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Introduction: The clinical characteristics of de novo inflammatory bowel disease (dnIBD) diagnosed after solid organ transplant (SOT) are not well-described, particularly since the advent of biologic therapy for treatment of IBD., Methods: We conducted a single-center, retrospective review of SOT recipients between 2010 and 2022 at the University of Minnesota Medical Center who were diagnosed with IBD after transplant., Results: Of 89 patients at our center with IBD and a history of SOT, five (5.6%) patients were diagnosed with IBD post-transplant (three liver, one kidney, and one simultaneous liver and kidney): three patients were female and four were Caucasian. Mean age at transplant and IBD diagnosis were 46.7 and 49.4 years respectively. Indication for transplant were alcohol-related cirrhosis ( n  = 2), idiopathic fulminant hepatic failure ( n  = 1), metabolic dysfunction-associated steatotic liver disease ( n  = 1), and IgA nephropathy ( n  = 1). Four patients were diagnosed with ulcerative colitis (UC) and one with Crohn's disease (CD). Three patients (all with UC) required escalation to a biologic therapy. Four patients were in clinical remission from IBD at last follow-up, one patient required IBD surgery, while there was no rejection and no deaths following IBD diagnosis., Conclusion: dnIBD post-SOT is uncommon, while newer IBD therapies may be safe and effective. Further study is required to better understand the natural history and IBD outcomes of this population relative to non-SOT patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2025 Johnson, Vaughn and Lim.)

Background and Aims: In 2013, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) steering group published recommendations to standardize reporting quality in randomized controlled trials (RCTs). We aim to assess adherence to SPIRIT reporting guidelines in RCTs on endoscopic colorectal cancer (CRC) screening and participants' adherence to trial protocols., Methods: We searched databases for RCTs evaluating flexible sigmoidoscopy or colonoscopy for CRC screening published in English language through September 2023. Each eligible study was evaluated using the 8 core SPIRIT statement areas, totaling 51 points. Each item received 1 point if it met the criteria and 0 points if it did not. Adherence to SPIRIT items was calculated, and participant adherence to RCT protocols was assessed as the proportion of participants screened compared to those invited., Results: Five RCTs, including 4 on flexible sigmoidoscopy and 1 on colonoscopy, were analyzed. Adherence to SPIRIT guidance ranged from 82.4% to 92.2%. The most missed recommendation was item 2b (trial registrations), scored 0 across all studies. Additionally, item 32 (informed consent materials) scored 20%, and items 17a & b (blinding) scored 40% each. In total, 587,572 participants were randomized across the 5 RCTs. Of these, 37% (200,610) underwent CRC screening, with 69.8% (139,983/200,610) adhering to the protocol. The Nordic-European Initiative on Colorectal Cancer (NordICC) trial, employing a unique invitation method, had a lower adherence rate of 42%. Excluding this trial would raise the adherence rate to 74.3% (128,050/172,390)., Conclusion: The published CRC screening trials have acceptable adherence to the SPIRIT reporting guidelines. However, reporting appended consent form materials and disclosing all WHO trial registration data can be improved., (© 2024 Published by Elsevier Inc. on behalf of the AGA Institute.)

Pseudoexfoliation glaucoma (PEXG) is characterized by dysregulated extracellular matrix (ECM) homeostasis that disrupts conventional outflow function and increases intraocular pressure (IOP). Prolonged IOP elevation results in optic nerve head damage and vision loss. Uniquely, PEXG is a form of open angle glaucoma that has variable penetrance, is difficult to treat and does not respond well to common IOP-lowering pharmaceuticals. Therefore, understanding modulators of disease severity will aid in targeted therapies for PEXG. Genome-wide association studies have identified polymorphisms in the long non-coding RNA lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) as a risk factor for PEXG. Risk alleles, oxidative stress and mechanical stretch all alter LOXL1-AS1 expression. As a long non-coding RNA, LOXL1-AS1 binds hnRNPL and regulates global gene expression. In this study, we focus on the role of LOXL1-AS1 in the ocular cells (trabecular meshwork and Schlemm's canal) that regulate IOP. We show that selective knockdown of LOXL1-AS1 leads to cell-type-specific changes in gene expression, ECM homeostasis, signaling and morphology. These results implicate LOXL1-AS1 as a modulator of cellular homeostasis, altering cell contractility and ECM turnover, both of which are well-known contributors to PEXG. These findings support LOXL1-AS1 as a key target for modifying the disease., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We assessed breakpoint changes of 13,101 Enterobacterales and Pseudomonas aeruginosa isolates from the past decade. All β-lactams and fluoroquinolones demonstrated decreased susceptibilities following breakpoint changes. Enterobacter cloacae experienced the largest average decrease in susceptibility amongst the Enterobacterales at 5.3% and P. aeruginosa experienced an average decrease in susceptibility of 9.3%., (© The Author(s) 2022.)

