Considerations for defining and diagnosing generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare, chronic skin disease, characterized by widespread pustules and erythema, often accompanied with systemic signs and symptoms. GPP flares occur episodically but may be protracted. Left untreated, GPP can be life-threatening. Despite being first reported over 100 years ago, definitions and diagnostic criteria for GPP have been inconsistent and varied due, in part, to its rarity and a limited understanding of its pathogenesis. As such, many patients with GPP face delays in diagnosis and subsequent treatment. This manuscript aims to increase the recognition of GPP and provide foundational considerations to aid in the definition and diagnosis of this disease.

'Primary' antibiotics in wastewater treatment plants.

There are anywhere from 5 to 8 priority antibiotics in typical wastewater treatment plants (WWTPs) whose concentrations exceed the maximum allowed, out of 12 priority antibiotics designated by the World Health Organization as the species to pose severe health hazard than others. If the priority antibiotics to deal with could be reduced to just one or two, such reduction would greatly simplify the construction and operation of the treatment plants. Introduced here is a concept of 'primary' antibiotic, the abatement of which ensures mitigation of all the other priority antibiotics in the wastewater. A criterion for determining primary antibiotic is developed. For a demonstration of the approach, the wastewater systems treated with solar-based photocatalysts are considered. The criterion reveals that the primary antibiotic in the typical European WWTP as well as in the typical municipal and hospital wastewater is ciprofloxacin, whereas the typical industrial wastewater contains ciprofloxacin and oxytetracycline.

Characterization of the Ruminal Microbiota in Sheep and Goats Fed Different Levels of Tannin-Rich Sericea Lespedeza Hay.

Understanding ruminal microbiota and diet-host breed interactions under forage feeding conditions is essential for optimizing rumen fermentation and improving feed efficiency in small ruminants. This study aimed to investigate the effects of different ratios of condensed tannin (CT)-rich Sericea lespedeza (Lespedeza cuneate) in the diets on changes and interactions of ruminal microbiota and host species (i.e., sheep and goats). Katahdin sheep (n = 12) and Alpine goats (n = 12) at approximately 10 to 12 months of age were blocked by body weight (BW = 30.3 kg and 25.5 kg, respectively) and randomly assigned to one of the three treatments. Diets contained 75% coarsely ground forage and 25% concentrate. The forages were (1) 100% alfalfa hay (AL), (2) 100% Sericea lespedeza hay (SL), and (3) 50 % AL + 50% SL (ASL). In the present study, the diversity and composition of ruminal microbiota differed between sheep and goats fed similar diets. Based on the taxonomic analysis, there was a distinct clustering pattern (P < 0.05) for sheep by diets, but such a pattern was not observed for goats (P > 0.1). The most predominant phyla were Firmicutes, Bacteroidetes, Ascomycota, and methanogen species of Methanobrevibactor sp. in the rumen of sheep and goats, regardless of diets. The Bacteroidetes and Ascomycota were enriched in sheep fed AL and ASL. In contrast, these microbial phyla were enhanced in goats fed tannin-rich SL diets, with the diet by host species interaction (P < 0.02) for the Bacteroidetes phylum. Sheep rumen fluid samples showed a higher degree of variability in microbial community composition compared to goat rumen fluid samples. The relative proportion of the Aspergillus fungi population was reduced to 90.7% in the SL group compared with the AL group, regardless of host species. The antimicrobial activity of tannins and greater sensitivities of selected microbiota species to these tannin compounds during SL feeding in sheep and goats perhaps caused this difference. The results from this study suggest that differences in the microbiota were associated with differences in diets and host species. Therefore, this study provides a better understanding of ruminal microbiota and diet-host species interactions under various tannin-rich diets, which could advance consolidative information on rumen microbiome community diversity changes and may improve sheep and goat production.

Efficacy of Upadacitinib and Dupilumab on Achieving Stringent and Composite Skin and Itch Outcomes: an Indirect Comparison of Adults with Moderate-to-Severe Atopic Dermatitis.

