Structural basis of Cas3 activation in type I-C CRISPR-Cas system.

CRISPR-Cas systems function as adaptive immune mechanisms in bacteria and archaea and offer protection against phages and other mobile genetic elements. Among many types of CRISPR-Cas systems, Type I CRISPR-Cas systems are most abundant, with target interference depending on a multi-subunit, RNA-guided complex known as Cascade that recruits a transacting helicase nuclease, Cas3, to degrade the target. While structural studies on several other types of Cas3 have been conducted long ago, it was only recently that the structural study of Type I-C Cas3 in complex with Cascade was revealed, shedding light on how Cas3 achieve its activity in the Cascade complex. In the present study, we elucidated the first structure of standalone Type I-C Cas3 from Neisseria lactamica (NlaCas3). Structural analysis revealed that the histidine-aspartate (HD) nuclease active site of NlaCas3 was bound to two Fe2+ ions that inhibited its activity. Moreover, NlaCas3 could cleave both single-stranded and double-stranded DNA in the presence of Ni2+ or Co2+, showing the highest activity in the presence of both Ni2+ and Mg2+ ions. By comparing the structural studies of various Cas3 proteins, we determined that our NlaCas3 stays in an inactive conformation, allowing us to understand the structural changes associated with its activation and their implication.

Allergic rhinitis phenotypes with distinct transcriptome profiles in children: A birth cohort.

BACKGROUND: Allergic rhinitis (AR) phenotypes in childhood are unclear. OBJECTIVES: This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic characteristics. METHODS: Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype. RESULTS: Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late-onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection-related defense response, whereas late-onset AR was associated with T cell-related immune response. CONCLUSIONS: Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late- and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well.

Novel structure of secreted small molecular weight antigen Mtb12 from Mycobacterium tuberculosis.

Mtb12, a small protein secreted by Mycobacterium tuberculosis, is known to elicit immune responses in individuals infected with the pathogen. It serves as an antigen recognized by the host's immune system. Due to its immunogenic properties and pivotal role in tuberculosis (TB) pathogenesis, Mtb12 is considered a promising candidate for TB diagnosis and vaccine development. However, the structural and functional properties of Mtb12 are largely unexplored, representing a significant gap in our understanding of M. tuberculosis biology. In this study, we present the first structure of Mtb12, which features a unique tertiary configuration consisting of four beta strands and four alpha helices. Structural analysis reveals that Mtb12 has a surface adorned with a negatively charged pocket adjacent to a central cavity. The features of these structural elements and their potential effects on the function of Mtb12 warrant further exploration. These findings offer valuable insights for vaccine design and the development of diagnostic tools.

Structural analysis of a bacterial ankyrin-like protein secreted by Acinetobacter baumannii.

In bacteria, the ankyrin-like protein AnkB helps overcome stress by regulating catalase activity when expressed under stressful conditions. As the structural properties of AnkB are largely unexplored, our understanding of various AnkB-mediated functions in bacteria remains limited. In the present study, we describe the structure of AnkB from Acinetobacter baumannii, hereafter referred to as "AbAnkB," which has a unique tertiary configuration compared with that of other ankyrin domain-containing proteins. Structural analysis revealed that AbAnkB has a relatively long loop between AKR3 and AKR4 and an oppositely positioned α8 helix. Based on amino acid conservation and protein surface analyses, we identified a hydrophobic patch that might be critical for the function of AbAnkB. To the best of our knowledge, our study is the first to report the structure of a bacterial AnkB protein; our findings will markedly enhance our understanding of its functions in bacteria.

Novel structure of the anti-CRISPR protein AcrIE3 and its implication on the CRISPR-Cas inhibition.

