Canine obesity is associated with metabolic disturbances, but specific lipid alterations remain poorly characterized. This study aimed to characterize the serum lipidome of dogs with obesity before and after weight loss and to identify lipid species and pathways associated with lipidomic remodeling following weight loss. Eight neutered dogs with obesity (four males and four females; 5.37 ± 1.41 years; 27.15 ± 12.02 kg; body condition score 9/9) were fed a commercial weight-loss diet. After a 3-week adaptation, blood was collected for lipidomic analysis before weight loss (OB). A weight-loss program was implemented for up to 6 months until dogs achieved a 20% reduction from initial body weight, followed by a second blood collection after weight loss (WL). Targeted lipidomic profiling was performed using two multiple reaction monitoring (MRM) methods on a triple quadrupole mass spectrometer, covering 3,437 lipid ion transitions. Data were processed in MetaboAnalyst 6.0 and analyzed using Student's t-test, volcano plot, partial least squares-discriminant analysis (PLS-DA), variable importance in projection (VIP) scoring, and Lipid Ontology (LION) enrichment analysis. Dogs achieved a total weight loss of 23.68 ± 3.18%, with a weekly rate of 1.01 ± 0.26%. A total of 630 lipid species were identified, and clear remodeling of the canine serum lipidome was observed following weight loss. Before weight loss, dogs had higher serum concentrations of cholesterol esters (P = 0.047), phosphatidylcholines (P = 0.043), phosphatidylinositols (P = 0.038), and sphingomyelins (P = 0.023) than after weight loss. At the individual lipid-species level, volcano plot analysis identified 34 differentially abundant lipid species before and after weight loss, including specific triglyceride, phospholipid, and cholesterol ester species. PLS-DA clearly discriminated the serum lipidomic profiles before and after weight loss with high predictive performance. Additionally, LION enrichment analysis revealed multiple significantly enriched terms related to lipid cellular components, functional roles, and physicochemical properties. These findings provide novel insights into serum lipidomic remodeling associated with weight loss in dogs with obesity and highlight lipid species potentially involved in the metabolic response to weight reduction. Obesity is a common health problem in dogs and affects how fats are processed and stored in the body. However, the specific fat molecules involved in canine obesity and how they change with weight loss are not well understood. In this study, we used a detailed lipid analysis technique to examine changes in serum fat composition in dogs with obesity before and after weight loss. Eight dogs with obesity followed a controlled weight-loss program using a commercial diet until they lost about 20% of their initial body weight. Blood samples were collected before and after weight loss to compare their lipid profiles. More than 600 different lipid molecules were identified in the dogs’ serum. Dogs with obesity showed higher levels of cholesterol-related fats and certain structural lipids compared with the same dogs after weight loss. Weight loss was associated with marked changes in the blood lipid profile. Some lipid changes observed in dogs with obesity resemble those reported in humans with obesity and are associated with metabolic and heart-related diseases. These findings improve our understanding of lipid profile changes associated with weight loss in dogs with obesity and may help guide future strategies for monitoring and managing canine obesity.
Participants in the All of Us research study differ from the U.S. population in myriad characteristics, limiting the generalizability of findings. A statistical reweighting tool to improve generalizability would enhance the scientific value of the data. To account for differences between All of Us and the nationally representative 1999-2018 National Health and Nutrition Examination Survey (NHANES), we generated selection weights using four models incorporating sociodemographic, self-reported health, and clinical characteristics. We assessed covariate balance and compared predictors of all-cause mortality in weighted All of Us to NHANES using the ratio of hazard ratios (RHRs), where an RHR of one indicates unbiased estimates in (weighted) All of Us relative to NHANES. Weighting improved balance on measured variables between All of Us and NHANES. Among the four weighting models, the most complex model which included sociodemographic, health, and clinical variables and their interactions achieved HRs in All of Us most similar to those in NHANES. For example, the RHR for hypertension for unweighted All of Us vs. NHANES (RHR=1.5; 95% CI=1.4 to 1.7) was reduced to 1.2 (95% CI=0.9 to 1.5) after applying weights from the clinical-interaction model. Even in this model, 17 of 35 HRs evaluated diverged by >20% (RHR <0.8 or >1.2) between weighted All of Us and NHANES. Predictors of mortality in All of Us differ from those in the U.S. population both in their distribution and in their associations with mortality. Reweighting can mitigate selection bias, but no model we tested comprehensively achieved generalizability.
