Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl-/HCO3- exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems

Co-Production and Collaboration: Examining the Application of Co-Production of Knowledge Principles and Practices at the Arctic Rivers Summit in Anchorage, Alaska

In the face of climate change impacts in the Arctic and sub-Arctic regions of Alaska and northwest Canada, there is a growing need to improve collaboration between Indigenous communities and western scientists to address multifaceted socio-environmental problems. These problems include shifts in the freezing of river-ice transportation corridors, permafrost thaw, and decreased salmon abundance in the Yukon River. These environmental problems pose drastic impacts for Indigenous communities in the region who depend on rivers for transportation, subsistence fishing, and cultural heritage. Addressing these challenges holistically and equitably requires employing a co-production of knowledge framework for producing useful and usable knowledge. This process requires high capacity for and commitment to building relationships between Indigenous Knowledge holders and western scientists. The Arctic Rivers Project is a multidisciplinary project led by Yukon River communities and organizations, the University of Colorado, Boulder, and the United States Geological Survey. The project attempts to employ a co-production of knowledge framework to understand climate change impacts in Alaska&rsquo;s Yukon River basin with the goal of producing useful and usable knowledge. In this work, I explore the application of co-production of knowledge principles and practices in the planning, preparation, and execution of the Arctic Rivers Summit, held by the Arctic Rivers Project in Anchorage, Alaska, December 6-8, 2022 to bring together Yukon River stakeholders and community members. I write a narrative of the preparation and sessions held at the Arctic Rivers Summit, analyzing them for their applications of co-production of knowledge principles and practices. I then explore the extent to which co-production of knowledge principles were employed, the scalability of co-production efforts, and challenges in co-production of knowledge between western scientists and Indigenous communities. In my analysis, I found that co-production practices were utilized throughout the process, beginning with the event&rsquo;s co-production by the Arctic Rivers Project research team, Indigenous Advisory Council, and the Institute for Tribal Environmental Professionals. The processes that were used in planning, preparing for, and executing the Arctic Rivers Summit serve as an example for how academic institutions can work to integrate co-production of knowledge processes and practices into events and research projects with Indigenous communities.</p

Recurrence of hepatitis C after liver transplantation is associated with increased systemic IL-10 levels.

BACKGROUND: Recurrence of hepatitis C after liver transplantation is an almost universal occurrence. T-cell derived cytokines have an important role in the development of liver damage associated with chronic hepatitis C, their post-transplant levels, however, have not been correlated with histologic recurrence of the disease. AIMS: We sought to analyze levels of TNF-alpha, soluble IL-2 receptor, IL-4 and IL-10 at 1 month, 6 months and 1 year after transplantation in 27 patients undergoing transplantation for hepatitis C related end-stage liver disease. METHODS: HCV RNA levels were monitored by a branched-chain DNA signal amplification assay. Diagnosis of recurrent hepatitis was based on 1-year protocol biopsies and on biopsies performed for liver enzyme elevations. RESULTS: Recurrent hepatitis C was detected in 52% (n=14) of the 27 patients. HCV RNA levels rose over time in all patients regardless of histologic recurrence. TNF-alpha, and IL-4 levels, although elevated, did not show specific patterns over time or in correlation with recurrence. Similarly, the early elevation followed by a gradual decrease over the first year in the amount of soluble IL-2 receptor was not related to histologic recurrence. We observed a significant increase in circulating IL-10 levels over the first year in patients with biopsy-proven recurrence, while patients with no signs of histologic recurrence displayed increased, but steady levels. CONCLUSIONS: These results suggest that while these cytokines are associated with post-transplant recurrence of hepatitis C, their production may be altered by additional factors

Feasibility and safety of liver transplantation or resection after transarterial radioembolization with Yttrium-90 for unresectable hepatocellular carcinoma.

