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Multi-variant genotyping identifies association of TRPC6 rs36111323 with diabetic kidney disease in a South Indian population

Mol Biol Rep. 2026 May 5;53(1):714. doi: 10.1007/s11033-026-11903-x.

ABSTRACT

BACKGROUND: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and end-stage kidney failure worldwide. Genetic factors contribute to inter-individual and population-specific susceptibility to DKD. Data from South Indian populations are limited, highlighting the need for region-specific genetic association studies in DKD.

METHODS AND RESULTS: This case-control study included 125 South Indian individuals: 60 patients with diabetes and proteinuria (DKD), 34 patients with diabetes without kidney disease, and 31 healthy controls. Genomic DNA was isolated and nine variants were genotyped using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Variant frequencies were compared among groups. In-silico pathogenicity prediction tools and Odds ratio (OR) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression analyses were used to assess the association between genetic variants and DKD risk. Data visualization was performed using R statistical software. Among the nine variants analyzed, the TRPC6 rs36111323 (G > A; p.A404V) was independently associated with DKD (OR = 2.76; 95% CI = 1.04-7.34; p = 0.0418). This variant was more frequent in patients with DKD compared with diabetic patients without nephropathy and healthy controls. Pathogenicity prediction analyses supported a potentially deleterious effect of the variant.

CONCLUSIONS: The TRPC6 rs36111323 variant appears to be associated with increased susceptibility to diabetic kidney disease in a South Indian population, suggesting a population-specific genetic risk factor. Validation in larger cohorts and functional studies is warranted to clarify its role and potential application in precision nephrology.

PMID:42084711 | DOI:10.1007/s11033-026-11903-x

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Epidemiological trends and burden of gout in China and the European Union: a GBD 2023 and Mendelian randomization study

Clin Rheumatol. 2026 May 5. doi: 10.1007/s10067-026-08135-6. Online ahead of print.

ABSTRACT

BACKGROUND: Gout is one of the most common inflammatory arthritides and represents a growing health burden worldwide. This study compares the disease burden of gout and its attributable risk factors between China and European Union (EU) countries from 1990 to 2023 using data from the Global Burden of Disease Study 2023 (GBD 2023). In addition, the study evaluates potential causal relationships between key risk factors and gout and projects future trends in disease burden.

METHODS: Using GBD 2023 data, we analyzed the epidemiology of gout in China and EU countries. Analyses included descriptive statistics and age- and sex-specific comparisons. Joinpoint regression models were used to calculate annual percentage changes (APC) and average annual percentage changes (AAPC) to assess long-term trends. An autoregressive integrated moving average (ARIMA) model was applied to project gout burden trends in China and EU countries from 2024 to 2040. In addition, a two-sample Mendelian randomization (MR) approach was used to investigate the potential causal relationship between key risk factors and gout at the genetic level.

RESULTS: In 2023, China’s age-standardized incidence rate (ASIR), prevalence rate (ASPR), and disability-adjusted life year rate (ASDR) for gout were 151.27/100,000, 809.69/100,000, and 25.14/100,000, respectively, all higher than in 1990. In comparison, EU countries showed lower levels for these indicators in both 1990 and 2023. Joinpoint regression analysis demonstrated an overall increasing trend in gout burden in both China and the EU between 1990 and 2023, although China experienced a brief decline in APC between 1990 and 1994. The burden of gout was higher among males than among females. Projections suggest that ASIR, ASPR, and ASDR will continue to increase in both China and European countries between 2024 and 2040. Mendelian randomization analysis further indicated a significant positive causal relationship between body mass index (BMI) and gout.

CONCLUSION: This study combines GBD 2023 epidemiological data with Mendelian randomization analysis to characterize trends in the burden of gout in China and EU countries. The findings show a continuing increase in gout burden over time, particularly in China. The identified causal association between elevated BMI and gout highlights the importance of addressing modifiable metabolic risk factors to help reduce the future burden of gout. Key Points • An increasing burden of gout could be observed in China and the European Union from 1990 to 2023. • A higher age-standardized burden of gout was observed in China than in the European Union. • Future projections indicate that the burden of gout will continue to increase through 2040. • A causal association between elevated body mass index and gout risk was supported by Mendelian randomization analysis.

PMID:42084706 | DOI:10.1007/s10067-026-08135-6

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Evolution of cefoperazone-sulbactam consumption in Romania between 2011 and 2024

Eur J Clin Microbiol Infect Dis. 2026 May 5. doi: 10.1007/s10096-026-05494-5. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study is to describe the evolution of cefoperazone-sulbactam consumption in Romania between 2011 and 2024. The use of this fixed-dose combination is not recommended by the World Health Organisation as it may result in selection of antimicrobial resistance.