Weighted Quantile Sum (WQS) regression is a statistical method for quantifying the association between multiple possibly correlated predictors and a health outcome, estimating both the joint effect of the predictors as well as their individual contributions to the total effect. WQS has become one of the most popular and widely used approaches for investigating complex mixtures in environmental epidemiology, yet its implementation has been largely restricted to R users. In this paper we present wqsreg, the first Stata command for WQS regression, implemented for continuous, binary and count outcomes. We describe command's architecture and present an application of the command on exposome data exploring the association between 38 exposures and a continuous outcome. Wqsreg provides a user-friendly command for WQS regression that integrates several flexible components of the framework such as bootstrap, training/validation splitting, and repeated holdout procedures. Wqsreg returns regression estimates as well as graphical displays of the individual weights. It requires Stata version 11 or higher and is freely available on GitHub [ https://github.com/PonzanoMarta/wqsreg ]. Given the increasing importance of appropriately exploring complex multidimensional exposures, this contribution will further promote the use of appropriate statistical methods in epidemiological settings with multiple correlated predictors.
Apparent diffusion coefficient (ADC) calculated from diffusion-weighted MRI (DWI) can predict tumor response to neoadjuvant chemotherapy for breast cancer. However, obtaining consistently adequate image quality in breast DWI can be challenging, and the effect of image quality on ADC's predictive performance is unclear. The objective of this study was to evaluate inter-reader variability in image quality assessment and the effect of DWI image quality on the predictive performance of ADC. This multi-institutional study included 428 patients. Two readers assessed three DWI image quality factors-fat suppression, artifacts, and signal-to-noise ratio (SNR). Inter-reader agreement was estimated using Fleiss' Kappa. The percent change in tumor ADC from pretreatment (T0) to early treatment (T1) was used to predict pathologic complete response (pCR), assessed at surgery. Out of 428 patients, 134 were excluded (missing pCR [n = 17]; missing/incorrect DWI [n = 23]; inability to define region-of-interest [ROI, n = 94]) and 294 were included in the analysis. Kappa coefficients were estimated as: 0.47 (95% confidence interval [CI]: 0.42, 0.52) for fat suppression, 0.54 (0.50, 0.59) for artifact, and 0.38 (0.32, 0.44) for SNR. The AUC of ADC calculated from DWI with adequate (high or medium at both time points) image quality was 0.61 (95% CI: 0.52, 0.702), while it was 0.68 (95% CI: 0.53, 0.83) from DWI with inadequate image quality at either T0 or T1. The p-value for the difference in AUCs was 0.45. The inter-reader agreement was moderate to fair across all three quality categories. When a manually delineated tumor ROI was possible, no statistically significant difference in ADC predictive performance was observed between the quality-adequate and quality-inadequate cohorts; still, both were predictive of pCR. Furthermore, no statistically significant differences were observed in inter-reader agreement or ADC predictive performance between 1.5T and 3T scanners. These findings are clinically relevant to the use of ADC as an imaging biomarker in real-world conditions.
Despite declining malaria transmission, maternal anaemia and low birthweight (LBW) remain high in Ghana, suggesting that non-malarial determinants now dominate these outcomes. A cohort of 5197 pregnant women was enrolled at eight health facilities across Ghana's Ashanti and Volta regions. Independent predictors of anaemia at term and LBW were identified by multivariable logistic regression using multiple imputation by chained equations. Anaemia at term prevalence was 60.57% and LBW was 11.54%. No intestinal helminths were detected. Anaemia at antenatal care (ANC) booking was the strongest predictor of anaemia at term (aOR 3.98; absolute risk increase of 31.4 percentage points). Three or more iron and folic acid doses and eight or more ANC contacts each reduced risk by only four to six percentage points. For LBW, household poverty (absolute risk increase 8.8%), short maternal stature, and male foetal sex dominated. Intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (aOR 0.65) remained protective despite booking parasitaemia being non-significant. The Volta region had higher anaemia (71.1%vs. 47.7%) but lower LBW (9.6%vs. 14.4%) than Ashanti, with markedly higher parasite densities among infected women, consistent with waning naturally acquired immunity. Persistent anaemia and LBW reflect nutritional depletion, structural poverty, and increased malaria vulnerability under declining transmission. Pre-conception nutrition, social protection, and sub-microscopic malaria surveillance must complement clinic care.