INTRODUCTION: Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 assessed efficacy of upadacitinib 30 mg and upadacitinib 15 mg against placebo, while Heads Up assessed efficacy of upadacitinib 30 mg in a head-to-head trial against dupilumab 300 mg. A head-to-head trial of upadacitinib 15 mg against dupilumab 300 mg has not been conducted. Network meta-analysis has shown that upadacitinib 30 mg and upadacitinib 15 mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated more stringent outcomes. METHODS: A population-adjusted indirect comparison was conducted using post hoc individual patient data from Measure Up 1 and 2 and Heads Up to estimate how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates. Absolute response rates at weeks 4, 16, and 24 were estimated for the following outcomes: no/minimal itch [Worst Pruritus Numerical Rating Scale (WP-NRS) score of 0/1], Eczema Area and Severity Index (EASI) score of ≤ 3 (EASI ≤ 3), 100% improvement in EASI (EASI 100), both ≥ 90% improvement in EASI (EASI 90) and WP-NRS 0/1, both EASI ≤ 3 and WP-NRS 0/1, and both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to treat population for the clinical trials, and used non-responder imputation. RESULTS: Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg and then dupilumab. This pattern was observed at week 4, week 16, and week 24. CONCLUSIONS: For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining more stringent and composite outcomes across multiple timepoints, followed by upadacitinib 15 mg and then dupilumab 300 mg.

Efficacy of lebrikizumab in adolescent patients with moderate-to-severe atopic dermatitis: 16-week results from three randomized phase 3 clinical trials.

BACKGROUND: Lebrikizumab, a high-affinity monoclonal antibody targeting IL-13, previously demonstrated clinical efficacy in three randomized, double-blind, placebo-controlled Phase 3 trials that included adults and adolescents with moderate-to-severe atopic dermatitis (AD): ADvocate1, ADvocate2, and ADhere. AIM: This subset analysis evaluated 16-week physician- and patient-reported outcomes of lebrikizumab in the adolescent patients enrolled in these three trials. METHODS: Eligible adolescents (≥12 to <18 years weighing ≥40kg) were randomized 2:1 to subcutaneous lebrikizumab (500 mg loading doses at baseline and Week 2 followed by 250 mg every 2 weeks) or placebo as monotherapy in ADvocate1&2, and in combination with topical corticosteroids (TCS) in the ADhere study. Week 16 analyses included clinical efficacy outcomes (IGA (0,1) with ≥2-point improvement, EASI 75, EASI 90), patient-reported Pruritus NRS ≥4-point improvement and Sleep-Loss Scale ≥2-point improvement. RESULTS: Pooled ADvocate1&2 16-week results in lebrikizumab (N = 67) vs placebo (N = 35) were: IGA (0,1) 46.6% vs 14.3% (p < 0.01), EASI 75 62.0% vs 17.3% (p < 0.001), EASI 90 40.7% vs 11.5% (p < 0.01), Pruritus NRS 48.9% vs 13.1% (p < 0.01), and Sleep-Loss Scale 26.9% vs 6.9% (p = 0.137). Corresponding results for ADhere, (lebrikizumab + TCS, N = 32; placebo + TCS, N = 14), were consistent. CONCLUSIONS: Lebrikizumab treatment demonstrated efficacy in improving the signs and symptoms of AD in adolescent patients, consistent with the ADvocate and ADhere overall population results.

