and the need for biological treatment., Method: Patients diagnosed with non-infectious uveitis in childhood and followed up for at least 1 year were included in the study. Demographic data, including age, gender, age at diagnosis, uveitis in first-degree relatives, and rheumatologic diseases, were obtained retrospectively from medical records. The presence of complications or the need for biologic therapy was considered a composite outcome suggesting severe disease., Results: The study included 123 patients (female: n = 59, 48%). The mean age at diagnosis was 14.89 ± 4.86 years. Uveitis was symptomatic in 104 patients (84.6%). Approximately one-quarter of the patients had at least one rheumatic disease (n = 35, 28.5%), the most common being juvenile idiopathic arthritis. Thirty-three patients (26.8%) had anti-nuclear antibody positivity. Biologic agents were needed in 60 patients (48.8%). Complications developed in 14 patients (11.4%). Early age at disease onset (aOR, 0.875; 95% C.I. 0.795-0.965, p = 0.007) and female gender (aOR, 2.99; 95% C.I. 1.439-6.248, p = 0.003) were significantly associated with the need for biologic treatment, while Behçet's disease (BD) was strongly associated with uveitis-related complications (aOR, 14.133; 95% C.I. 2.765-72.231, p = 0.001)., Conclusion: We suggest that among pediatric patients with non-infectious uveitis, females, those with an early age of disease onset, and those with BD need to be closely monitored due to a significantly increased risk of severe disease. Key Points • Limited data exist on the clinical course of non-infectious uveitis in children and the associated risk factors for severe disease. • Our study reveals that nearly a quarter of pediatric patients with non-infectious uveitis also have a rheumatic disease. • Among pediatric patients diagnosed with non-infectious uveitis, we observed an increased risk of severe disease in those with an earlier onset age, in female patients, and in those diagnosed with Behçet's disease., (© 2024. The Author(s).)

Purpose: The aim of this study was to evaluate the validity and reliability of the Turkish version of the Medication Practical Barriers to Adherence Questionnaire (MPRAQ-TR)., Methods: This is a validation study conducted between August 2022 and March 2023 in the ambulatory services of a secondary care private hospital located in Istanbul, Türkiye, among patients (18 years of age and older) with chronic diseases. After the Turkish translation and cultural adaptation of the MPRAQ, and a pilot think-aloud study, the following psychometric properties were assessed: internal consistency by calculating the Cronbach's alpha coefficient, 2-week test-retest reliability, convergent validity by calculating Spearman's rank correlation between the MPRAQ-TR and the Turkish version of Medication Adherence Report Scale (MARS), and predictive validity by evaluating the association between the MPRAQ-TR score and nonadherence to medications., Results: Among the 380 patients (response rate = 89.6%), 72.1% were nonadherent to their medications. The intraclass correlation coefficient was 0.99 for MPRAQ-TR scores (95% CI, 0.98-0.99; p < 0.001). The Cronbach's alpha of the MPRAQ-TR was 0.853. There was a moderate negative correlation between the scores on the MARS and the MPRAQ-TR (Spearman's rho = - 0.525; p < 0.01), supporting the convergent validity of the MPRAQ-TR. In the univariate analysis, the total score of MPRAQ-TR was associated with increased odds of nonadherence to medications (p < 0.01)., Conclusion: MPRAQ-TR shows good psychometric properties and can be used to evaluate the practical adherence barriers of patients with chronic diseases., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Japanese Encephalitis remains a significant global health concern, contributing to millions of deaths annually worldwide. Microglial cells, as key innate immune cells within the central nervous system (CNS), exhibit intricate cellular structures and possess molecular phenotypic plasticity, playing pivotal roles in immune responses during CNS viral infections. Particularly under viral inflammatory conditions, microglial cells orchestrate innate and adaptive immune responses to mitigate viral invasion and dampen inflammatory reactions. This review article comprehensively summarizes the pathophysiology of viral invasion into the CNS and the cellular interactions involved, elucidating the roles of various immune mediators, including pro-inflammatory cytokines, in neuroinflammation. Leveraging this knowledge, strategies for modulating inflammatory responses and attenuating hyperactivation of glial cells to mitigate viral replication within the brain are discussed. Furthermore, current chemotherapeutic and antiviral drugs are examined, elucidating their mechanisms of action against viral replication. This review aims to provide insights into therapeutic interventions for Japanese Encephalitis and related viral infections, ultimately contributing to improved outcomes for affected individuals., (© 2024. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Biologic agents are increasingly being used to treat adult patients with systemic lupus erythematosus (SLE). However, the available data on biologic agents' use in childhood-onset SLE (cSLE) remains limited. To collate available evidence related to the efficacy and safety of using biologic agents in cSLE. The study followed the PRISMA checklist for reporting the data and conducted a thorough search using PubMed, Cochrane Library, and Scopus from January 2005 to August 2023. Only articles meeting specific criteria were included, focusing on cSLE, the use of biologic agents, and having outcome measures at six- and 12-month follow-ups for safety and efficacy. Case reports were excluded, and four independent reviewers screened the articles for accuracy, with a fifth reviewer resolving any discrepancies that arose to achieve a consensus. The final selection included 18 studies with a total of 593 patients treated with biologic agents for severe and/ or refractory cSLE. The most common indication for using biologic agents was lupus nephritis. Rituximab was used in 12 studies, while belimumab was used in six studies. The studies evaluated the efficacy of biologic agents based on SLE disease activity scores, laboratory parameter improvements, and reduced corticosteroid dosage. Positive outcomes were reported, with improvements in renal, hematologic, and immunologic parameters along with mild adverse effects, mostly related to mild infections and infusion reactions. Belimumab and rituximab have shown promise as potential treatments for severe and refractory cSLE cases, leading to decreased disease activity and complete or partial remission in many patients with an acceptable safety profile. However, further research is needed to better understand their benefits and potential risks in these patients. Key Points • This review emphasizes the lack of sufficient randomized controlled trials exploring the use of biologics in childhood systemic lupus erythematosus (cSLE). • Treatment plans for cSLE are being derived from those used for adult systemic lupus erythematosus. • According to current evidence, belimumab and rituximab can be potential treatment options for refractory and severe cases of cSLE. • Additional studies are required to reach more definitive conclusions., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

The temporal and spatial pattern of microglia colonization of the nervous system implies a role in early stages of organ development including cell proliferation, differentiation, and neurovascularization. As microglia colonize and establish within the developing nervous system, they assume a neural-specific identity and contribute to key developmental events. Their association around blood vessels implicates them in development of the vascular system or vice versa. A similar association has been reported for neural cell proliferation and associated phenotypic shifts and for cell fate differentiation to neuronal or glial phenotypes. These processes are accomplished by phagocytic activities, cell-cell contact relationships, and secretion of various factors. This chapter will present data currently available from studies evaluating the dynamic and interactive nature of these processes throughout the progression of nervous system development., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Purpose: Endosome associated trafficking regulator 1 (ENTR1) is a novel endosomal protein, which can affect multiple cellular biological behavior by remodeling plasma membrane structures. However, little is known regarding its function and underlying mechanisms in glioblastoma multiforme., Methods: Expression profile and clinical signature were obtained from The Public Database of human tumor. Immunohistochemical staining and western blotting assays were used to measure ENTR1 expression level. Human primary GBM tumor cells and human GBM cell lines A172, U87 and U251 were used to clarify the precise role of ENTR1. CCK-8 assays, wound healing and transwell invasion assays were designed to investigate cell viability, invasion and migration of GBM cells, respectively. Underlying molecular mechanisms of ENTR1 were determined via RNA-seq analysis. Tumor formation assay was used to validate the influence of ENTR1 in vivo., Results: Compared with normal brain tissues, ENTR1 was highly expressed in gliomas and correlated with malignant grades of gliomas and poor overall survival time. The