Case Report: Superior mesenteric artery vasculitis causing aneurysm following COVID-19 infection.

Objective: Arteritis refers to all infectious and non-infectious conditions that lead to inflammation of the arterial wall. However, little is known about its presence in patients with coronavirus disease 2019 (COVID-19). Most patients improved with steroids along with conservative treatments in a few studies. We report our experience with superior mesenteric artery (SMA) arteritis causing an aneurysm following COVID-19 infection. Case presentation: A 66-year-old female patient who was infected with COVID-19 1 month prior presented with abdominal pain. A computed tomography scan revealed proximal SMA arteritis. Although preliminary antibacterial treatment was initiated, the follow-up CT revealed an aggressive and fast-growing 5.7-cm SMA aneurysm. Subsequently, an open interposition bypass of the SMA aneurysm was performed successfully. As the specimens retrieved during surgery showed no bacterial colonization in the tissue or blood cultures, the patient was discharged without complications. Conclusions: The mechanism of arteritis in patients with COVID-19 has not been elucidated. In the absence of evidence of bacterial infection in arteritis, it is necessary to consider the possibility of viral infection caused by COVID-19 during the COVID-19 pandemic era and start with high-dose steroid therapy promptly.

Heat Stress Induces Alterations in Gene Expression of Actin Cytoskeleton and Filament of Cellular Components Causing Gut Disruption in Growing-Finishing Pigs.

We aimed to investigate the impact of heat stress (HS) on the expression of tight junction (TJ) proteins and the interaction between genes affecting intestinal barrier function using transcriptomics in the porcine jejunum. Twenty-four barrows (crossbred Yorkshire × Landrace × Duroc; average initial body weight, 56.71 ± 1.74 kg) were placed in different temperatures (normal temperature [NT]; HS) and reared for 56 days. At the end of the experiment, jejunal samples were collected from three pigs per treatment for transcriptome and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) analyses. We identified 43 differentially expressed genes, involving five Kyoto Encyclopedia of Genes and Genomes pathways, eight molecular functions, seven cellular components (CCs), and nine biological processes, using gene ontology enrichment analysis. Genes associated with the actin cytoskeleton, filament-binding pathways, and TJ proteins were selected and analyzed by RT-qPCR. Significant differences in relative mRNA expression showed that downregulated genes in the HS group included ZO1, CLDN1, OCLN, PCK1, and PCK2, whereas ACTG2, DES, MYL9, MYLK, TPM1, TPM2, CNN1, PDLIM3, and PCP4 were upregulated by HS (p < 0.05). These findings indicate that HS in growing-finishing pigs induces depression in gut integrity, which may be related to genes involved in the actin cytoskeleton and filaments of CC.

Association of Renal Hyperfiltration with Incidence of New-Onset Diabetes Mellitus: A Nationwide Cohort Study.

Background and Objectives: While the connection between decreased kidney function and diabetes mellitus (DM) is commonly acknowledged, there is insufficient research examining the relationship between higher-than-normal estimated glomerular filtration rate (eGFR) and the incidence risk of new-onset DM. Our research aimed to explore the relationship between an eGFR and the incidence risk of new-onset DM in the Korean general population through a nationwide longitudinal study. Methods: This research employed the cohort records of the National Health Insurance Service in Korea, analyzing records from 2,294,358 individuals between the ages of 20 and 79 who underwent health check-ups between 2010 and 2011. The eGFR levels from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were used to assess the renal function. New-onset DM was defined as two or more claims with the International Classification of Diseases-10 classification codes E10 to E14, being prescribed any medication for lowering blood glucose, or having a record of fasting plasma glucose levels of ≥126 mg/dL from a health examination after the index date. Results: The mean age of subjects was 47.34 ± 13.76 years. The 150,813 (6.57%) new-onset DM cases were identified over a median follow-up of 9.63 years. In the multivariable Cox regression analysis, in comparison with the 5th decile, the 10th (≥114.12 mL/min/1.73 m2) (hazard ratio (HR): 0.52, 95% confidence interval (CI) (0.50-0.54), p < 0.001) eGFR decile was significantly associated with a decreased incidence of new-onset DM. Moreover, eGFR >120 mL/min/1.73 m2 was associated with a reduced risk of new-onset DM (HR: 0.40, 95% CI (0.39-0.42), p < 0.001). These results were consistent regardless of the presence of impaired glucose tolerance, age, or obesity. Conclusion: Our study showed higher-than-normal eGFR levels were associated with a lower risk of incidence for new-onset DM regardless of the presence of impaired glucose tolerance, age, or obesity. In general population, higher-than-normal eGFR may be associated with a lower risk of incidence of new-onset DM.