Objectives: This study evaluated the utility of adaptive complex signal average (ACSA) diffusion-weighted imaging (DWI) specifically in breath-hold (BH) liver imaging, with a focus on signal intensity (SI) improvement, intrahepatic signal homogeneity, and apparent diffusion coefficient (ADC) behavior, and compared these findings with conventional non-ACSA DWI and free-breathing (FB) ACSA DWI. Methods: This retrospective study included 62 patients (mean age, 67.8 ± 13.6 years; 27 women) who underwent liver MRI with both FB and BH DWI on a 3-T system. Non-ACSA images were generated using conventional magnitude reconstruction, and ACSA images were reconstructed from identical raw data. SI, signal-to-noise ratio (SNR) and ADC were measured in the left lateral segment and right hepatic lobe. The signal intensity difference ratio (SIDR) between ACSA and non-ACSA, signal intensity ratio (SIR) and ADC ratio between right lobe and lateral segment were calculated. Results: In both FB and BH imaging, SI and SNR in both liver regions were significantly higher on ACSA DWI than on non-ACSA DWI (p < 0.01). ADC values were significantly lower with ACSA. SIDR was significantly higher in the left lateral segment (p < 0.01), indicating greater SI improvement in motion-prone regions. SIR and ADC ratios between lobes were significantly smaller with ACSA in both respiratory conditions (p < 0.01). FB-ACSA showed smaller SIR than BH-ACSA, while ADC ratios did not differ. Conclusions: ACSA DWI significantly improves SI, intrahepatic uniformity, and ADC reliability even under BH liver imaging. BH ACSA DWI may represent a potentially useful application complementary to FB ACSA DWI, supporting its consideration as a post-processing strategy for improving qualitative and quantitative liver DWI in future investigations.
White matter (WM) tract detection is critical in the presurgical planning of tumor resection. However, standard-of-care imaging techniques including T1-weighted, T2-weighted, and Diffusion Tensor Imaging (DTI) often fail to identify WM tracts within edematous regions. In T1/T2-weighted imaging, edema increases extracellular water and reduces tissue contrast, and in diffusion-weighted imaging, edema elevates isotropic diffusion, reducing sensitivity to anisotropic diffusion along WM tracts. Advanced biophysical diffusion modeling techniques such as Neurite Orientation Dispersion and Density Imaging (NODDI) and the Standard Model (SM) address this limitation by compartmentalizing the diffusion signal into free-water, intra-neurite, and extra-neurite contributions. Here, we test if biophysical multi-compartment models can robustly identify WM tracts and recover tractography streamlines within edematous regions. In this study, we use multi-shell diffusion-weighted MRI data obtained from patients with meningiomas-a pathology allowing for isolation of the effects of edema without the confounding effects of tumor cell invasion. We compared FA from standard and free-water-corrected DTI, the orientation dispersion index (ODI) from NODDI, and P2 (a scalar descriptor of fiber orientation coherence) from the SM fODF in edematous and unaffected contralateral WM regions. As a proof of concept, we visually evaluated the tractography performance across models. Our results show that (1 - ODI) and P2 values in edema remained close to within-subject contralateral measurements, contrasting with substantial reductions in FA and FW-FA. (1 - ODI) showed a small but statistically significant increase in edema (~8%, p = 0.02), while P2 was unchanged. These results highlight the potential of biophysical diffusion models for preoperative mapping in edema.
