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Abstract Background Dengue virus (DENV) causes the most significant mosquito-borne viral disease with a wide spectrum of clinical manifestation, including neurological symptoms associated with lethal dengue diseases. Dopamine receptors are expressed in central nervous system, and dopamine antagonists have been reported to exhibit antiviral activity against DENV infection in vivo and in vitro. Although identification of host-cell receptor is critical to understand dengue neuropathogenesis and neurotropism, the involvement of dopamine receptors in DENV infection remains unclear. Results We exploited the sensitivity and precision of force spectroscopy to address whether dopamine type-2 receptors (D2R) directly interact with DENV particles at the first step of infection. Using optical tweezers, we quantified and characterized DENV binding to D2R expressed on Chinese hamster ovary (CHO) cells. Our finding suggested that the binding was D2R- and DENV-dependent, and that the binding force was in the range of 50–60 pN. We showed that dopamine antagonists prochlorperazine (PCZ) and trifluoperazine (TFP), previously reported to inhibit dengue infection, interrupt the DENV-D2R specific binding. Conclusions This study demonstrates that D2R could specifically recognize DENV particles and function as an attachment factor on cell surfaces for DENV. We propose D2R as a host receptor for DENV and as a potential therapeutic target for anti-DENV drugs. Graphical abstract

The inherent ambiguity in reconstructed images from coherent diffraction imaging (CDI) poses an intrinsic challenge, as images derived from the same dataset under varying initial conditions often display inconsistencies. This study introduces a method that employs the Noise2Noise approach combined with neural networks to effectively mitigate these ambiguities. We applied this methodology to hundreds of ambiguous reconstructed images retrieved from a single diffraction pattern using a conventional retrieval algorithm. Our results demonstrate that ambiguous features in these reconstructions are effectively treated as inter-reconstruction noise and are significantly reduced. The post-Noise2Noise treated images closely approximate the average and singular value decomposition analysis of various reconstructions, providing consistent and reliable reconstructions.

This study explores the development of an energy harvesting chip (EHC) using a complementary metal oxide semiconductor (CMOS) process, addressing the need for efficient micro-scale energy harvesters in modern electronics. The EHC integrates a thermoelectric energy harvester (TEH) and a photovoltaic energy harvester (PEH) to maximize energy conversion efficiency. A key challenge in TEH design is enhancing power output, which is addressed by suspending the cold ends of 41 thermocouples within the TEH structure through post-processing. Experimental methods were employed to assess the performance of the TEH, revealing an output voltage of 21.4 mV and a maximum output power of 9.32 nW under a 3 K temperature difference. The TEH demonstrated a voltage factor of 8.9 mV/(mm2·K) and a power factor of 1.3 nW/(mm2·K2). The PEH was designed with novel patterned p-n junctions, integrating lightly doped n-type regions with interdigitated p-type doping to increase junction density, resulting in high conversion efficiency. The experimental results confirm the effectiveness of the EHC design, showcasing its potential in energy harvesting applications.

We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular antiviral response which increases viral transcript presence in the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection. In the absence of robust virus replication, we found trabectedin enhanced viroimmunotherapy efficacy by reducing infiltrating immunosuppressive CD4 T and myeloid cells and stimulating granzyme expression in infiltrating T and natural killer cells to cause immune-mediated tumor regressions. Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.

Sugar-based block co-oligomer (BCO) consisting of saccharide block exhibits high segregation strength that overcomes the limitation of the traditional block copolymers for accessing the ordered nanostructures with ultrasmall feature size. This study explores the influence of molecular chirality on the self-assembly behavior of glucose-block-tocopherol (Glc-b-Toc) BCOs, wherein the Toc blocks were either pure in chirality or being a mixture of the stereoisomers. Both the chiral and racemic BCOs formed a hexagonal perforated layer (HPL) structure with an unusually small aspect ratio (c/a) of the unit cell, attributable to the propensity of the Glc block to enhance hydrogen bonding formation. As the temperature was increased, the dominance of hydrogen bonding interactions diminished, resulting in a gradual increase in the c/a ratio and eventually a transformation of the HPL structure to a double gyroid (DG) phase. The chirality of the Toc block enhanced the effective segregation strength of the BCO, leading to elevated order-order transition temperatures associated with the HPL-to-DG and DG-to-hexagonally packed cylinder (HEX) transitions. Within the HPL phase window, the chiral BCO exhibited significantly slower kinetics during thermally-induced structural reorganization in adjusting the c/a ratio, especially in the cooling process. Consequently, a pronounced hysteresis in the structural reorganization of the chiral BCO was observed. This phenomenon was ascribed to the chiral interaction between the Toc blocks, which limited the diffusion of the BCO molecules for the structural reorganization.

IntroductionMalignant peripheral nerve sheath tumors (MPNST) pose a significant therapeutic challenge due to high recurrence rates after surgical resection and a largely ineffective response to traditional chemotherapy. An alternative treatment strategy is oncolytic viroimmunotherapy, which can elicit a durable and systemic antitumor immune response and is Food and Drug Administration (FDA)-approved for the treatment of melanoma. Unfortunately, only a subset of patients responds completely, underscoring the need to address barriers hindering viroimmunotherapy effectiveness. MethodsHere we investigated the therapeutic utility of targeting key components of the MPNST immunosuppressive microenvironment to enhance viroimmunotherapy’s antitumor efficacy in three murine models, one of which showed more immunogenic characteristics than the others. ResultsMyelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model. However, tumor regressions or shrinkages were not observed. Depletion experiments confirmed that the enhanced survival benefit relied on a T cell response. Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment. DiscussionIn summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.

Abstract Essential hypertension involves complex cardiovascular regulation. The autonomic nervous system function fluctuates throughout the sleep–wake cycle and changes with advancing age. However, the precise role of the autonomic nervous system in the development of hypertension during aging remains unclear. In this study, we characterized autonomic function during the sleep–wake cycle in different age groups with essential hypertension. This study included 97 men (53 with and 44 without hypertension) aged 30–79 years. They were stratified by age into young (

Abstract Insects and pathogens release effectors into plant cells to weaken the host defense or immune response. While the imports of some bacterial and fungal effectors into plants have been previously characterized, the mechanisms of how caterpillar effectors enter plant cells remain a mystery. Using live cell imaging and real-time protein tracking, we show that HARP1, an effector from the oral secretions of cotton bollworm (Helicoverpa armigera), enters plant cells via protein-mediated endocytosis. The entry of HARP1 into a plant cell depends on its interaction with vesicle trafficking components including CTL1, PATL2, and TET8. The plant defense hormone jasmonate (JA) restricts HARP1 import by inhibiting endocytosis and HARP1 loading into endosomes. Combined with the previous report that HARP1 inhibits JA signaling output in host plants, it unveils that the effector and JA establish a defense and counter-defense loop reflecting the robust arms race between plants and insects.