Content Analysis of Online Resources Regarding Needs for Advance Care Planning.

Purpose: This study aimed to investigate advance care planning needs expressed online. Methods: This study collected data from online community posts and healthcare news sites. The search keywords included "death," "euthanasia," "life-sustaining medical care," "life-sustaining treatment," "advance directives," "advance medical directives," and "advance care planning." Data collection spanned from February 2018 to February 14, 2020. Out of 2,288 posts, 1,190 were included in the final analysis. Data analysis was conducted using NVivo 12, a qualitative data analysis software program. Results: Content analysis categorized patients' advance care planning needs into eight themes, 11 theme clusters, and 33 meaningful statements. Similarly, care providers' advance care planning needs were categorized into eight themes, 14 theme clusters, and 42 meaningful statements. The identified themes of care needs included life-sustaining medical care, decision-making related to life-sustaining medical care, physical care, environmental care, supportive and spiritual care, respect, preparing for death, and family. Conclusion: This study identified care needs from the perspectives of patients and their families. The findings may serve as preliminary data for future research and clinical applications.

Postoperative Calcaneocuboid Joint Subluxation and Midtarsal Joint Changes in Pediatric Idiopathic Flexible Flatfoot Treated With Calcaneal Lengthening Osteotomy: A Midterm Follow-up Study.

BACKGROUND: Calcaneal lengthening osteotomy (CLO) is one of the main surgical options for treatment of pediatric idiopathic flexible flatfoot (FFF). Reportedly, calcaneocuboid (CC) joint subluxation occurs after CLO; however, its effect on the midfoot remains unclear. This study aimed to investigate the radiologic midterm results after CLO treatment in pediatric idiopathic FFF. METHODS: We evaluated 23 pediatric patients with idiopathic FFF aged ≥8 years, who underwent CLO from 1999 to 2017 owing to moderate to severe flatfoot deformity (assessed by visual inspection). Patients aged between 8 and 14 years were included (mean follow-up: 6.3 years; range, 3.1-11.4 years). Anteroposterior and lateral weightbearing foot radiographs were assessed for radiologic parameters preoperatively and at the 3-month, 1-year, and final follow-ups postoperatively. RESULTS: All patients had immediate postoperative radiologic correction of the flatfoot deformity, and these improvements were maintained until the final follow-up. The mean allograft length inserted was 9 (range, 8-10) mm. There was increased CC joint subluxation after CLO, but it improved continuously until the final follow-up. A CC joint spur was newly noted in 1 case. There were 24 cases (24/39, 61.5%) of talonavicular (TN) joint spurs at the final follow-up, but 19 of these were already present on the preoperative radiographs (19/24, 79.2%). Further, the new-onset TN joint spurs were not associated with preoperative clinicoradiologic factors. CONCLUSION: In pediatric patients with idiopathic FFF receiving CLO treatment, preoperative radiologic angles improved. CC joint subluxation increased after surgery; however, it gradually reduced without evidence of CC joint arthritic changes over the time period studied in this cohort.

Distraction impact of concurrent conversation on event-related potential based brain-computer interfaces.

Objective.This study investigates the impact of conversation on the performance of visual event-related potential (ERP)-based brain-computer interfaces (BCIs), considering distractions in real life environment. The research aims to understand how cognitive distractions from speaking and listening activities affect ERP-BCI performance.Approach.The experiment employs a dual-task paradigm where participants control a smart light using visual ERP-BCIs while simultaneously conducting speaking or listening tasks.Main results.The findings reveal that speaking notably degrades BCI accuracy and the amplitude of ERP components, while increases the latency variability of ERP components and occipital alpha power. In contrast, listening and simple syllable repetition tasks have a lesser impact on these variables. The results suggest that speaking activity significantly distracts visual attentional processes critical for BCI operationSignificance. This study highlights the need to take distractions by daily conversation into account of the design and implementation of ERP-BCIs.

Opioid-Free Using Ketamine versus Opioid-Sparing Anesthesia during the Intraoperative Period in Video-Assisted Thoracoscopic Surgery: A Randomized Controlled Trial.