METHODS: This retrospective study analyzed the data on antibiotic consumption collected by the National Center for Surveillance and Control of Communicable Diseases which is based on data provided by the National Health Insurance Fund and the IQVIA-Multinational Integrated Data Analysis System. Antibiotic sales were converted into defined daily doses (DDDs) per 1,000 inhabitants per day.

RESULTS: The consumption of cefoperazone-sulbactam in Romania between 2011 and 2024 ranged from 0.016 to 0.021 DDD per 1000 inhabitants per day, with an average of 0.019 DDD per 1000 inhabitants per day. When adjusted for population, the RO1 macroregion registered the highest average consumption (0.033 DDDs per 1000 inhabitants per day). One-way ANOVA on DDD per 1,000 inhabitants per day data suggested that there were no statistically significant differences between macroregions (F = 2.78, p = 0.054). Although differences are observed in the mean values, they can be explained by counties with abnormally high consumption.

CONCLUSION: Educational and training activities focused on the outlier counties are necessary to raise awareness about the risk of increased selection of antimicrobial resistance. In line with the rejection of the reclassification proposal of cefoperazone-sulbactam in the updated 2025 WHO AWaRe classification of antibiotics, new government policies to ensure the discontinuation of cefoperazone-sulbactam use in Romania are needed.

PMID:42084702 | DOI:10.1007/s10096-026-05494-5

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Ceftazidime-avibactam as monotherapy or in combination for targeted treatment of KPC-producing Klebsiella pneumoniae infections in ICUs: a comparative analysis through counterfactual framework and desirability of outcome ranking

Eur J Clin Microbiol Infect Dis. 2026 May 5. doi: 10.1007/s10096-026-05529-x. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the causal effect of ceftazidime/avibactam (C/A) combination therapy versus monotherapy on mortality and clinical success in patients with KPC-producing Klebsiella pneumoniae (KPC-Kp) infections in intensive care unit.

METHODS: This multi-centre, retrospective observational study (2021-2023) included adults with KPC-Kp bloodstream infections or pneumonia treated with C/A-based regimens. We employed a counterfactual framework using inverse probability of treatment weighting (IPTW) to estimate the average treatment effect on 30-day mortality. Clinical success was further assessed using Desirability of Outcome Ranking (DOOR) analysis and partial credit scoring based on patient-perspective scenarios.

RESULTS: Among 123 included patients, 77 (62.6%) received monotherapy and 46 (37.4%) received combination therapy. The combination group presented with significantly higher baseline severity, including higher APACHE II scores and rates of septic shock. In the IPTW-adjusted analysis, 30-day survival was 73.8% (95% CI: 56-92%) with combination therapy compared with 60.8% (95% CI: 46.8-77%) with monotherapy. The survival probability ratio was 1.21 (95% CI: 0.80-1.45), indicating no statistically significant survival benefit. The DOOR analysis showed a 54.7% (95% CI: 48.9%-60.4%) probability of a more favourable outcome with combination therapy, which was not statistically significant. Mean partial credit scores did not differ significantly across scenarios prioritizing survival or adverse event avoidance.

CONCLUSIONS: In this cohort, C/A-based combination therapy did not provide a significant survival advantage or an improved clinical desirability ranking compared with monotherapy, after adjusting for confounding factors.

PMID:42084701 | DOI:10.1007/s10096-026-05529-x

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[11C]PS13 PET shows that age is positively correlated with constitutively expressed cyclooxygenase-1 in the brain

J Cereb Blood Flow Metab. 2026 May 5:271678X261444895. doi: 10.1177/0271678X261444895. Online ahead of print.

ABSTRACT

Cyclooxygenase-1 (COX-1), an essential enzyme in the synthesis of pro-inflammatory prostanoids from arachidonic acid, is widely expressed in the brain, primarily in microglia. Previous studies from our laboratory found that the novel positron emission tomography (PET) radioligand [11C]PS13 has excellent in vivo selectivity for constitutively expressed COX-1 in human brain. This study sought to further evaluate the effects of age and sex on levels of constitutive COX-1 expression in the brains of 56 healthy volunteers. COX-1 density in the brain measured by [11C]PS13 PET showed a significant positive correlation with age in the whole brain, as well as in regions with the highest COX-1 expression, such as the hippocampus, lateral occipital cortex, and pericentral cortex. No significant sex differences were observed in any regions. Consistent findings were observed regardless of partial volume correction (PVC), while overall statistical significance was enhanced with PVC. In conclusion, the present study found that constitutive COX-1 binding in the brain, which is associated with microglial density, increased with age with no significant sex differences. The physiological roles of COX-1 in these regions and its potential contributions to the aging process remain largely unknown, and further investigation is warranted. Clinical trial registration information: NCT03324646; NCT04396873 in ClinicalTrials.gov.