Abstract Background Use of combinations of long-acting β2 agonists/long-acting muscarinic antagonists (LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD) is increasing. Nevertheless, existing evidence on cardiovascular risk associated with LABA/LAMA versus another dual combination, LABA/inhaled corticosteroids (ICS), was limited and discrepant. Aim The present cohort study aimed to examine comparative cardiovascular safety of LABA/LAMA and LABA/ICS with a target trial emulation framework, focusing on dual fixed-dose combination (FDC) therapies. Methods We identified patients with COPD who initiated LABA/LAMA FDC or LABA/ICS FDC from a nationwide Taiwanese database during 2017–2020. The outcome of interest was a hospitalized composite cardiovascular events of acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for composite and individual cardiovascular events after matching up to five LABA/LAMA FDC initiators to one LABA/ICS FDC initiator using propensity scores (PS). Results Among 75,926 PS-matched patients, use of LABA/LAMA FDC did not show a higher cardiovascular risk compared to use of LABA/ICS FDC, with a HR of 0.89 (95% CI, 0.78–1.01) for the composite events, 0.80 (95% CI, 0.61–1.05) for acute myocardial infarction, 1.48 (95% CI, 0.68–3.25) for unstable angina, 1.00 (95% CI, 0.80–1.24) for congestive heart failure, 0.62 (95% CI, 0.37–1.05) for cardiac dysrhythmia, and 0.82 (95% CI, 0.66–1.02) for ischemic stroke. The results did not vary substantially in several pre-specified sensitivity and subgroup analyses. Conclusion Our findings provide important reassurance about comparative cardiovascular safety of LABA/LAMA FDC treatment among patients with COPD.

Abstract Introduction Fever may serve as the primary indicator of underlying infection in children admitted to the pediatric emergency department (PED), especially in high-risk young infants. This study aimed to identify early clinical factors that could help predict bacteremia in young febrile infants. Methods The study included infants under 90 days of age who were admitted to the PED due to fever. Patients were divided into two groups based on the presence or absence of bacteremia and further divided into three age groups: (1) less than 30 days, (2) 30 to 59 days, and (3) 60 to 90 days. Several clinical and laboratory variables were analyzed, and logistic regression and receiver operating characteristic (ROC) analyses were used to identify potential risk factors associated with bacteremia in young febrile infants. Results A total of 498 febrile infants were included, of whom 6.4% were diagnosed with bacteremia. The bacteremia group had a higher body temperature (BT) at triage, especially in neonates, higher pulse rates at triage, longer fever subsidence time, longer hospital stays, higher neutrophil counts, and higher C-reactive protein (CRP) levels than those of the non-bacteremia group. ROC analysis showed that the best cut-off values for predicting bacteremia in infants with pyrexia were a BT of 38.7 °C, neutrophil count of 57.9%, and CRP concentration of 53.8 mg/L. Conclusions A higher BT at triage, increased total neutrophil count, and elevated CRP levels may be useful for identifying bacteremia in young febrile infants admitted to the PED.

Oncolytic viruses, modified for tumor-restricted infection, are a promising cancer immunotherapeutic, yet much remains to be understood about factors driving their activity and outcome in the tumor microenvironment. Here, we report that oncolytic herpes simplex virus C134, previously found to exert T cell-dependent efficacy in mouse models of glioblastoma, exerts T cell-independent efficacy in mouse models of medulloblastoma, indicating this oncolytic virus uses different mechanisms in different tumors. We investigated C134’s behavior in mouse medulloblastomas, using single cell RNA sequencing to map C134-induced gene expression changes across cell types, timepoints, and medulloblastoma subgroup models at whole-transcriptome resolution. Our work details substantial oncolytic virus-induced transcriptional remodeling of medulloblastoma-infiltrating immune cells, 10 subpopulations of monocytes and macrophages collectively demonstrating M1-like responses to C134, and suggests C134 be investigated as a potential new therapy for medulloblastoma.

This review explores the complex challenges and advancements in the treatment of traumatic brain injury (TBI) and spinal cord injury (SCI). Traumatic injuries to the central nervous system (CNS) trigger intricate pathophysiological responses, frequently leading to profound and enduring disabilities. This article delves into the dual phases of injury—primary impacts and the subsequent secondary biochemical cascades—that worsen initial damage. Conventional treatments have traditionally prioritized immediate stabilization, surgical interventions, and supportive medical care to manage both the primary and secondary damage associated with central nervous system injuries. We explore current surgical and medical management strategies, emphasizing the crucial role of rehabilitation and the promising potential of stem cell therapies and immune modulation. Advances in stem cell therapy, gene editing, and neuroprosthetics are revolutionizing treatment approaches, providing opportunities not just for recovery but also for the regeneration of impaired neural tissues. This review aims to emphasize emerging therapeutic strategies that hold promise for enhancing outcomes and improving the quality of life for affected individuals worldwide.

Background: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. Methods: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. Results: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (β ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. Conclusion: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.

The study aimed to validate a newly developed postoperative stability score for evaluating clinical follow-up in elderly patients with low-energy hip fractures. From 1 January 2020 to 31 December 2021, we enrolled patients aged over 65 who underwent cephalomedullary nail fixation using proximal femoral nail antirotation II (PFNAII) and had at least 6 months of follow-up; excluding multiple fractures, pathological fractures, and periprosthetic fractures. We collected general patient data. Parameters such as TAD, Parker’s ratio (AP and lateral), and the new postoperative stability score were recorded. A loss of reduction was defined using the decline in the Chang reduction quality criteria (CRQC) score within one month. Among the 108 enrolled patients, 23 (21.3%) experienced a loss of reduction, with a mean age of 82.1 years and a mean follow-up time of 7.4 months. Univariate analysis showed no significant association between loss of reduction and general data. However, the new postoperative stability score correlated significantly with loss of reduction (mean scores: 6.68 vs. 4.83, p = 0.045). Multivariate analysis confirmed this association (odds ratio: 0.076, 95% confidence interval: 0.022–0.263, p < 0.05). The newly developed postoperative stability score, incorporating surgical technique assessment, improves prediction accuracy for loss of reduction in elderly intertrochanteric fracture (ITF) patients.

Background: Acute appendicitis is a common abdominal emergency observed in emergency departments (ED). Distinguishing between uncomplicated and complicated appendicitis is important in determining a treatment strategy. Serum soluble vascular cell adhesion molecule-1 (VCAM-1) is an inflammatory biomarker. We aimed to determine the role of VCAM-1 in predicting complicated appendicitis in children. Methods: Pediatric patients with suspected appendicitis admitted to the ED were enrolled in this prospective study. Pre-surgical serum VCAM-1 was tested in children with acute appendicitis within 72 h of symptoms (from day 1 to day 3). Serum VCAM-1 levels were further analyzed and compared between patients with and without complicated appendicitis. Results: Among the 226 pediatric appendicitis patients, 70 had uncomplicated appendicitis, 138 had complicated appendicitis, and 18 had normal appendices. The mean serum VCAM-1 levels in patients with perforated appendicitis were higher than in those with simple appendicitis (p < 0.001). On day 1 to day 3, the mean VCAM-1 levels in patients with complicated appendicitis were all significantly higher than in those with uncomplicated appendicitis (all p < 0.001). Conclusion: Serum VCAM-1 levels may be helpful in differentiating uncomplicated and complicated appendicitis in children and could predict appendiceal perforation.