This study was designed to determine whether gestational age at birth, the method of delivery, or birth weight were associated with the risk of developing atopic dermatitis (AD), and whether the association of risk factors differed between the sexes. A large population-based Northern Finland Birth Cohort 1986 Study that has been followed since birth. The dataset consisted of 8993 subjects who were divided into two groups based on presence or absence of AD. The prevalence of AD was 23.7%. The probability of later AD was unaffected by either method of delivery or gestational age at birth. However, low birth weight compared to normal birth weight was a protective factor against AD, albeit only in men (adjusted risk ratio RR 0.54 [95% CI 0.30-0.97]). No such effect was observed in women. These findings suggest the existence of sex-specific risk factors for AD.
Confirmed porcine sapovirus (PoSaV) infection in young pigs have been increasing in swine farms; however, studies evaluating strategies to control PoSaV under field conditions remain scarce. In a commercial farm, one group of pregnant sows and gilts (n = 13 sows and 2 gilts) were vaccinated intramuscularly twice with an RNA particle vaccine containing the PoSaV VP1 gene, while the other group served as non-vaccinated controls. We evaluated the viral neutralizing (VN) antibodies in colostrum and milk collected at 1, 2, and 3 weeks post-farrowing. Fecal PoSaV shedding in 2-week- and 3-week-old piglets from both groups was assessed by reverse transcription-quantitative PCR. Body weight was measured at birth and 3 weeks of age when piglets were weaned. The vaccination group had higher VN antibody titers than the non-vaccinated group in colostrum and milk samples, with significance for colostrum and milk samples at 1-week post-farrowing. The colostrum and milk samples from both groups contained high VN antibody titers (>103.5 VNT50/mL) and remained high for at least three weeks, suggesting previous exposure to PoSaV. Corresponding to these high VN titers, all piglets were negative for PoSaV and had similar body weights at birth and 3 weeks of age. Future vaccination-challenge studies are warranted to confirm the efficacy of this vaccine.
Background: As survival improves in transfusion-dependent β-thalassemia, long-term adult morbidity, including cognitive dysfunction, has become increasingly relevant. Adult data remain limited, particularly in Eastern Europe, and many studies rely on single screening tools with limited control for confounding. Methods: We conducted a single-center case-control study (2024-2025) at the Congenital Hemolytic Anemia Treatment Center, University Hospital "Sv. Georgi" Plovdiv, Bulgaria. Fifty adults with transfusion-dependent β-thalassemia (86% thalassemia major; 14% transfusion-dependent intermedia) and 30 frequency-matched healthy controls completed a multi-domain cognitive battery: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Trail Making Test (TMT-A/B), and timed verbal fluency. Associations between thalassemia status and cognitive outcomes were estimated using three prespecified models: unadjusted, adjusted for age and sex, and a doubly robust model combining covariate balancing propensity score inverse probability weighting (balancing BMI, smoking, education, and comorbidity) with age/sex regression adjustment. Results: Patients performed worse than controls on global cognition and executive/visuospatial measures. MoCA scores were lower in patients (-2.26 unadjusted, p = 0.016; -2.83 doubly robust, p = 0.001), as were MMSE scores (-1.64, p = 0.015; -1.87, p = 0.002). CDT performance was consistently poorer (OR ≈ 0.28-0.30 across models). Patients were slower on TMT-B (time ratio 1.35 unadjusted, p = 0.003; 1.42 doubly robust, p < 0.001); TMT-A reached significance only after weighting (ratio 1.32, p = 0.001). Verbal fluency was modestly lower with borderline significance (p ≈ 0.05-0.06). Conclusions: Transfusion-dependent β-thalassemia in adults is associated with poorer cognitive performance, particularly in global cognition and executive/visuospatial domains, with results robust across adjustment strategies. Routine multi-domain cognitive screening may be warranted in adult thalassemia care.