Opioids effectively manage perioperative pain but have numerous adverse effects. Opioid-free anesthesia (OFA) eliminates intraoperative opioid use; however, evidence for its use in video-assisted thoracoscopic surgery (VATS) is limited. This study assessed the effect of OFA using ketamine in VATS patients compared to opioid-sparing anesthesia (OSA). A total of 91 patients undergoing VATS lobectomy or segmentectomy were randomized to either the OFA group (ketamine) or the OSA group (remifentanil). The primary outcome was the quality of recovery (QoR) on postoperative day (POD) 1, measured with the QoR-40 questionnaire. Secondary outcomes included postoperative pain scores and adverse events. Both groups had comparable baseline and surgical characteristics. On POD 1, the QoR-40 score was higher in the OFA group than in the OSA group (164.3 ± 10.8 vs. 158.7 ± 10.6; mean difference: 5.6, 95% CI: 1.1, 10.0; p = 0.015), though this did not meet the pre-specified minimal clinically important difference of 6.3. The visual analog scale score was lower in the OFA group as compared to the OSA group at 0-1 h (4.2 ± 2.3 vs. 6.2 ± 2.1; p < 0.001) and 1-4 h after surgery (3.4 ± 1.8 vs. 4.6 ± 1.9; p = 0.003). The OFA group had a lower incidence of PONV (2 [4.4%] vs. 9 [19.6%]; p = 0.049) and postoperative shivering (4 [8.9%] vs. 13 [28.3%]; p = 0.030) than the OSA group at 0-1 h after surgery. Using OFA with ketamine proved feasible, as indicated by the stable intraoperative hemodynamics and absence of intraoperative awareness. Patients undergoing VATS with OFA using ketamine showed a statistically significant, but clinically insignificant, QoR improvement compared to those receiving OSA with remifentanil.

Construction and validation of a synthetic phage-displayed nanobody library.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

A Brg1-Rme1 circuit in Candida albicans hyphal gene regulation.

Major Candida albicans virulence traits include its ability to make hyphae, to produce a biofilm, and to damage host cells. These traits depend upon expression of hypha-associated genes. A gene expression comparison among clinical isolates suggested that transcription factor Rme1, established by previous studies to be a positive regulator of chlamydospore formation, may also be a negative regulator of hypha-associated genes. Engineered RME1 overexpression supported this hypothesis, but no relevant rme1Δ/Δ mutant phenotype was detected. We reasoned that Rme1 may function within a specific regulatory pathway. This idea was supported by our finding that an rme1Δ/Δ mutation relieves the need for biofilm regulator Brg1 in biofilm formation. The impact of the rme1Δ/Δ mutation is most prominent under static or "biofilm-like" growth conditions. RNA sequencing (RNA-seq) of cells grown under biofilm-like conditions indicates that Brg1 activates hypha-associated genes indirectly via repression of RME1: hypha-associated gene expression levels are substantially reduced in a brg1Δ/Δ mutant and partially restored in a brg1Δ/Δ rme1Δ/Δ double mutant. An rme1Δ/Δ mutation does not simply bypass Brg1, because iron homeostasis genes depend upon Brg1 regardless of Rme1. Rme1 thus connects Brg1 to the targets relevant to hypha and biofilm formation under biofilm growth conditions.IMPORTANCECandida albicans is a major fungal pathogen of humans, and its ability to grow as a surface-associated biofilm on implanted devices is a common cause of infection. Here, we describe a new regulator of biofilm formation, RME1, whose activity is most prominent under biofilm-like growth conditions.

Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma.

