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Abstract Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder exacerbated by obesity. Single Anastomosis Sleeve-Ileal Bypass (SASI) has emerged as a promising metabolic bariatric procedure that combines sleeve gastrectomy and ileal bypass, facilitating substantial weight loss and T2DM remission through restrictive and malabsorptive mechanisms. This study aims to evaluate the effects of SASI on T2DM remission, weight loss, and safety in one year follow-up. A retrospective cohort study analyzed 31 patients with obesity and T2DM who underwent SASI. Data collected included demographic characteristics, preoperative and postoperative BMI, HbA1c levels, and bariatric outcomes, including %TWL and T2DM changes. The mean age was 45 years, with a mean preoperative BMI of 40.7 kg/m². One year postoperatively, the mean %EWL was 85.6% and %TWL was 31.7%. T2DM remission was achieved in 24 (77.4%) patients, improvement in 4 (12.9%), and no change in 3 (9.7%). Hypertension improved in 21 (87.5%) patients, with 12 (50%) achieving remission. Significant reductions in BMI and HbA1c levels were observed (p

Abstract The article presents the results of a three-year field study that was conducted in Poland to evaluate the yield and quality of seeds and oil from traditional (SAM) and canola-quality white mustard (SAC) in response to different N fertilizer rates (0, 40, 80, 120, and 160 kg ha–1). Seed yields were 25% higher in SAM than SAC. The seeds of SAC contained more crude fat (by 3%) and crude fiber (by 6%) than the seeds of SAM. In turn, the seeds of SAM were a richer source of total protein (by 7%). The content of glucosinolates (GSLs) was 8–10 times lower in the seeds of SAC than SAM. The seeds of both mustard cultivars were most abundant in γ-tocopherol (γ-T) (90–94%). The seeds of SAC were characterized by a higher content of γ-T and a lower α-T/γ-T ratio than SAM seeds. White mustard oil contained mostly MUFAs (69–75%). However, C22:1 accounted for more than 50% of MUFAs in the oil SAM. In the oil SAC, the proportion of C22:1 did not exceed 6%, whereas C18:1 accounted for nearly 85% of total MUFAs. Nitrogen fertilization induced a significant increase in seed yields (by 33%), a decrease in crude fat content (by 3–4%), and an increase in total protein content (by 4%), and crude fiber content (by 7%). Nitrogen decreased GSL levels by 31% in SAM seeds. In SAC, N fertilization induced differences in the qualitative composition of GSLs, but did not affect the total GSL content of seeds. Higher N rates increased the content of α-T and γ-T, the α-T/γ-T ratio, and total T content. Nitrogen fertilization decreased the content of C18:3 in the seeds of the SAM. In SAC, the application of N decreased the content of C18, C18:1, and C18:3, and increased the biosynthesis of C18:2, C20:1, and C22:1.

Abstract Background Microglia (MG) are myeloid cells of the central nervous system that support homeostasis and instigate neuroinflammation in pathologies. Single-cell RNA sequencing (scRNA-seq) revealed the functional heterogeneity of MG in mouse brains. Microglia are self-renewing cells and inhibition of colony-stimulating factor 1 receptor (CSF1R) signaling depletes microglia which rapidly repopulate. The functions of repopulated microglia are poorly known. Methods We combined scRNA-seq, bulk RNA-seq, immunofluorescence, and confocal imaging to study the functionalities and morphology of repopulated microglia. Results A CSRF1R inhibitor (BLZ-945) depleted microglia within 21 days and a number of microglia was fully restored within 7 days, as confirmed by TMEM119 staining and flow cytometry. ScRNA-seq and computational analyses demonstrate that repopulated microglia originated from preexisting progenitors and reconstituted functional clusters but upregulated inflammatory genes. Percentages of proliferating, immature microglia displaying inflammatory gene expression increased in aging mice. Morphometric analysis of MG cell body and branching revealed a distinct morphology of repopulated MG, particularly in brains of old mice. We demonstrate that with aging some repopulated MG fail to reach the homeostatic phenotype. These differences may contribute to the deterioration of MG protective functions with age.

