Distribution, sources, and risk assessment of polycyclic aromatic hydrocarbons in surface soils and plants from industrial and agricultural areas, Junggar Basin, Xinjiang.

The contamination characteristics of Polycyclic Aromatic Hydrocarbons (PAHs) in different environmental functional areas are different. In this study, the contamination of PAHs in soils and common plants in typical mining and farmland areas in Xinjiang, China, was analyzed. The results showed that the contamination levels of PAHs in mining soils were significantly higher than those in farmland soils, and the mining soils were dominated by 4-5-ring PAHs and farmland soils by 3-4-ring PAHs. Analysis of their sources using a positive definite factor matrix model showed that PAHs in mining soils mainly originated from coal and natural gas combustion, and transportation processes; while farmland soils mainly came from biomass and coal combustion, and fossil fuel volatile spills. The cancer risk of PAHs in soils was evaluated using a combination of the Monte Carlo and the lifetime carcinogenic risk models, and the results showed that the overall level of cancer risk for mining soils was higher than that for farmland soils, and can put some people in high risk of cancer. For plant samples, except for individual crop samples, the contamination levels of mining plants and crops were similar, with 4-5-ring PAHs dominating in desert plants in mining areas and the highest proportion of 3-ring PAHs in crops in agricultural fields, and PAHs in both plants were mainly from biomass and coal combustion. The results of correlation analysis showed that 2-ring PAHs in crop roots were significantly positively correlated with it in corresponding soils, and some high-ring PAHs in crop leaves were significantly negatively correlated with it in corresponding soils. Therefore, there were significant differences in the pollution characteristics of PAHs in soils and common plants in mining and agricultural areas. Human health risks and ecological risks are mainly concentrated in mining areas, and appropriate intervention measures should be taken for pollution remediation.

Human Umbilical Cord Mesenchymal Stem Cells-Derived Extracellular Vesicles for Rat Jawbone Regeneration in Periapical Periodontitis.

Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) have great potential for bone remodeling and anti-inflammatory therapy. For the repair and reconstruction of inflammatory jawbone defects caused by periapical periodontitis, bone meal filling after debridement is commonly used in the clinic. However, this treatment has disadvantages such as large individual differences and the need for surgical operation. Therefore, it is of great significance to search for other bioactive substances that can promote jawbone regeneration in periapical periodontitis. Herein, it is found that CT results showed that local injection of human umbilical cord mesenchymal stem cells-derived extracellular vesicles (HUC-MSCs-EVs) and bone meal filling into the alveolar bone defect area could promote bone tissue regeneration using a rat model of a jawbone defect in periapical periodontitis. Histologically, the new periodontal tissue in the bone defect area was thicker, and the number of blood vessels was higher by local injection of HUC-MSCs-EVs, and fewer inflammatory cells and osteoclasts were formed compared to bone meal filling. In vitro, HUC-MSCs-EVs can be internalized by rat bone marrow mesenchymal stem cells (BMSCs), enhancing the ability for proliferation and migration of BMSCs. Additionally, 20 µg/mL HUC-MSCs-EVs can facilitate the expression of osteogenic genes and proteins including runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin (OPN). In summary, in vivo and in vitro experiments showed that HUC-MSCs-EVs can promote bone regeneration in periapical periodontitis, and the effect of tissue regeneration is better than that of traditional bone meal treatment. Therefore, local injection of HUC-MSCs-EVs may be an effective method to promote jawbone regeneration in periapical periodontitis.

