A pilot pharmacokinetic and Metabolite identification study of Erinacine A in a Single landrace pig model.

Erinacine A has been proven to have the ability to protect nerves and have the benefit of neurohealth. However, the pharmacokinetic and metabolites study of erinacine A in pigs, whose physiology and anatomy are similar to humans, have not been reported. In this study, 5 mg/kg of erinacine A was intravenously administered to the landrace pig. Blood, cerebrospinal fluid, and brain tissue samples were collected and analyzed by HPLC-QQQ/MS and UPLC-QTOF/MS. The results indicated the following pharmacokinetic parameters in plasma samples: with an area under the plasma concentration versus time curve (AUC) were 38.02 ± 0.03 mg∙min/L (AUC0-60) and 43.60 ± 0.06 mg∙min/L (AUC0-∞), clearance (CL) was 0.11 ± 0.00 L/min∙kg, volume of distribution (Vd) was 4.24 ± 0.00 L/kg, and terminal half-life (T1/2ß) was 20.85 ± 0.03 min. In the cerebrospinal fluid samples, erinacine A was detected after 15 min and the highest concentration (5.26 ± 0.58 µg/L) was observed at 30 min. In the brain tissue sample, 77.45 ± 0.58 µg/L of erinacine A was found. In the study of metabolites, there were 6 identical metabolites in plasma and brain tissue. To our surprise, erinacine B was found to be the metabolite of erinacine A, and its concentration increased over time as erinacine A was metabolized. In summary, this study is the first to demonstrate that erinacine A can be found in the cerebrospinal fluid of landrace pigs. Additionally, the metabolite identification of erinacine A in landrace pigs is also investigated.

Synthesis of Silver(I) Complexes through In Situ Reactions of dppeda with dmp in the Presence of Silver Halides for Photocatalysis.

Due to the unique photosensitivity of silver compounds, they exhibit good photocatalytic activity as photocatalysts in the degradation of water pollutants. However, silver compounds have poor cycling stability and are prone to decomposition and reaction under light to form metallic silver, which greatly limits their practical application. Herein, a (2-(2-(diphenylphosphaneyl)ethyl)-9-methyl-1.10-phenanthroline (PSNNP)) pincer ligand was designed for stabilizing the central metal. The in situ-formed PSNNP ligand could be readily generated in one pot with the participation of silver halides. The reaction of silver halides with dppeda (N,N,N',N'-tetra(diphenylphosphanylmethyl)ethylene diamine) in the presence of dmp (2,9-dimethyl-1,10-phenanthroline) in acetonitrile afforded complexes Ag2X2 (PSNNP)2 (complexes 1, 2) (X = Cl, Br). Single-crystal X-ray diffraction shows that the tridentate coordination of the pincer ligand provides strong binding with metal centers and leads to high stability of the pincer metal unit. The removal rate of rhodamine B (RhB) by complexes 1 and 2 can reach up to 100%, demonstrating an excellent photocatalytic degradation performance for organic dyes. The important effect of PSNNP ligands on photocatalytic properties after coordination with central metals was studied through experiments and discrete Fourier transform (DFT) calculations. The photocatalytic reaction mechanism of complexes 1 and 2 was also studied. This result provides an effective pathway for the first synthesis of PSNNP and interesting insights into photocatalytic degradation chemistry.

Role of Agrin in tissue repair and regeneration: From mechanisms to therapeutic opportunities (Review).

Tissue regeneration is a complex process that involves the recruitment of various types of cells for healing after injury; it is mediated by numerous precise interactions. However, the identification of effective targets for improving tissue regeneration remains a challenge. As an extracellular matrix protein, Agrin plays a critical role in neuromuscular junction formation. Furthermore, recent studies have revealed the role of Agrin in regulating tissue proliferation and regeneration, which contributes to the repair process of injured tissues. An in­depth understanding of the role of Agrin will therefore be of value. Given that repair and regeneration processes occur in various parts of the human body, the present systematic review focuses on the role of Agrin in typical tissue and highlights the potential signaling pathways that are involved in Agrin­induced repair and regeneration. This review offers important insight into novel strategies for the future clinical applications of Agrin­based therapies, which may represent a feasible treatment option for patients who require organ replacement or repair.