Introduction Nicotine pouches are a new type of nicotine-containing product that have been marketed in many countries worldwide, generating growing acceptance among consumers. The aim of this study was to assess factors associated with public awareness and use of nicotine pouches among adults in Poland. Methods A cross-sectional survey was conducted with a nationally representative sample of 1080 adults in Poland (February 2024). Awareness of nicotine pouches, history of use, current (past 30-day) use of nicotine pouches, as well as perception of harm was assessed using a purpose-designed questionnaire. Results Awareness of nicotine pouches was reported by 24% of the sample, while 9.2% reported ever having used a nicotine pouch product, and 4.3% using a nicotine pouch in the past 30 days. Among all respondents, 60.7% perceived nicotine pouches as harmful as combustible cigarettes, 28.2% perceived nicotine pouches as less harmful, and 11% as more harmful than combustible cigarettes. In multivariable logistic regression model, women (adjusted odds ratio, AOR=1.40; 95% CI: 1.03–1.91; p

Abstract Transcription enhancers are genomic sequences regulating common and tissue-specific genes and their disruption can contribute to human disease development and progression. Klotho, a sexually dimorphic gene specifically expressed in kidney, is well-linked to kidney dysfunction and its deletion from the mouse genome leads to premature aging and death. However, the sexually dimorphic regulation of Klotho is not understood. Here, we characterize two candidate Klotho enhancers using H3K27ac epigenetic marks and transcription factor binding and investigate their functions, individually and combined, through CRISPR-Cas9 genome engineering. We discovered that only the distal (E1), but not the proximal (E2) candidate region constitutes a functional enhancer, with the double deletion not causing Klotho expression to further decrease. E1 activity is dependent on HNF1b transcription factor binding site within the enhancer. Further, E1 controls the sexual dimorphism of Klotho as evidenced by qPCR and RNA-seq. Despite the sharp reduction of Klotho mRNA, unlike germline Klotho knockouts, mutant mice present normal phenotype, including weight, lifespan, and serum biochemistry. Lastly, only males lacking E1 display more prominent acute, but not chronic kidney injury responses, indicating a remarkable range of potential adaptation to isolated Klotho loss, especially in female E1 knockouts, retaining renoprotection despite over 80% Klotho reduction.

This study examines how Americans’ narratives of pain are connected to social inequalities using more than 1,500 in-depth interviews collected as part of the American Voices Project. Our novel mixed-method approach to these “big (qualitative) data” uses machine learning and qualitative analysis to demonstrate that discussions of physical pain are prevalent across groups, but narrative content varies by demographics including educational background and gender identity. Our findings demonstrate (1) that pain is commonly described as a challenge that shapes everyday life, (2) that pain narratives often invoke morality and distinction, and (3) that narratives diverge around discussions of unequal medical treatment, illness identities, vulnerability and suffering. We discuss the implications of our findings for scholarship on inequality and experience, social scientific methods, and health policy.

Abstract Emerging evidence highlights cellular senescence’s pivotal role in chronic kidney disease (CKD). Proximal tubule epithelial cells (PTECs) and fibroblasts are major players in CKD and serve as cellular sources of senescence. The generation of a conditionally immortalized human kidney cell model would allow to better understand the specific mechanisms and factors associated with cellular senescence in a controlled setting, devoid of potential confounding factors such as age and comorbidities. In addition, the availability of human kidney cell lines for preclinical research is sparse and most cell lines do not reflect their in vivo counterparts due to their altered behavior as immortalized cancer-like cells. In this study, PTECs and fibroblasts from human kidneys were isolated and transduced with doxycycline-inducible simian virus 40 large T antigen (SV40LT) vector. By comparing their gene expression with single-cell RNA sequencing data from human kidneys, the newly produced human kidney cell lines demonstrated significant resemblances to their in vivo counterparts. As predicted, PTECs showed functional activity and fibroblasts responded to injury with fibrosis. Withdrawal of the immortalizing factor doxycycline led to p21+ cell-cycle arrest and the key hallmarks of senescence. The obtained senescence gene set largely overlapped between both cell lines and with the previously published SenMayo set of senescence-associated genes. Furthermore, crosstalk experiments showed that senescent PTECs can cause a profibrotic response in fibroblasts by paracrine actions. In 76 human kidney sections, the number of p21+ cells correlated with the degree of fibrosis, age and reduced glomerular filtration, validating the role of senescence in CKD. In conclusion, we provide a novel cellular ex vivo model to study kidney senescence which can serve as a platform for large scale compounds testing.