Aims: This study aims to compare the outcomes of immediate (followed by closed-incision negative-pressure therapy use) versus delayed ORIF in patients with Schatzker type IV–VI TPFs. Patients and Methods: A prospective study of patients undergoing ORIF between January 2018 and December 2019 was performed. The inclusion criteria were patients (>18 years) with a closed fracture sent to the emergency room (ER) within 24 h of injury. All the patients underwent preoperative image evaluation. Two senior orthopedic trauma surgeons evaluated the soft tissue condition in the ER by 5P’s of the compartment syndrome, judging the timing of the operation of definitive ORIF. Group 1 (n = 16) received delayed ORIF. Group 2 (n = 16) received immediate ORIF and ciNPT use. Patient follow-up occurred after 2 and 6 weeks and 3, 6, and 12 months after surgery. The assessments included the time to definitive fixation, the length of hospital stay, the time to bone union, surgical site complications, and reoperation within 12 months. A universal goniometer was used to measure the postoperative 3 m, 6 m, and 12 m ROM. Results: The patient demographics were similar between the groups (p > 0.05). Group 2 displayed significantly a shorter time to definitive fixation (5.94 ± 2.02 vs. 0.61 ± 0.28, p < 0.0001) and hospital stay (14.90 ± 8/78 vs. 10.30 ± 6.78, p = 0.0016). No significant difference was observed in the time to bone union, surgical site complication incidence, and reoperation rates (p > 0.05). Flexion and flexion–extension knee ROM were demonstrated to be significantly improved in Group 2, 3, 6, and 12 months postoperatively (p < 0.0001). Conclusions: In this study, early ORIF and ciNPT use resulted in a shorter hospital length of stay, a reduced time to early active motion of the knee, and improved knee ROM. These results suggest that early ORIF with ciNPT for Schatzker type IV–VI TPFs is safe and effective in some patients. However, further research to confirm these findings across larger and more diverse populations is needed.

Abstract Background Urinary C–C motif chemokine ligand 14 (CCL14) has been described as an effective marker for delayed recovery of acute kidney injury (AKI), yet its efficacy has been found to vary between different trials. The goal of this research was to assess the predictive performance of urinary CCL14 as a marker for persistent AKI. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to April 2023 for studies of adults (> 18 years) that reported the diagnostic performance of urinary CCL14. The sensitivity, specificity, number of events, true positive, and false positive results were extracted and evaluated. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. Results We included six studies with 952 patients in this meta-analysis. The occurrence of persistent AKI among these patients was 39.6% (377/952). The pooled sensitivity and specificity results of urinary CCL14 in predicting persistent AKI were 0.81 (95% CI 0.72–0.87) and 0.71 (95% CI 0.53–0.84), respectively. The pooled positive likelihood ratio (LR) was 2.75 (95% CI 1.63–4.66), and the negative LR was 0.27 (95% CI 0.18–0.41). The HSROC with pooled diagnostic accuracy was 0.84. Conclusion Our results suggest that urinary CCL14 can be used as an effective marker for predicting persistent AKI.

Abstract Abnormal polyglutamine (polyQ) expansion and fibrillization occur in Huntington’s disease (HD). Amyloid modifier SERF enhances amyloid formation, but the underlying mechanism is not revealed. Here, the fibrillization and toxicity effect of SERF1a on Htt-exon1 are examined. SERF1a enhances the fibrillization of and interacts with mutant thioredoxin (Trx)-fused Httex1. NMR studies with Htt peptides show that TrxHttex1-39Q interacts with the helical regions in SERF1a and SERF1a preferentially interacts with the N-terminal 17 residues of Htt. Time-course analysis shows that SERF1a induces mutant TrxHttex1 to a single conformation enriched of β-sheet. Co-expression of SERF1a and Httex1-polyQ in neuroblastoma and lentiviral infection of SERF1a in HD-induced polypotent stem cell (iPSC)-derived neurons demonstrates the detrimental effect of SERF1a in HD. Higher level of SERF1a transcript or protein is detected in HD iPSC, transgenic mice, and HD plasma. Overall, this study provides molecular mechanism for SERF1a and mutant Httex1 to facilitate therapeutic development for HD.

Purpose: Comminuted fractures with poor bone quality in the elderly are associated with poor outcomes. An alternative to open reduction and internal fixation (ORIF) alone, primary or acute total hip arthroplasty (aTHA), allows early mobilization with full weight bearing. In this study, we aim to analyze whether treatment of aTHA with/withtout ORIF (limited ORIF) vs ORIF alone yields better intra-operative results, functional outcomes, and less complications. Methods: PubMed, Cochrane, Embase, and Scopus databases were searched in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Random-effects model and 95% confidence intervals were used. The outcomes of interest were surgery time, blood loss, length of hospital stay, Harris hip score (HHS), 36-Item Short Form Survey (SF-36), complication rate, surgical site infection rate, heterotopic ossification rate, reoperation rate, and mortality rate. Results: Ten observational studies with a total of 642 patients (415 ORIF alone and 227 aTHA with/without ORIF) were included in the systematic review. Compared to ORIF alone, aTHA with limited ORIF provided higher HHS (P = 0.029), better physical function (P = 0.008), better physical component summary (P = 0.001), better mental component summary (P = 0.043) in postoperative 1-year SF-36, lesser complication rate (P = 0.001), and lesser reoperation rate (P = 0.000), but however greater bodily pain (P = 0.001) in acetabular fractured elderlies. Conclusions: Acute THA with limited ORIF is favorable alternative to ORIF technique alone. It provided better HHS, physical, and mental component summary in SF-36 and yielded lower complication and reoperation rate compare to ORIF alone.

The use of oncolytic viruses (OVs) and adoptive cell therapies (ACT) have independently emerged as promising approaches for cancer immunotherapy. More recently, the combination of such agents to obtain a synergistic anticancer effect has gained attention, particularly in solid tumors, where immune-suppressive barriers of the microenvironment remain a challenge for desirable therapeutic efficacy. While adoptive cell monotherapies may be restricted by an immunologically cold or suppressive tumor microenvironment (TME), OVs can serve to prime the TME by eliciting a wave of cancer-specific immunogenic cell death and inducing enhanced antitumor immunity. While OV/ACT synergy is an attractive approach, immune-suppressive barriers remain, and methods should be considered to optimize approaches for such combination therapy. In this review, we summarize current approaches that aim to overcome these barriers to enable optimal synergistic antitumor effects.