Introduction: We aimed to evaluate the generalizability of retrospective single-center cohort studies on prognosis of hepatocellular carcinoma (HCC) by comparing overall survival (OS) after various treatments between a nationwide multicenter cohort and a single-center cohort of HCC patients. Methods: Patients newly diagnosed with HCC between January 2008 and December 2018 were analyzed using data from the Korean Primary Liver Cancer Registry (multicenter cohort, n=16,443), and the Asan Medical Center HCC registry (single-center cohort, n=15,655). The primary outcome, OS after initial treatment, was compared between the two cohorts for both the entire population and for subcohorts with Child-Pugh A liver function (n=2797 and n=5151, respectively) treated according to the Barcelona-Clinic-Liver-Cancer (BCLC) strategy, using Log rank test and Cox proportional hazard models. Results: Patients of BCLC stages 0 and A (59.3% vs 35.2%) and patients who received curative treatment (42.1% vs 32.1%) were more frequently observed in the single-center cohort (Ps<0.001). Multivariable analysis revealed significant differences between the two cohorts in OS according to type of treatment: the multicenter cohort was associated with higher risk of mortality among patients who received curative (adjusted hazard ratio [95% confidence interval], 1.48 [1.39-1.59]) and non-curative (1.22 [1.17-1.27]) treatments, whereas the risk was lower in patients treated with systemic therapy (0.83 [0.74-0.92]) and best supportive care (0.85 [0.79-0.91]). Subcohort analysis also demonstrated significantly different OS between the two cohorts, with a higher risk of mortality in multicenter cohort patients who received chemoembolization (1.72 [1.48-2.00]) and ablation (1.44 [1.08-1.92]). Conclusion: Comparisons of single-center and multicenter cohorts of HCC patients revealed significant differences in OS according to treatment modality after adjustment for prognostic variables. Therefore, the results of retrospective single-center cohort studies of HCC treatments may not be generalizable to real-world practice.

Lead exposure estimation through a physiologically based toxicokinetic model using human biomonitoring data and comparison with scenario-based exposure assessment: A case study in Korean adults.

Pb toxicity is linked to cardiovascular and nephrotoxicity issues. Exposure to this heavy metal can occur through food and drinking water. Therefore, this study aimed to evaluate Pb exposure and assess health risks in Korean adults using a physiologically based toxicokinetic (PBTK) model. Human blood Pb concentrations were monitored using the Korean National Environmental Health Survey (KoNEHS) Cycle 4. The average Pb exposure in Korean adults was 0.520 µg/kg bw/day. The PBTK results were compared with scenario-based results from the 2021 risk assessment report of five heavy metals, including Pb, conducted by the MFDS. Exposure determined through reverse dosimetry was approximately two times higher than scenario-based exposure (0.264 µg/kg bw/day). The higher exposure levels obtained during PBTK analysis may be attributed to sustained exposure within historically more contaminated living environments and the long half-life of Pb. These findings suggest that the PBTK-based method can quantify aggregated exposure levels in the body over time, potentially serving as a complementary tool to address the constraints of scenario-based assessment methods for integrated risk assessment. Moreover, this model is convenient and cost-effective compared with scenario-based exposure estimation. These findings can facilitate the application of model for tracking continuous national changes in hazardous substance levels.

Systematic analysis of the Candida albicans kinome reveals environmentally contingent protein kinase-mediated regulation of filamentation and biofilm formation in vitro and in vivo.

Protein kinases are critical regulatory proteins in both prokaryotes and eukaryotes. Accordingly, protein kinases represent a common drug target for a wide range of human diseases. Therefore, understanding protein kinase function in human pathogens such as the fungus Candida albicans is likely to extend our knowledge of its pathobiology and identify new potential therapies. To facilitate the study of C. albicans protein kinases, we constructed a library of 99 non-essential protein kinase homozygous deletion mutants marked with barcodes in the widely used SN genetic background. Here, we describe the construction of this library and the characterization of the competitive fitness of the protein kinase mutants under 11 different growth and stress conditions. We also screened the library for protein kinase mutants with altered filamentation and biofilm formation, two critical virulence traits of C. albicans. An extensive network of protein kinases governs these virulence traits in a manner highly dependent on the specific environmental conditions. Studies on specific protein kinases revealed that (i) the cell wall integrity MAPK pathway plays a condition-dependent role in filament initiation and elongation; (ii) the hyper-osmolar glycerol MAPK pathway is required for both filamentation and biofilm formation, particularly in the setting of in vivo catheter infection; and (iii) Sok1 is dispensable for filamentation in hypoxic environments at the basal level of a biofilm but is required for filamentation in normoxia. In addition to providing a new genetic resource for the community, these observations emphasize the environmentally contingent function of C. albicans protein kinases.IMPORTANCECandida albicans is one of the most common causes of fungal disease in humans for which new therapies are needed. Protein kinases are key regulatory proteins and are increasingly targeted by drugs for the treatment of a wide range of diseases. Understanding protein kinase function in C. albicans pathogenesis may facilitate the development of new antifungal drugs. Here, we describe a new library of 99 protein kinase deletion mutants to facilitate the study of protein kinases. Furthermore, we show that the function of protein kinases in two virulence-related processes, filamentation and biofilm formation, is dependent on the specific environmental conditions.