As a response to viral infections, bacteria have evolved the CRISPR-Cas system as an adaptive immune mechanism, enabling them to target and eliminate viral genetic material introduced during infection. However, viruses have also evolved mechanisms to counteract this bacterial defense, including anti-CRISPR proteins, which can inactivate the CRISPR-Cas adaptive immune system, thus aiding the viruses in their survival and replication within bacterial hosts. In this study, we establish the high-resolution crystal structure of the Type IE anti-CRISPR protein, AcrIE3. Our structural examination showed that AcrIE3 adopts a helical bundle fold comprising four α-helices, with a notably extended loop at the N-terminus. Additionally, surface analysis of AcrIE3 revealed the presence of three acidic regions, which potentially play a crucial role in the inhibitory function of this protein. The structural information we have elucidated for AcrIE3 will provide crucial insights into fully understanding its inhibitory mechanism. Furthermore, this information is anticipated to be important for the application of the AcrIE family in genetic editing, paving the way for advancements in gene editing technologies.

Metabolomic pathways in food allergy.

Food allergy (FA) is a widespread issue, affecting as many as 10% of the population. Over the past two to three decades, the prevalence of FA has been on the rise, particularly in industrialized and westernized countries. FA is a complex, multifactorial disease mediated by type 2 immune responses and involving environmental and genetic factors. However, the precise mechanisms remain inadequately understood. Metabolomics has the potential to identify disease endotypes, which could beneficially promote personalized prevention and treatment. A metabolome approach would facilitate the identification of surrogate metabolite markers reflecting the disease activity and prognosis. Here, we present a literature overview of recent metabolomic studies conducted on children with FA.

Development and validation of a prediction model for postoperative urinary retention after prolapse surgery: A retrospective cohort study.

BACKGROUND: Postoperative urinary retention (POUR), a common condition after prolapse surgery with potential serious sequelae if left untreated, lacks a clearly established optimal timing for catheter removal. This study aimed to develop and validate a predictive model for postoperative urinary retention lasting > 2 and > 4 days after prolapse surgery. METHODS: We conducted a retrospective review of 1,122 patients undergoing prolapse surgery. The dataset was divided into training and testing cohorts. POUR was defined as the need for continuous intermittent catheterization resulting from a failed spontaneous voiding trial, with passing defined as two consecutive voids ≥ 150 mL and a postvoid residual urine volume ≤ 150 mL. We performed logistic regression and the predicted model was validated using both training and testing cohorts. RESULTS: Among patients, 31% and 12% experienced POUR lasting > 2 and > 4 days, respectively. Multivariable logistic model identified 6 predictors. For predicting POUR, internal validation using cross-validation approach showed good performance, with accuracy lasting > 2 (area under the curve [AUC] 0.73) and > 4 days (AUC 0.75). Split validation using pre-separated dataset also showed good performance, with accuracy lasting > 2 (AUC 0.73) and > 4 days (AUC 0.74). Calibration curves demonstrated that the model accurately predicted POUR lasting > 2 and > 4 days (from 0 to 80%). CONCLUSIONS: The proposed prediction model can assist clinicians in personalizing postoperative bladder care for patients undergoing prolapse surgery by providing accurate individual risk estimates.

Molecular basis of anti-CRISPR operon repression by Aca10.

CRISPR-Cas systems are bacterial defense systems for fighting against invaders such as bacteriophages and mobile genetic elements. To escape destruction by these bacterial immune systems, phages have co-evolved multiple anti-CRISPR (Acr) proteins, which inhibit CRISPR-Cas function. Many acr genes form an operon with genes encoding transcriptional regulators, called anti-CRISPR-associated (Aca) proteins. Aca10 is the most recently discovered Aca family that is encoded within an operon containing acrIC7 and acrIC6 in Pseudomonas citronellolis. Here, we report the high-resolution crystal structure of an Aca10 protein to unveil the molecular basis of transcriptional repressor role of Aca10 in the acrIC7-acrIC6-aca10 operon. We identified that Aca10 forms a dimer in solution, which is critical for binding specific DNA. We also showed that Aca10 directly recognizes a 21 bp palindromic sequence in the promoter of the acr operon. Finally, we revealed that R44 of Aca10 is a critical residue involved in the DNA binding, which likely results in a high degree of DNA bending.