proliferation and invasion of GBM cells could be weaken and the sensitivity to temozolomide (TMZ) chemotherapy increased after knocking down ENTR1. Overexpression of ENTR1 could reverse this effect. RNA-seq analysis showed that tumor necrosis factor (TNF) signaling pathway might be a putative regulatory target of ENTR1. Tumor formation assay validated that ENTR1 was a significant factor in tumor growth., Conclusion: Our results indicated that ENTR1 played an important role in cell proliferation, invasion and chemotherapeutic sensitivity of GBM, suggesting that ENTR1 might be a novel prognostic marker and significant therapeutic target for GBM., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Studies have demonstrated bacterial inactivation by radiations at wavelengths between 400 and 500 nm emitted by low-power light sources. The phototoxic activity of these radiations could occur by oxidative damage in DNA and membrane proteins/lipids. However, some cellular mechanisms can reverse these damages in DNA, allowing the maintenance of genetic stability. Photoreactivation is among such mechanisms able to repair DNA damages induced by ultraviolet radiation, ranging from ultraviolet A to blue radiations. In this review, studies on the effects of violet and blue lights emitted by low-power LEDs on bacteria were accessed by PubMed, and discussed the repair of ultraviolet-induced DNA damage by photoreactivation mechanisms. Data from such studies suggested bacterial inactivation after exposure to violet (405 nm) and blue (425-460 nm) radiations emitted from LEDs. However, other studies showed bacterial photoreactivation induced by radiations at 348-440 nm. This process occurs by photolyase enzymes, which absorb photons at wavelengths and repair DNA damage. Although authors have reported bacterial inactivation after exposure to violet and blue radiations emitted from LEDs, pre-exposure to such radiations at low fluences could activate the photolyases, increasing resistance to DNA damage induced by ultraviolet radiation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

West Nile virus (WNV) has emerged as a significant cause of viral encephalitis in humans and horses. However, the pathogenesis of the West Nile encephalitis remains unclear. Microglia are activated by WNV infection, and the pathogenic involvement of their phenotypes is controversial. In this study, we examined the diversity of microglia phenotypes caused by WNV infection by assessing various microglia markers and identified disease-associated microglia in WNV-infected mouse brain tissue. Cells positive for general microglia markers such as Iba1, P2RY12, or TMEM119 were detected in the control and WNV-infected brain tissue. The morphology of the positive cells in brain tissue infected by WNV was different from that of control brain tissue, indicating that WNV infection induced activation of microglia. The activated microglia were classified into various phenotypes by investigation of specific marker expression. Among the activated microglia, disease-associated microglia that were positive for CD11c and weakly positive for TMEM119 were detected close to the WNV-infected cells. These results indicate that WNV infection induces activation of diverse microglia phenotypes and that disease-associated microglia may be associated with the pathogenicity of WNV infection in the mouse brain., (© 2023. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Kestanbol is one of the most important geothermal fields in NW Turkey. This study conducted the first-ever surveys over a 10 ha reach of the Kestanbol geothermal field using an unmanned aerial vehicle (UAV) equipped with visible (RGB) and thermal infrared (TIR) cameras. Low-altitude flights below 40 m above the ground were operated above the Kestanbol geothermal field. Approximately 3500 RGB and TIR images were captured using the UAV. We recorded high-resolution RGB and TIR data of the Kestanbol geothermal field and applied the structure from motion (SfM) algorithm to identify the distribution of geothermal springs and seeps. The Kestanbol geothermal field was monitored to create a georeferenced RGB orthophoto, RGB 3D surface model, thermal anomaly map, and digital surface model (DSM) of the area with centimeter-level accuracy. In the TIR orthophoto, the surface temperature in the geothermal field was found to be between 15 and 75 °C. All the thermal anomalies revealed by the survey were verified by field observations. The geothermal springs and seeps were parallel to the NE-SW regional tectonic trends. The results of this study demonstrate an effective technique for monitoring and assessing geothermal water using UAV-based RGB and TIR imaging and provide an accurate basis for geothermal development projects. RGB