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.

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.

Comparative analysis of image quality and interchangeability between standard and deep learning-reconstructed T2-weighted spine MRI.

RATIONALE AND OBJECTIVES: MRI reconstruction of undersampled data using a deep learning (DL) network has been recently performed as part of accelerated imaging. Herein, we compared DL-reconstructed T2-weighted image (T2-WI) to conventional T2-WI regarding image quality and degenerative lesion detection. MATERIALS AND METHODS: Sixty-two patients underwent C-spine (n = 27) or L-spine (n = 35) MRIs, including conventional and DL-reconstructed T2-WI. Image quality was assessed with non-uniformity measurement and 4-scale grading of structural visibility. Three readers (R1, R2, R3) independently assessed the presence and types of degenerative lesions. Student t-test was used to compare non-uniformity measurements. Interprotocol and interobserver agreement of structural visibility was analyzed with Wilcoxon signed-rank test and weighted-κ values, respectively. The diagnostic equivalence of degenerative lesion detection between two protocols was assessed with interchangeability test. RESULTS: The acquisition time of DL-reconstructed images was reduced to about 21-58% compared to conventional images. Non-uniformity measurement was insignificantly different between the two images (p-value = 0.17). All readers rated DL-reconstructed images as showing the same or superior structural visibility compared to conventional images. Significantly improved visibility was observed at disk margin of C-spine (R1, p < 0.001; R2, p = 0.04) and dorsal root ganglia (R1, p = 0.03; R3, p = 0.02) and facet joint (R1, p = 0.04; R2, p < 0.001; R3, p = 0.03) of L-spine. Interobserver agreements of image quality were variable in each structure. Clinical interchangeability between two protocols for degenerative lesion detection was verified showing <5% in the upper bounds of 95% confidence intervals of agreement rate differences. CONCLUSIONS: DL-reconstructed T2-WI demonstrates comparable image quality and diagnostic performance with conventional T2-WI in spine imaging, with reduced acquisition time.

Impaired cognitive flexibility and disrupted cognitive cerebellum in degenerative cerebellar ataxias.

There is a clinically unmet need for a neuropsychological tool that reflects the pathophysiology of cognitive dysfunction in cerebellar degeneration. We investigated cognitive flexibility in degenerative cerebellar ataxia patients and aim to identify the pathophysiological correlates of cognitive dysfunction in relation to cerebellar cognitive circuits. We prospectively enrolled degenerative cerebellar ataxia patients with age-matched healthy controls who underwent 3 T 3D and resting-state functional MRI. All 56 participants were evaluated with the Scale for Assessment and Rating of Ataxia and neuropsychological tests including the Wisconsin Card Sorting Test, Trail Making Test, Montreal Cognitive Assessment and Mini-Mental State Examination. From MRI scans, we analysed the correlation of whole-brain volume and cortico-cerebellar functional connectivity with the Wisconsin Card Sorting Test performances. A total of 52 participants (29 ataxia patients and 23 healthy controls) were enrolled in this study. The Wisconsin Card Sorting Test scores (total error percentage, perseverative error percentage, non-perseverative error percentage and categories completed), Trail Making Test A and Montreal Cognitive Assessment were significantly impaired in ataxia patients (P < 0.05) compared to age-matched healthy controls. The Wisconsin Card Sorting Test error scores showed a significant correlation with the ataxia score (P < 0.05) controlling for age and sex. In volumetric analysis, the cerebellar right crus I, II, VIIb and VIII atrophy correlated with non-perseverative error percentage in the ataxia group. In functional connectivity analysis, the connectivity between crus I, II and VIIb of the cerebellum and bilateral superior parietal and superior temporal gyrus was significantly altered in ataxia patients. The functional connectivity between left crus II and VIIb of the cerebellum and dorsolateral prefrontal and superior frontal/parietal cortices showed a positive correlation with perseverative error percentage. The connectivity between left crus VIIb and pontine nucleus/middle cerebellar peduncle showed a significant negative correlation with non-perseverative error percentage in the ataxia group. The impaired cognitive flexibility represented by the Wisconsin Card Sorting Test was significantly impaired in degenerative cerebellar ataxia patients and correlated with disease severity. The Wisconsin Card Sorting Test performance reflects hypoactivity of the cognitive cerebellum and disrupted cortico-cerebellar connectivity in non-demented patients with degenerative cerebellar ataxia.

Two-Year Therapeutic Efficacy and Safety of Initial Triple Combination of Metformin, Sitagliptin, and Empagliflozin in Drug-Naïve Type 2 Diabetes Mellitus Patients.