BackgroundRecently, there have been conflicting results reporting an increased risk of AR or MR associated with oral fluoroquinolones (FQs).This study investigated whether the use of FQs increases the risk of mitral regurgitation (MR) or aortic regurgitation (AR).MethodsA retrospective cohort study was conducted by using the Taiwan National Health Insurance research database. A unidirectional case-crossover design without selecting controls from an external population was adopted in this study. A total of 26,650 adult patients with new onset of AR or MR between January 1, 2000, and December 31, 2012, were identified. The risk of outcomes was compared between the hazard period and one of the randomly selected referent periods of the same individuals.ResultsBefore exclusion of pneumonia diagnosed within 2 months before the index date, patients who took FQs had a significantly greater risk of AR or MR (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.30-1.77), any AR (combined AR and MR) (aOR 1.50, 95% CI 1.10-2.04), and any MR (combined AR and MR) (aOR 1.37, 95% CI 1.16-1.62). After exclusion of pneumonia, FQs exposure remained significantly associated with a greater risk of MR (aOR 1.38, 95% CI 1.17-1.62) and any MR (aOR 1.25, 95% CI 1.05-1.48).ConclusionsThe findings suggested that patients treated with FQs could be warned about the potential risk for MR even after considering the possibility of protopathic bias. Reducing unnecessary FQs prescriptions may be considered to reduce the risk of valvular heart disease.

Background The widely used Bentall procedure is the criterion standard treatment for aortic root pathology. Studies comparing the long‐term outcomes of bioprosthetic and mechanical valves in patients undergoing the Bentall procedure are limited. Methods and Results Patients who underwent the Bentall procedure with a bioprosthetic or mechanical valve between 2001 and 2018 were identified from Taiwan's National Health Insurance Research Database. The primary outcome of interest was all‐cause mortality. Inverse probability of treatment weighting was performed to compare the 2 prosthetic types. In total, 1052 patients who underwent the Bentall procedure were identified. Among these patients, 351 (33.4%) and 701 (66.6%) chose bioprosthetic and mechanical valves, respectively. After inverse probability of treatment weighting, no significant differences in the in‐hospital mortality (odds ratio, 0.96 [95% CI, 0.77–1.19]; P=0.716) and all‐cause mortality (34.1% vs. 38.1%; hazard ratio, 0.90 [95% CI, 0.78–1.04]; P=0.154) were observed between the groups. The benefits of relative mortality associated with mechanical valves were apparent in younger patients and persisted until ≈50 years of age. Conclusions No differences in survival benefits were observed between the valves in patients who underwent the Bentall procedure. Additionally, bioprosthetic valves may be a reasonable choice for patients aged >50 years when receiving the Bentall procedure in this valve‐in‐valve era.

Development of factor VIII (FVIII) inhibitors is a serious complication in the treatment of hemophilia A (HemA) patients. In clinical trials, anti-CD3 antibody therapy effectively modulates the immune response of allograft rejection or autoimmune diseases without eliciting major adverse effects. In this study, we delivered mRNA-encapsulated lipid nanoparticles (LNPs) encoding therapeutic anti-CD3 antibody (αCD3 LNPs) to overcome the anti-FVIII immune responses in HemA mice. It was found that αCD3 LNPs encoding the single-chain antibodies (Fc-scFv) can efficiently deplete CD3+ and CD4+ effector T cells, whereas αCD3 LNPs encoding double-chain antibodies cannot. Concomitantly, mice treated with αCD3 (Fc-scFv) LNPs showed an increase in the CD4+CD25+Foxp3+ regulatory T cell percentages, which modulated the anti-FVIII immune responses. All T cells returned to normal levels within 2 months. HemA mice treated with αCD3 LNPs prior to hydrodynamic injection of liver-specific FVIII plasmids achieved persistent FVIII gene expression without formation of FVIII inhibitors. Furthermore, transgene expression was increased and persistent following secondary plasmid challenge, indicating induction of long-term tolerance to FVIII. Moreover, the treated mice maintained their immune competence against other antigens. In conclusion, our study established a potential new strategy to induce long-term antigen-specific tolerance using an αCD3 LNP formulation.

Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix. This study aimed to identify systemic biomarkers to predict pediatric appendicitis at various time points. The study group comprised pediatric patients with clinically suspected appendicitis between 2016 and 2019. Pre-surgical serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), intercellular cell-adhesion molecule-1 (ICAM-1), and endothelial selectin (E-selectin) levels were tested from day 1 to day 3 of the disease course. The biomarker values were analyzed and compared between children with normal appendices and appendicitis and those with perforated appendicitis (PA) and non-perforated appendicitis. Among 226 pediatric patients, 106 had non-perforated appendicitis, 102 had PA, and 18 had normal appendices. The levels of all serum proinflammatory biomarkers were elevated in children with acute appendicitis compared with those in children with normal appendices. In addition, the serum IL-6 and TNF-α levels in children with PA were significantly higher, with an elevation in TNF-α levels from days 1 and 2. In addition, serum IL-6 levels increased significantly from days 2 and 3 (both p < 0.05). Serum ICAM-1 and E-selectin levels were elevated in the PA group, with consistently elevated levels within the first three days of admission (all p < 0.05). These results indicate that increased serum levels of proinflammatory biomarkers including IL-6, TNF-α, ICAM-1, and E-selectin could be used as parameters in the prediction and early diagnosis of acute appendicitis, especially in children with PA.

Abstract Diabetic kidney disease is the leading cause of end-stage kidney disease worldwide; however, the integration of high-dimensional trans-omics data to predict this diabetic complication is rare. We develop artificial intelligence (AI)-assisted models using machine learning algorithms to identify a biomarker signature that predisposes high risk patients with diabetes mellitus (DM) to diabetic kidney disease based on clinical information, untargeted metabolomics, targeted lipidomics and genome-wide single nucleotide polymorphism (SNP) datasets. This involves 618 individuals who are split into training and testing cohorts of 557 and 61 subjects, respectively. Three models are developed. In model 1, the top 20 features selected by AI give an accuracy rate of 0.83 and an area under curve (AUC) of 0.89 when differentiating DM and non-DM individuals. In model 2, among DM patients, a biomarker signature of 10 AI-selected features gives an accuracy rate of 0.70 and an AUC of 0.76 when identifying subjects at high risk of renal impairment. In model 3, among non-DM patients, a biomarker signature of 25 AI-selected features gives an accuracy rate of 0.82 and an AUC of 0.76 when pinpointing subjects at high risk of chronic kidney disease. In addition, the performance of the three models is rigorously verified using an independent validation cohort. Intriguingly, analysis of the protein–protein interaction network of the genes containing the identified SNPs (RPTOR, CLPTM1L, ALDH1L1, LY6D, PCDH9, B3GNTL1, CDS1, ADCYAP and FAM53A) reveals that, at the molecular level, there seems to be interconnected factors that have an effect on the progression of renal impairment among DM patients. In conclusion, our findings reveal the potential of employing machine learning algorithms to augment traditional methods and our findings suggest what molecular mechanisms may underlie the complex interaction between DM and chronic kidney disease. Moreover, the development of our AI-assisted models will improve precision when diagnosing renal impairment in predisposed patients, both DM and non-DM. Finally, a large prospective cohort study is needed to validate the clinical utility and mechanistic implications of these biomarker signatures.