Asiaticoside inhibits breast cancer progression and tumor angiogenesis via YAP1/VEGFA signal pathway.

Objective: Breast cancer poses a major health risk to millions of females globally. Asiaticoside (AC) is a naturally occurring compound derived from Centella asiatica, a widely used medicinal plant in the oriental countries and has potential antitumor properties. The primary aim of this study was to investigate the anti-cancer effects of synthesized AC at the cellular level and assess its ability to inhibit tumor growth and angiogenesis in breast cancer. Methods: The proliferative capacities of MCF-7 and MDA-MB-231 cells were determined using CCK-8 assay. To analyze invasion and migration, Transwell assays were conducted on the same cell lines. Additionally, apoptosis was analyzed in vitro using flow cytometry. Real-time RT-PCR was used to examine mRNA expression, and Western-blotting assay was employed to examine protein expression. Subcutaneous injection of MDA-MB-231 cells into female BALB/c nude mice was followed by treatment with AC to study its anti-tumor effects in vivo. Results: AC treatment reduced cell proliferation and triggered apoptosis in MCF-7 and MDA-MB-231 cells. The invasive and pro-angiogenesis ability were also impaired upon AC treatment. AC administration also impeded the tumor growth and tumor-associated angiogenesis of MDA-MB-231 cells in nude mice, which was accompanied by the decreased levels of YAP1 and VEGFA. Conclusion: Taken together, our results demonstrated the anti-cancer activity of AC in breast cancer. AC is able to suppress the malignancy of breast cancercells via YAP1/VEGFA signal pathway.

Benefits of chest wall mobilization on respiratory efficiency and functional exercise capacity in people with severe chronic obstructive pulmonary disease (COPD): A randomized controlled trial.

BACKGROUND: Coexistence of chest wall hypomobility and lung hyperinflation compromises respiratory muscle function and respiratory efficiency in people with severe chronic obstructive pulmonary disease (COPD). This study aimed to investigate the effect of chest wall mobilization on functional exercise capacity, respiratory muscle activity and respiratory muscle tissue oxygen saturation for people with severe COPD. METHODS: Thirty male adults (age: 75 ± 6) diagnosed with severe COPD completed a 6-week programme (twice/week) according to intervention randomization (chest wall mobilization group, CWMG, n = 15; control group, CG, n = 15). Both groups received standardized education and walking exercise, while CWMG also received chest wall and thoracic spine mobilization. Electromyography of the essential and accessory respiratory muscles and tissue oxygen saturation of the intercostal muscle (StO2, measured by near-infrared spectroscopy) during incremental cycle exercise test were measured and compared between the two groups at pre-programme, post-programme and 3-month follow-up. RESULTS: Patients in CWMG demonstrated a significant increase in exercise tolerance from <3 METS to 4-6 METS (p = 0.000) after intervention. A significant decrease in activity of scalene, sternocleidomastoids and intercostal muscle during exercise test (p < 0.01) was found in CWMG, as compared to CG. A significant decrease in StO2 (p < 0.05) and greater decline in the slope of oxygenation dissociation (p = 0.000) were seen in CWMG during exercise test. These positive results were maintained at 3-month follow-up in CWMG. CONCLUSION: Improvements in exercise tolerance, respiratory muscle efficiency and oxygenation extraction ability in CWMG suggest a potential clinical benefit of integrating chest wall and thoracic spine mobilization for rehabilitation of people with severe COPD.

The clinical application value of multi-site mNGS detection of patients with sepsis in intensive care units.