Molecular basis of dual anti-CRISPR and auto-regulatory functions of AcrIF24.

CRISPR-Cas systems are adaptive immune systems in bacteria and archaea that provide resistance against phages and other mobile genetic elements. To fight against CRISPR-Cas systems, phages and archaeal viruses encode anti-CRISPR (Acr) proteins that inhibit CRISPR-Cas systems. The expression of acr genes is controlled by anti-CRISPR-associated (Aca) proteins encoded within acr-aca operons. AcrIF24 is a recently identified Acr that inhibits the type I-F CRISPR-Cas system. Interestingly, AcrIF24 was predicted to be a dual-function Acr and Aca. Here, we elucidated the crystal structure of AcrIF24 from Pseudomonas aeruginosa and identified its operator sequence within the regulated acr-aca operon promoter. The structure of AcrIF24 has a novel domain composition, with wing, head and body domains. The body domain is responsible for recognition of promoter DNA for Aca regulatory activity. We also revealed that AcrIF24 directly bound to type I-F Cascade, specifically to Cas7 via its head domain as part of its Acr mechanism. Our results provide new molecular insights into the mechanism of a dual functional Acr-Aca protein.

Sequential Assessment of External Nasal Deviation Angle Changes in Patients With a Deviated Nose Who Underwent Bilateral Osteotomy.

OBJECTIVE: A deviated nose is traditionally classified as bony, cartilaginous, or combined deviation. Osteotomy is commonly used to correct bony deviation, and accurate surgical techniques and postoperative patient management are important for favorable outcomes. The authors investigated the change in the external nasal deviation angle over time using sequential clinical photographs to identify the optimal postoperative follow-up duration. METHODS: Medical records and sequential standardized clinical photographs of 22 patients who underwent bilateral medial and lateral osteotomies without dorsal augmentation from January 1, 2014 to May 31, 2021, were retrospectively reviewed. Clinical photographs were classified into 4 periods: "a" preoperative, "b" postoperative day (POD) ≤3 weeks, "c" POD ≤9 weeks, and "d" POD >9 weeks. The angle of deviation (AoD) was measured in both frontal and chin-on-chest views for each period. Differences in AoD between temporally adjacent periods were analyzed. RESULTS: Nineteen men and 3 women (mean age: 28.8 y) were included. Thirteen patients showed rightward deviation, whereas 9 showed leftward deviation. Eleven patients underwent surgery through an endonasal approach, whereas the other 11 underwent surgery through an external approach. In the frontal view, AoD differences (mean ± SD) between periods "a" and "b," "b" and "c," and "c" and "d" were 5.79 ± 3.36 degrees (P < 0.001), 1.44 ± 1.14 degrees (P < 0.001), and 1.07 ± 1.24 degrees (P < 0.05), respectively. In the chin-on-chest view, the values were 5.17 ± 2.69 degrees (P < 0.001), 2.06 ± 2.63 degrees (P < 0.001), and 1.46 ± 1.31 degrees (P < 0.001), respectively. No statistically significant difference in AoD differences was observed between the two approaches. CONCLUSIONS: Angle of deviation can change even 9 weeks after bilateral osteotomy. Thus, long-term follow-up using sequential clinical photographs is mandatory. If needed, close follow-up with early postoperative interventions may be required. The chin-on-chest view showed better sensitivity for assessing AoD than the frontal view.

Insights from the COCOA birth cohort: The origins of childhood allergic diseases and future perspectives.