The benefit of transarterial radioembolization (TARE) in patients with unresectable hepatocellular carcinoma (HCC) is increasingly evidenced. However, data on outcome of liver transplantation or resection after TARE remain scarce. This study aimed to assess the safety and feasibility of surgery after TARE in patients with unresectable HCC. Patients exclusively undergoing TARE followed by either orthotopic liver transplantation (OLT) or liver resection (LR) for HCC between 2012 and 2016 were included. Primary outcomes were postoperative morbidity and mortality. Secondary outcomes were overall survival (OS) and response to TARE. Among 349 patients with HCC treated with TARE, 32 (9%) underwent either OLT (n = 22) or LR (n = 10), which represent the study cohort. In this group, TARE induced decreased viable nodules (p &lt; 0.001), an efficient downsizing (p &lt; 0.001) as well as a significant downstaging based on BCLC classification (p &lt; 0.001). Overall, major complications and mortality after surgery occurred in 5 (16%) and 1 (3%) patients, respectively. For the whole study cohort, OS was 47 months while survival rates at 1-, 3- and 5-years reached 97%, 86% and 86%, respectively. Liver surgery after TARE is feasible and safe. This strategy allows to offer a curative treatment in a subset of patients with unresectable HCC

Bacterial migration through punctured surgical gloves under real surgical conditions

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to confirm recent results from a previous study focussing on the development of a method to measure the bacterial translocation through puncture holes in surgical gloves under real surgical conditions.</p> <p>Methods</p> <p>An established method was applied to detect bacterial migration from the operating site through the punctured glove. Biogel™ double-gloving surgical gloves were used during visceral surgeries over a 6-month period. A modified Gaschen-bag method was used to retrieve organisms from the inner glove, and thus-obtained bacteria were compared with micro-organisms detected by an intra-operative swab.</p> <p>Results</p> <p>In 20 consecutive procedures, 194 gloves (98 outer gloves, 96 inner gloves) were examined. The rate of micro-perforations of the outer surgical glove was 10% with a median wearing time of 100 minutes (range: 20-175 minutes). Perforations occurred in 81% on the non-dominant hand, with the index finger most frequently (25%) punctured. In six cases, bacterial migration could be demonstrated microbiologically. In 5% (5/98) of outer gloves and in 1% (1/96) of the inner gloves, bacterial migration through micro-perforations was observed. For gloves with detected micro-perforations (n = 10 outer layers), the calculated migration was 50% (n = 5). The minimum wearing time was 62 minutes, with a calculated median wearing time of 71 minutes.</p> <p>Conclusions</p> <p>This study confirms previous results that bacterial migration through unnoticed micro-perforations in surgical gloves does occur under real practical surgical conditions. Undetected perforation of surgical gloves occurs frequently. Bacterial migration from the patient through micro-perforations on the hand of surgeons was confirmed, limiting the protective barrier function of gloves if worn over longer periods.</p

Rapid biolayer interferometry measurements of urinary CXCL9 to detect cellular infiltrates noninvasively after kidney transplantation

Introduction: measuring the chemokine CXCL9 in urine by enzyme-linked immunosorbent assay (ELISA) can diagnose acute cellular rejection (ACR) noninvasively after kidney transplantation, but the required 12- to 24-hour turnaround time is not ideal for rapid, clinical decision-making. Methods: we developed a biolayer interferometry (BLI)−based assay to rapidly measure urinary CXCL9 in 200 pg/ml in subjects with ACR and ≤100 pg/ml in subjects with stable kidney function without cellular infiltrates. In samples obtained after treatment for ACR, BLI CXCL9 measurements detected biopsy-proven intragraft infiltrates despite treatment-induced reduction in serum creatinine. Discussion: together, our proof-of-principle results demonstrate that BLI-based urinary CXCL9 detection has potential as a point-of-care noninvasive biomarker to diagnose and guide therapy for ACR in kidney transplantation recipients

One-Year HbA1c Predicts Long-Term Pancreas Graft Survival Following SPK Transplantation: A US Population Cohort Study