The locking attachment washer (LAW) plate offers an advancement in fixation techniques for supracondylar distal femur fractures. This study compared fixation outcomes for supracondylar distal femur fractures managed with traditional fixation techniques (ie, retrograde intramedullary nail, locking plate) versus DePuy Synthes RFN-ADVANCED Retrograde Femoral Nailing System incorporating the LAW plate. A retrospective single-center comparative analysis was conducted of adult patients with supracondylar distal femur fractures treated between December 2022 and December 2024. Patients were divided into two groups: (1) traditional fixation and (2) nail plate construct using retrograde femoral nail with LAW plate. Outcomes focused on surgical parameters, functional recovery, and clinical implications. Forty-five patients met inclusion criteria: 17 treated with traditional fixation, 28 with the LAW construct. Patients in the LAW group were significantly more likely to have an estimated 76.43-minute reduction in operative time compared to patients in the traditional group (P = .009). Hospital length of stay trended shorter with LAW (7.5 vs 15.2 days) but failed to achieve statistical significance in both univariate and multivariate analyses. Postoperative weight bearing was significantly more common with LAW (67.8% vs 23.6%, P = .032), and the rate of radiographic union trended lower with LAW but did not achieve statistical significance. The LAW construct demonstrated shorter operative times and earlier advancement in weight-bearing protocols, despite use in an older cohort. Radiographic union and complication rates were comparable. Potential advantages of the LAW construct lend to clinical and research opportunities for these complex injuries.
A 6-year-old girl with high-risk neuroblastoma achieved a complete response following multimodal therapy. During routine post-therapeutic surveillance, 123I-MIBG SPECT/CT revealed progressive focal tracer uptake within the right T8-T9 intervertebral foramen. Serial imaging demonstrated interval enlargement of the lesion. On contrast-enhanced MRI, the mass exhibited homogeneous hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and intense, uniform enhancement after intravenous gadolinium administration. Radiologic assessment initially favored a schwannoma. Histopathologic examination of the resected specimen confirmed metastatic neuroblastoma involving the dorsal root ganglion.
The adoption of robotic partial nephrectomy has grown significantly over the past decade, prompting a debate on the merits of transperitoneal versus retroperitoneal surgical access. This study evaluated the association between surgical route (transperitoneal, TRPN; retroperitoneal, RRPN) and pentafecta achievement using a detailed location classification. We retrospectively analyzed 368 patients who underwent RPN. Tumor location was classified into four main categories (anteromedial, AM; anterolateral, AL; posteromedial, PM; posterolateral, PL). Inverse probability of treatment weighting (IPTW) with covariate balancing propensity score (CBPS) balanced baseline covariates. Weighted logistic regression assessed the interaction between surgical approach and location on pentafecta achievement. Statistical methods employed included the binomial test, chi-square test, and Mann-Whitney U test. After IPTW, all covariates were balanced (SMD < 0.1). Compared with RRPN, TRPN significantly reduced pentafecta odds for PL (OR = 0.03, 95% CI 0.005-0.13, p < 0.001) and PM tumors (OR = 0.08, 95% CI 0.015-0.39, p = 0.002), but significantly increased odds for AL tumors (OR = 10.45, 95% CI 2.91-37.48, p < 0.001). No significant difference was found for AM tumors (OR = 0.13, p = 0.053). Low R.E.N.A.L. complexity independently predicted higher pentafecta odds (OR = 3.67, p = 0.034). A location-guided strategy is supported: TRPN is superior for AL tumors, while RRPN achieves better pentafecta rates for PL and PM tumors. Individualized approach selection based on detailed tumor anatomy is essential. Prospective multicenter studies are warranted to validate these findings.
The present study was conducted to evaluate the hepatoprotective potential of Strobilanthes callosa using a well-established rat model of experimentally induced liver injury. The investigation assessed biochemical, hematological, oxidative stress, and histopathological parameters to determine the protective efficacy of the plant extract. Body weight was recorded at the beginning and end of the treatment period, while liver weight was measured after sacrifice to evaluate physiological changes associated with hepatic injury. Serum biochemical markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, albumin, and triglycerides, were analyzed using standardized enzymatic assay kits. Treatment with S. callosa significantly reduced serum ALT, AST, and ALP levels respectively, compared with the toxic control group (p < 0.05), indicating improved liver function. Bilirubin levels were significantly decreased, whereas albumin levels were restored toward normal values following treatment. Oxidative stress biomarkers revealed a significant reduction in malondialdehyde (MDA) levels by along with increased antioxidant defense through restoration of catalase and glutathione levels respectively (p < 0.05). Hematological parameters, including hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC) counts, packed cell volume (PCV), and differential leukocyte count, were evaluated to assess systemic toxicity, inflammatory response, and general physiological status. Histopathological examination of liver tissues using hematoxylin and eosin staining demonstrated marked improvement in hepatic architecture, with reduced necrosis, fatty degeneration, inflammatory infiltration, and tissue disorganization in treated groups compared with toxin-treated animals. Statistical analysis was performed using GraphPad Prism 8.0, with results expressed as mean ± SD. Data were analyzed using one-way and two-way ANOVA followed by appropriate post hoc tests, and differences were considered statistically significant at p < 0.05.