The ongoing COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study is a prospective birth cohort investigating the origin and natural courses of childhood allergic diseases, including atopic dermatitis, food allergy, allergic rhinitis and asthma, with long-term prognosis. Initiated under the premise that allergic diseases result from a complex interplay of immune development alterations, environmental exposures, and host susceptibility, the COCOA study explores these dynamic interactions during prenatal and postnatal periods, framed within the hygiene and microbial hypotheses alongside the developmental origins of health and disease (DOHaD) hypothesis. The scope of the COCOA study extends to genetic predispositions, indoor and outdoor environmental variables affecting mothers and their offsprings such as outdoor and indoor air pollution, psychological factors, diets, and the microbiomes of skin, gut, and airway. We have embarked on in-depth investigations of diverse risk factors and the pathophysiological underpinnings of allergic diseases. By employing multi-omics approaches-proteomics, transcriptomics, and metabolomics-we gain deeper insights into the distinct pathophysiological processes across various endotypes of childhood allergic diseases, incorporating the exposome using extensive resources within the COCOA study. Integration with large-scale datasets, such as national health insurance records, enhances robustness and mitigates potential limitations inherent to birth cohort studies. As part of global networks focused on childhood allergic diseases, the COCOA study fosters collaborative research across multiple cohorts. The findings from the COCOA study are instrumental in informing precision medicine strategies for childhood allergic diseases, underpinning the establishment of disease trajectories.

Impact of Intraoperative Nefopam on Postoperative Pain, Opioid Use, and Recovery Quality with Parietal Pain Block in Single-Port Robotic Cholecystectomy: A Prospective Randomized Controlled Trial.

Background and Objectives: This study explored how nefopam, a non-opioid analgesic in a multimodal regimen, impacts postoperative pain, opioid use, and recovery quality in single-port robot-assisted laparoscopic cholecystectomy (RALC) patients with a parietal pain block, addressing challenges in postoperative pain management. Materials and Methods: Forty patients scheduled for elective single-port RALC were enrolled and randomized to receive either nefopam or normal saline intravenously. Parietal pain relief was provided through a rectus sheath block (RSB). Postoperative pain was assessed using a numeric rating scale (NRS) in the right upper quadrant (RUQ) of the abdomen, at the umbilicus, and at the shoulder. Opioid consumption and recovery quality, measured using the QoR-15K questionnaire, were also recorded. Results: The 40 patients had a mean age of 48.3 years and an average body mass index (BMI) of 26.2 kg/m2. There were no significant differences in the pre- or intraoperative variables between groups. Patients receiving nefopam reported significantly lower RUQ pain scores compared to the controls, while the umbilicus and shoulder pain scores were similar. Rescue fentanyl requirements were lower in the nefopam group in both the PACU and ward. The QoR-15K questionnaire scores for nausea and vomiting were better in the nefopam group, but the overall recovery quality scores were comparable between the groups. Conclusions: Nefopam reduces RUQ pain and opioid use post-single-port RALC with a parietal pain block without markedly boosting RSB's effect on umbilicus or shoulder pain. It may also better manage postoperative nausea and vomiting, underscoring its role in analgesia strategies for this surgery.

Development of a Semiquantitative Whole-Body MRI Scoring System for Multiple Myeloma.

Background In patients with multiple myeloma (MM), the serum marker ß2-microglobulin does not always accurately reflect tumor load. In contrast, whole-body (WB) MRI has shown high sensitivity for detecting bone lesions. Purpose To develop and validate a semiquantitative WB MRI scoring system for newly diagnosed MM and to compare it with the International Staging System (ISS) and Revised ISS (R-ISS). Materials and Methods This study included two retrospective groups (group 1, July 2015 to September 2021; group 2, February 2020 to September 2021) and one prospective group (group 3, October 2021 to February 2022) of patients with newly diagnosed MM. A new scoring system for MM was developed using spine MRI scans in group 1 and WB MRI scans in group 2 that integrated three features: (a) background marrow pattern, (b) number of focal bone lesions, and (c) presence of extramedullary or paramedullary lesions. The summed total score ranged from zero to nine. The interobserver agreement for each feature was assessed using Fleiss or Cohen weighted κ. WB MRI total scores in group 3 were compared across ISS and R-ISS stages using two-way analysis of variance. Results Groups 1, 2, and 3 included 103 patients (mean age, 62.1 years ± 9.1 [SD]; 60 men), 36 patients (mean age 65.4 years ± 11.3 [SD]; 19 women), and 39 participants (mean age, 62.0 years ± 11.7 [SD]; 20 men), respectively. The interobserver agreements for the three features composing the scoring system were substantial (κ range, 0.69-0.80). WB MRI total score increased with increasing ISS stage (mean score for ISS 1, 2, and 3 was 2.2, 4.2, and 5.8, respectively; P = .009) and R-ISS stage (mean score for R-ISS 1, 2, and 3 was 2.1, 3.8, and 5.9, respectively; P = .005). Conclusion The developed WB MRI scoring system for MM demonstrated substantial observer agreement and corresponded well with ISS and R-ISS stages. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Dragan and Messiou in this issue.