PACAP/VIP in the prefrontal cortex mediates the rapid antidepressant effects of zhizichi decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhizichi decoction (ZZCD) is a traditional Chinese medicine formula that consists of Gardenia jasminoides J.Ellis (GJ) and Semen Sojae Praeparatum. It is used to treat insomnia and emotion-related disorders, such as irritability. Previous studies have found that GJ has a rapid antidepressant effect. The study found that ZZCD is safer than GJ at the same dosage. Consequently, ZZCD is a superior drug with quicker antidepressant effects than GJ. The rapid antidepressant effects of ZZCD were examined in this study, along with the components that make up this effect. It was determined that the activation of prefrontal Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)/Vasoactive Intestinal Polypeptide (VIP) is essential for ZZCD's rapid antidepressant effects. AIM: This study identified and discussed the rapid antidepressant effects and biological mechanisms of ZZCD. MATERIALS AND METHODS: The tail suspension test (TST) and the forced swimming test (FST) were used to screen the effective dosage of ZZCD (0.67 g/kg, 1 g/kg, 4 g/kg). The effective dosage of ZZCD (1 g/kg) was tested in the TST conducted on Institute of Cancer Research (ICR) mice that were treated with lipopolysaccharide (LPS) at a concentration of 0.1 mg/mL. To confirm the expression of c-Fos, PACAP, and VIP in the prefrontal cortex (PFC), immunohistochemistry tests were conducted on mice following intragastric injection of ZZCD. Chemical characterization analysis and HPLC quality control analysis were conducted using UHPLC-Q-Obitrap-HRMS and chromatographic analysis. RESULTS: The results showed that an acute administration of ZZCD (1 g/kg) decreased the immobility time of Kunming (KM) mice in TST and FST. Depressive behaviors in TST-induced ICR mice treated with LPS (0.1 mg/mL) were reversed by ZZCD (1 g/kg). The results of immunohistochemical experiments showed that ZZCD (1 g/kg) activated neurons in the PFC and PACAP/VIP in the PFC. In this study, 22 substances in ZZCD were identified. Five primary distinctive fingerprint peaks-geniposide, genistin, genipin-1-ß-D-gentiobioside, glycitin, and daidzin-were found among the ten common peaks. CONCLUSION: ZZCD (1 g/kg) had significant rapid antidepressant effects. PACAP/VIP in the PFC was found to mediate the rapid antidepressant effects of ZZCD.

Non-neoplastic B-cell predominant lymphoid proliferations at the organs exposed to external environment mimicking lymphoma: A potential diagnostic pitfall.

Background: Typically, lymphatic tissue proliferative lesions include either benign lesions or lymphoma. However, not all lymphatic lesions can currently be accurately classified into one category, particularly in mucosal areas that are in contact with the external environment.Aims: To explore the morphology, immunophenotype, and molecular changes of Non-neoplastic B-cell predominant lymphoid proliferations (NBPLP) in pathological areas that are exposed to external surroundings which mimicked lymphoma.Methods and Results: 18 cases of Atypical lymphoid hyperplasia (AtLP)  were retrieved in this study. The biopsy samples were mucosal samples obtained from areas exposed to external surroundings, including intestines, urethra, cervix, tonsils, and tongue. Microscopically, there is a different level of B cell hyperplasia accompanied by morphological atypia. We categorized the morphology into 4 groups: type A (7/18), type B (3/18), type C (3/18), type D (5/18). Part of the AtLP was found positive for BCR gene rearrangement (6/15), and TCR gene rearrangement (1/4). The follow-up period ranged from 14.2 to 70 months. No evidence of lymphoma was found. Therefore, we diagnosed all of the presented cases as NBPLP. We illustrated the key differential points and provided valuable diagnostic experience on each subtype.Conclusions: Areas exposed to the external environment are commonly exposed to antigen and easily present with AtLP of NBPLP, accompanying with positive IGH rearrangement. Therefore, a comprehensive evaluation of macroscopic, morphology, immunophenotype, and molecular diagnostics is required to prevent the overdiagnosis of lymphoma.

Injectable thermo-sensitive hydrogel enhances anti-tumor potency of engineered Lactococcus lactis by activating dendritic cells and effective memory T cells.

Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells. In previous studies, FOLactis was designed, which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand, leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral injection. However, it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal pressure. For patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors, intratumoral injection is not feasible and peritumoral maybe a better choice. Herein, an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 hydrogels. Peritumoral injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells (TEM), playing the role of artificial lymph island. Besides, administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors, resulting in an extended survival time. Therefore, these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.

Functional and Genetic Analyses Unveil the Implication of CDC27 in Hemifacial Microsomia.

Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27. cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27-/- mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation.

Quality Characteristics and Storage Stability of Frying Steak Utilizing Wax-Based Korean Pine Seed Oil.