BACKGROUND: Sepsis remains a leading cause of mortality in intensive care units, and rapid and accurate pathogen detection is crucial for effective treatment. This study evaluated the clinical application of multi-site metagenomic next-generation sequencing (mNGS) for the diagnosis of sepsis, comparing its performance against conventional methods. METHODS: A retrospective analysis was conducted on 69 patients with sepsis consecutively admitted to the Department of Intensive Care Medicine, Meizhou People's Hospital. Samples of peripheral blood and infection sites were collected for mNGS and conventional method tests to compare the positive rate of mNGS and traditional pathogen detection methods and the distribution of pathogens. The methods used in this study included a comprehensive analysis of pathogen consistency between peripheral blood and infection site samples. Additionally, the correlation between the pathogens detected and clinical outcomes was investigated. RESULTS: Of the patients with sepsis, 57.97% experienced dyspnea, and 65.2% had underlying diseases, with hypertension being the most common. mNGS demonstrated a significantly higher pathogen detection rate (88%) compared to the conventional method tests (26%). The pathogen consistency rate was 60% between plasma and bronchoalveolar lavage fluid samples, and that of plasma and local body fluid samples was 63%. The most frequently detected pathogens were gram-negative bacteria, and Klebsiella pneumonia. There were no significant differences in the clinical features between the pathogens. CONCLUSION: mNGS is significantly superior to conventional methods in pathogen detection. There was a notable high pathogen consistency detection between blood and local body fluid samples, supporting the clinical relevance of mNGS. This study highlights the superiority of mNGS in detecting a broad spectrum of pathogens quickly and accurately. TRIAL REGISTRATION: Not applicable.

Global bibliometric mapping of the research trends in artificial intelligence-based digital pathology for lung cancer over the past two decades.

Background and Objective: The rapid development of computer technology has led to a revolutionary transformation in artificial intelligence (AI)-assisted healthcare. The integration of whole-slide imaging technology with AI algorithms has facilitated the development of digital pathology for lung cancer (LC). However, there is a lack of comprehensive scientometric analysis in this field. Methods: A bibliometric analysis was conducted on 197 publications related to digital pathology in LC from 502 institutions across 39 countries, published in 97 academic journals in the Web of Science Core Collection between 2004 and 2023. Results: Our analysis has identified the United States and China as the primary research nations in the field of digital pathology in LC. However, it is important to note that the current research primarily consists of independent studies among countries, emphasizing the necessity of strengthening academic collaboration and data sharing between nations. The current focus and challenge of research related to digital pathology in LC lie in enhancing the accuracy of classification and prediction through improved deep learning algorithms. The integration of multi-omics studies presents a promising future research direction. Additionally, researchers are increasingly exploring the application of digital pathology in immunotherapy for LC patients. Conclusions: In conclusion, this study provides a comprehensive knowledge framework for digital pathology in LC, highlighting research trends, hotspots, and gaps in this field. It also provides a theoretical basis for the application of AI in clinical decision-making for LC patients.

Acupuncture and Acupoints for Managing Pediatric Cerebral Palsy: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Acupuncture is frequently used to manage pediatric cerebral palsy (CP), yet updated evidence is needed to guide future research and clinical practice. METHODS: Seven databases were searched from 1994 to 26 June 2023. Randomized controlled trials (RCTs) involving body, scalp, or ear acupuncture for managing CP, excluding acupoint injection, catgut embedding, electro-acupuncture, or laser acupuncture, were included. RESULTS: Twenty RCTs with 1797 participants were analyzed. Acupuncture groups had better improvements in gross motor function measure (GMFM) scores by 5% (mean difference: 5.93, 95% CI: 3.67-8.19, p < 0.001, I2 = 57%); a 16% higher probability to yield prominent improvement in effectiveness rate (ER) (risk ratio: 1.16, 95% CI: 1.08-1.25, p < 0.001, I2 = 0%); and better outcomes in the Modified Ashworth Scale (MAS) (standardized mean difference [SMD]: 0.3, 95%, CI: 0.11-0.49, p < 0.001, I2 = 0%), the Berg Balance Scale (BBS) (SMD: 2.48; 95% CI: 2.00-2.97, p < 0.001, I2 = 72%) and ADL (SMD: 1.66; 95% CI: 1.23-2.08, p < 0.001, I2 = 91%). Studies with eight core acupoints identified from all ninety-five acupoints had better ER. CONCLUSIONS: Acupuncture, especially using core acupoints, may be effective for managing symptoms in children with CP.