Lebrikizumab Provides Rapid Clinical Responses Across All Eczema Area and Severity Index Body Regions and Clinical Signs in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) affects multiple areas of the body, some of which may be more refractory to treatment. We evaluated improvements in the Eczema Area and Severity Index (EASI) by body region and clinical signs for each body region in lebrikizumab-treated patients with moderate-to-severe AD. METHODS: ADvocate 1 and ADvocate 2 compared lebrikizumab 250 mg as monotherapy every 2 weeks versus placebo for 16 weeks. Efficacy measures included EASI, which rates the extent and severity of four clinical signs (erythema, edema/papulation, excoriation, lichenification) in four body regions (head/neck, upper extremities, trunk, lower extremities). Analyses are post hoc. RESULTS: Mean baseline EASI, body region EASI subscores, and the severity of clinical signs were consistent across both studies (EASI ranging from 16.0 to 72.0). At week 16 in both studies, patients treated with lebrikizumab showed significantly greater percent improvement in EASI across all body regions versus placebo (p ≤ 0.001), with improvements as early as week 2. In ADvocate 1, all clinical signs significantly improved across all body regions at week 16 with lebrikizumab (51.4-71.6% improvement) versus placebo (23.1-43.5%, p ≤ 0.001), with significant improvements as early as week 2 for all signs. Significant improvements for all clinical signs at week 16 were also seen in ADvocate 2 for lebrikizumab (53.5-75.6%) versus placebo (28.5-41.2%, p ≤ 0.001) and as early as week 2 for all body regions and signs except head/neck erythema and lower extremity erythema, edema/papulation, and lichenification, which showed significant improvement by week 4. CONCLUSIONS: Lebrikizumab as monotherapy consistently and rapidly reduced the extent of involvement and severity of AD in all EASI clinical signs and body regions, including the head and neck region and clinical sign of lichenification, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ADvocate 1 (NCT04146363) and ADvocate 2 (NCT04178967).

Cedirogant in adults with psoriasis: a phase 2, randomized, placebo-controlled clinical trial.

BACKGROUND: Dysregulated interleukin (IL)-17/IL-23 signaling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage program. OBJECTIVE: To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. METHODS: In this phase 2b, multicenter, double-blind, 16-week study (NCT05044234), adults aged 18-65 years were randomized 1:1:1:1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg, or placebo. Assessments included ≥50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician Global Assessment 0/1, Psoriasis Symptoms Scale 0, and improvements in itch, adverse events (AEs), pharmacokinetics, and IL-17A/F levels. Efficacy results based on observed cases were summarized descriptively. RESULTS: Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early due to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 28.6%, 7.7%, and 41.7% in the cedirogant 75 mg, 150 mg, and 375 mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75 mg, 150 mg, and placebo groups and higher in the cedirogant 375-mg group; most AEs were mild or moderate. CONCLUSIONS: Patients with psoriasis who received cedirogant showed PASI improvement and cedirogant was generally well tolerated. Results should be interpreted in the context of early study termination. Cedirogant development has been discontinued.

Long-term safety and effectiveness of roflumilast cream 0.3% in adults with chronic plaque psoriasis: A 52-week, phase 2, open-label trial.

BACKGROUND: Efficacy and/or safety profiles limit topical psoriasis treatments. OBJECTIVE: Evaluate long-term effects of once-daily roflumilast cream 0.3% in patients with psoriasis. METHODS: In this open-label phase 2 trial, adult patients (N = 332) with psoriasis who completed the phase 2b parent trial or were newly enrolled applied roflumilast once-daily for 52 weeks. Safety and effectiveness were assessed. RESULTS: Overall, 244 patients (73.5%) completed the trial; 13 patients (3.9%) discontinued due to adverse events (AEs) and 3 (0.9%) due to lack of efficacy. Twelve patients (3.6%) reported treatment-related AEs; none were serious. ≥97% of patients had no irritation. No tachyphylaxis was observed with 44.8% of the patients achieving Investigator Global Assessment (IGA) Clear or Almost Clear at Week 52. LIMITATIONS: Intertriginous-IGA and Psoriasis Area and Severity Index (PASI) were not evaluated in all patients. CONCLUSIONS: In this long-term trial, once-daily roflumilast cream was well-tolerated and efficacious up to 64 weeks in patients in the earlier trial, suggesting it is suitable for chronic treatment, including the face and intertriginous areas.

[Research on epidemiological characteristics of pneumonia and correlative factors of length of hospitalization in the elderly aged 60 years and older in Ningbo].