To investigate the disparities in product quality and storage stability between wax-based Korean pine seed oil gel and butter when used for frying steak, a comparative analysis was conducted on cooking loss, color, texture characteristics, sensory evaluation, and volatile flavor substances using headspace solid phase microextraction combined with GM-MS. Furthermore, the storage stability was assessed. The findings revealed that the cooking loss rate of steaks significantly increased with doneness, with butter steak exhibiting a significantly higher loss rate compared to the three oil gel steaks. Hardness, chewiness, and adhesiveness greatly increased as doneness progressed; however, cohesiveness, elasticity, and resilience showed minimal variation. The L* value and b* value of steaks initially increased before stabilizing with increasing doneness levels while the a* value first rose before gradually declining. Medium rare steak received the highest sensory score among all categories tested and 69 volatile flavor compounds were detected. Multivariate data analysis indicated similarities in volatile compounds between butter steak and BW (wax-based Korean pine seed oil gel) steak groups. Additionally, during storage at 4 °C temperature conditions pH level retention water content TVB-N (total volatile basic nitrogen), TBARS (thiobarbituric acid reactive substances) were evaluated to determine advantages or disadvantages within each group: Beeswax (BW) > Carnauba wax (CW) > Rice bran wax (RBW) > butter based on these parameters' values. It can be concluded that utilizing wax-based Korean pine seed oil gel for frying steaks not only effectively retains significant amounts of unsaturated fatty acids but also preserves steak quality while extending shelf life-a healthier cooking method resulting in reduced oil absorption.

Petersen's hernia after gastric cancer surgery: Unravelling clinical characteristics and optimal management approaches.

INTRODUCTION: Petersen's hernia is a rare and serious complication that can occur after radical gastrectomy and digestive tract reconstruction for gastric cancer. This article summarises the symptoms, diagnosis and treatment of Petersen's hernia after surgery for gastric cancer. PATIENTS AND METHODS: A retrospective analysis was conducted on 11 male patients who were diagnosed with Petersen's hernia and underwent surgical treatment at our hospital from January 2020 to December 2022. Their clinical manifestations, perioperative conditions and follow-up after treatment were collected. RESULTS: The median age was 58.5 years (range: 45-73), and the median time since gastrectomy was 24 months (range: 4-125). Open distal gastrectomy (45.5%) and open total gastrectomy (27.3%) were the most common procedures. Roux-en-Y (81.8%) was the predominant anastomosis method. All patients underwent emergency surgery within a median time of 30 h (range: 4-45). Intestine necrosis occurred in 36.4% of cases, with a perioperative death rate of 27.3%. CONCLUSION: Petersen's hernia after gastric cancer surgery can quickly lead to necrotising intestinal obstruction and poor prognosis. Enhanced abdominal computed tomography should be performed as soon as possible, and early exploratory laparotomy should be done to avoid intestinal necrosis. Routine closure of the mesenteric defect after gastric cancer resection can prevent the occurrence of Petersen's hernia. This article highlights the need for increased awareness and preventive measures to minimise the occurrence of Petersen's hernia in gastric cancer patients. It emphasises the importance of early detection and appropriate management strategies for improved patient outcomes.

Intra-bone marrow injection with engineered Lactococcus lactis for the treatment of metastatic tumors: Primary report.

Bone marrow has the capacity to produce different types of immune cells, such as natural killer cells, macrophages, dendritic cells (DCs) and T cells. Improving the activation of immune cells in the bone marrow can enhance the therapy of bone metastases. Previously, we designed an engineered probiotic Lactococcus lactis, capable of expressing a fusion protein of Fms-like tyrosine kinase 3 ligand and co-stimulator OX40 ligand (FOLactis), and proved that it can induce the activation and differentiation of several immune cells. In this research, we successfully establish mouse models of bone metastasis, lung metastasis and intraperitoneal dissemination, and we are the first to directly inject the probiotics into the bone marrow to inhibit tumor growth. We observe that injecting FOLactis into the bone marrow of mice can better regulate the immune microenvironment of tumor-bearing mice, resulting in a tumor-suppressive effect. Compared to subcutaneous (s.c.) injection, intra-bone marrow (IBM) injection is more effective in increasing mature DCs and CD8+ T cells and prolonging the survival of tumor-bearing mice. Our results confirm that IBM injection of FOLactis reprograms the immune microenvironment of bone marrow and has remarkable effectiveness in various metastatic tumor models.