The miRNAs 203a/210-3p/5001-5p regulate the androgen/androgen receptor/YAP-induced migration in prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) patients with elevated level of androgen receptor (AR) correlate with higher metastatic incidence. Protein expression of AR and its target gene prostate-specific antigen (PSA) are elevated in metastatic prostate tumors as compared to organ-confined tumors. Androgen treatment or elevation of AR promotes metastasis of PCa in cell culture and murine model. However, under androgen depleted condition, AR suppressed cell mobility and invasiveness of PCa cells. Androgen deprivation therapy in PCa patients is associated with higher risk of cancer metastasis. We therefore investigated the dual roles of AR and miRNAs on PCa metastasis. METHODS: The PC-3AR (PC-3 cells re-expressing AR) and LNCaP cells were used as PCa cell model. Transwell migration and invasion assay, wound-healing assay, zebrafish xenotransplantation assay, and zebrafish vascular exit assay were used to investigate the role of AR and androgen on PCa metastasis. Micro-Western Array, co-immunoprecipitation and Immunofluorescence were applied to dissect the molecular mechanism lying underneath. The miRNA array, miRNA inhibitors or plasmid, and chromatin immunoprecipitation assay were used to study the role of miRNAs on PCa metastasis. RESULTS: In the absence of androgen, AR repressed the migration and invasion of PCa cells. When androgen was present, AR stimulated the migration and invasion of PCa cells both in vitro and in zebrafish xenotransplantation model. Androgen increased phospho-AR Ser81 and yes-associated protein 1 (YAP), decreased phospho-YAP Ser217, and altered epithelial-mesenchymal transition (EMT) proteins in PCa cells. Co-IP assay demonstrated that androgen augmented the interaction between YAP and AR in nucleus. Knockdown of YAP or treatment with YAP inhibitor abolished the androgen-induced migration and invasion of PCa cells, while overexpression of YAP showed opposite effects. The miRNA array revealed that androgen decreased hsa-miR-5001-5p but increased hsa-miR-203a and hsa-miR-210-3p in PC-3AR cells but not PC-3 cells. Treatment with inhibitors targeting hsa-miR-203a/hsa-miR-210-3p, or overexpression of hsa-miR-5001-5p decreased YAP expression as well as suppressed the androgen-induced migration and invasion of PCa cells. Chromatin immunoprecipitation (ChIP) assay demonstrated that AR binds with promoter region of has-miR-210-3p in the presence of androgen. CONCLUSIONS: Our observations indicated that miRNAs 203a/210-3p/5001-5p regulate the androgen/AR/YAP-induced PCa metastasis.

An engineered self-biomineralized oncolytic adenovirus induces effective antitumor immunity and synergizes with immune checkpoint blockade.

Oncolytic adenoviruses (oADV) are promising cancer treatment agents. However, in vivo hepatic sequestration and the host immunological response against the agents limit the therapeutic potential of oADVs. Herein, we present a combined, rational design method for improving oADV infection efficiency, immunogenicity, and treatment efficacy by self-biomineralization. We integrated the biomimetic nucleopeptide W6p into the capsid of oADV using reverse genetics, allowing calcium phosphate mineralization to be biologically induced on the surface of oADV under physiological conditions, resulting in a mineral exterior. This self-biomineralized, modified oADV (oADV-W6-CaP) enhanced infection efficiency and therapeutic efficacy in coxsackie and adenovirus receptor (CAR)-negative cancer cells while protecting them against neutralization by pre-existing neutralizing antibodies. In subcutaneous mouse tumor models, systemic injection of oADV-W6-CaP demonstrated improved antitumor effectiveness, which was associated with increased T-cell infiltration and CD8+ T-cell activation. In addition, the anticancer immune response elicited by oADV-W6-CaP was dependent on CD8+ T cells, which mediated long-term immunological memory and systemic antitumor immunity against the same tumor. Finally, the addition of PD-1 or CD47 inhibition boosted the anticancer effects of oADV-W6-CaP and raised the rate of complete tumor clearance in tumor-bearing animals. The self-biomineralized oADV shifted the suppressive tumor microenvironment from a "cold" state to a "hot" state and synergized with immune checkpoint blockade to exert outstanding tumoricidal effects, demonstrating promising potential for cancer immunotherapy.