Frequency-Dependent Dielectric Permittivity and Water Permeability in Ordered Mesoporous Silica-Grafted Fluorinated Polyimides.

Polymers with a low dielectric constant (Dk) are promising materials for high-speed communication networks, which demand exceptional thermal stability, ultralow Dk and dissipation factor, and minimum moisture absorption. In this paper, we prepared a series of novel low-Dk polyimide films containing an MCM-41-type amino-functionalized mesoporous silica (AMS) via in situ polymerization and subsequent thermal imidization and investigated their morphologies, thermal properties, frequency-dependent dielectric behaviors, and water permeabilities. Incorporating 6 wt.% AMS reduced the Dk at 1 MHz from 2.91 of the pristine fluorinated polyimide (FPI) to 2.67 of the AMS-grafted FPI (FPI-g-AMS), attributed to the free volume and low polarizability of fluorine moieties in the backbone and the incorporation of air voids within the mesoporous AMS particles. The FPI-g-AMS films presented a stable dissipation factor across a wide frequency range. Introducing a silane coupling agent increased the hydrophobicity of AMS surfaces, which inhibited the approaching of the water molecules, avoiding the hydrolysis of Si-O-Si bonds of the AMS pore walls. The increased tortuosity caused by the AMS particles also reduced water permeability. All the FPI-g-AMS films displayed excellent thermooxidative/thermomechanical stability, including a high 5% weight loss temperature (>531 °C), char residue at 800 °C (>51%), and glass transition temperature (>300 °C).

Comparison of Nefopam-Based Patient-Controlled Analgesia with Opioid-Based Patient-Controlled Analgesia for Postoperative Pain Management in Immediate Breast Reconstruction Surgery: A Randomized Controlled Trial.

Background/Objectives: Immediate breast reconstruction surgery (BRS) often leads to significant postoperative pain, necessitating effective analgesia. This study aimed to compare the analgesic efficacy of patient-controlled analgesia (PCA) containing nefopam with that of PCA containing opioids alone in patients undergoing BRS. Methods: A prospective, double-blind, randomized controlled trial was conducted on 120 patients undergoing immediate BRS after mastectomy. Patients were randomly allocated to receive PCA with fentanyl alone (Group F: fentanyl 10 mcg/kg), fentanyl and nefopam (Group FN: fentanyl 5 mcg/kg + nefopam 1 mg/kg), or nefopam alone (Group N: nefopam 2 mg/kg). Pain intensity (expressed in VASr and VASm), opioid consumption, and opioid-related complications were assessed. Results: PCA with nefopam, either alone or in combination with opioids, demonstrated non-inferior analgesic efficacy compared to PCA with fentanyl alone. At 24 h postoperatively, the VASr scores were 2.9 ± 1.0 in Group F, 3.1 ± 1.2 in Group FN, and 2.8 ± 0.9 in Group N (p = 0.501). At the same timepoint, the VASm scores were 4.1 ± 1.2 in Group F, 4.5 ± 1.5 in Group FN, and 3.8 ± 1.4 in Group N (p = 0.129). Significant differences among the three groups were observed at all timepoints except for PACU in terms of the total opioid consumption (p < 0.0001). However, there were no significant differences in opioid-related complications among the three groups. Conclusions: PCA with nefopam, whether alone or in combination with opioids, offers non-inferior analgesic efficacy compared to PCA with fentanyl alone in patients undergoing immediate BRS.

Effect of Preoperative Clear Liquid Consumption on Postoperative Recovery in Pediatric Patients Undergoing Minimally Invasive Repair of Pectus Excavatum: A Prospective Randomized Controlled Study.