and TIR imaging using UAVs are considered promising methods for improving the assessment of the effects of geothermal water on the environment., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In this study, a new enzyme-free glucose sensor was constructed using the transition metal-based composite material. The synthesis of ZIF-67 entailed the addition of NiO with high catalytic performance. Two-dimensional NiO/Co 3 O 4 @C heterojunctions were obtained via pyrolysis of NiO@ZIF-67 in the air at a temperature of 500 ℃. The enzyme-free glucose sensor Nafion/NiO/Co 3 O 4 @C/GCE was constructed by modifying NiO/Co 3 O 4 @C on a glassy carbon electrode (GCE). The performance of the modified electrode was tested via cyclic voltammetry (CV) and a time-current curve (i-t curve). The linear ranges of the modified electrode were 5 -1000 μM and 1.0- 4.0 mM with sensitivities of 690 and 215.4 μA mM -1  cm -2 , respectively. The detection limit was 2.28 μΜ (S/N = 3). The recoveries were in the range of 98.9-99.7% during the detection of real samples. The prepared sensor Nafion/NiO/Co 3 O 4 @C/GCE showed excellent electrocatalytic properties with superb reproducibility, stability and anti-interference capability. The sensor has been successfully utilized to determine glucose in real serum samples., (© 2022. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

This study aimed to explore the role of IL-10 in the pathogenesis of HIV/AIDS patients with cryptococcal meningitis (CM).Patients were assigned into 4 groups (n = 40/group): group A (HIV/AIDS with CM), group B (HIV/AIDS with tuberculosis), group C (HIV/AIDS), and group D (CM). The levels of IL-10 and associated indicators were measured and the correlations were analyzed by Pearson correlation and partial correlation method. In plasma and cerebrospinal fluid (CSF), no significant difference was observed on IL-10 level between group A and other groups (P > 0.050). R values for IL-10 and relevant indicators in blood were as follows (P < 0.050): group A, IFN-γ (-0.377), IL-12 (0.743), IL-4 (0.881), and IL-6 (0.843); group B, IL-12 (0.740), IL-4 (0.573), and IL-6 (0.900); group C, IL-12 (0.402) and IL-4 (0.896); group D, IL-12 (0.575), IL-4 (0.852), and CD8 (0.325). R values for IL-10 and related indicators in CSF were as follows (P < 0.050): group A, TNF-α (0.664), IL-4 (0.852), white blood cells (WBCs, 0.321) and total protein (TP, 0.330); group B, TNF-α (0.566), IL-4 (0.702), and lactate dehydrogenase (LDH, 0.382); group D, IFN-γ (0.807) and IL-4 (0.441). IL-10 level was positively correlated with IL-4, IL-6, IL-12, TNF-α, WBC, and TP in blood or CSF, and negatively correlated with IFN-γ in blood, suggesting that IL-10 affected both pro-inflammatory and anti-inflammatory activities in the pathogenesis of HIV/AIDS with CM., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

RNA virus infections have been a leading cause of pandemics. Aided by global warming and increased connectivity, their threat is likely to increase over time. The flaviviruses are one such RNA virus family, and its prototypes such as the Japanese encephalitis virus (JEV), Dengue virus, Zika virus, West Nile virus, etc., pose a significant health burden on several endemic countries. All viruses start off their life cycle with an infected cell, wherein a series of events are set in motion as the virus and host battle for autonomy. With their remarkable capacity to hijack cellular systems and, subvert/escape defence pathways, viruses are able to establish infection and disseminate in the body, causing disease. Using this strategy, JEV replicates and spreads through several cell types such as epithelial cells, fibroblasts, monocytes and macrophages, and ultimately breaches the blood-brain barrier to infect neurons and microglia. The neurotropic nature of JEV, its high burden on the paediatric population, and its lack of any specific antivirals/treatment strategies emphasise the need for biomedical research-driven solutions. Here, we highlight the latest research developments on Japanese encephalitis virus-infected cells and discuss how these can aid in the development of future therapies., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Japanese Encephalitis Virus (JEV) is a neurotropic virus that invades Central Nervous System (CNS) and causes severe neuroinflammation. Given the abundance and the position of astrocytes in the CNS, we speculate that they might play a critical role in the process of neuroinflammation. Unfortunately, the role of astrocytes in JEV-mediated neuroinflammation has long been understated. In this study, we have attempted to assess the role of astrocyte-mediated neuroinflammation upon JEV infection. Mouse model of JEV infection, generated by intraperitoneal