Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

The Primary Afferents of Trigeminal Autonomic Reflex May not be Nociceptive: A Case Report.

Autonomic symptoms have been long noticed coming along with pain in the head, e.g. Trigeminal Neuralgia, trigeminal autonomic cephalalgias. The symptoms show up during pain attacks, so they are assumed to be activated by the nociceptive afferents of the trigeminal nerve. Here, we present a case with hypersalivation as the complication after percutaneous balloon compression for trigeminal neuralgia, although the patient was pain-free after the treatment. A 71-year-old female with excessive salivation on the affected side after percutaneous balloon compression is described. The patient underwent microvascular decompression several years ago, and both the microvascular decompression and the preoperative imaging examination confirmed that there was no offending vessel at the root entry zone of the trigeminal nerve. After the percutaneous balloon compression, the patient was free of pain, but the autonomic symptoms (hypersalivation) still showed up. The autonomic symptoms which usually came along with pain presented solely as post-percutaneous balloon compression complication in the case. Contrary to popular belief, for the patient who was pain-free after percutaneous balloon compression, the transiently overactivated nerve fibers that led to hypersalivation were not nociceptive afferents of the trigeminal nerve.

Corrigendum: Clinical value of serum complement component 1q levels in the prognostic analysis of aneurysmal subarachnoid hemorrhage: a prospective cohort study.

[This corrects the article DOI: 10.3389/fneur.2024.1341731.].

Diagnostic and Predictive Efficacy of Synovial Fluid Versus Serum C-Reactive Protein Levels for Periprosthetic Joint Infection and Reimplantation Success.

BACKGROUND: A 2-stage exchange revision for periprosthetic joint infection (PJI) is associated with major risks for reinfection. Although serum markers are frequently used for diagnosis, their effectiveness remains debatable. Synovial fluid markers may offer a more accurate diagnosis of PJI; however, the importance of these biomarkers, notably synovial fluid C-reactive protein (syCRP), remains controversial, particularly in the context of reimplantation. The present study aimed to clarify these diagnostic uncertainties by evaluating the diagnostic efficacy of syCRP versus serum CRP (seCRP) levels in the context of PJI and recurring or persisting infections before reimplantation. METHODS: A total of 186 patients were enrolled and divided into 2 groups: aseptic revision (n = 112) and PJI revision (n = 74). Of the PJI group, 65 were categorized as success and 9 as failure, based on the presence of recurrent or persistent infection before reimplantation. The syCRP and seCRP levels and their changes were assessed preoperatively and in the first-stage and second-stage revisions. Additionally, receiver operating characteristic (ROC) curves and area under the ROC curves (AUCs) were analyzed. RESULTS: Both seCRP and syCRP levels were significantly elevated in the PJI group compared with the aseptic group (P < .001). The ROC curve analysis highlighted the enhanced diagnostic accuracy of syCRP for PJI, with an AUC of 0.93 versus 0.80 for seCRP. Furthermore, syCRP proved to be more reliable in predicting reimplantation success, exhibiting an AUC of 0.86 versus 0.63 for seCRP. In evaluating trends in CRP levels to determine reimplantation timing, changes in syCRP levels demonstrated superior diagnostic utility, exhibiting an AUC of 0.79 versus 0.63 for changes in seCRP levels. CONCLUSIONS: In assessing PJI and infections before reimplantation, syCRP may offer enhanced accuracy compared with seCRP. Nevertheless, variations in both syCRP and seCRP levels did not consistently predict the outcome of reimplantation.

A GITRL-mTORC1-GM-CSF Positive Loop Promotes Pathogenic Th17 Response in Primary Sjögren Syndrome.