BACKGRUOUND: We investigated the long-term efficacy and safety of initial triple therapy using metformin, a dipeptidyl peptidase-4 inhibitor, and a sodium-glucose cotransporter-2 inhibitor, in patients with type 2 diabetes mellitus. METHODS: We enrolled 170 drug-naïve patients with glycosylated hemoglobin (HbA1c) level >7.5% who had started triple therapy (metformin, sitagliptin, and empagliflozin). Glycemic, metabolic, and urinary parameters were measured for 24 months. RESULTS: After 24 months, HbA1c level decreased significantly from 11.0%±1.8% to 7.0%±1.7%. At 12 and 24 months, the rates of achievement of the glycemic target goal (HbA1c <7.0%) were 72.5% and 61.7%, respectively, and homeostasis model assessment of ß-cell function and insulin resistance indices improved. Whole-body fat percentage decreased by 1.08%, and whole-body muscle percentage increased by 0.97% after 24 months. Fatty liver indices and albuminuria improved significantly. The concentration of ketone bodies was elevated at the baseline but decreased after 24 months. There were no serious adverse events, including ketoacidosis. CONCLUSION: Initial triple combination therapy with metformin, sitagliptin, and empagliflozin led to achievement of the glycemic target goal, which was maintained for 24 months without severe hypoglycemia but with improved metabolic function and albuminuria. This combination therapy may be a good strategy for drug-naïve patients with type 2 diabetes mellitus.

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.

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.

Vitamin D supplementation can enhance therapeutic effects of excimer laser in patients with vitiligo.

PURPOSE: Vitiligo is a disease of acquired depigmentation characterized by the destruction of melanocytes. A theoretical association between low level of 25-hydroxyvitamin D [25(OH)D] and vitiligo has been previously suggested. The objective of this study was to determine the efficacy of intramuscular injection of cholecalciferol with excimer laser compared with the excimer laser alone for vitiligo treatment. METHODS: This study included 26 patients diagnosed with non-segmental vitiligo and low serum 25(OH)D levels (<20 ng/mL). The participants were randomly divided into two groups through randomization. The treatment using a 308-nm excimer laser was administered to both groups, and the study group additionally received cholecalciferol injection. RESULTS: The Vitiligo Area Scoring Index (VASI) scores showed an 83.6% improvement over the initial score in the study group, whereas the control group showed a 54.7% improvement after 6 months of treatment. After 6 months of treatment, the study group showed a significantly higher proportion of patients who achieved VASI50 and VASI75 compared with the control group. CONCLUSION: Intramuscular injection of cholecalciferol can be a supplemental option for the treatment of vitiligo patients with vitamin D deficiency with excimer laser therapy.

Deep learning-based k-space-to-image reconstruction and super resolution for diffusion-weighted imaging in whole-spine MRI.

PURPOSE: To assess the feasibility of deep learning (DL)-based k-space-to-image reconstruction and super resolution for whole-spine diffusion-weighted imaging (DWI). METHOD: This retrospective study included 97 consecutive patients with hematologic and/or oncologic diseases who underwent DL-processed whole-spine MRI from July 2022 to March 2023. For each patient, conventional (CONV) axial single-shot echo-planar DWI (b = 50, 800 s/mm2) was performed, followed by DL reconstruction and super resolution processing. The presence of malignant lesions and qualitative (overall image quality and diagnostic confidence) and quantitative (nonuniformity [NU], lesion contrast, signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and ADC values) parameters were assessed for DL and CONV DWI. RESULTS: Ultimately, 67 patients (mean age, 63.0 years; 35 females) were analyzed. The proportions of vertebrae with malignant lesions for both protocols were not significantly different (P: [0.55-0.99]). The overall image quality and diagnostic confidence scores were higher for DL DWI (all P ≤ 0.002) than CONV DWI. The NU, lesion contrast, SNR, and CNR of each vertebral segment (P ≤ 0.04) but not the NU of the sacral segment (P = 0.51) showed significant differences between protocols. For DL DWI, the NU was lower, and lesion contrast, SNR, and CNR were higher than those of CONV DWI (median values of all segments; 19.8 vs. 22.2, 5.4 vs. 4.3, 7.3 vs. 5.5, and 0.8 vs. 0.7). Mean ADC values of the lesions did not significantly differ between the protocols (P: [0.16-0.89]). CONCLUSIONS: DL reconstruction can improve the image quality of whole-spine diffusion imaging.

Adipose-Derived Stem Cell Exosomes Alleviate Psoriasis Serum Exosomes-Induced Inflammation by Regulating Autophagy and Redox Status in Keratinocytes.

Introduction: Exosomes play a key role in cell communication and are involved in both pathological and physiological processes. Autophagy dysfunction and oxidative stress are linked to immune-mediated inflammatory diseases such as psoriasis. Stem cell-derived exosomes exhibit immunomodulatory and antioxidant efficacy. Methods: We aimed to investigate the impact of psoriasis serum-derived exosomes on inflammation, oxidative stress, and autophagy in keratinocytes. Additionally, we explored the therapeutic potential of adipose-derived stem cell (ADSC) exosomes against inflammation induced by psoriasis serum exosomes. To validate psoriasis patient serum-derived exosomes and ADSC exosomes, we used nanoparticle tracking analysis, Western blotting, flow cytometry, and immunofluorescence. qPCR was used to study changes in the gene expression of proinflammatory cytokines and oxidative stress markers in HaCaT cells treated with psoriasis serum-derived exosomes or ADSC exosomes. The effects of these exosomes on autophagy in HaCaT cells were evaluated by Western blotting and immunofluorescence. Result: The treatment of HaCaT cells with psoriasis serum-derived exosomes increased proinflammatory cytokine production and oxidative stress-related factor (Nox2 and Nox4) expression and decreased Nrf2 expression via P65/NF-κB and P38/MAPK activation. Compared with healthy control serum-derived exosomes, psoriasis serum-derived exosomes decreased ATG5, P62, Beclin1, and LC3 expression and autophagosome production in HaCaT cells. Conversely, ADSC exosomes suppressed proinflammatory cytokine and oxidative stress production, and restored autophagy in HaCaT cells treated with psoriasis serum-derived exosomes. Discussion: These findings suggest that ADSC exosomes exhibit a suppressive effect on psoriasis serum exosome-induced inflammation and oxidative stress by regulating autophagy in keratinocytes.