Sumizyme PEG, a glucanase/cellulase enzyme preparation produced by Talaromyces versatilis PF8, was investigated to characterize its systemic and genotoxic toxicity profile to support its intended use in food processing applications. A comprehensive toxicological program was conducted in accordance with OECD guidelines, comprising a bacterial reverse mutation (Ames) test, an in vitro chromosomal aberration assay, an in vivo micronucleus test, and a 90-day repeated-dose oral toxicity study in male and female Crl:CD(SD) rats. In the subchronic study, Sumizyme PEG was administered by oral gavage at doses of 107, 1070, and 10,700 U/kg/day. No treatment-related adverse effects were observed across clinical, hematological, biochemical, urinalysis, organ weight, or histopathological endpoints, and the highest dose was identified as the NOAEL. Genotoxic testing showed no consistent mutagenic or clastogenic response across the test battery. A positive in vitro signal was observed in CHL/IU cells; however, this was not reproduced in a human TK6 cell assay or in vivo micronucleus testing, indicating assay-dependent sensitivity within a weight-of-evidence framework. Overall, the integrated dataset does not indicate a consistent treatment-related systemic or genotoxic effect under the conditions of the studies conducted.
Intrinsic capacity (IC), introduced by the World Health Organization, provides a multidimensional framework for evaluating functional aging across locomotion, cognition, sensory, psychological, and vitality domains. However, gut microbial features associated with IC among community-dwelling older adults remain incompletely understood. In this exploratory cross-sectional study, we enrolled 52 community-dwelling older adults and assessed gut microbiota using full-length 16S rRNA sequencing. Participants were stratified into IC quartiles, and additional analyses examined composite IC and domain-specific IC scores as continuous measures. Alpha diversity indices were not significantly associated with composite IC after false discovery rate correction, although vitality showed nominal positive associations with observed features and Chao1 richness (both rho = 0.316, P = 0.024, q = 0.288). PERMANOVA did not show statistically robust differences in beta diversity across IC quartile groups using Bray-Curtis distance (R2 = 0.061, P = 0.060, q = 0.383), weighted UniFrac distance (R2 = 0.083, P = 0.140, q = 0.436), or unweighted UniFrac distance (R2 = 0.063, P = 0.211, q = 0.443). Selected bacterial taxa, including Ruminococcaceae, Lachnospiraceae, Alistipes, and Faecalibacterium, showed nominal associations with composite or domain-specific IC measures, but none remained significant after FDR correction or covariate-adjusted regression. In PICRUSt2-predicted functional analyses, several COG features related to transport systems, multidrug efflux, and site-specific recombination were positively associated with the vitality domain after false discovery rate correction. Because functional profiles were inferred from 16S rRNA sequencing rather than directly measured by shotgun metagenomics, metabolomics, or inflammatory biomarkers, these findings should be interpreted as exploratory and hypothesis-generating. This study identifies candidate microbiota and predicted functional features for future longitudinal and mechanistic studies of multidimensional functional aging.