Occurrence and risk factors for post-stroke delirium: A systematic review and meta-analysis.

OBJECTIVES: Delirium is a significant health concern in acute stroke patients. We aim to systematically summarize existing evidence to conduct a meta-analysis to quantify the occurrence and risk factors for delirium after acute stroke. METHOD: PubMed, EMBASE and MEDLINE were searched from inception to Feb. 2023 for prospective observational studies that reported the incidence or prevalence of post-stroke delirium and/or evaluated potential risk factors. The search strategy was created using controlled vocabulary terms and text words for stroke and delirium. We performed a meta-analysis of the estimates for occurrence and risk factors using random-effects models. Meta-regression and subgroup meta-analyses were conducted to explore the sources of heterogeneity. Study quality and quality of evidence were assessed using the customized Newcastle-Ottawa Scale and GRADE, respectively. RESULTS: Forty-nine studies that enrolled 12383 patients were included. The pooled occurrence rate of post-stroke delirium was 24.4 % (95 %CI, 20.4 %-28.9 %, I2=96.2 %). The pooled occurrence of hyperactive, hypoactive, and mixed delirium was 8.5 %, 5.7 % and 5.0 %, respectively. Study location, delirium assessment method and stroke type independently affected the heterogeneity of the pooled estimate of delirium. Statistically significant risk factors were older age, low education level, cigarette smoking, alcohol drinking, atrial fibrillation, lower ADL level, higher pre-stroke mRS score, premorbid cognitive impairment or dementia, aphasia, total anterior circulation impairment, higher National Institute of Health Stroke Scale score and infection. CONCLUSIONS: Delirium affected 1 in 4 acute stroke patients, although reported rates may depend on assessment method and stroke type. Timely prevention, recognition and intervention require prioritizing patients with dominant risk factors.

Superparamagnetic photonic crystals with DNA probes for rapid visual detection of mercury.

A novel superparamagnetic photonic crystal DNA probe (Fe3O4@SiO2@amino@DNA SPC) was developed to enable rapid visual detection of Hg2+. This unique photonic crystal (PC) was synthesized by combining superparamagnetic nanospheres with DNA probes. The DNA probe, rich in thymine (T), detects mercury ions through base mismatch, resulting in the formation of T-Hg2+-T loop hairpin structures. With the binding of Hg2+ to the probe attached to superparamagnetic nanospheres, the PC structure assembled by these nanospheres, formed by the magnetic field, was changed. This change enhanced the reflection intensity; it could be quantified using a fiber optic spectrometer and was visible to the naked eye. The Fe3O4@SiO2@amino@DNA SPC, specific to Hg2+, exhibited a reflection peak at 679 nm, which intensified with increasing Hg2+ concentration. The reflection intensity increased by 132.58 a.u., and the PC color shifted from red to yellow as the Hg2+ concentration increased from 0.1 µg/L to 1 mg/L.

[Congenital Fâ ¦ Deficiency Associated with a Novel Mutation in F7 Gene].