OBJECTIVE: Glucocorticoid-induced tumor necrosis factor receptor superfamily-related protein (GITR), with its ligand (GITRL), plays an important role in CD4+ T cell-mediated autoimmunity. This study aimed to investigate the underlying mechanisms of GITRL in primary Sjögren syndrome (pSS). METHODS: Patients with pSS and healthy controls were recruited. Serum GITRL and Th17-related cytokines were determined. RNA sequencing was performed to decipher key signal pathways. Nonobese diabetes (NOD) mice were adopted as experimental Sjögren models and recombinant adeno-associated virus (rAAV) transduction was conducted to verify the therapeutic potentials of targeting GITRL in vivo. RESULTS: Serum GITRL was significantly higher in patients with pSS and showed a positive correlation with leukopenia, thrombocytopenia, autoantibodies, lung involvement, and disease activity. Serum GITRL was correlated with Th17-related cytokines. GITRL promoted the expansion of Th17 and Th17.1 cells. Expansion of granulocyte-macrophage colony-stimulating factor positive (GM-CSF+) CD4+ T cells induced by GITRL could be inhibited by blockade of GITRL. Moreover, GM-CSF could stimulate GITRL expression on monocytes. RNA sequencing revealed mammalian target of rapamycin complexes 1 (mTORC1) might be the key modulator. The increased phosphorylation of S6 and STAT3 and the expansion of Th17 and Th17.1 cells induced by GITRL were effectively inhibited by rapamycin, suggesting a GITRL-mTORC1-GM-CSF positive loop in pathogenic Th17 response in pSS. Administration of an rAAV vector expressing short hairpin RNA targeting GITRL alleviated disease progression in NOD mice. CONCLUSION: Our results identified the pathogenic role of GITRL in exacerbating disease activity and promoting pathogenic Th17 response in pSS through a GITRL-mTORC1-GM-CSF loop. These findings suggest GITRL might be a promising therapeutic target in the treatment of pSS.

Clinical value of serum complement component 1q levels in the prognostic analysis of aneurysmal subarachnoid hemorrhage: a prospective cohort study.

Objective: To analyze the relationship between serum complement component 1q (C1q) levels and functional prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH), and to reveal its clinical value. Methods: In this prospective cohort study, we collected clinical data of aSAH patients admitted to the Department of Neurosurgery, Hangzhou First People's Hospital from January 2020 to October 2022. Parameters such as serum C1q levels, Hunt-Hess grade, modified Fisher grade, and the modified Rankin scale (mRS) at 3 months were included for evaluation. Patients were grouped based on the occurrence of delayed cerebral ischemia (DCI). Spearman rank correlation test and Kruskal-Wallis rank sum test were used to analyze the correlation between serum C1q levels, disease severity, and prognosis. Potential risk factors affecting prognosis and the occurrence of DCI were screened through Independent sample t-test or Mann-Whitney U test. Variables with significant differences (p < 0.05) were incorporated into a logistic regression model to identify independent risk factors affecting prognosis and DCI occurrence. Serum C1q levels were plotted as a ROC curve for predicting prognosis and DCI, and the area under the curve was calculated. Results: A total of 107 aSAH patients were analyzed. Serum C1q levels positively correlated with Hunt-Hess grade, modified Fisher grade and mRS (all p < 0.001). Significant differences were observed in C1q levels among different Hunt-Hess grade, mFisher grade and mRS (all p < 0.001). Notably, higher serum C1q levels were seen in the poor prognosis group and DCI group, and correlated with worse prognosis (OR = 36.927, 95%CI 2.003-680.711, p = 0.015), and an increased risk for DCI (OR = 17.334, 95%CI 1.161-258.859, p = 0.039). ROC analysis revealed the significant discriminative power of serum C1q levels for poor prognosis (AUC 0.781; 95%CI 0.673-0.888; p < 0.001) and DCI occurrence (AUC 0.763; 95%CI 0.637-0.888; p < 0.001). Higher C1q levels independently predicted a poor prognosis and DCI with equivalent predictive abilities to Hunt-Hess grade and modified Fisher grade (both p < 0.05). Conclusion: High levels of C1q in the blood is an independent risk factor for poor prognosis and the development of DCI in patients with aSAH. This can more objectively and accurately predict functional outcomes and the incidence of DCI. C1q may have a significant role in the mechanism behind DCI after aSAH.

Electrochemical sensor for hydrogen sulfide detection using electrocatalysis-assisted amplification and chemical reaction-mediated signal enhancement.