Copyright \ua9 2025 Kourounis, Tingle, Maillo-Nieto, Wroe, Thompson, Owen, van Leeuwen, Holzner, Wadhera, Zeeshan Akhtar, Florman, Shaw, White and Wilson.Understanding which factors shape long-term pancreas graft outcomes after the critical first year post-transplantation is an ongoing challenge. This study assesses one-year HbA1c as a predictor of subsequent pancreas graft survival. A retrospective cohort study was conducted using the UNOS registry on all simultaneous pancreas-kidney (SPK) transplants between 2017 and 2023. Regression models with multiple imputations for missing data were used to evaluate predictors of long-term function. Non-linear relationships were modelled with restricted cubic splines (RCS). Among 2,917 SPK recipients (median follow-up 44 months, IQR: 25–60), one-year HbA1c was the strongest independent predictor of long-term graft survival. An HbA1c of 6.8% versus 4.4% (95th vs. 5th percentile) was associated with significantly worse graft survival (aHR = 2.48, 95% CI: 1.72–3.58). Simulated trial sample size calculations found that detecting a statistically and clinically significant reduction in one-year HbA1c from 7% to 6.5% would require 65 patients per group, whereas detecting a reduction in one-year graft loss from 12% to 9% would require 1,631 patients per group. HbA1c at 1 year is a robust, continuous marker of long-term graft function and may serve as a feasible, objective surrogate endpoint in future clinical trials, enabling smaller, more efficient study designs to evaluate interventions

Human male gamete endocrinology: 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates different aspects of human sperm biology and metabolism

<p>Abstract</p> <p>Background</p> <p>A wider biological role of 1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D3, in tissues not primarily related to mineral metabolism was suggested. Recently, we evidenced the ultrastructural localization the 1,25(OH)2D3 receptor in the human sperm. However, the 1,25(OH)2D3 action in human male reproduction has not yet been clarified.</p> <p>Methods and Results</p> <p>By RT-PCR, Western blot and Immunofluorescence techniques, we demonstrated that human sperm expresses the 1,25(OH)2D3 receptor (VDR). Besides, 25(OH)D3-1 alpha-hydroxylase, evidenced by Western blot analysis, indicated that in sperm 1,25(OH)2D3 is locally produced, highlighting the potential for autocrine-paracrine responses. 1,25(OH)2D3 through VDR, increased intracellular Ca2+ levels, motility and acrosin activity revealing an unexpected significance of this hormone in the acquisition of fertilizing ability. In sperm, 1,25(OH)2D3 through VDR, reduces triglycerides content concomitantly to the increase of lipase activity. Rapid responses stimulated by 1,25(OH)2D3 have been observed on Akt, MAPK and GSK3 implying that this secosteroid is involved in different sperm signalling pathways.</p> <p>Conclusion</p> <p>Our data extended the role of 1,25(OH)2D3 beyond its conventional physiological actions, paving the way for novel therapeutic opportunities in the treatment of the male reproduction disorders.</p

What Values in Design? The Challenge of Incorporating Moral Values into Design

Recently, there is increased attention to the integration of moral values into the conception, design, and development of emerging IT. The most reviewed approach for this purpose in ethics and technology so far is Value-Sensitive Design (VSD). This article considers VSD as the prime candidate for implementing normative considerations into design. Its methodology is considered from a conceptual, analytical, normative perspective. The focus here is on the suitability of VSD for integrating moral values into the design of technologies in a way that joins in with an analytical perspective on ethics of technology. Despite its promising character, it turns out that VSD falls short in several respects: (1) VSD does not have a clear methodology for identifying stakeholders, (2) the integration of empirical methods with conceptual research within the methodology of VSD is obscure, (3) VSD runs the risk of committing the naturalistic fallacy when using empirical knowledge for implementing values in design, (4) the concept of values, as well as their realization, is left undetermined and (5) VSD lacks a complimentary or explicit ethical theory for dealing with value trade-offs. For the normative evaluation of a technology, I claim that an explicit and justified ethical starting point or principle is required. Moreover, explicit attention should be given to the value aims and assumptions of a particular design. The criteria of adequacy for such an approach or methodology follow from the evaluation of VSD as the prime candidate for implementing moral values in design