Background/Objectives: Preoperative fasting guidelines traditionally aim to reduce pulmonary aspiration risk. However, concerns over the adverse effects of prolonged fasting have led to exploring alternatives. This study aimed to investigate the impact of preoperative clear liquid intake on postoperative outcomes in children undergoing minimally invasive repair of pectus excavatum (MIRPE). Methods: A prospective randomized controlled study was conducted on children aged 3-6 years scheduled for elective MIRPE. Patients were randomized into either a routine overnight fasting group (NPO) or a clear liquid group. The incidence and severity of emergence delirium (ED) were assessed using Pediatric Anesthesia Emergence Delirium (PAED) and Watcha scales at recovery room. Postoperative pain scores and opioid requirements were evaluated at intervals of 1-6 h, 6-12 h, and 12-24 h after surgery. Results: Fasting time was 178.6 ± 149.5 min and 608.9 ± 148.4 min in the clear liquid group compared and NPO group, respectively. The incidence of ED, measured by PAED and Watcha scales, was lower in the clear liquid group (PAED score ≥ 12: 55.6% vs. 85.2%, p = 0.037; Watcha score ≥ 3: 51.9% vs. 85.2%, p = 0.019). The highest PAED score recorded in the recovery room was significantly lower in the clear liquid group (11.4 ± 2.8 vs. 14.6 ± 2.8, p < 0.001). Clear liquid group showed significantly lower pain scores at 1-6, 6-12, and 12-24 h postoperatively. Additionally, clear liquid group had lower opioid requirement at 1-6 and 6-12 h postoperatively. Conclusions: Preoperative clear liquid consumption was associated with a lower incidence of ED in pediatric patients undergoing MIRPE.

NF2-Related Schwannomatosis (NF2): Molecular Insights and Therapeutic Avenues.

NF2-related schwannomatosis (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2 deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2 deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

Virus-like particles expressing microneme-associated antigen of Plasmodium berghei confer better protection than those expressing apical membrane antigen 1.

Malaria is a global disease affecting a large portion of the world's population. Although vaccines have recently become available, their efficacies are suboptimal. We generated virus-like particles (VLPs) that expressed either apical membrane antigen 1 (AMA1) or microneme-associated antigen (MIC) of Plasmodium berghei and compared their efficacy in BALB/c mice. We found that immune sera acquired from AMA1 VLP- or MIC VLP-immunized mice specifically interacted with the antigen of choice and the whole P. berghei lysate antigen, indicating that the antibodies were highly parasite-specific. Both VLP vaccines significantly enhanced germinal center B cell frequencies in the inguinal lymph nodes of mice compared with the control, but only the mice that received MIC VLPs showed significantly enhanced CD4+ T cell responses in the blood following P. berghei challenge infection. AMA1 and MIC VLPs significantly suppressed TNF-α and interleukin-10 production but had a negligible effect on interferon-γ. Both VLPs prevented excessive parasitemia buildup in immunized mice, although parasite burden reduction induced by MIC VLPs was slightly more effective than that induced by AMA1. Both VLPs were equally effective at preventing body weight loss. Our findings demonstrated that the MIC VLP was an effective inducer of protection against murine experimental malaria and should be the focus of further development.

Comparison of the impact of longitudinal body mass index changes on cardiac arrest risk between normal and overweight populations.

BACKGROUND: Being overweight is a key modifiable risk factor for cardiovascular disease. However, the impact of longitudinal changes in body mass index (BMI) on the risk of out-of-hospital cardiac arrests (OHCA) remains unclear, especially among overweight populations. METHODS: This nested case-control study utilized data from the Korean National Health Information Database between 2009 and 2018. A total of 23 453 OHCA patients, who underwent national health check-ups within 1 and 2-4 years before OHCA occurrence, and 31 686 controls, who underwent similar national health check-ups, were included. The study population was matched for sex, age and survival status. Conditional logistic regression was employed to analyse the odds ratios (ORs) and 95% confidence intervals (CIs) of each BMI per cent change in assessing the risk of OHCA occurrence within 1 year. RESULTS: A reverse J-shaped association between BMI per cent change and OHCA risk was observed, even among overweight populations. Among the overweight populations, weight loss significantly increased OHCA risk, with ORs (95% CI) of 4.10 (3.23-5.20) for severe weight loss (BMI decrease > 15%), 2.72 (2.33-3.17) for moderate weight loss (BMI decrease 10-15%) and 1.46 (1.35-1.59) for mild weight loss (BMI decrease 5-10%). Conversely, mild weight gain (BMI increase 5-10%) did not significantly increase OHCA risk. The impact of weight changes on the occurrence of OHCA differed by sex, being more prominent in males. CONCLUSIONS: Significant weight changes within a 4-year period increase the risk of OHCA with a reverse J-shaped association, even among overweight and obese individuals. Maintaining a stable weight could be a reliable public health strategy irrespective of the weight status, particularly for males.

Tonic type 2 immunity is a critical tissue checkpoint controlling autoimmunity in the skin.

Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.