Background: The pathogenesis of acute respiratory distress syndrome (ARDS) is attributed to the dysregulation of oxidative stress and neutrophil recruitment. We aimed to investigate the anti-inflammatory effects of apremilast on human neutrophils and assess its efficacy for treating ARDS. Methods: We analysed superoxide anion generation, integrin expression, and adhesion in activated human neutrophils using spectrophotometry, flow cytometry, and immunofluorescence microscopy. Phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was determined using immunoblotting. A murine lipopolysaccharide (LPS)-induced ARDS model was used to evaluate the therapeutic effects of apremilast. Results: Apremilast significantly decreased superoxide anion production, reactive oxygen species (ROS) generation, cluster of differentiation (CD)11 b expression, and neutrophil adhesion in formyl-l-methionyl-l-leucyl-l-phenylalanine activated human neutrophils. Apremilast elevated cyclic 3′,5′-adenosine monophosphate (cAMP) and protein kinase A (PKA) activity in activated neutrophils. It reduced cellular cAMP-specific phosphodiesterase (PDE) activity and selectively inhibited enzymatic PDE4 activity. The activated cAMP/PKA pathway suppressed the phosphorylation of ERK and JNK as well as Ca2+ mobilization in activated neutrophils. All inhibitory effects of apremilast on activated neutrophils were reversed by a PKA inhibitor. In vivo examinations indicated that apremilast alleviated lung neutrophil infiltration, myeloperoxidase (MPO) activity, pulmonary oedema, and alveolar damage in LPS-induced ARDS. Conclusion: Apremilast inhibits inflammatory responses after neutrophil activation via cAMP/PKA-dependent inhibition of ERK and JNK activation. Our study revealed apremilast suppresses oxidative stress and chemotaxis by selectively inhibiting PDE4 in neutrophils and thus protects against endotoxin-induced ARDS in mice. Apremilast can be used as an alternative off-label drug in treating acute lung damage.

The electrostatic interaction between of poly(amidoamine) (PAMAM) G9 dendrimer and an achiral surfactant, dodecylbenzenesulfonic acid (DBSA), leads to the formation of nucleosome-like structure, where the globular dendrimer molecule directs the DBSA cylindrical micelle to wrap around it spirally with a regular pitch length of 3.2 ∼ 4.3 nm. Molecular dynamics simulation demonstrates that the spherical micelles of DBSA in the aqueous solution first condense on the dendrimer surface via the electrostatic attraction. The micelles then merge with their neighbors to form cylinders bending around the dendrimer, which further connect with one another to form a spring-like helix wrapping around the dendrimer. The discovery of the helical supramolecular structure attests the universality of soft cylindrical building block such as DNA and micelle to twist and wrap helically around the oppositely charged particle such as histone protein and dendrimer for attaining the optimal charge matching at the expense of the bending energy of the cylinder.

Introduction: Hematuria is a worrisome symptom in children and is sometimes associated with urinary tract infections (UTIs). This study aimed to identify useful clinical factors that can predict UTIs in hematuria patients without pyuria in the pediatric emergency department (ED). Methods: We retrospectively recruited patients with hematuria from the pediatric ED. Clinical symptoms, urine biochemistry and microscopic examination results, and blood laboratory tests were analyzed to identify the predictors of UTIs. Patients were divided into the verbal group (age ≥ 2 years) and non-verbal group (age < 2 years) for identifying predictors of UTIs. Causes of hematuria were also investigated. Results: A total of 161 patients with hematuria without pyuria were evaluated. Among symptoms, dysuria was significantly correlated with UTIs. Regarding urine biochemistry data, urine esterase and urine protein > 30 mg/dl were found to be significant parameters for predicting UTIs, while urine esterase and urine nitrite showed significant differences in children with age < 2 years. In the urine microscopic examinations, urine red blood cells (RBC) > 373/µL in children aged ≥ 2 years and urine RBC > 8/µL in children aged < 2 years were associated with UTIs. In addition, UTIs and urinary tract stones were found to be the top two causes of hematuria. Conclusions: Dysuria, urine esterase, urine nitrite, and urine protein may be useful parameters for predicting UTIs in pediatric patients with hematuria but no pyuria in the ED. In addition, a UTI was the most commonly identified etiology of hematuria without pyuria, followed by urinary tract stones.

Background: Acute infectious diarrhea is a common cause of hospitalization in children. Hence, early identification of acute bacterial gastroenteritis with suspected sepsis in pediatric emergency departments (EDs) is important. This study aimed to describe the clinical spectrum and initial characteristics of children who were presented to a pediatric ED with acute infectious diarrhea and suspected sepsis. Methods: Between April 2020 to March 2021, children with clinical diagnoses of acute bacterial colitis and suspected sepsis who were admitted to the pediatric ED were prospectively enrolled. The following data were obtained and compared between different age groups of children: including demographics, presentation, laboratory tests, culture results, treatment modalities, complications, and short-term outcomes. Results: A total of 105 patients (70 males and 35 females; mean age: 3.75 ± 3.52 years) were enrolled in this study. Of them, 89 (84.8%) patients were p < 0.001) and anti-biotic treatment groups (both p < 0.001). Salmonella enteritidis was the most common organism cultured from the stool and blood samples (39 of 91 (38.5%) and 2 of 105 (1.9%), respectively). Conclusions: The primary causative organism of acute infectious diarrhea identified in this study was S. enteritidis. Age and elevated serum CRP or PCT levels could be important factors in the decisions of emergency physicians regarding hospitalization and antibiotic therapies for pediatric acute infectious diarrhea.