A Quantitative Measure of Pain with Current Perception Threshold, Pain Equivalent Current, and Quantified Pain Degree: A Retrospective Study.

Background: As a subjective sensation, pain is difficult to evaluate objectively. The assessment of pain degree is largely dependent on subjective methods such as the numeric rating scale (NRS). The PainVisionTM system has recently been introduced as an objective pain degree measurement tool. The purpose of this study was to analyze correlations between the NRS and the current perception threshold (CPT), pain equivalent current (PEC), and quantified pain degree (QPD). Methods: Medical records of 398 subjects who visited the pain clinic in a university hospital from March 2017 to February 2019 were retrospectively reviewed. To evaluate the pain degree, NRS, CPT, PEC, and QPD were measured. Subjects were categorized into two groups: the Pain group (n = 355) and the No-pain group (n = 43). Results: The NRS showed a negative correlation with CPT (R = -0.10, p = 0.054) and a positive correlation with QPD (R = 0.13, p = 0.008). Among various diseases, only spinal disease patients showed a negative correlation between CPT and NRS (R = -0.22, p = 0.003). Additionally, there were significant differences in CPT and QPD between the Pain and No-pain groups (p = 0.005 and p = 0.002, respectively). Conclusions: CPT and QPD measured using the PainVisionTM system could be used to estimate pain intensity and the presence of pain. These parameters would be considered useful for predicting pain itself and its intensity.

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 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.

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.

Identification of NIFTP-Specific mRNA Markers for Reliable Molecular Diagnosis of Thyroid Tumors.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a low-risk thyroid tumor with a favorable prognosis. Nonetheless, differentiating NIFTP from other thyroid tumors remains challenging, necessitating reliable diagnostic markers. This study is aimed at discovering NIFTP-specific mRNA markers through RNA sequencing analysis of thyroid tumor tissues. We performed mRNA expression profiling for 74 fresh frozen thyroid tissue samples, including NIFTP and benign and malignant follicular-cell-derived tumors. NIFTP/malignant tumors showed 255 downregulated genes and 737 upregulated genes compared to benign tumors. Venn diagram analysis revealed 19 significantly upregulated and 7 downregulated mRNAs in NIFTP. Akaike information criterion analysis allowed us to select OCLN, ZNF423, LYG1, and AQP5 mRNA markers. We subsequently developed a predictive model based on logistic regression analysis using these four mRNAs, which we validated in independent samples (n = 90) using a qRT-PCR assay. This model demonstrated high accuracy in predicting NIFTP in discovery dataset (AUC (area under the receiver operating characteristic) = 0.960) and the validation dataset (AUC = 0.757). Our results suggest that OCLN, ZNF423, LYG1, and AQP5 mRNA markers might serve as reliable molecular markers for identifying NIFTP among other thyroid tumors, ultimately aiding in accurate diagnosis and management of NIFTP patients.

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.

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.

Anatomic Criterion for Clinically Relevant Apical Prolapse in Urogynecology Populations.

IMPORTANCE: Despite recognition of the critical role of the apex in vaginal support, there is no consensus on the anatomic criteria for clinically relevant apical prolapse. OBJECTIVE: The aim of this study was to define an optimal anatomic criterion for clinically relevant apical prolapse. STUDY DESIGN: This retrospective cohort study included 3,690 patients who had visited a tertiary hospital for ambulatory urogynecologic care. Vaginal bulge symptom was defined as a response of "somewhat," "moderately," or "quite a bit" to Question 3 on the Pelvic Floor Distress Inventory-20. Receiver operating characteristic curves were generated for a vaginal bulge symptom and apical support (Pelvic Organ Prolapse Quantification point C and C/total vaginal length [TVL]). RESULTS: Both point C and the C-to-TVL ratio (C/TVL) had excellent performance for predicting vaginal bulge symptoms (area under the curve, 0.917 and 0.927, respectively). The optimal cutoffs were -3.0 for C and -0.50 for C/TVL. When we analyzed the data set according to the TVL, there was a significant difference in the cutoffs for C, whereas those for C/TVL had little difference. There was no difference in the cutoffs of C and C/TVL according to hysterectomy status. CONCLUSIONS: The C/TVL is more appropriate than point C as a measure to define an anatomic criterion for clinically relevant apical prolapse. Descent of the vaginal apex beyond the halfway point of the vagina could be considered as an anatomic threshold for clinically relevant apical prolapse. This finding needs to be validated in nonurogynecology populations.