An ultrasensitive electrochemical biosensing platform has been designed by combining electrocatalysis-assisted H2S amplification with a chemical reaction-mediated electrochemical signal-boosted system for H2S detection based on Cu-Mn(OH)2 hexagonal nanorings. The signal amplification is initiated by an electrocatalysis reaction that can grasp specific H2S substrates and further highly amplify electrochemical signals. Then, the unique chemical reaction is powered by copper ion and generates a large amount of electroactive CuxS products on the electrode surface, thus achieving the multiple amplification of H2S detection. Finally, the Cu-Mn(OH)2 loaded with plenty of electroactive CuxS can be captured on the electrode for further improving the electrochemical signal thus obtaining ultra-high sensitive determination of H2S. The established electrochemical biosensing platform displays a wide analytical range of 0.1 µM to 265 µM with a low detection limit of 0.096 µM. The satisfactory selectivity allows the electrochemical sensor to distinguish H2S from other interfering substances without any complicated pretreatment, even in complex tumor cell samples. Thus, our designed electrocatalysis-assisted amplification strategy offers a powerful analysis toolkit for the early determination of H2S-related disease in clinical diagnosis.

Superior Mechanical Properties of Invar36 Alloy Lattices Structures Manufactured by Laser Powder Bed Fusion.

Invar36 alloy is a low expansion alloy, and the triply periodic minimal surfaces (TPMS) structures have excellent lightweight, high energy absorption capacity and superior thermal and acoustic insulation properties. It is, however, difficult to manufacture by traditional processing methods. Laser powder bed fusion (LPBF) as a metal additive manufacturing technology, is extremely advantageous for forming complex lattice structures. In this study, five different TPMS cell structures, Gyroid (G), Diamond (D), Schwarz-P (P), Lidinoid (L), and Neovius (N) with Invar36 alloy as the material, were prepared using the LPBF process. The deformation behavior, mechanical properties, and energy absorption efficiency of these structures under different load directions were studied, and the effects and mechanisms of structure design, wall thickness, and load direction were further investigated. The results show that except for the P cell structure, which collapsed layer by layer, the other four TPMS cell structures all exhibited uniform plastic collapse. The G and D cell structures had excellent mechanical properties, and the energy absorption efficiency could reach more than 80%. In addition, it was found that the wall thickness could adjust the apparent density, relative platform stress, relative stiffness, energy absorption, energy absorption efficiency, and deformation behavior of the structure. Printed TPMS cell structures have better mechanical properties in the horizontal direction due to intrinsic printing process and structural design.

Trigeminal neuralgia caused by vertebrobasilar dolichoectasia: efficacy of stepwise decompression technique.

OBJECTIVE: To explore and analyze the clinical efficacy of a stepwise decompression technique in the treatment of trigeminal neuralgia (TN) caused by vertebrobasilar dolichoectasia (VBD). METHODS: A total of 918 patients with TN admitted to our hospital from June 2015 to May 2020 were divided into the VBD group (n = 61) and the conventional group (n = 857). The VBD group underwent stepwise decompression, while the conventional group received traditional microvascular decompression (MVD) surgery. Patients associated with the VBD were divided into direct compression (n = 14) and indirect compression group (n = 47) who had compression by other vessels in the presence of the VBD. Thereafter, the clinical data, intraoperative findings, efficacy, and complications were analyzed. RESULTS: The curative ratio, efficacy, and recurrence rate for the VBD and conventional group were 83.6% and 89.6%, 93.4% and 95.3%, and 8.2% and 5.3%, respectively. The curative ratio, efficacy, and recurrence rate for the direct compression and indirect compression group were 85.7% and 83.0%, 92.9% and 93.6%, and 7.1% and 8.5%, separately. There were no significant differences in the curative ratio, efficacy, recurrence rate, and the incidence of complications between the two series (P > 0.05). CONCLUSION: For TN caused by VBD, stepwise decompression not only reduces the direct compression of the trigeminal nerve by VBA but also allows identification and decompression of the actual vessels responsible for the compression. It has a good curative ratio, efficacy, and long-term pain relief rate, and it does not significantly increase the incidences of complications after surgery.

Transcriptome changes for Nile tilapia (Oreochromis niloticus) in response to alkalinity stress.