Stachydrine, a prominent bioactive alkaloid derived from Leonurus heterophyllus, is a significant herb in traditional medicine. It has been noted for its anti-inflammatory and antioxidant characteristics. Consequently, we conducted a study of its hepatoprotective effect and the fundamental mechanisms involved in acetaminophen (APAP)-induced liver injury, utilizing a mouse model. Mice were intraperitoneally administered a hepatotoxic dose of APAP (300 mg/kg). Thirty minutes after APAP administration, mice were treated with different concentrations of stachydrine (0, 2.5, 5, and 10 mg/kg). Animals were sacrificed 16 h after APAP injection for serum and liver tissue assays. APAP overdose significantly elevated the serum alanine transferase levels, hepatic pro-inflammatory cytokines, malondialdehyde activity, phospho-extracellular signal-regulated kinase (ERK), phospho-protein kinase B (AKT), and macrophage-stimulating protein expression. Stachydrine treatment significantly decreased these parameters in mice with APAP-induced liver damage. Our results suggest that stachydrine may be a promising beneficial target in the prevention of APAP-induced liver damage through attenuation of the inflammatory response, inhibition of the ERK and AKT pathways, and expression of macrophage-stimulating proteins.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects individuals of all age groups, manifesting as a spectrum of symptoms varying from mild to severe. Allergen immunotherapy (AIT) involves the administration of allergen extracts and has emerged as a potential treatment strategy for modifying immune responses. Its pathogenesis involves epidermal barrier dysfunction, microbiome imbalance, immune dysregulation, and environmental factors. Existing treatment strategies encompass topical steroids to systemic agents, while AIT is under investigation as a potential immune-modifying alternative. Several studies have shown reductions in the severity scoring of atopic dermatitis (SCORAD) scores, daily rescue medication use, and visual analog scale (VAS) scores following AIT. Biomarker changes include increased IgG4 levels and decreased eosinophil counts. This review provides valuable insights for future research and clinical practice, exploring AIT as a viable option for the management of AD.

Severe asthma is a complex and heterogeneous clinical condition presented as chronic inflammation of the airways. Conventional treatments are mainly focused on symptom control; however, there has been a shift towards personalized medicine. Identification of different phenotypes driven by complex pathobiological mechanisms (endotypes), especially those driven by type-2 (T2) inflammation, has led to improved treatment outcomes. Combining biomarkers with T2-targeting monoclonal antibodies is crucial for developing personalized treatment strategies. Several biological agents, including anti-immunoglobulin E, anti-interleukin-5, and anti-thymic stromal lymphopoietin/interleukin-4, have been approved for the treatment of severe asthma. These biological therapies have demonstrated efficacy in reducing asthma exacerbations, lowering eosinophil count, improving lung function, diminishing oral corticosteroid use, and improving the quality of life in selected patients. Severe asthma management is undergoing a profound transformation with the introduction of ongoing and future biological therapies. The availability of novel treatment options has facilitated the adoption of phenotype/endotype-specific approaches and disappearance of generic interventions. The transition towards precision medicine plays a crucial role in meticulously addressing the individual traits of asthma pathobiology. An era of tailored strategies has emerged, allowing for the successful targeting of immune-inflammatory responses that underlie uncontrolled T2-high asthma. These personalized approaches hold great promise for improving the overall efficacy and outcomes in the management of severe asthma. This article comprehensively reviews currently available biological agents and biomarkers for treating severe asthma. With the expanding repertoire of therapeutic options, it is becoming increasingly crucial to comprehend the influencing factors, understand the pathogenesis, and track treatment progress in severe asthma.

Abstract Background At present, skeletal tuberculosis (TB) diagnosis is mostly by histopathology, but the positivity rate is low. There is a need to develop new methods for the molecular identification of this disorder. Therefore, we aimed to investigate the clinical utility of quantitative PCR (qPCR)-based diagnosis of skeletal TB from formalin-fixed paraffin-embedded (FFPE) tissues and its comparative evaluation with acid-fast bacillus staining (AFS). Methods We detected Mycobacterium tuberculosis (M. tuberculosis/MTB) DNA using qPCR and AFS in FFPE tissue samples from 129 patients suspected of having skeletal TB. The sensitivity, specificity as well as area under the curve (AUC) of qPCR and AFS were calculated. Meanwhile, some factors potentially affecting qPCR and AFS results were investigated. Results Overall, qPCR outperformed AFS in detecting M. tuberculosis. The AUC of qPCR was higher than that of AFS (0.744 vs.0.561, p

Abstract This study aims to investigate whether an augmented wire in the treatment of patella distal pole fracture could improve knee range of motion (ROM) and radiographic features. Thirty-five consecutive patients with patellar distal pole fracture were analyzed from January 2014 to July 2019. The treatment is divided into two groups according to the presence or absence of augmented wire. Knee ROM, bone union, extension lag, and patellar height were compared between these two groups as the clinical and radiological outcomes. There was no significant difference in mean knee ROM (110° vs. 108°, p = 0.79), proportion of patella baja or bone union. More extension lag was noted in the augmentation group (5/20, 25%) than in the tendon reattachment group (1/15, 6.7%) with no statistically significant difference. In the augmentation group, four cases (20%) would need to remove the fixator due to irritation or broken hardware. Maintaining the patella length by preserving the distal pole and repairing the torn retinaculum allowed early motion to avoid knee stiffness safely without augmentation wire, which doesn’t improve knee ROM. The patellar tendon reattachment alone could achieve a great recovery and prevent the need for a second surgery due to broken wire or irritation.

IntroductionThe prevalence of cardiovascular disease (CVD) and CVD-related deaths in patients with schizophrenia is high. An elevated risk of CVD has been associated with low heart rate variability (HRV). There is increasing evidence that fatty acid-binding protein (FABP)3 and FABP4 play roles in the development and progression of CVD. This study aimed to explore the association of circulating FABP3/FABP4 levels with HRV in patients with chronic schizophrenia.MethodsWe included 265 consecutive patients with chronic schizophrenia who attended a disease management program. We used an enzyme-linked immunosorbent assay for the measurement of plasma concentrations of FABP3 and FABP4. Standard HRV was recorded at baseline following a standard protocol. Mean high- and low-frequency (HF/LF) HRV values were analyzed by tertile of FABP3 and FABP4 using one-way analysis of variance, and linear regression analysis was performed to assess trends.ResultsA positive association between FABP3 and creatinine was found in multiple regression analysis. In addition, negative associations between levels of hematocrit, hemoglobin, HF HRV, and estimated glomerular filtration rate (eGFR) with FABP3 were also found. Moreover, positive associations between FABP4 with body mass index, diabetes mellitus, hypertension, systolic blood pressure, low-density lipoprotein-cholesterol, triglycerides, creatinine, and FABP3 were found. Furthermore, negative associations between levels of high-density lipoprotein-cholesterol, eGFR, and HF HRV with FABP4 were found. We also found a significant inverse association between FABP3 and HF HRV (p for trend = 0.008), and significant inverse associations between FABP4 with HF and LF HRV (p for trend = 0.007 and 0.017, respectively).DiscussionTogether, this suggests that elevated levels of FABP3 and FABP4 may be linked to health problems related to CVD in patients with chronic schizophrenia.