Engineered lactococcus lactis intrapleural therapy promotes regression of malignant pleural effusion by enhancing antitumor immunity.

Intrapleural immunotherapies have emerged as a prominent field in treating malignant pleural effusion (MPE). Among these, bacteria-based intrapleural therapy has exerted an anti-MPE effect by immuno-stimulating or cytotoxic properties. We previously engineered a probiotic Lactococcus lactis (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 and co-stimulator OX40 ligands. FOLactis activates tumor antigen-specific immune responses and displays systemic antitumor efficacy via intratumoral delivery. However, no available lesions exist in the pleural cavity of patients with MPE for intratumoral administration. Therefore, we further optimize FOLactis to treat MPE through intrapleural injection. Intrapleural administration of FOLactis (I-Pl FOLactis) not only distinctly suppresses MPE and pleural tumor nodules, but also significantly extends noticeable survival in MPE-bearing murine models. The proportion of CD103+ dendritic cells (DCs) in tumor-draining lymph nodes increases three-fold in FOLactis group, compared to the wild-type bacteria group. The enhanced DCs recruitment promotes the infiltration of effector memory T and CD8+ T cells, as well as the activation of NK cells and the polarization of macrophages to M1. Programmed death 1 blockade antibody combination further enhances the antitumor efficacy of I-Pl FOLactis. In summary, we first develop an innovative intrapleural strategy based on FOLactis, exhibiting remarkable efficacy and favorable biosafety profiles. These findings suggest prospective clinical translation of engineered probiotics for managing MPE through direct administration into the pleural cavity.

An Injectable Magnesium-Based Cement Stimulated with NIR for Drug-Controlled Release and Osteogenic Potential.

Magnesium phosphate bone cement (MPC) has gained widespread usage in orthopedic implantation due to its fast-setting and high initial strength benefits. However, the simultaneous attainment of drug-controlled release and osteogenic potential in MPC remains a significant challenge. Herein, a strategy to create a smart injectable cement system using nanocontainers and chondroitin sulfate is proposed. It employs nanocontainers containing alendronate-loaded mesoporous silica nanoparticles, which are surface-modified with polypyrrole to control drug release in response to near-infrared (NIR) stimulation. The alendronate-incorporated cement (ACMPC) exhibits improved compressive strength (70.6 ± 5.9 MPa), prolonged setting time (913 s), and exceptional injectability (96.5% of injection rate and 242 s of injection time). It also shows the capability to prevent degradation, thus preserving mechanical properties. Under NIR irradiation, the cement shows good antibacterial properties due to the combined impact of hyperthermia, reactive oxygen species, and alendronate. Furthermore, the ACMPC (NIR) group displays good biocompatibility and osteogenesis capabilities, which also lead to an increase in alkaline phosphatase activity, extracellular matrix mineralization, and the upregulation of osteogenic genes. This research has significant implications for developing multifunctional biomaterials and clinical applications.

amer1 Regulates Zebrafish Craniofacial Development by Interacting with the Wnt/ß-Catenin Pathway.

Microtia-atresia is a rare type of congenital craniofacial malformation causing severe damage to the appearance and hearing ability of affected individuals. The genetic factors associated with microtia-atresia have not yet been determined. The AMER1 gene has been identified as potentially pathogenic for microtia-atresia in two twin families. An amer1 mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. The phenotype and the development process of cranial neural crest cells of the knockdown zebrafish were examined. Components of the Wnt/ß-catenin pathway were examined by qPCR, Western blotting, and immunofluorescence assay. IWR-1-endo, a reversible inhibitor of the Wnt/ß-catenin pathway, was applied to rescue the abnormal phenotype. The present study showed that the development of mandibular cartilage in zebrafish was severely compromised by amer1 knockdown using CRISPR/Cas9. Specifically, amer1 knockdown was found to affect the proliferation and apoptosis of cranial neural crest cells, as well as their differentiation to chondrocytes. Mechanistically, amer1 exerted an antagonistic effect on the Wnt/ß-catenin pathway. The application of IWR-1-endo could partially rescue the abnormal phenotype. We demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/ß-catenin pathway. These findings provide important insight into the role of amer1 in zebrafish mandibular development and the pathology of microtia-atresia caused by AMER1 gene mutations in humans.