Nile tilapia is an important economic fish in the world because of its fast growth, high meat yield and strong adaptability. It is more adaptable to high alkalinity than common freshwater fish and provides valuable material for developing alkaline-tolerant strains and understanding the adaptation mechanism of fish to extreme environmental stress. In this study, we employed high throughput RNA sequencing to reveal the tissues (gill, kidney and liver) transcriptome differences of O. niloticus at different carbonate alkalinities (FW, AW40 and AW60). A total of 1,369,381,790 raw reads were obtained, including 496,441,232 reads in FW group, 437,907,696 reads in AW40 and 435,032,862 reads in AW60. In addition, 484,555,626 reads in gill, 451,618,224 reads in kidney and 433,207,940 reads in liver. A large number of stress-regulated changes were detected comprehensively. We focused on 3 significantly change pathways (steroid biosynthesis, drug metabolism and protein digestion/absorption) and 17 DEGs (HMG-CoA reductase, UDP-glucuronosyltransferase, and carbonic anhydrase etc.) which were shared among compared groups (AW40 vs FW, AW60 vs FW, AW40 vs 60 AW60) in gill, kidney and liver, respectively. These pathways/genes are sensitive to alkalinity stress and crucial to the alkalinity adaptation of tilapia. Overall, we found a large number of candidate genes, which encode important regulators of stress tolerance and ultimately contribute to future alkaline-tolerant fish breeding. Among these genes, lipid metabolism (involving signal transduction), detoxification and immune related genes are more prominent to the response and adaptability of fish to alkalinity stress.

Prevalence of Depression and Anxiety Symptoms of High School Students in Shandong Province During the COVID-19 Epidemic.

Background: The coronavirus disease 2019 (covid-19) has brought physical risks as well as psychological challenges to the whole world. High school students are a special group suffering from both the academic pressure and the threat of the epidemic. The present study aims to conduct an online survey to investigate the psychological status of high school students in Shandong Province. Methods: Using a web-based cross-sectional survey, data was collected from 1,018 voluntary high school students assessed with demographic information, the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7) and a self-designed online-study effect survey. Correlation analysis was performed to explore the relationships between depression symptoms, anxiety symptoms, and study effect. Result: The prevalence of depressive symptoms, anxiety symptoms, and a combination of depressive and anxiety symptoms was 52.4, 31.4, and 26.8%, respectively, among high school students in Shandong Province during the COVID-19 epidemic. And from moderate to severe severity level, the rates of depressive symptoms and anxious symptoms were 17.6 and 4.6%. Female students exhibited a higher rate and severity of mental symptoms than male, and grade one senior high school students got a higher rate and severity of mental symptoms than the other two grades. Nearly half of the students were not satisfied with their online-study effect. The PHQ-9 score had a strong positive correlation with the GAD-7 score. Both the PHQ-9 score the GAD-7 score had a negative correlation with the study-effect survey score. Conclusion: Quite a number of high school students suffered from depression and anxiety symptoms during the COVID-19 epidemic. Sufficient attentions should be paid, and necessary supports should be provided, to protect the mental health of this special group.

Anti-GAPDH Autoantibody Is Associated with Increased Disease Activity and Intracranial Pressure in Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an immune disease characterized by multiorgan involvement. Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most devastating complications of SLE, which lacks efficient diagnostic biomarkers. The recent studies on the anti-GAPDH autoantibodies suggested its potential pathogenic roles in NPSLE. However, the clinical relevance of the anti-GAPDH autoantibodies in patients with SLE is still elusive. In this study, we sought to determine the serum levels of the anti-GAPDH autoantibodies in patients with SLE to investigate the clinical significance of the anti-GAPDH autoantibodies in SLE. METHODS: Concentrations of the glyceraldehyde 3-phosphate dehydrogenase autoantibodies (anti-GAPDH autoantibodies) in the serum of 130 SLE patients and 55 healthy individuals were determined by enzyme-linked immunosorbent assay (ELISA). Among the 130 SLE patients, 95 were SLE patients without neuropsychiatric symptoms and 35 had NPSLE. White blood cell (WBC) count, hemoglobin (HB), platelet count (PLT), IgG, IgA, IgM, anti-dsDNA, C3, C4, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), RF, anti-cardiolipin (Acl), ANA, AnuA, anti-SSA, anti-SSB, ß2-GPI, urinalysis, and 24 h urine protein were measured by standard laboratory techniques. Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index scores were evaluated accordingly. RESULTS: The serum levels of the anti-GAPDH autoantibodies were significantly elevated in the SLE patients, especially in the patients with NPSLE (P = 0.0011). Elevated serum anti-GAPDH was correlated with increased SLEDAI-2K (P = 0.017), ESR, IgG, and IgM and associated with increased intracranial pressure and incidence of cerebrovascular lesions, but it was protective for seizure disorder incidence. CONCLUSIONS: Serum anti-GAPDH autoantibody was increased in both groups of SLE patients with or without neuropsychiatric symptoms and associated with disease severity. It could become an indicator of tissue damages in the brain for the future clinical practice.