Diagnosis of Marginal Infiltration in Soft Tissue Sarcoma by Radiomics Approach Using T2-Weighted Dixon Sequence.

BACKGROUND: Determination of preoperative soft tissue sarcoma (STS) margin is crucial for patient prognosis. PURPOSE: To evaluate diagnostic performance of radiomics model using T2-weighted Dixon sequence for infiltration degree of STS margin. STUDY TYPE: Retrospective. POPULATION: Seventy-two STS patients consisted of training (n = 58) and test (n = 14) sets. FIELD STRENGTH/SEQUENCE: A 3.0 T; T2-weighted Dixon images. ASSESSMENT: Pathologic result of marginal infiltration in STS (circumscribed margin; n = 27, group 1, focally infiltrative margin; n = 31, group 2-A, diffusely infiltrative margin; n = 14, group 2-B) was the reference standard. Radiomic volume and shape (VS) and other (T2) features were extracted from entire tumor volume and margin, respectively. Twelve radiomics models were generated using four combinations of classifier algorithms (R, SR, LR, LSR) and three different inputs (VS, T2, VS + T2 [VST2] features) to differentiate the three groups. Three radiologists (reader 1, 2, 3) analyzed the marginal infiltration with 6-scale confidence score. STATISTICAL TESTS: Area under the receiver operating characteristic curve (AUC) and concordance rate. RESULTS: Averaged AUCs of R, SR, LR, LSR models were 0.438, 0.466, 0.438, 0.466 using VS features, 0.596, 0.584, 0.814, 0.815 using T2 features, and 0.581, 0.587, 0.821, 0.821 using VST2 features, respectively. The LR and LSR models constructed with T2 or VST2 features showed higher AUC and concordance rate compared to radiologists' analysis (AUC; 0.730, 0.675, 0.706, concordance rate; 0.46, 0.43, 0.47 in reader 1, 2, 3). DATA CONCLUSION: Radiomics model constructed with features from tumor margin on T2-weighted Dixon sequence is a promising method for differentiating infiltration degree of STS margin. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Broncho-Vaxom bacterial lysate prevents asthma via acetate enhancement in mouse model.

PURPOSE: Broncho-Vaxom (BV) is known to attenuate allergic airway inflammation and chronic bronchitis in humans, but the underlying mechanism of this gut-mediated immunity remains unclear. This study investigated the effects of an oral BV on gut and systemic short-chain fatty acids (SCFAs) and immune responses. METHODS: Oral BV was administered daily for 15 days prior to commencing the study in an asthma mouse model. Asthma was induced by ovalbumin (OVA) sensitization followed by a challenge with 1% OVA by inhalation. Asthmatic phenotypes, gut- and systemic- immune responses, and SCFAs in the cecum and blood were then investigated. RESULTS: Airway hyperresponsiveness, total immunoglobulin E production, and pulmonary inflammation were all significantly suppressed by BV. The interleukin-13 level was also suppressed, whereas TGF-ß expression was increased, in the lungs of the BV-treated mice. The regulatory T (Treg) cell numbers were increased in the small intestine, and the acetate level was increased in the cecum and serum after BV treatment. The levels of acetate in the cecum and serum were negatively correlated with airway hyperresponsiveness and with the eosinophil numbers in the BAL fluid of the OVA-induced mice. There was a positive correlation between the acetate levels in the feces and serum and the lung expression of TGF-ß in the asthma mice. CONCLUSIONS: Oral BV administration appears to prevent allergic inflammation by enhancing Treg cell proliferation and acetate production in an asthmatic mouse model.