PMID:42083927 | DOI:10.1177/0271678X261444895

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R WE ready for reimbursement? A round-up of developments in real-world evidence relating to health technology assessment: part 26

J Comp Eff Res. 2026 May 5:e260074. doi: 10.57264/cer-2026-0074. Online ahead of print.

ABSTRACT

In this update, we review a framework for identifying and mitigating information bias in electronic health records and administrative claims data, highlighting practical recommendations for study design, variable definition, and statistical analysis. We also discuss a perspective on emerging privacy-preserving technologies – synthetic data and federated networks – that enable secure cross-border data access while maintaining patient privacy.

PMID:42083917 | DOI:10.57264/cer-2026-0074

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Comparative Study on Burden, Features and Determinants of Disorders of Gut-Brain Interaction Between Southern Europe and the Rest of Continent: Results From the Rome Foundation Global Epidemiology Study

United European Gastroenterol J. 2026 May;14(4):e70226. doi: 10.1002/ueg2.70226.

ABSTRACT

BACKGROUND AND AIM: Disorders of gut-brain interaction (DGBI) are highly prevalent worldwide. Although the epidemiology of DGBIs in Europe has been previously investigated, data comparing disease prevalence across European regions in relation to sociodemographic and lifestyle factors are lacking. Therefore, this study aimed to assess the prevalence, regional distribution, and associated factors of DGBI in Southern Europe, and to compare findings with other European regions.

METHODS: Data were drawn from the Rome Foundation Global Epidemiology Study (RFGES). A representative sample of 20,420 European adults completed a comprehensive internet-based questionnaire assessing DGBI presence, psychological distress, somatic symptoms, dietary habits, and healthcare utilization. Comparative analyses were conducted between Southern European countries and the rest of the continent (Northern, Western, and Eastern European countries). Multivariate logistic regression identified independent associated factors.

RESULTS: The prevalence of adults with at least one DGBI was significantly higher in Southern Europe than in the rest of Europe (44.0% [42.4-45.5] vs. 39.0% [38.3-39.8]; p < 0.001). Irritable bowel syndrome and functional dyspepsia were more prevalent in Southern Europe than in the rest of Europe. Similar trends were found for functional constipation and functional diarrhea. Individuals with DGBI in Southern Europe showed higher psychological distress but lower somatic symptom burden and lower work productivity and activity impairment. In multivariable models, residence in Southern Europe, female sex, younger age, higher psychological distress, greater somatic symptom burden, higher educational attainment, urban residence and more frequent healthcare utilization were independently associated with DGBI.

CONCLUSIONS: Southern European populations exhibit a higher prevalence of DGBI compared with other European regions. Individuals with DGBI in Southern Europe showed higher rates of psychological distress, whereas those in the rest of Europe showed higher somatic symptom burden, greater work productivity and activity impairment. DGBI rates in Europe appear to be driven by a multifactorial interplay of demographic and psychosocial factors.

PMID:42083911 | DOI:10.1002/ueg2.70226

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Optimal Methods for Estimating Cactus Pear Biomass Using Cladode Dimensions of Morphologically Diverse Accessions

Plant Cell Environ. 2026 May 5. doi: 10.1111/pce.70587. Online ahead of print.

ABSTRACT

Current allometric methods for photosynthetic-stem (cladode) plants, such as cactus pear (Opuntia spp.), require refinement to be used in field settings in which diverse accessions are grown. We analysed cladode dimensional data using 14 accessions representing four species and two hybrids to quantify statistically significant morphological differences among accessions and derived cross-accession models to approximate cladode fresh weight. A Box model using cladode dimensions (e.g., length, width, thickness and diameter) and factorial combinations of these measures (e.g., length*width*thickness*diameter vs. fresh weight) resulted in the highest coefficient of determination (R2 = 0.95 general fit) across all accessions for estimating fresh weight along with parsimony estimates using the Schwarz-Bayes Criterion (SBC), which assesses the most consistent performance on individual accessions. A Fitting-box modelling approach used the measured cladode area captured using ImageJ (R2 = 0.93 general fit). Lastly, an Elliptical model used an elliptical approximation for the measured area and performed well over all accessions (R2 = 0.94 general fit) while avoiding extensive manual measurements. These models meet or exceed the performance of previously published approaches when applied across morphologically diverse accessions, providing efficient tools for nondestructive estimation of cactus pear biomass under the conditions tested.