Objective: To investigate the epidemiological characteristics of pneumonia and the related factors of the length of hospitalization of pneumonia in the elderly aged 60 years and older in Ningbo in 2019. Methods: Data on hospitalized cases of pneumonia in the elderly aged 60 years and older in Ningbo in 2019 were collected through the regional health information platform, and the population data of Ningbo in 2019 were obtained through the Zhejiang Provincial Bureau of Statistics. A descriptive epidemiological analysis was conducted on hospitalized cases of pneumonia in the elderly population, and factors related to the length of hospitalization were explored. Results: A total of 15 956 hospitalized cases of pneumonia aged 60 years and older were reported in Ningbo in 2019, and the incidence of pneumonia requiring hospitalization was 1.02% (15 956/1 571 431). The incidence was 1.13% (8 613/760 357) in males and 0.83% (6 759/811 074) in females, and the ratio of male to female cases was 1.27∶1. The highest incidence was found in the ≥80 age group (2.52%), and the lowest incidence was found in the 60-69 age group (0.58%). March, February, and January were the peak period of pneumonia hospitalization. The main types of pneumonia diagnosed were not specified (65.12%), followed by bacterial pneumonia (34.60%). The M(Q1, Q3) of hospitalized patients with pneumonia was 9 (7, 13) days. The results of multivariate logistic regression analysis showed that gender (female: OR=0.911, 95%CI: 0.849-0.978) and older age (70-79 years old: OR=1.211, 95%CI: 1.111-1.321; ≥80 years old group: OR=1.486, 95%CI: 1.365-1.617), settlement method (self-payment: OR=0.567, 95%CI: 0.464-0.691), higher level of hospitals (Grade Ⅱ: OR=1.902,95%CI:1.723-2.100; Grade Ⅲ: OR=1.546,95%CI:1.407-1.698) were associated with the length of hospitalization for pneumonia in people aged 60 years and older in Ningbo. Conclusions: Hospitalization with pneumonia in people aged 60 years and older was high in winter and spring, men and older adults were in high-risk groups in Ningbo in 2019. Gender, age, billing method, and level of hospitals may be related factors to the length of hospitalization for pneumonia.

Speed and Cumulative Responses According to Body Regions in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Ixekizumab (Interleukin-17A Antagonist) versus Guselkumab (Interleukin-23p19 Inhibitor).

INTRODUCTION: When assessing the effect of a therapy for psoriasis (PsO), it is important to consider speed of response and cumulative response. However, responses among biologics may differ by body regions. This post hoc analysis compares speed of response and cumulative response for ixekizumab (IXE), an interleukin-17A antagonist, and guselkumab (GUS), an interleukin-23p19 inhibitor, in different body regions of patients with moderate-to-severe plaque PsO participating in the IXORA-R study, up to week 24. METHODS: The IXORA-R design has been previously described. Patients received the respective on-label dosing of IXE or GUS. The median time to first Psoriasis Area and Severity Index (PASI) 50, 75, 90, and 100 response (50%, 75%, 90%, and 100% improvement from baseline, respectively) and the cumulative days with clear skin for PASI 50, 75, 90, and 100 responses were assessed in four body regions: head, trunk, upper extremities, and lower extremities. RESULTS: A total of 1027 patients were enrolled and received IXE (N = 520) or GUS (N = 507). Median time to first PASI 50, 75, 90, and 100 response was shortest in the head region, followed by the remaining body regions in both IXE and GUS cohorts. In each body region, IXE was significantly faster than GUS (p < 0.001) in achieving PASI 50, 75, 90, and 100. Through 24 weeks, the number of days with clear skin for PASI 90 and 100 was greater in the head region, followed by trunk, upper extremities, and lastly lower extremities in both IXE and GUS cohorts. In each body region, through 24 weeks, patients on IXE experienced a significantly higher number of days with clear skin for PASI 50, 75, 90, and 100 than patients on GUS (p < 0.01). CONCLUSIONS: As compared to GUS, IXE provided a faster skin clearance and more days with clear skin in all body regions of patients with moderate-to-severe plaque PsO through 24 weeks. TRIAL REGISTRATION NUMBER: https://www. CLINICALTRIALS: gov/ : NCT03573323 (IXORA-R).