OBJECTIVE: To identify the genetic mutation of coagulation factor Ⅶ ( F7) gene in a pedigree with coagulation factor Ⅶ (FⅦ) deficiency and explore the molecular pathogenesis. METHODS: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (DD), fibrin degradation products (FDP) and coagulation factor Ⅶ activity (FⅦ:C) of the proband and her family members were detected by Sysmex-CS5100 analyzer. All exons and exon-intron boundaries of the F7 gene were amplified by PCR followed by direct sequencing. The detected mutation was confirmed by reverse sequencing. The ClustalW software was used to analyze the conservatism of the mutant site. Pathogenicity of the mutation was assessed with Mutation Taster and PolyPhen-2 online bioinformatics software. Structure of the mutant protein was analyzed using Swiss-PdbViewer software. RESULTS: The results of routine coagulation tests showed that PT of the proband was markedly extended to 42.5 s, and her FⅦ:C significantly reduced to 2%. The FⅦ:C of her grandmother, mother and sister had slightly reduced to 49%, 51%, and 42%, respectively. These coagulant parameters of her father were within the normal range. Genetic analysis reveled a heterozygous G>A change at cDNA 646 in exon 6 of F7 gene in the proband, resulting in a replacement of glycine at 156 of FⅦ catalytic region with serine (p.Gly156Ser). The sequencing results of other exons and exon-intron boundaries of her F7 gene were normal. The proband's grandmother, mother and sister were all the carriers of this missense mutation except her father. Bioinformatics analysis showed that the p.Gly156Ser mutation caused polarity change of the amino acid at this site and formation of side chains, leading to increase of protein instability, which may affect catalytic activity of structural domain. Meanwhile, both Mutation Taster and PolyPhen-2 online bioinformatics software also predicted the pathogenicity of this missense mutation with high scores. CONCLUSION: The heterozygous p.Gly156Ser mutation is the direct cause of the reduced FⅦ in this proband.

Endoluminal Sigmoid Sinus Occlusion During Jugular Foramen Tumor Surgery: Novel Technique, Operative Nuances, and Clinical Experience With 33 Patients.

BACKGROUND AND IMPORTANCE: Surgery of jugular foramen tumors (JFTs) often requires vascular control by means of ligating the internal jugular vein and sigmoid sinus (SS) to allow intrabulbar access. Occlusion of the SS traditionally involves presigmoid and retrosigmoid durotomies allowing introduction of ligature devices, predisposing to cerebrospinal fluid (CSF) leakage and pseudomeningoceles. We describe a simple and novel endoluminal sigmoid sinus occlusion (ESSO) technique with Gelfoam that is entirely extradural. CLINICAL PRESENTATION: An extended anterolateral infralabyrinthine approach with ESSO was performed in 33 patients with JFTs. After ligating the internal jugular vein, the SS is opened and Gelfoam is placed endoluminally into the proximal SS. Care is taken to avoid occlusion of the venous outflow of the vein of Labbe to avoid temporal lobe venous infarction. Hemostatic gelatin matrix is injected distally to stop venous backflow from the inferior petrosal sinus. The jugular venous system is isolated, and the outer jugular wall can be opened to expose the JFT for resection. There were no complications of temporal lobe venous infarction or postoperative hematoma observed. Four patients with intradural tumor extension developed pseudomeningoceles. For patients with purely extradural JFTs, none developed postoperative incisional CSF leaks and one had pseudomeningocele. CONCLUSION: This ESSO technique is fast and effective, permitting occlusion of the SS during JFT surgery. It has the advantage of being entirely extradural, avoiding durotomy which can result in postoperative CSF leak. It is important to keep the Gelfoam distal to the transverse-sigmoid junction to avoid occlusion of the vein of Labbe inlet and temporal lobe venous infarction.

Regulatory effects of microRNAs on monocytic HLA-DR surface expression.

Decreased monocytic HLA-DR expression is the most studied biomarker of immune competency in critically ill and autoimmune disease patients. However, the underlying regulatory mechanisms remain largely unknown. One probable HLA-DR dysregulation is through microRNAs. The aim of this study was to investigate the effects of specific microRNAs on HLA-DR expression in human monocytic cells. Four up- and four down-HLA-DR-regulating microRNAs were identified, with hsa-miR-let-7f-2-3p showing the most significant upregulation and hsa-miR-567 and hsa-miR-3972 downregulation. Anti-inflammatory glucocorticoid medication Dexamethasone-decreased HLA-DR was significantly restored by hsa-miR-let-7f-2-3p and hsa-miR-5693. Contrarily, proinflammatory cytokines IFN-γ and TNF-α-increased HLA-DR were significantly reversed by hsa-miR-567. Clinically, paired plasma samples from patients before and one day after cardiac surgery revealed up-regulated expression of hsa-miR-5693, hsa-miR-567, and hsa-miR-3972, following the major surgical trauma. In silico approaches were applied for functional microRNA-mRNA interaction prediction and candidate target genes were confirmed by qPCR analysis. In conclusion, novel monocytic HLA-DR microRNA modulators were identified and validated in vitro. Moreover, both the interaction between the microRNAs and anti- and proinflammatory molecules and the up-regulated microRNAs identified in cardiac surgery highlight the potential clinical relevance of our findings.