The alternative bile acid pathway can predict food allergy persistence in early childhood.

BACKGROUND: Mechanisms underlying persistent food allergy (FA) are not well elucidated. The intestinal mucosa is the primary exposure route of food allergens. However, no study has examined intestinal metabolites associated with FA persistence. The goal of this study was to investigate intestinal metabolites and associated microbiomes in early life that aid in determining the development and persistence of FA. METHODS: We identified metabolomic alterations in the stool of infants according to FA by mass spectrometry-based untargeted metabolome profiling. The targeted metabolomic analysis of bile acid metabolites and stool microbiome was performed. Bile acid metabolite composition in infancy was evaluated by characterizing the subjects at the age of 3 into FA remission and persistent FA. RESULTS: In untargeted metabolomics, primary bile acid biosynthesis was significantly different between subjects with FA and healthy controls. In targeted metabolomics for bile acids, intestinal bile acid metabolites synthesized by the alternative pathway were reduced in infants with FA than those in healthy controls. Subjects with persistent FA were also distinguished from healthy controls and those with FA remission by bile acid metabolites of the alternative pathway. These metabolites were negatively correlated with specific IgE levels in egg white. The abundance of intestinal Clostridia was decreased in the FA group and was correlated with ursodeoxycholic acid. CONCLUSION: Intestinal bile acid metabolites of the alternative pathway could be predictive biomarkers for persistent FA in early childhood. These findings require replication in future studies.

Associations of prenatal antibiotic exposure and delivery mode on childhood asthma inception.

BACKGROUND: Prenatal antibiotic exposure and delivery mode may affect the gut microbiome in early life and influence the development of childhood asthma, but the combined effect of these 2 factors is unknown. OBJECTIVE: To identify the individual and combined effects of prenatal antibiotic exposure and delivery mode on the development of asthma in children and the potential mechanisms underlying these associations. METHODS: A total of 789 children from the Cohort for Childhood Origin of Asthma and Allergic Diseases birth cohort study were enrolled. Asthma was defined as a physician-confirmed diagnosis with asthma symptoms in the previous 12 months at age 7 years. Information on prenatal antibiotic exposure was obtained by mothers using a questionnaire. Logistic regression analysis was used. Gut microbiota analysis using 16S rRNA gene sequencing of fecal specimens obtained at 6 months was undertaken for 207 infants. RESULTS: Prenatal antibiotic exposure and cesarean section delivery (adjusted odds ratio [aOR], 95% confidence interval [CI], 5.70 [1.25-22.81] and 1.57 [1.36-6.14], respectively) were associated with childhood asthma, especially synergistically when compared with the vaginal delivery-prenatal antibiotic exposure reference group (aOR, 7.35; 95% CI, 3.46-39.61; Interaction P = .03). Prenatal antibiotic exposure was associated with childhood asthma with aORs 21.79 and 27.03 for 1 and 2 or more exposures, respectively. Considerable small-airway dysfunction (R5-R20 in impulse oscillometry) was observed with prenatal antibiotic exposure and cesarean section delivery, compared with those with spontaneous delivery without prenatal antibiotic exposure. There was no significant difference in the diversity of gut microbiota among the 4 groups. However, the relative abundance of Clostridium was significantly increased in infants with prenatal antibiotic exposure and delivered by means of cesarean section. CONCLUSION: Prenatal antibiotic exposure and delivery mode might modulate asthma development in children and small-airway dysfunction, potentially through early-life gut microbiota alterations.