injection, showed severe reactive astrogliosis. To further address our hypothesis, we employed immortalized astrocytic cell line (in vitro) and primary astrocyte-enriched culture (ex vivo) as experimental models. JEV infection in the astrocytes induces proinflammatory cytokines like MCP1/CCL2 and IL6 in both ex vivo and in vitro cultures as observed from the cytometric bead array analysis. A significantly altered cytokine profile was observed using PCR analysis in in vitro and ex vivo models upon infection, with respect to control, validating our previous results. We also show that there exists a major inconsistency in the viral replication kinetics, wherein the cell line showed a robust rate of replication whereas the primary astrocyte-enriched culture showed negligibly low number of plaques, underlining the importance of the selection of appropriate experimental model system. In conclusion, we claim that astrocytes significantly contribute to JEV-mediated neuroinflammation, despite not being a CNS immune cell., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Two new cyclometalated Ru(II)-β-carboline complexes, [Ru(dmb) 2 (Cl-Ph-βC)](PF 6 ) (dmb = 4,4'-dimethyl-2,2'-bipyridine; Cl-Ph-βC = Cl-phenyl-9H-pyrido[3,4-b]indole; RuβC-3) and [Ru(bpy) 2 (Cl-Ph-βC)](PF 6 ) (bpy = 2,2'-bipyridine; RuβC-4) were synthesized and characterized. The Ru(II) complexes display high cytotoxicity against HeLa cells, the stabilized human cervical cancer cell, with IC 50 values of 3.2 ± 0.4 μM (RuβC-3) and 4.1 ± 0.6 μM (RuβC-4), which were considerably lower than that of non-cyclometalated Ru(II)-β-carboline complex [Ru(bpy) 2 (1-Py-βC)] (PF 6 ) 2 (61.2 ± 3.9 μM) by 19- and 15-folds, respectively. The mechanism studies indicated that both Ru(II) complexes could significantly inhibit HeLa cell migration and invasion, and effectively induce G0/G1 cell cycle arrest. The new Ru(II) complexes could also trigger apoptosis through activating caspase-3 and poly (ADP-ribose) polymerase (PARP), increasing the Bax/Bcl-2 ratio, enhancing reactive oxygen species (ROS) generation, decreasing mitochondrial membrane potential (MMP), and inducing cytochrome c release from mitochondria. Further research revealed that RuβC-3 could deactivate the ERK/Akt signaling pathway thus inhibiting HeLa cell invasion and migration, and inducing apoptosis. In addition, RuβC-3-induced apoptosis in HeLa cells was closely associated with the increase of intracellular ROS levels, which may act as upstream factors to regulate ERK and Akt pathways. More importantly, RuβC-3 exhibited low toxicity on both normal BEAS-2B cells in vitro and zebrafish embryos in vivo. Consequently, the developed Ru(II) complexes have great potential on developing novel low-toxic anticancer drugs., (© 2021. Society for Biological Inorganic Chemistry (SBIC).)

Multiple Sclerosis (MS) is a progressive neurodegenerative disease with clinical signs of neuroinflammation and the central nervous system's demyelination. Numerous studies have identified the role of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) overexpression and the low level of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in MS pathogenesis. Guggulsterone (GST), an active component derived from 'Commiphora Mukul,' has been used to treat various diseases. Traditional uses indicate that GST is a suitable agent for anti-inflammatory action. Therefore, we assessed the therapeutic potential of GST (30 and 60 mg/kg) in ethidium bromide (EB) induced demyelination in experimental rats and investigated the molecular mechanism by modulating the JAK/STAT and PPAR-γ receptor signaling. Wistar rats were randomly divided into six groups (n = 6). EB (0.1%/10 μl) was injected selectively in the intracerebropeduncle (ICP) region for seven days to cause MS-like manifestations. The present study reveals that long-term administration of GST for 28 days has a neuroprotective effect by improving behavioral deficits (spatial cognition memory, grip, and motor coordination) associated with lower STAT-3 levels. While elevating PPAR-γ and myelin basic protein levels in rat brains are consistent with the functioning of both signaling pathways. Also, GST modulates the neurotransmitter level by increasing Ach, dopamine, serotonin and by reducing glutamate. Moreover, GST ameliorates inflammatory cytokines (TNF, IL-1β), and oxidative stress markers (AchE, SOD, catalase, MDA, GSH, nitrite). In addition, GST prevented apoptosis, as demonstrated by the reduction of caspase-3 and Bax. Simultaneously, Bcl-2 elevation and the restoration of gross morphology alterations are also recovered by long-term GST treatment. Therefore, it can be concluded that GST may be a potential alternative drug candidate for MS-related motor neuron dysfunctions.