Background: Previous research demonstrates hamstring muscle-tendon stiffness (HMTS) influences isometric strength, landing biomechanics and architectural tissue properties. However, the influence on kinetics & kinematics during other modes of strength testing (isotonic dynamometry) has yet to be established., Purpose: Investigate how HMTS influences kinetics and kinematics during a novel isotonic muscle performance test which has never been done for the hamstrings. Previous work using dynamometry has been limited to isometric or isokinetic contractions, so the novelty arises from our custom isotonic protocol which allows quantitative assessment of the stretch-shortening cycle., Methods: Twenty-six recreationally active individuals (15 males, 11 females, 23.8 ± 2.5 years) completed baseline testing for anthropometry and maximum isometric hamstring strength (MVIC). At least 48 h later, subjects completed a measure of HMTS (damped oscillation technique) followed by an isotonic knee flexion test (eccentric velocity 180°/s; concentric torque 25% of MVIC). Separate linear regression models with examination of residuals were conducted between HMTS and each muscle performance variable. Standardized coefficients determined the magnitude of the relationships., Results: Significance was found for all outcome variables tested. HMTS and rate of torque development demonstrated the strongest relationship followed by isotonic concentric peak torque. The weakest relationship observed was with isometric peak torque., Conclusions: These findings build off previous work quantifying HMTS by showing HMTS more strongly relates to dynamic versus static muscle testing and identifies the potential clinical utility of isotonic dynamometry.

Auxotrophy, or an organism's requirement for an exogenous source of an organic molecule, is widespread throughout species and ecosystems. Auxotrophy can result in obligate interactions between organisms, influencing ecosystem structure and community composition. We explore how auxotrophy-induced interactions between aquatic microorganisms affect microbial community structure and stability. While some studies have documented auxotrophy in aquatic microorganisms, these studies are not widespread, and we therefore do not know the full extent of auxotrophic interactions in aquatic environments. Current theoretical and experimental work suggests that auxotrophy links microbial community members through a complex web of metabolic dependencies. We discuss the proposed ways in which auxotrophy may enhance or undermine the stability of aquatic microbial communities, highlighting areas where our limited understanding of these interactions prevents us from being able to predict the ecological implications of auxotrophy. Finally, we examine an example of auxotrophy in harmful algal blooms to place this often theoretical discussion in a field context where auxotrophy may have implications for the development and robustness of algal bloom communities. We seek to draw attention to the relationship between auxotrophy and community stability in an effort to encourage further field and theoretical work that explores the underlying principles of microbial interactions., (© The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.)

Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of fibrillary material in the conventional outflow pathway. However, the molecular mechanisms that drive pathogenesis and genetic risk remain poorly understood. PEX glaucoma-associated single-nucleotide polymorphisms are located in and affect activity of the promoter of LOXL1-AS1, a long non-coding RNA (lncRNA). Nuclear and non-nuclear lncRNAs regulate a host of biological processes, and when dysregulated, contribute to disease. Here we report that LOXL1-AS1 localizes to the nucleus where it selectively binds to the mRNA processing protein, heterogeneous nuclear ribonucleoprotein-L (hnRNPL). Both components of this complex are critical for the regulation of global gene expression in ocular cells, making LOXL1-AS1 a prime target for investigation in PEX syndrome and glaucoma., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Intraocular pressure (IOP), the primary risk factor for primary open-angle glaucoma, is determined by resistance to aqueous outflow through the trabecular meshwork (TM). IOP homeostasis relies on TM responses to mechanical stretch. To model the effects of elevated IOP on the TM, this study sought to identify coding and non-coding RNAs differentially expressed in response to mechanical stretch., Methods: Monolayers of TM cells from non-glaucomatous donors (n = 5) were cultured in the presence or absence of 15% mechanical stretch, 1 cycle/second, for 24 hours using a computer-controlled Flexcell unit. We profiled mRNAs and lncRNAs with stranded total RNA sequencing and microRNA (miRNA) expression with NanoString-based miRNA assays. We used two-tailed paired t-tests for mRNAs and long non-coding RNAs (lncRNAs) and the Bioconductor limma package for miRNAs. Gene ontology and pathway analyses were performed with WebGestalt. miRNA-mRNA interactions were identified using Ingenuity Pathway Analysis Integrative miRNA Target Finder software. Validation of differential expression was conducted using droplet digital PCR., Results: We identified 219 mRNAs, 42 miRNAs, and 387 lncRNAs with differential expression in TM cells upon cyclic mechanical stretch. Pathway analysis indicated significant enrichment of genes involved in steroid biosynthesis, glycerolipid metabolism, and extracellular matrix-receptor interaction. We also identified several miRNA master regulators (miR-125a-5p, miR-30a-5p, and miR-1275) that regulate several mechanoresponsive genes., Conclusions: To our knowledge, this is the first demonstration of the differential expression of coding and non-coding RNAs in a single set of cells subjected to cyclic mechanical stretch. Our results validate previously identified, as well as novel, genes and pathways.

Endothelial-to-mesenchyme-like transition (Endo-MT) of trabecular meshwork (TM) cells is known to be associated with primary open angle glaucoma (POAG). Here, we investigated whether the prion protein (PrP C ), a neuronal protein known to modulate epithelial-to-mesenchymal transition in a variety of cell types, is expressed in the TM, and plays a similar role at this site. Using a combination of primary human TM cells and human, bovine, and PrP-knock-out (PrP -/- ) mouse models, we demonstrate that PrP C is expressed in the TM of all three species, including endothelial cells lining the Schlemm's canal. Silencing of PrP C in primary human TM cells induces aggregation of β1-integrin and upregulation of α-smooth muscle actin, fibronectin, collagen 1A, vimentin, and laminin, suggestive of transition to a mesenchyme-like phenotype. Remarkably, intraocular pressure is significantly elevated in PrP -/- mice relative to wild-type controls, suggesting reduced pliability of the extracellular matrix and increased resistance to aqueous outflow in the absence of PrP C . Since PrP C is cleaved by members of the disintegrin and matrix-metalloprotease family that are increased in the aqueous humor of POAG arising from a variety of conditions, it is likely that concomitant cleavage of PrP C exaggerates and confounds the pathology by inducing Endo-MT-like changes in the TM.

Several DSM-5 criteria lasting 6 months or longer can help identify complicated grief, as can available assessment tools. Treatment has a unique focus.

ADHD diagnostic criteria are different for adults than they are for children. Plus, prescribing psychostimulants for adults raises the risk of misuse and diversion.

Microbes, the foundation of the marine foodweb, do not function in isolation, but rather rely on molecular level interactions among species to thrive. Although certain types of interactions between autotrophic and heterotrophic microorganisms have been well documented, the role of specific organic molecules in regulating inter-species relationships and supporting growth are only beginning to be understood. Here, we examine one such interaction by characterizing the metabolic response of a heterotrophic marine bacterium, Ruegeria pomeroyi DSS-3, to growth on dimethylsulfoniopropionate (DMSP), an abundant organosulfur metabolite produced by phytoplankton. When cultivated on DMSP, R. pomeroyi synthesized a quorum-sensing molecule, N-(3-oxotetradecanoyl)-l-homoserine lactone, at significantly higher levels than during growth on propionate. Concomitant with the production of a quorum-sensing molecule, we observed differential production of intra- and extracellular metabolites including glutamine, vitamin B2 and biosynthetic intermediates of cyclic amino acids. Our metabolomics data indicate that R. pomeroyi changes regulation of its biochemical pathways in a manner that is adaptive for a cooperative lifestyle in the presence of DMSP, in anticipation of phytoplankton-derived nutrients and higher microbial density. This behavior is likely to occur on sinking marine particles, indicating that this response may impact the fate of organic matter.