Psoriasis, a long-term, inflammatory skin disease, impacts patient's lives, and response to treatment varies depending on the body region affected. Here, we assessed the speed of response and cumulative response through 24 weeks in different body regions (head, trunk, upper extremities, and lower extremities) of patients with moderate-to-severe plaque psoriasis treated with currently approved therapies: ixekizumab (IXE), an interleukin-17A antagonist, or guselkumab (GUS), an interleukin-23p19 inhibitor. We calculated the speed of response as the number of weeks to achieve first skin clearance, based on the Psoriasis Area and Severity Index (PASI) tool, and the cumulative response as the number of days with clear skin throughout the 24-week period. We found that the head region achieved skin clearance fastest and had a higher number of days with clear skin compared to the trunk, upper extremities, and lower extremities, in both groups of patients treated with IXE or GUS. Compared to GUS, IXE provided faster skin clearance and a higher number of days with clear skin in all body regions. For example, the head region of patients treated with IXE, as compared to GUS, achieved complete skin clearance twofold faster and experienced 18.7% more days of complete skin clearance. In conclusion, treatment with IXE through 24 weeks provided a faster response and a higher cumulative response than treatment with GUS in all four body regions of patients with moderate-to-severe plaque psoriasis.

Indoor air pollution is associated with respiratory symptoms in children in urban Vietnam.

Exposure to indoor air pollution (IAP) is a leading environmental risk for respiratory diseases. We investigated the relationship between respiratory symptoms and polluting indoor activities such as smoking, cooking and contact with pets among children in Ho Chi Minh City (HCMC), Vietnam. A cross-sectional survey applied a multistage sampling method in 24 randomly selected secondary schools across the city. Approximately 15,000 students completed self-administrated questionnaires on risk factors and respiratory health outcomes within the preceding 12 months. Data were analyzed using a multivariable logistic regression model with robust standard errors. Wheeze was the most common respiratory symptom (39.5 %) reported, followed by sneezing and runny nose (28.3 %). A small percentage of students self-reported asthma (8.6 %). Approximately 56 % of participants lived with family members who smoked. A positive association between exposure to indoor secondhand smoke and respiratory symptoms was observed, with adjusted odds ratios (aOR) of 1.41 (95 % CI: 1.25-1.60, p < 0.001) for wheezing and 1.64 (95 % CI: 1.43-1.87, p < 0.001) for sneezing and runny nose, respectively. Using an open stove fuelled by coal, wood, or kerosene for cooking was associated with wheeze (aOR: 1.36, CI 95 %: 1.10-1.68, p = 0.01) and sneezing and runny nose (aOR: 1.36, CI 95 %: 1.09-1.69, p = 0.01). In the present study, IAP was associated with adverse health outcomes, as evidenced by an increase in respiratory symptoms reported within the previous 12 months.

Evaluation of QSAR models for predicting mutagenicity: outcome of the Second Ames/QSAR international challenge project.

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating. The DGM/NIHS provided a curated training dataset of approximately 12,000 chemicals and a trial dataset of approximately 1,600 chemicals, and each participating team predicted the Ames mutagenicity of each trial chemical using various Ames/QSAR models. The DGM/NIHS then provided the Ames test results for trial chemicals to assist in model improvement. Although overall model performance on the Second Project was not superior to that on the First, models from the eight teams participating in both projects achieved higher sensitivity than models from teams participating in only the Second Project. Thus, these evaluations have facilitated the development of QSAR models.

[Epidemiological characteristics and spatiotemporal distribution of schizophrenia in Ningbo, 2018-2022].