Tick-borne encephalitis (TBE) is a relatively severe and clinically variable central nervous system (CNS) disease with a significant contribution of a secondary immunopathology. Monocytes/macrophages play an important role in the CNS inflammation, but their pathogenetic role and migration mechanisms in flavivirus encephalitis in humans are not well known. We have retrospectively analyzed blood and cerebrospinal fluid (CSF) monocyte counts in 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114), or meningoencephalomyelitis (n = 16), searching for associations with other laboratory parameters, clinical presentation, and severity. We have measured concentrations of selected monocytes-attracting chemokines (CCL7, CXCL12, CCL20) in serum and CSF of the prospectively recruited patients with TBE (n = 15), with non-TBE aseptic meningitis (n = 6) and in non-infected controls (n = 8). The data were analyzed with non-parametric tests, p < 0.05 considered significant. Monocyte CSF count correlated with other CSF inflammatory parameters, but not with the peripheral monocytosis, consistent with an active recruitment into CNS. The monocyte count did not correlate with a clinical presentation. The median CSF concentration of CCL7 and CXCL12 was increased in TBE, and that of CCL7 was higher in TBE than in non-TBE meningitis. The comparison of serum and CSF concentrations pointed to the intrathecal synthesis of CCL7 and CXCL12, but with no evident concentration gradients toward CSF. In conclusion, the monocytes are recruited into the intrathecal compartment in concert with other leukocyte populations in TBE. CCL7 and CXCL12 have been found upregulated intrathecally but are not likely to be the main monocyte chemoattractants.

Excitation energy transfer (EET) as a fundamental photophysical process is well-explored for developing functional materials with tunable photophysical properties. Compared to traditional fluorophores, aggregation-induced emission luminogens (AIEgens) exhibit unique advantages for building EET systems, especially serving as energy donors, due to their outstanding photophysical properties such as bright fluorescence in aggregation state, broad absorption and emission spectra, large Stokes shift, and high photobleaching resistance. In addition, the photophysical properties of AIEgens can be modulated by energy transfer for improved luminescence performance. Therefore, a variety of EET systems based on AIEgens have been constructed and their applications in different areas have been explored. In this review, we summarize recent progress in the design strategy of AIE-based energy transfer systems for light-harvesting, fluorescent probes and theranostic systems, with an emphasis on design strategies to achieve desirable properties. The limitations, challenges and future opportunities of AIE-EET systems are briefly outlined. Design strategies and applications (light-harvesting, fluorescent probe and theranostics) of AIEgen-based excitation energy systems are discussed in this review.

Arsenic (As) exposure is associated with adverse health outcomes to the living organisms. In the present study, the hepato-protective ability of thymoquinone (TQ), the active principle of Nigella sativa seed, or ebselen (Eb), an organoselenium compound, against As intoxication in female rats was investigated. For this purpose, animals were allocated randomly into control, As (20 mg/kg), TQ (10 mg/kg), Eb (5 mg/kg), As+TQ, and As+Eb groups that were orally administered for 28 consecutive days. Arsenic exposure resulted in hepatic oxidative damage which was evidenced by marked decreases in antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH)) concomitant with high malondialdehyde (MDA) level. Furthermore, As toxicity induced significant elevations in liver accumulation of As, serum hepatic indices (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (TB)), and apoptotic marker (B cell lymphoma 2(Bcl2), Bcl-2-associated X protein (Bax), and caspase 3) levels. Additionally, notable increments in hepatic fibrotic markers (epidermal growth factor (EFG) and transforming growth factor beta 1 (TGF-β1)) associated with high nitric oxide, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and myeloperoxidase (MPO) levels were noticed following As intoxication. Biochemical findings were well-supported by hepatic histopathological screening. The co-treatment of As-exposed rats with TQ or Eb considerably improved liver function and antioxidant status together with lessened hepatic As content, inflammation, apoptosis, and fibrosis. The overall outcomes demonstrated that TQ or Eb ameliorates As-induced liver injury through their favorable antioxidant, anti-inflammatory, anti-apoptotic, and fibrolytic properties.

While family engagement at the individual level of health care, such as families partnering with providers in decision-making about health care for an individual child has been well studied, family engagement in systems-level activities (e.g., participation in advisory and other decision-making groups, or creation and revision of policies) that impact the health services families and children receive has not. This note from the field presents a framework that describes the information and supports that help families partner with professionals and contribute to systems-level activities. Without attention to these components of family engagement, family presence and participation may be only token. We engaged an expert Family/Professional Workgroup whose members represented key constituencies and diverse geography, race/ethnicity, and areas of expertise; conducted a review of peer-reviewed publications and grey literature; and conducted a series of key informant interviews to identify best practices for supporting meaningful family engagement at the systems level. Based on an analysis of the findings, the authors identified four action-oriented domains of family engagement and key criteria that support and strengthen meaningful family engagement in systems-level initiatives. Child- and family-serving serving organizations can use this Family Engagement in Systems framework to support meaningful family engagement in the design of policies, practices, services, supports, quality improvement projects, research, and other systems-level activities., Author(s): Beth Dworetzky [sup.1] , Clarissa G. Hoover [sup.1] , Deborah Klein Walker [sup.2] Author Affiliations: (1) Family Voices, , 561 Virginia Rd, Bldg. 4, Suite 300, 01742, Concord, MA, [...]