Natural History of Untreated Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: Although corticosteroids and other treatments for idiopathic sudden sensorineural hearing loss (ISSNHL) have been described, understanding its prognosis without intervention provides valuable information for patient management. The objective of this study is to provide a comprehensive, quantitative statistical analysis of the natural history of untreated idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY TYPE AND DESIGN: A systematic review and meta-analyses. METHODS: Two independent searches of PubMed, Scopus, Web of Science, and Cochrane Library databases up to June 30, 2022, were performed. Adults with idiopathic sudden sensorineural hearing loss who received placebo or were untreated and had audiometric outcome measures in all study types were reviewed. These data indicative of the natural history of ISSNHL were analyzed, as were study characteristics related to risk of bias. Heterogeneity as assessed via I2 and random effects analyses were performed. RESULTS: Six studies meeting the inclusion criteria yielded 319 untreated patients whose natural history could be assessed. Heterogeneity among studies was moderate, with a variety of reported outcomes. A hearing improvement of at least 30 dB HL was observed in 36% (95% CI 0.28-0.44) of untreated patients, and of at least 10 dB HL was observed in 70% (95% CI 0.57-0.82) of untreated patients at 3 months. The mean hearing gain among untreated patients was 24.0 dB HL (95% CI 2.65-45.37) at 2-3 months. CONCLUSIONS: The observed natural history of ISSNHL suggests that patients can regain some hearing without active treatment. In the absence of future studies collecting prospective natural history data from untreated or placebo-treated ISSNHL patients, the data presented here provide the best available historical control data for reconsideration of results in past ISSNHL studies, as well as a roadmap for design and interpretation of future ISSNHL treatment clinical trials. Furthermore, knowing there is a statistically significant mean hearing gain of 24.0 dB HL in the untreated/placebo group provides an ethical basis for future placebo study of ISSNHL. The current status on ISSNHL management calls for a multi-institutional, randomized, double-blind placebo-controlled trial with validated outcome measures to provide science-based treatment guidance. Laryngoscope, 134:S1-S15, 2024.

First Report of Xanthomonas perforans Causing Bacterial Spot of Pepper (Capsicum annuum) in North Carolina.

North Carolina (NC) is the fifth largest producer of bell pepper (Capsicum annuum) in the US with an estimated 2,400 acres in production (NASS-USDA, 2022). A survey of bacterial diseases of peppers was initiated in 2020 after numerous bacterial spot outbreaks were reported in NC. Bacterial spot is caused by a complex of four Xanthomonads: X. euvesicatoria, X. vesicatoria, X. perforans, and X. hortorum pv. gardneri (Larrahondo-Rodríguez et al., 2022). If not preemptively managed, bacterial spot can cause up to 40% yield loss (Kousik and Ritchie, 1998). During the 2020 and 2021 growing seasons, 103 yellow mucoid colonies were isolated from plants representing 51 pepper cultivars symptomatic of bacterial spot, i.e., water-soaked leaf lesions that become necrotic spots on leaves and fruits across 22 commercial fields in NC following published methods (Klein-Gordon et al., 2021). All colonies were characterized to species using the qPCR species-specific primers and probes described by Strayer et al. 2016. Of the 103 colonies, 12 isolates tested positive for X. perforans. To confirm qPCR results, a Multi-Locus Sequence Analysis (MLSA) was run using fusA, gapA, gltA, gyrB, and lacF following previously described methods (Almeida et al., 2010) on three representative isolates: AHX61, collected in September 2020 from a field with 20% disease severity in Wake County on cv. Canary Bell; AHX261, collected in July 2021 from a field with 50% disease severity in Sampson County on Jalapeño; and AHX426, collected in August 2021 from a field with 50% disease severity in Dublin County on Jalapeño. All gene sequences were deposited to NCBI (GenBank Accessions: OQ799538-OQ799552) and compared to those from X. euvesicatoria, X. hortorum pv. gardneri, X. perforans, and X. vesicatoria type strains (Almeida et al., 2010). The MLSA showed AHX61, AHX261, and AHX426 cluster with X. perforans ICMP16690T, sharing 99-100% nucleotide similarity. Koch's postulates were performed with the three strains, Xp1484T [ X. perforans type strain, (Wilson 1987)], and water as a negative control. Three 10-week-old bell pepper plants (cv. Early Cal Wonder) were dip-inoculated in 600 mL of a bacterial suspension at an OD600 of 0.3 (~5x108 CFU/mL) and 0.04% Silwet L-77 per strain or water. All 18 plants were individually incubated in a plastic bag for 48 h post-inoculation at 28°C, 80% relative humidity, and 14 h:10 h light-dark cycle in a growth chamber, after which plastic bags were removed. Water-soaking and necrotic spots characteristic of bacterial spot were first observed at six days post-inoculation (dpi). At 14 dpi, symptomatic leaves were removed from treated plants to attempt pathogen re-isolation. Yellow mucoid colonies similar in morphology to those originally inoculated were recovered from all plants and confirmed to be X. perforans through sequencing; no isolates were recovered from water-treated plants. To our knowledge, this is the first time X. perforans is isolated in commercial bell pepper and specialty pepper fields in the state. This is an indication that the Xanthomonas population on peppers in the state is more diverse than previously reported and that pathogen populations will require monitoring for possible species shifts for this crop in NC.