Hearing outcomes following cochlear implantation with anatomic or default frequency mapping in postlingual deafness adults.

PURPOSE: The aim of this study was to compare the outcomes of different mapping procedures based on anatomic or default frequency distribution in postlingual deafness adults who underwent cochlear implantation (CI). METHODS: Forty-eight adults with postlingual deafness who underwent CI (MED-EL) from January 2021 to May 2022 in our hospital were prospectively recruited. The participants were randomly assigned to two groups (the anatomic group and the default group). Postoperative computerized tomography (CT) scans were evaluated with Otoplan® to determine the angular insertion depth (AID) and the specific locations of the intracochlear electrodes. Anatomic maps were imported into MAESTRO 9.0 software (MED-EL) for anatomy-based fitting for anatomic group, while default mapping program was set up for the default group. Hearing thresholds, Speech Recognition Scores (SRS), and subjects' auditory and musical abilities were evaluated 1 year after using the CI. Differences were determined in two groups using Stata statistical software, with significance defined as p < 0.05. RESULTS: SRS under noisy conditions was significantly greater for anatomic group than the default group (p = 0.02). Under quiet conditions, however, mean hearing thresholds (0.5, 1, 2, and 4 kHz) and SRS did not differ significantly between the two groups (p = 0.07). Modified questionnaires showed that auditory (p = 0.02) and musical (p = 0.01) quality were significantly better following the anatomic mapping than the default procedure. CONCLUSION: CI program based on the anatomic distribution may bring better SRS under noise conditions as well as better auditory and musical qualities than based on the default frequency distribution.

Ovarian carcinoma immune-related microRNA affects the heterogeneity of the endocrine microenvironment and anti-tumor immune pattern.

BACKGROUND: The eighth-leading cause of cancer-related mortality and the seventh-most prevalent malignancy in women globally is ovarian cancer (OV). However, 5-year survival expectancy after conventional treatment is not good. Therefore, there is an urgent need for novel signatures to guide the designation of therapeutic schemes for OV patients. METHODS: We used univariate Cox analysis to screen hormone secretion regulation axis-related microRNAs (miRNAs), least absolute shrinkage and selection operator analysis to select candidate miRNAs and multivariate Cox analysis to build the risk model. To evaluate possible route and functional differences, enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the differentially expressed genes (DEGs) across various risk groups. We compared Tumor Immune Dysfunction and Exclusion (TIDE) scores across risk categories by analyzing immune cell infiltration, immune checkpoint gene expression, immunological function and TIDE scores. In the end, we determined the half maximal inhibitory concentration (IC50 ) of chemotherapy and targeted medicines for individual patients. Cell assays were determined to test the migration of the miRNA-target genes and western blotting was used to test the correlation of the miRNA-target genes and the pathways. RESULTS: We finally identified hormone secretion regulation axis-related 13 microRNAs to build a risk model. The validation of observed and anticipated values revealed a fair level of agreement. To evaluate the molecular pathways between various groups in accordance with the GO and KEGG analyses, we then discovered 173 DEGs between distinct risk groups. The risk score was shown to be inversely related to the number of immune cells, including myeloid dendritic, granulocytes, M1 and M2 macrophages, B cells, t-lymphocytes, and CD4+ and CD8+ cells, suggesting that immune cells are more frequent in the low-risk group. Immune cell infiltration investigation yielded these results. Finally, we recognized 11 chemotherapeutic drugs and 30 novels targeted drugs on the basis of IC50 between the different risk groups. GJB5 was determined to be the mir-219 target gene and was identified as promoting the cell cycle process. In addition, hormone secretion regulation axis related miRNAs were reported to affects the heterogeneity of endocrine microenvironment and anti-tumor immune pattern. CONCLUSIONS: In conclusion, a 13-miRNA prognostic model was constructed to know the immune status, prognosis, immunotherapeutic response and anti-tumor drug sensitivity for OV, which provides theoretical guidance for the effective and individualized treatment of OV patients.