Cinnamon oil exhibits therapeutic potential against constipation-predominant irritable bowel syndrome (IBS-C). This study aimed to evaluate the efficacy and mechanisms of its main components-cinnamaldehyde (CAL), cinnamyl alcohol (COL), and trans-cinnamic acid (TCA)-in IBS-C. This study established an IBS-C mouse model using loperamide hydrochloride and restraint stress, and evaluated indicators such as body weight, the number of fecal pellets, fecal water content, visceral hypersensitivity, and small intestinal propulsion rate. The analysis was performed via HE staining, ELISA, Western blot, qRT-PCR, and 16S rRNA sequencing. All three components ameliorated low-grade immune cell infiltration in colonic tissue and reduced serum levels of IL-6, IL-8, and TNF-α. They also increased motilin (MTL) and acetylcholine (Ach) levels; all except trans-cinnamic acid low-dose (TCA-L) increased gastrin (Gas) levels, and all except TCA-L and trans-cinnamic acid high-dose (TCA-H) increased 5-HT levels. Cinnamaldehyde high-dose (CAL-H), cinnamyl alcohol high-dose (COL-H), and TCA-H upregulated the expression of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and 5-hydroxytryptamine receptor 4 (5-HT4R) and partially modulated gut microbiota composition. CAL showed favorable effects under the present experimental conditions. The three components alleviated IBS-C symptoms partially through modulating the 5-HT signaling pathway and gut microbiota, with CAL showing the most pronounced effects under the present experimental conditions.
Pancreatic cancer incidence is rising, yet few modifiable risk factors have been identified. The Mediterranean diet, which lowers inflammation and improves healthy weight maintenance and insulin control, may lower pancreatic cancer risk, yet the evidence for this association is inconsistent. To investigate the association, we conducted a pooled analysis of 2,315,406 individuals from 23 prospective cohorts in the Pooling Project of Prospective Studies of Diet and Cancer (DCPP), of whom 10,748 developed incident pancreatic cancer over a mean follow-up duration ranging from 8.1 to 23.3 years across studies. Adherence to the Mediterranean diet was assessed using the alternative Mediterranean diet score (aMED) and a modified score excluding alcohol (maMED). Study- and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models and then pooled using random effect models. No statistically significant association was found between aMED or maMED and pancreatic cancer or pancreatic ductal adenocarcinoma (PDAC) risk. For aMED, the pooled pancreatic cancer HR was 0.96 (95% CI: 0.90-1.02) comparing the fourth to the first quartile, 0.94 (0.88-1.00) comparing high (6-9) versus low (0-3) scores, and 0.98 (0.96-1.00) per 2-unit increment in the score. Overall, there was no evidence of heterogeneity in these associations by sex, attained age, race, BMI, physical activity, or follow-up time; a positive association between maMED and pancreatic cancer risk was observed in past smokers (HR = 1.04, 95% CI 1.00-1.09) but not in never or current smokers (Pinteraction=0.04). In conclusion, there was little evidence of an association between a Mediterranean diet score and pancreatic cancer risk in this large international pooled analysis.
Adolescents and young adults seeking contraceptive care face many considerations related to differences in contraceptive indications and knowledge, which are often overlooked and can lead to contraceptive non-adherence or non-use and adverse health outcomes. Develop a digital decision-aid tool that meets the contraceptive decisional needs of adolescents and young adults from diverse backgrounds. We developed a web-based decision aid using a user-informed design framework by Elwyn et al. and the International Patient Decision Aid Standards. The design and development process was informed by a literature review, consultations with scientific experts, health informatics specialists, clinicians experienced in adolescent reproductive health, and a diverse group of adolescent and young adult advisors. We gathered feedback on the decision aid's content and functionality from clinicians, adolescents, and young adult stakeholders during focus group interviews conducted across two user testing cycles. Each focus group was recorded and transcribed, and analyses were conducted using a focus group guide to identify key attributes, patterns, and perspectives among users. Two qualitative researchers employed rapid qualitative analysis to explore and summarize findings across four key domains, contributing to the refinement of the decision aid content and improved functionality. Twenty-four clinicians, adolescents, and young adult participants from diverse backgrounds shared their perspectives on the decision aid's content, relevance, design, and usability across two user testing cycles from February 2023 to June 2024. The decision aid includes a survey, a decision algorithm that generates a summary of contraceptive method recommendations, infographics, and a provider summary view. The decision algorithm applies a weighted scoring system ranging from ±1 to ±10 for each method, reflecting the user's primary indication for seeking contraception, contraceptive usage preferences, and relevant health history. This approach allowed us to capture rich perspectives from a diverse group of stakeholders that account for the unique contraceptive decision-making needs of adolescents and young adults, resulting in a functional, youth-informed decision aid prototype, MyPlanMyChoice©, ready for pilot and feasibility evaluation in a clinical setting.