IntroductionHemodynamic stability is important during neurointerventional procedures. However, ICP or blood pressure may increase due to endotracheal extubation. The aim of this study was to compare the hemodynamic effects of sugammadex and neostigmine with atropine in neurointerventional procedures during emergence from anesthesia.MethodsPatients undergoing neurointerventional procedures were allocated to the sugammadex group (Group S) and the neostigmine group (Group N). Group S was administered IV 2 mg/kg sugammadex when a train-of-four (TOF) count of 2 was present, and Group N was administered neostigmine 50 mcg/kg with atropine 0.2 mg/kg at a TOF count of 2. We recorded heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure (MAP), and peripheral arterial oxygen saturation during administration of the reverse agent and at 2, 5, 10, 15, 30, 120 min, and 24 h thereafter. The primary outcome was blood pressure and heart rate change after the reversal agent was given. The secondary outcomes were systolic blood pressure variability standard deviation (a measure of the amount of variation or dispersion of a set of values), systolic blood pressure variability-successive variation (square root of the average squared difference between successive blood pressure measurements), nicardipine use, time-to-TOF ratio ≥0.9 after the administration of reversal agent, and time from the administration of the reversal agent to tracheal extubation.ResultsA total of 31 patients were randomized to sugammadex, and 30 patients were randomized to neostigmine. Except for anesthesia time, there were no significant differences in any of the clinical characteristics between the two groups. The results demonstrated that the increase in MAP from period A to B was significantly greater in Group N than in Group S (regression coefficient = −10, 95% confidence interval = −17.3 to −2.7, P = 0.007). The MAP level was significantly increased from period A to B in the neostigmine group (95.1 vs. 102.4 mm Hg, P = 0.015), but it was not altered in Group S. In contrast, the change in HR from periods A to B was not significantly different between groups.ConclusionWe suggest that sugammadex is a better option than neostigmine in interventional neuroradiological procedures due to the shorter extubation time and more stable hemodynamic change during emergence.

This study develops a photovoltaic microgenerator based on the complementary metal oxide semiconductor (CMOS) process. The photovoltaic microgenerator converts the absorbed light energy into electrical energy using the photovoltaic effect. The material for the photovoltaic microgenerator is silicon, and its structure consists of patterned p–n junctions. The design of the photovoltaic microgenerator utilizes a grid-like shape, forming a large-area p–n junction with a patterned p-doping and N-well structure to enhance the photocurrent and improve the device’s performance. The photovoltaic microgenerator is fabricated employing the CMOS process with post-processing step. Post-processing is applied to enhance the microgenerator’s light absorption and energy-conversion efficiency. This involves using wet etching with buffered-oxide etch (BOE) to remove the silicon dioxide layer above the p–n junctions, allowing direct illumination of the p–n junctions. The area of the photovoltaic microgenerator is 0.79 mm2. The experimental results show that under an illumination intensity of 1000 W/m2, the photovoltaic microgenerator exhibits an open-circuit voltage of 0.53 V, a short-circuit current of 233 µA, a maximum output power of 99 µW, a fill factor of 0.8, and an energy-conversion efficiency of 12.5%.

Pediatric traumatic brain injury is a cause of major mortality, and resultant neurological sequelae areassociated with long-term morbidity. Increasing studies have revealed stem cell therapy to be a potential new treatment. However, much work is still required to clarify the mechanism of action of effective stem cell therapy, type of stem cell therapy, optimal timing of therapy initiation, combination of cocurrent medical treatment and patient selection criteria. This paper will focus on stem cell therapy in children with traumatic brain injury.

Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond the respiratory system, affecting various organs and functions. In severe cases, it can progress to acute respiratory distress syndrome (ARDS) and multi-organ failure, often fueled by an excessive immune response known as a cytokine storm. Mesenchymal stem cells (MSCs) have considerable potential because they can mitigate inflammation, modulate immune responses, and promote tissue regeneration. Accumulating evidence underscores the efficacy and safety of MSCs in treating severe COVID-19 and ARDS. Nonetheless, critical aspects, such as optimal routes of MSC administration, appropriate dosage, treatment intervals, management of extrapulmonary complications, and potential pediatric applications, warrant further exploration. These research avenues hold promise for enriching our understanding and refining the application of MSCs in confronting the multifaceted challenges posed by COVID-19.

Abstract Introduction The volar locking plate has been widely used for unstable distal radius fractures to provide early recovery of wrist function. Volar plate prominence to the watershed line has been reported to be related to flexor tendon irritation, and avoid implant prominence in this area was suggested. On the other hand, marginal distal radius fracture patterns required the plate to cross the watershed line, making conflict over plate positioning on marginal distal radius fractures. This study compared functional outcomes in patients with marginal distal radius fractures treated with two different implants. Materials and methods A retrospective study was conducted, all patients who received a Synthes 2.4 mm LCP or an Acumed Acu-Loc VLP between January 2015 and December 2018 were reviewed. The marginal distal radius fracture pattern was the most distal horizontal fracture line within 10 mm of the lunate fossa’s joint line. The primary outcomes including patient-reported pain scores, range of motion, and grip strength were assessed. Secondary outcomes included patient-based subjective satisfaction scores of the injured wrist and hand function. The Mayo Wrist Score and the requirement for a secondary procedure related to hardware complications were also recorded. Results Forty-two patients met our inclusion criteria. Twenty-one patients were treated with the Synthes 2.4 mm LCP, and 21 patients with the Acumed Acu-Loc VLP. The primary outcome revealed that post-operative range of motion (P = 0.016) and grip strengths (P = 0.014) were significantly improved in the Acu-Loc VLP group. The MAYO wrist score in the Acu-Loc VLP group was also significantly better (P = 0.006). Conclusions Despite advances in implant designs, flexor tendon irritation or rupture is still a complication following distal radius’s volar plating. We believe the Acumed Acu-Loc VLP design provided better functional outcomes than the Synthes 2.4 mm LCP if appropriately and carefully placed into its designed-for position. This positioning results in promising patient satisfaction when treating marginal distal radius fractures.

Lophatherum gracile (L. gracile) has long been used as a functional food and herbal medicine. Previous studies have demonstrated that extracts of L. gracile attenuate inflammatory response and inhibit SARS-CoV-2 replication; however, the underlying active constituents have yet to be identified. This study investigated the bioactive components of L. gracile. Flavone C-glycosides of L. gracile were found to dominate both anti-inflammatory and antiviral effects. A simple chromatography-based method was developed to obtain flavone C-glycoside-enriched extract (FlavoLG) from L. gracile. FlavoLG and its major flavone C-glycoside isoorientin were shown to restrict respiratory bursts and the formation of neutrophil extracellular traps in activated human neutrophils. FlavoLG and isoorientin were also shown to inhibit SARS-CoV-2 pseudovirus infection by interfering with the binding of the SARS-CoV-2 spike on ACE2. These results provide scientific evidence indicating the efficacy of L. gracile as a potential supplement for treating neutrophil-associated COVID-19.