Co-Occurrence of Sensorineural Hearing Loss and Congenital Heart Disease: Etiologies and Management.

OBJECTIVES/HYPOTHESIS: The co-occurrence of sensorineural hearing loss (SNHL) and congenital heart disease (CHD) is a rare condition with complex etiologies. The purpose of this study is to assess the etiologies, clinical features, and outcomes of cochlear implant (CI) in this patient population. STUDY DESIGN: Case series and literature review. METHODS: Clinical data of children who were diagnosed with SNHL and CHD and received CIs at a tertiary hospital from 2016 to 2021 were retrospectively analyzed. A literature review was performed to identify patients with SNHL and CHD. FINDINGS: Of the 382 children who underwent cochlear implantation at our center, eight (2.1%) were diagnosed with SNHL and CHD. A literature review identified 1525 patients from 254 studies; the database therefore consisted of 1533 patients. The most common genetic etiologies of co-occurring SNHL and CHD were CHARGE syndrome (36.3%), Turner syndrome (8.4%), 22q11.2 deletion (3.0%), Noonan syndrome (2.9%), and Down syndrome (2.5%), whereas the most common non-genetic etiologies were congenital rubella syndrome (22.9%) and SNHL after early cardiac surgery (5.5%). Most of the patients presented with congenital, bilateral, severe-profound SNHL requiring early rehabilitation. Of the 126 children who received CIs at a median age of 2.5 years, half showed delayed speech development at last follow-up. CONCLUSIONS: Co-occurring SNHL and CHD is a rare condition with complex etiologies. Timely hearing intervention with long-term follow-up and proper timing of heart surgery is essential for these children. LEVEL OF EVIDENCE: 4, case series Laryngoscope, 134:400-409, 2024.

Statistical analysis plan for the LAKANA trial: a cluster-randomized, placebo-controlled, double-blinded, parallel group, three-arm clinical trial testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1-11-month-old infants in Mali.

BACKGROUND: The Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin (LAKANA) trial in Mali aims to evaluate the efficacy and safety of azithromycin (AZI) mass drug administration (MDA) to 1-11-month-old infants as well as the impact of the intervention on antimicrobial resistance (AMR) and mechanisms of action of azithromycin. To improve the transparency and quality of this clinical trial, we prepared this statistical analysis plan (SAP). METHODS/DESIGN: LAKANA is a cluster randomized trial that aims to address the mortality and health impacts of biannual and quarterly AZI MDA. AZI is given to 1-11-month-old infants in a high-mortality setting where a seasonal malaria chemoprevention (SMC) program is in place. The participating villages are randomly assigned to placebo (control), two-dose AZI (biannual azithromycin-MDA), and four-dose AZI (quarterly azithromycin-MDA) in a 3:4:2 ratio. The primary outcome of the study is mortality among the intention-to-treat population of 1-11-month-old infants. We will evaluate relative risk reduction between the study arms using a mixed-effects Poisson model with random intercepts for villages, using log link function with person-years as an offset variable. We will model outcomes related to secondary objectives of the study using generalized linear models with considerations on clustering. CONCLUSION: The SAP written prior to data collection completion will help avoid reporting bias and data-driven analysis for the primary and secondary aims of the trial. If there are deviations from the analysis methods described here, they will be described and justified in the publications of the trial results. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT04424511 . Registered on 11 June 2020.

Fatal bacteremia caused by Staphylococcus argenteus: A case report.