The Diagnostic Accuracy of a Retrograde Voiding Trial for Restoration of Spontaneous Voiding Function after Prolapse and Urinary Incontinence Surgery.

STUDY OBJECTIVE: To assess the diagnostic accuracy of a retrograde voiding trial for the restoration of spontaneous voiding function after prolapse and urinary incontinence surgery and thereby determine whether the retrograde method can be a reliable alternative to the spontaneous voiding trial. DESIGN: A retrospective cohort study. SETTING: A single tertiary hospital in South Korea. PATIENTS: Women who underwent operations for prolapse, urinary incontinence, or both. INTERVENTION: Sequential voiding trials on postoperative day 1 or 2-retrograde voiding trial followed by spontaneous voiding trial. MEASUREMENTS AND MAIN RESULTS: Of the 408 women analyzed, 278 (68.1%) passed the spontaneous voiding trial on the first day of assessment and none experienced urinary retention after a successful voiding trial. Receiver operating characteristic analyses of retrograde voiding trials evaluating voided volume (VV), postvoid residual (PVR), and voiding efficiency (VE) all demonstrated high diagnostic accuracy for restoration of spontaneous voiding function, whereas measuring PVR and VE had better discriminative ability than VV (area under the curve [95% confidence interval] = 0.93 [0.90-0.95] for PVR, 0.94 [0.91-0.96] for VE, and 0.88 [0.85-0.91] for VV; DeLong's test between PVR/VE and VV p < .01). The optimal cutoffs determined by the Youden index were 200 mL for VV (sensitivity 85.0%, specificity 78.0%), 100 mL for PVR (sensitivity 84.0%, specificity 87.0%), and 66.7% for VE (sensitivity 86.0%, specificity 88.0%). CONCLUSIONS: The retrograde voiding trial is an accurate predictor for restoration of spontaneous voiding function after prolapse and incontinence surgery and can be a useful alternative to the spontaneous voiding trial.

Blood eosinophil related to maternal allergic rhinitis is associated with the incidence of allergic rhinitis in offspring: COCOA study.

OBJECTIVE: The identification of allergic rhinitis (AR) in early life is important for the target of intervention. AR is caused by various environmental factors, including house dust mites. We investigated the relationship between the Dermatophagoides farinae (Der f)-IgE and eosinophil in mothers with AR at delivery and the eosinophil levels and AR incidence in children. METHODS: The study participants were 983 mother-child pairs from the COhort for Childhood Origin of Asthma and Allergic Diseases. AR was diagnosed by a doctor at delivery in mother and at 3 years of age in offspring. The association between eosinophil level and AR was assessed using logistic regression analysis. RESULTS: The Der f-IgE level in mother having AR at delivery was associated with the mother's eosinophil level, and the mother's eosinophil level was associated with the child's eosinophil level both at age 1 and 3. The risk of AR at age 3 in children was increased according to increased eosinophil levels in mothers at delivery and in children both aged 1 and 3 years (adjusted odds ratio [aOR] and 95% confidence interval [CI]: 2.57 [1.14-5.78], 2.28 [1.02-5.13], respectively). The risk of childhood AR at the age of 3 is increased when both mothers and children have high eosiniophils (aOR and 95% CI: 2.62 [1.01-6.79], 1.37 [0.98-1.91]). CONCLUSIONS: Der f-IgE in mothers at delivery was related to eosinophil levels in mothers with AR and higher level of eosinophils in both mother and children was associated with the increased risk of AR incidence at the first 3 years of life of children.

Loss of Neutralizing Activity of Tixagevimab/Cilgavimab (Evusheld™) Against Omicron BN.1, a Dominant Circulating Strain Following BA.5 During the Seventh Domestic Outbreak in Korea in Early 2023.

Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/cilgavimab administration and the average PRNT ND50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.