Patient-Reported Outcome Measures (PROMs) with Refractive and Diffractive Extended Depth of Focus (EDOF) Intraocular Lenses.

BACKGROUND: Extended depth of focus intraocular lenses (EDOF-IOLs) provide unaided far- and mid-range vision. Refractive IOLs, in contrast to diffractive designs, are associated with a lower depth of focus and absence of dysphotopsia. The aim of this study was to assess spectacle independence for far-range, mid-range, and near-vision activities in patients after implantation of refractive or diffractive EDOF-IOLs using patient-reported outcome measures (PROMs) in a real-world setting. PATIENTS AND METHODS: In 2021 and 2022, all patients in a single center referred for bilateral cataract surgery were assigned to 7 experienced cataract surgeons who either bilaterally implanted only a diffractive EDOF-IOL (Carl Zeiss Meditec AG, AT LARA Jena, Germany, three surgeons) or refractive EDOF-IOL (Johnson & Johnson Vision Inc., Tecnis Eyhance Irvine, California, USA, four surgeons) at the surgeon's discretion, with the aim of bilateral emmetropia. Six months after both cataract surgeries, all patients were contacted by telephone and asked to report their outcomes using a structured questionnaire investigating their spectacle usage for various daily activities and their experience with night glare or halos. Inclusion criteria were a normal postoperative visual potential based on the preoperative examination and completion of the questionnaire regarding postoperative visual experience. RESULTS: Of the patients, 514 underwent bilateral cataract surgery aiming for bilateral emmetropia with the implantation of EDOF-IOLs (422 with Tecnis Eyhance and 92 with AT LARA). A complete questionnaire was obtained from 472 (92%) patients, who were included in the study (393 vs. 79). Comparing Tecnis Eyhance with AT LARA IOL, 54 vs. 57% patients were able to perform most of their daily activities without spectacles, 9 vs. 19% reported not being dependent on spectacles at all, 25 vs. 29% reported using their smartphones without spectacles, 15 vs. 49% patients reported experiencing glares or halos at night, and 1 vs.15% with driving disturbance. Overall, 95 vs. 93% patients described themselves as "satisfied" or "highly satisfied" with their IOL. CONCLUSIONS: With both types of EDOF-IOLs, the majority of patients could perform most of their daily activities without spectacles, except reading, and were highly satisfied with their IOLs. Patients with diffractive Zeiss AT LARA EDOF-IOLs were more likely to accomplish unaided near-range visual tasks; however, they were also at a higher risk of experiencing glares or halos at night.