Conflating Temporal Advancement and Epistemic Advancement: The Progression Bias in Judgment and Decision Making.

When seeking out the truth about a certain aspect of the world, people frequently conduct several inquiries successively over a time span. Later inquiries usually improve upon earlier ones; thus, it is typically rational to expect the finding of a later inquiry to be closer to the truth than that of an earlier one. However, when no meaningful differences exist between earlier and later inquiries, later findings should not be considered epistemically superior. However, in these cases, people continue to regard findings from later inquiries as closer to the truth than earlier ones. In 10 experiments, when later inquiries conflicted with-but did not epistemically improve upon-earlier ones, participants' global judgments about the truth aligned more with later findings than earlier ones, an effect referred to as progression bias. The liability to progression bias may have severe ramifications for the well-being of the society and its members.

Suppression of miR-26a attenuates physiological disturbances arising from exposure of Nile tilapia (Oreochromis niloticus) to ammonia.

MicroRNAs may affect stress responses because they act as rapid responders at the post-translation level. In this study, we found that miR-26a is abundantly expressed in the brain and gill tissues of tilapia. Expression of miR-26a in the brain decreased significantly with increasing ammonia concentrations using stem-loop qPCR. To analyze the function of miRNA in vivo, miR-26a was stably knocked down with an antagomir in tilapia. Following ammonia challenge, miR-26a antagomir treatment significantly suppressed blood ammonia/[Cl-]/[K+] concentration and the reactive oxygen species production, while it markedly enhanced glutamine accumulation and antioxidant enzyme activity in the brain of tilapia, indicating that miR-26a may be involved in the remission of physiological disturbances resulting from ammonia stress. We strongly conclude that there is a direct link between miR-26a and the responses to ammonia in tilapia. Furthermore, bioinformatics analysis and luciferase assays demonstrated that miR-26a regulates HSP70 (heat shock protein 70) and GS (glutamine synthetase) expression by targeting their 3'-UTR and that the suppression of miR-26a could increase the intracellular level of HSP70 and GS in vivo.

Inferring Perspective Versus Getting Perspective: Underestimating the Value of Being in Another Person's Shoes.

People use at least two strategies to solve the challenge of understanding another person's mind: inferring that person's perspective by reading his or her behavior (theorization) and getting that person's perspective by experiencing his or her situation (simulation). The five experiments reported here demonstrate a strong tendency for people to underestimate the value of simulation. Predictors estimated a stranger's emotional reactions toward 50 pictures. They could either infer the stranger's perspective by reading his or her facial expressions or simulate the stranger's perspective by watching the pictures he or she viewed. Predictors were substantially more accurate when they got perspective through simulation, but overestimated the accuracy they had achieved by inferring perspective. Predictors' miscalibrated confidence stemmed from overestimating the information revealed through facial expressions and underestimating the similarity in people's reactions to a given situation. People seem to underappreciate a useful strategy for understanding the minds of others, even after they gain firsthand experience with both strategies.

The pitfall of experimenting on the web: How unattended selective attrition leads to surprising (yet false) research conclusions.

The authors find that experimental studies using online samples (e.g., MTurk) often violate the assumption of random assignment, because participant attrition-quitting a study before completing it and getting paid-is not only prevalent, but also varies systemically across experimental conditions. Using standard social psychology paradigms (e.g., ego-depletion, construal level), they observed attrition rates ranging from 30% to 50% (Study 1). The authors show that failing to attend to attrition rates in online panels has grave consequences. By introducing experimental confounds, unattended attrition misled them to draw mind-boggling yet false conclusions: that recalling a few happy events is considerably more effortful than recalling many happy events, and that imagining applying eyeliner leads to weight loss (Study 2). In addition, attrition rate misled them to draw a logical yet false conclusion: that explaining one's view on gun rights decreases progun sentiment (Study 3). The authors offer a partial remedy (Study 4) and call for minimizing and reporting experimental attrition in studies conducted on the Web. (PsycINFO Database Record