RATIONALE: Staphylococcus argenteus (S argenteus) is a novel and emerging species that is part of the Staphylococcus aureus (S aureus) complex. Fatal cases of bloodstream infection caused by S argenteus are rarely reported and should be considered in medical practice. PATIENT CONCERNS: A 44-year-old male was admitted to our hospital with reduced appetite, high fever and unconsciousness. Laboratory tests indicated infection, muscle damage, and alkalosis in the patient. Brain computed tomography (CT) demonstrated small hematoma in left frontal lobe with peripheral cerebral edema. Chest CT demonstrating chronic bronchitis, emphysema, and bullae in the right lung. Blood culture was collected on the first day of hospitalization for microbial culture and pathological examination. DIAGNOSIS: The isolate from blood culture was identified as S argenteus by MALDI-TOF MS after the patient death. INTERVENTIONS: The patient was subjected to empirical antibiotic treatment with piperacillin/tazobactam. OUTCOMES: After 48 hours of hospitalization, the patient died after ineffective rescue. LESSONS: The patient had long-term heavy drinking and smoking as well as chronic malnutrition, which may account for his immune deficiency. The immunocompromised people are more vulnerable to infection by S argenteus and then develop bacteremia. The use of piperacillin/tazobactam may have contributed to the patient death.

Formation and In Vitro Simulated Digestion Study of Gelatinized Korean Pine Seed Oil Encapsulated with Calcified Wax.

Natural waxes have demonstrated exceptional potential as oil gels for saturated and trans fatty acids, but their application has been limited by issues such as temperature sensitivity, lack of stability and durability, and compatibility. In this study, three types of wax (Beeswax (BW), Rice bran wax (RBW), and Carnauba wax (CW)) were combined with calcium hydroxide to produce calcified wax. The calcified Korean pine seed oil gel obtained by heating and stirring with Korean pine seed oil is responsive to temperature and has environmental adaptability. The effects of critical gel concentration, temperature regulation, texture properties, microstructure, oil-holding capacity, and FT-IR on the quality parameters of oil gel were investigated. Additionally, an in vitro digestion model was developed to comprehend the decomposition rate of fat during gel structure digestion and transportation. The results demonstrated a close correlation between the critical gelation concentration and calcium ion content. Furthermore, after calcification, the hardness followed the order BW > CW > RBW. Moreover, there was an approximate 10 °C increase in wax melting point. Conversely, BW:Ca exhibited the lowest oil leakage. The microstructures revealed that the oil gels formed post-wax calcification exhibited similar fractal dimension (Db) values (<7 µm), and the intermolecular forces were characterized by van der Waals forces, which were consistent with those observed in the non-calcified group. In conjunction with the vitro digestion simulation, our findings demonstrated that RBW and CW oil gels gradually released 20%, 35%, and 35% of free fatty acids (FFA) within the initial 30 min of intestinal digestion. Importantly, the FFA release rate was significantly attenuated, thereby providing a foundation for developing wax-based gel processed foods that facilitate gentle energy release benefits for healthy weight management.

Presence of SARS-CoV-2 in middle ear fluid and characterization of otitis media with effusion in patients with COVID-19.

OBJECTIVES: This study sought to determine whether SARS-CoV-2 is present in the middle ear fluid (MEF) of patients with COVID-19 who have otitis media with effusion (OME). METHODS: A case-control study was designed to detect SARS-CoV-2 and six other common respiratory viruses (influenza A virus, influenza B virus, respiratory syncytial virus, adenovirus, human rhinovirus [HRV], and mycoplasma pneumonia) by polymerase chain reaction (PCR) in the MEF of patients with OME. Follow-up tests, including pure-tone audiometry and tympanometry, were conducted. RESULTS: In the COVID-19 group, 18 of 27 MEF specimens were PCR-positive for SARS-CoV-2, with cycle thresholds ranging from 24.9-42.2. And one patient tested positive for the HRV. In the control group, all 15 MEF specimens were PCR-negative for SARS-CoV-2, but two patients tested positive for the HRV. After treatment for OME, 11 patients (40.7%) reported complete resolution, 14 (51.9%) reported improvement, and two (7.4%) reported no change. The average improvement in hearing was 14.5 ± 8.1 dB, and the average air-bone gap decrease was 13.5 ± 9.0 dB. CONCLUSION: This study confirmed the presence of SARS-CoV-2 in the MEF of patients who were previously COVID-19-positive suggesting a possible association between COVID-19 and OME. OME should be considered a possible symptom of COVID-19.