PMID:42083905 | DOI:10.1111/pce.70587

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Curriculum Resources for Integrating Respectful Maternity Care Into Health Professions Education: A Rapid Scoping Review

J Midwifery Womens Health. 2026 May 5. doi: 10.1111/jmwh.70129. Online ahead of print.

ABSTRACT

INTRODUCTION: Respectful maternity care (RMC) ensures that every childbearing woman is treated with dignity, safety, and respect. Health care professionals play a critical role in RMC but can also contribute to disrespectful and abusive practices, inflicting lasting trauma. Educating pre-service health care learners is one promising strategy for change. As part of our larger Mothering and Albinism research project, we sought timely evidence to develop educational resources supporting RMC for people impacted by albinism.

METHODS: Our international team conducted a rapid scoping review to answer the question, “What curriculum resources are available for integrating RMC into the education of nursing, midwifery, medical, and other health care students, and what are their key pedagogical components and contextual factors shaping implementation?” We searched key databases and online sources for qualitative, quantitative, and mixed-methods studies of RMC education initiatives and curriculum resources relevant to teaching RMC to pre-service learners. Two reviewers screened abstracts/full texts, and data were charted and synthesized using descriptive statistics and content analysis. Our diverse author network was consulted to ensure rigor and relevance for a range of populations.

RESULTS: Our analysis of 25 research reports and 8 curriculum resources produced 5 synthesized categories. The first 4 categories illuminate how RMC education initiatives are conceptualized, their core content, effective pedagogical strategies, and how researchers studied the impact of RMC education. The fifth category addresses contextual influences and the need for taking a systems perspective within RMC education initiatives. Significant gaps remain with few initiatives addressing the unique needs of structurally disadvantaged groups or including trauma-informed, violence-informed, or equity-oriented approaches.

DISCUSSION: RMC education has potential, but it must be paired with systemic change and attention to equity for meaningful change. These findings lay the groundwork for developing context-specific, effective educational resources to support RMC for all women, including those impacted by albinism.

PMID:42083903 | DOI:10.1111/jmwh.70129

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Capillary dried blood microsampling is not suited for dihydropyrimidine dehydrogenase (DPD) phenotyping

Clin Chem Lab Med. 2026 May 6. doi: 10.1515/cclm-2026-0146. Online ahead of print.

ABSTRACT

OBJECTIVES: Dihydropyrimidine dehydrogenase (DPD) phenotyping through uracil and dihydrouracil determination is a well-established approach to identify (partial) DPD deficiencies prior to fluoropyrimidine chemotherapy. However, preanalytical stability has challenged this test for years. This study therefore investigated whether dried blood spots (DBS) can improve preanalytical stability.

METHODS: Uracil, dihydrouracil, and uridine were determined in 6 mm DBS sub-punch extracts by liquid chromatography-tandem mass spectrometry. Paired venous and capillary DBS were collected from 15 healthy volunteers across three days to evaluate venous-capillary DBS differences. The impact of blood spotting, drying and preanalytical stability for up to two weeks was assessed using venous DBS of the same volunteers.

RESULTS: Uracil was elevated in all capillary DBS, with a median of 219 % relative to venous DBS. In addition, the variation between capillary DBS replicates was 29 %, opposed to only 7 % in venous DBS. For dihydrouracil, a small bias of -7 % was observed, while uridine showed no difference, with similar inter-spot variation in venous and capillary DBS. Generation and drying of DBS had statistically significant yet minor effects on all analytes. Venous DBS enhanced preanalytical stability, yielding median uracil levels of 105 % and 107 % after 1 and 2 weeks at room temperature, and no differences for dihydrouracil or uridine relative to overnight dried DBS.

CONCLUSIONS: Capillary DBS are unsuitable for uracil determination in DPD phenotyping owing to poor agreement with venous DBS and substantial variability. Venous DBS, however, demonstrate superior preanalytical stability over liquid samples and may provide a practical solution for managing preanalytical variables.

PMID:42083890 | DOI:10.1515/cclm-2026-0146