Collagen has been considered a key treatment option in preventing damage to the articular cartilage over time and supporting the healing process, following the onset of osteoarthritis (OA). This study aimed to investigate the effect of collagen fermented from jellyfish (FJC) by Bacillus subtilis natto on anterior cruciate ligament transection with medial meniscectomy (ACLT + MMx)-induced knee OA in high-fat diet (HFD)-induced obesity in rats. The male Sprague–Dawley rats were fed an HFD for 6 weeks before ACLT + MMx surgery, after which they were administered a daily oral gavage of saline (control, OA, and OBOA), either with FJC (20 mg/kg, 40 mg/kg, and 100 mg/kg body weight) or glucosamine sulfate as a positive control (GS; 200 mg/kg body weight) for 6 weeks. Treatment with FJC decreased the fat weight, triglyceride, and total cholesterol levels in obese rats. Additionally, FJC downregulated the expression of some proinflammatory cytokines, including tumor necrosis factor-α, cyclooxygenase-2, and nitric oxide; suppressed leptin and adiponectin expression; and attenuated cartilage degradation. It also decreased the activities of matrix metalloproteinase (MMP)-1 and MMP-3. These results demonstrated that FJC showed a protective effect on articular cartilage and also suppressed the degradation of cartilage in an animal OA model, suggesting its potential efficacy as a promising candidate for OA treatment.

Abstract Background The WALANT (wide-awake local anesthesia with no tourniquet) technique was based on local infiltration of lidocaine and epinephrine. This technique has rapidly gained popularity in recent years and can perform most hand operations. This study aimed to investigate the time spent on anesthesia and operation and perform an economic analysis among general anesthesia, wrist block with a tourniquet, and the WALANT technique for the internal fixation of metacarpal fractures. Methods We retrospectively reviewed all the single metacarpal fractures managed with the same procedure, open reduction, and internal fixation with the plate between January 2015 and December 2019. They were divided into three groups according to the method of anesthesia: (1) general anesthesia (GA group), (2) wrist block with a tourniquet (WB group), and (3) WALANT technique (WALANT group). We collected and analyzed patient demographic data, perioperative or postoperative complications, number of hospital days, and postoperative functional recovery assessment. Results A total of 63 patients met the inclusion criteria, including 24 in the GA group, 28 in the wrist block group using a tourniquet, and 11 in the WALANT group. There were no complications during the operation and follow-up in each group. The GA group had an average of 32.8 min of anesthesia time, significantly longer than the other two groups. However, there is no significant difference regarding surgical time among the presenting three groups. The discomfort of vomiting and nausea after surgery occurred in 20 patients in the GA group (38.1%). Nevertheless, there was no postoperative vomiting and nausea present in both the WB and WALANT groups. Most patients achieved full recovery of pre-injury interphalangeal and metacarpophalangeal motion at the final assessment of functional recovery. Conclusions The patients undergoing metacarpal fixation surgery under WALANT or WB had significantly less anesthesia time and postoperative vomiting and nausea. Moreover, there was no difference in surgical time and intraoperative complications. The time-related reduction improved the utilization of the operation room for additional cases. The reduction of the preoperative examination, anesthesia fee, postoperative recovery room observation, and hospitalization can effectively reduce medical costs. Furthermore, the WALANT group is more acceptable because of no tourniquet, which commonly causes discomfort.

Abstract Negative pressure wound therapy (NPWT) is usually applied in wound management and soft-tissue salvage after the development of complications. However, immediate postoperative application of NPWT over the flap coverage is seldom reported. We evaluate the effectiveness of immediate postoperative application of NPWT following fasciocutaneous or muscle flap coverage for lower leg reconstruction. A retrospective review of patients who underwent either fasciocutaneous or muscle flap coverage of lower leg soft-tissue defects applied with NPWT immediately after surgery was conducted in a level I trauma center. Sixteen patients, with an average age of 51.2 years, were included in the study. Nine patients had trauma-related soft-tissue loss, six had subsequent soft-tissue defects after debridement, and one had burn injury. Two patients had been treated with free anterolateral thigh flaps, 11 with pedicle flaps, and three with muscle flaps. All flaps survived except for those in two patients with venous congestion on postoperative day 1, which needed further debridement and skin grafting. Therefore, the use of immediate incisional NPWT is an alternative for wound care following flap coverage. The U-shaped design allows easy flap observation and temperature check. Furthermore, this method eliminates any concerns of vascular pedicle compression under negative pressure.

Abstract Associations between hepatitis C virus (HCV) and chronic kidney disease (CKD) have been reported; however, differences of renal progression between general and CKD population remain to be elucidated in prospective studies. A total of 1179 participants, who have tested for anti-HCV antibody, were enrolled and prospectively followed for 3 years. The risks associated with HCV infection, in terms of incidence of CKD, annual estimated glomerular filtration rate (eGFR) changes and 50% decline of eGFR at 3-year from baseline, were compared between normal renal function subjects and CKD patients. Overall, 111 of 233 (47.6%) CKD patients and 167 of 946 (17.7%) non-CKD subjects had HCV infection. The crude incidence rates of CKD were 226.9 per 1000 person-years and 14.8 per 1000 person-years in in HCV and non-HCV infected patients, respectively. The adjusted hazard ratio of HCV infection for incident CKD was 7.9 (95% CI 5–12.7). The HCV-infected normal renal function subjects were independently associated with increased risks of eGFR decline in the 1-year, 2-year and 3-year, respectively. The risk associations remained significant in 50% decline of eGFR at 3 years models and in different subgroup analyses. The increases of risks of eGFR decline were also notorious among overall HCV-infected CKD patients. However, the risk associations were less prominent in subgroup analyses (elderly, women and diabetic patients). The findings highlighted the importance of viral diagnosis with not only prognostic but also public health implications for preserving kidney function.

Introduction: Two common variants of sortilin-related receptor 1 gene (SORL1), rs2298813 and rs1784933, have been associated with late-onset Alzheimer’s disease (AD) in the Han Chinese population in Taiwan. However, neuroimaging correlates of these two SORL1 variants remain unknown. We aimed to determine whether the two SORL1 polymorphisms were associated with any volumetric differences in brain regions in late-onset AD patients.Methods: We recruited 200 patients with late-onset AD from Taipei Veterans General Hospital. All patients received a structural magnetic resonance (MR) imaging brain scan and completed a battery of neurocognitive tests at enrollment. We followed up to assess changes in Mini-Mental State Examination (MMSE) scores in 155 patients (77.5%) at an interval of 2 years. Volumetric measures and cortical thickness of various brain regions were performed using FreeSurfer. Regression analysis controlled for apolipoprotein E status. Multiple comparisons were corrected for using the false discovery rate.Results: The homozygous major allele of rs2298813 was associated with larger volumes in the right putamen (p = 0.0442) and right pallidum (p = 0.0346). There was no link between the rs1784933 genotypes with any regional volume or thickness of the brain. In the rs2298813 homozygous major allele carriers, the right putaminal volume was associated with verbal fluency (p = 0.008), and both the right putaminal and pallidal volumes were predictive of clinical progression at follow-up (p = 0.020). In the minor allele carriers, neither of the nuclei was related to cognitive test performance or clinical progression.Conclusion: The major and minor alleles of rs2298813 had differential effects on the right lentiform nucleus volume and distinctively modulated the association between the regional volume and cognitive function in patients with AD.