Objective: To explore the temporal and spatial distribution characteristics of reported incidence of schizophrenia in Ningbo from 2018 to 2022 and to provide a scientific basis for rational allocation of mental health resources and comprehensive prevention and treatment of schizophrenia. Methods: The reported incidence data of schizophrenia from 2018 to 2022 were collected from Ningbo's mental health information management system, and the reported incidence was calculated by township. The spatial correlation analysis and the spatiotemporal scan analysis were used to study the spatiotemporal distribution of schizophrenia. Results: The reported incidence of schizophrenia decreased from 2018 to 2022, with 4 133 new cases reported, and the annual average reported incidence was 9.76/100 000. Global and local spatial autocorrelation analysis showed positive spatial correlations and hot spots in 2018-2020. The space-time scan analysis showed an incidence cluster in Dongqiao Town, Haishu District, during 2018-2019. The RR was 2.46, and the log-likelihood ratio was 256.89. Conclusions: The reported incidence of schizophrenia in Ningbo has obvious temporal and spatial aggregation, and the high incidence area explored can provide clues for further research on the correlation between environmental factors and the incidence of schizophrenia and has certain guiding significance for the rational allocation of mental health resources in Ningbo.

Physical Properties and Clinical Performance of Short Fiber Reinforced Resin-based Composite in Posterior Dentition: Systematic Review and Meta-analysis.

OBJECTIVE: This study compares the physical properties and clinical performance of short fiber reinforced composites (SFRC) to those of particulate-filled resin-based composites (PFRC) for class I and II direct restorations in permanent dentition. METHODS: Systematic review and meta-analysis was conducted using PubMed, Embase (Elsevier), and Dentistry and Oral Sciences Source (EBSCO) databases. The outcomes evaluated were physical properties including flexural strength, flexural modulus, elastic modulus, microhardness, shrinkage, fracture toughness, degree of conversion, and depth of cure. Clinical performance was evaluated with a systematic review. RESULTS: The meta-analyses favored SFRC for flexural strength and fracture toughness compared to every PFRC subgroup, with a high quality of evidence. For all other properties, the meta-analyses favored SFRC to overall PFRC, with some non-significant differences with certain PFRC subgroups. The most recent clinical trial showed SFRC performed similarly to PFRC, however older studies suggest inferior surface texture and discoloration of SFRC compared to PFRC. CONCLUSION: This study can aid dental professionals in clinical decision making, supporting that SFRC offers improved physical properties, especially fracture resistance and flexural strength, compared to PFRC.

Genetic Variations in TrkB.T1 Isoform and Their Association with Somatic and Psychological Symptoms in Individuals with IBS.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is often comorbid with somatic pain and psychological disorders. Dysregulated signaling of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), has been implicated in somatic-psychological symptoms in individuals with IBS. Thus, we investigated the association of 10 single nucleotide polymorphisms (SNPs) in the regulatory 3' untranslated region (UTR) of NTRK2 (TrkB) kinase domain-deficient truncated isoform (TrkB.T1) and the BDNF Val66Met SNP with somatic and psychological symptoms and quality of life in a U.S. cohort (IBS n=464; healthy controls n=156). We found that the homozygous recessive genotype (G/G) of rs2013566 in individuals with IBS is associated with worsened somatic symptoms, including headache, back pain, joint pain, muscle pain, and somatization as well as diminished sleep quality, energy level and overall quality of life. Validation using U.K. BioBank (UKBB) data confirmed the association of rs2013566 with increased likelihood of headache. Several SNPs (rs1627784, rs1624327, rs1147198) showed significant associations with muscle pain in our U.S. cohort. Notably, these SNPs are predominantly located in H3K4Me1-enriched regions, suggesting their enhancer and/or transcription regulation potential. Together, our findings suggest that genetic variation within the 3'UTR region of the TrkB.T1 isoform may contribute to comorbid conditions in individuals with IBS, resulting in a spectrum of somatic and psychological symptoms that may influence their quality of life. These findings advance our understanding of the genetic interaction between BDNF/TrkB pathways and somatic-psychological symptoms in IBS, highlighting the importance of further exploring this interaction for potential clinical applications.