Background CD151 is a cell-surface molecule of the tetraspanin family. Its lateral interaction with laminin-binding integrin É3[beta]1 is important for podocyte adhesion to the glomerular basement membrane (GBM). Deletion of Cd151 in mice induces glomerular dysfunction, with proteinuria and associated focal glomerulosclerosis, disorganisation of GBM and tubular cystic dilation. Despite this, CD151 is not routinely screened for in patients with nephrotic-range proteinuria. We aimed to better understand the relevance of CD151 in human kidney disease. Methods Next-generation sequencing (NGS) was used to detect the variant in CD151. Electron and light microscopy were used to visualise the filtration barrier in the patient kidney biopsy, and immunoreactivity of patient red blood cells to anti-CD151/MER2 antibodies was performed. Further validation of the CD151 variant as disease-causing was performed in zebrafish using CRISPR-Cas9. Results We report a young child with nail dystrophy and persistent urinary tract infections who was incidentally found to have nephrotic-range proteinuria. Through targeted NGS, a novel, homozygous truncating variant was identified in CD151, a gene rarely reported in patients with nephrotic syndrome. Electron microscopy imaging of patient kidney tissue showed thickening of GBM and podocyte effacement. Immunofluorescence of patient kidney tissue demonstrated that CD151 was significantly reduced, and we did not detect immunoreactivity to CD151/MER2 on patient red blood cells. CRISPR-Cas9 depletion of cd151 in zebrafish caused proteinuria, which was rescued by injection of wild-type CD151 mRNA, but not CD151 mRNA containing the variant sequence. Conclusions Our results indicate that a novel variant in CD151 is associated with nephrotic-range proteinuria and microscopic haematuria and provides further evidence for a role of CD151 in glomerular disease. Our work highlights a functional testing pipeline for future analysis of patient genetic variants. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Richard W. Naylor [sup.1] , Elizabeth Watson [sup.2] , Samantha Williamson [sup.3] , Rebecca Preston [sup.1] , J Bernard Davenport [sup.1] , Nicole Thornton [sup.4] , Martin Lowe [sup.5] [...]

We present a new experimental dataset for reaction experiments between natural amphibole-clinopyroxene metasomes (hornblendite) and synthetic lherzolite that produced Na-rich alkaline melts. Experiments were conducted at 1, 3 and 4 GPa and 1000-1300 °C. The generated melts range from foidite over basanite to phonotephrite. At 1 GPa between 1000 and 1100 °C amphibole decompression-breakdown products generate a phonotephritic melt. Among the breakdown components rhönite was found to be stable up to 1100 °C and 1 GPa. At 3 and 4 GPa the melt compositions are affected by phlogopite melting and shift to more foiditic compositions. We find that the melting of hornblendites and the reaction of the melt with the lherzolite produce wehrlitic residues with different olivine/clinopyroxene ratios. Wehrlite formation does not always require separate metasomatic processes but can be a direct by-product of alkaline volcanism. We applied a metasome melting model to the magmas of the Kula volcanic province, Turkey, and show that at 1 GPa basanite melts and phonotephrite melts cover the whole range of known Kula lava compositions. The Kula lava compositional trend can be therefore generated by basanite-phonotephrite melt mixing. A comparison of high-pressure (3-4 GPa) melts with natural nephelinite data shows overlap with many major, minor, and trace elements but differences in SiO.sub.2, FeO, and TiO.sub.2 argue that the natural nephelinite data do not represent primary metasome melts., Author(s): Tobias Grützner [sup.1] [sup.2] [sup.3], Dejan Prelevic [sup.4] [sup.5], Jasper Berndt [sup.3], Stephan Klemme [sup.3] Author Affiliations: (1) https://ror.org/04cvxnb49, grid.7839.5, 0000 0004 1936 9721, Institut Für Geowissenschaften, Goethe-Universität Frankfurt, [...]