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Even when successfully induced, immunological tolerance to solid organs remains vulnerable to inflammatory insults, which can trigger rejection. In a mouse model of cardiac allograft tolerance in which infection with Listeria monocytogenes (Lm) precipitates rejection of previously accepted grafts, we showed that recipient CD4+ TCR75 cells reactive to a donor MHC class I–derived peptide become hypofunctional if the allograft is accepted for more than 3 weeks. Paradoxically, infection-induced transplant rejection was not associated with transcriptional or functional reinvigoration of TCR75 cells. We hypothesized that there is heterogeneity in the level of dysfunction of different allospecific T cells, depending on duration of their cognate antigen expression. Unlike CD4+ TCR75 cells, CD4+ TEa cells specific for a peptide derived from donor MHC class II, an alloantigen whose expression declines after transplantation but remains inducible in settings of inflammation, retained function in tolerant mice and expanded during Lm-induced rejection. Repeated injections of alloantigens drove hypofunction in TEa cells and rendered grafts resistant to Lm-dependent rejection. Our results uncover a functional heterogeneity in allospecific T cells of distinct specificities after tolerance induction and reveal a strategy to defunctionalize a greater repertoire of allospecific T cells, thereby mitigating a critical vulnerability of tolerance.

A new class of feed additives and nutritional supplements, known as probiotics, include bacterial, fungal, and yeast cultures from various sources. Overall, probiotics are believed to promote the health and well-being of animals, birds, and humans in a variety of settings. Incorporating probiotics into the diets of cattle and poultry has been demonstrated to improve growth, feed conversion efficiency, immunological responses, and the animal's ability to manage enteric infections. The use of probiotic-enriched chicken feed has been shown to enhance egg production by as much as 30% among laying chickens. Probiotics may be used to fight off harmful microorganisms, create antibacterial compounds (such as bacteriocins or colicins), and alter the immunological response of the host, according to the National Institutes of Health. Pathogenic microbial strains such as Lactobacillus, Streptococcus, Bacillus, Enterococcus, Pediococcus, Aspergillus, and Saccharomyces are employed in the making of chicken products. The use of subtherapeutic doses of antimicrobial agents, including antibiotics, to combat or remove harmful bacteria and promote animal growth and feed efficiency has resulted in the accumulation of antibiotic residues in animal feed as well as the emergence of drug-resistant microbes in the feed supply chain. As a result of public health concerns, there has been a renewed emphasis on the use of probiotics in chicken production rather than antibiotics in recent years. This research examines the effects of probiotics and direct-fed microorganisms (DFM) on chicken health and performance, with a particular emphasis on the favourable effects they have on poultry health and performance.

The equivalent circuit model (ECM)-based traditional state-of-charge (SoC) estimate approaches combine all state variables into a single enhanced state vector. However, the stability and accuracy of the estimates are compromised by the correlations between RC voltages and SOC. In this article, the four battery chemistries have been discussed for their state variable characterization i.e. state of charge (SOC). The battery types considered are lead acid, nickel metal hydride, lithium ion. The manufacturer’s battery discharge curves are used to determine the model parameters, and a method is also described for doing this. An improved battery model is suggested in this study that can be applied to HEV design and analysis. By incorporating the electrical characteristics of the battery, the model generates precise results.

Because they fully utilize the filler and matrix features, dielectric composites are a beneficial addition to the family of energy conversion and storage materials. An overview of current advancements in the production of high-performance polymer-ceramic dielectric composites is the goal of this essay. High performance applications, thermal stability, electromechanical energy conversion, solid-state cooling, and capacitive energy harvesting and storage are prioritized. Dielectric composites are produced using new methods such as electrospinning, cold sintering and 3D printing.. The limitations of these approaches as well as their possibilities for further study are covered. In order to develop high- performance dielectric composites, the benefits and drawbacks of popular theoretical computational techniques—such as the phase field model, the finite element model, and machine learning approaches—are investigated. To wrap up this analysis, let me briefly discuss how composite dielectrics will evolve in the future.

Solid organ transplantation is the preferred treatment for end-stage organ failure. Although transplant recipients take life-long immunosuppressive drugs, a substantial percentage of them still reject their allografts. Strikingly, barrier organs colonized with microbiota have significantly shorter half-lives than non-barrier transplanted organs, even in immunosuppressed hosts. We previously demonstrated that skin allografts monocolonized with the common human commensal Staphylococcus epidermidis (S.epi) are rejected faster than germ-free (GF) allografts in mice because the presence of S.epi augments the effector alloimmune response locally in the graft. Here, we tested whether host immune responses against graft-resident commensal microbes, including S.epi, can damage colonized grafts independently from the alloresponse. Naive hosts mounted an anticommensal T cell response to colonized, but not GF, syngeneic skin grafts. Whereas naive antigraft commensal T cells modestly damaged colonized syngeneic skin grafts, hosts with prior anticommensal T cell memory mounted a post-transplant immune response against graft-resident commensals that significantly damaged colonized, syngeneic skin grafts. Importantly, allograft recipients harboring this host-versus-commensal immune response resisted immunosuppression. The dual effects of host-versus-commensal and host-versus-allograft responses may partially explain why colonized organs have poorer outcomes than sterile organs in the clinic.

Global warming and climate changes are among the biggest modern-day environmental problems, the main factor causing these problems is the greenhouse gas effect. The increased concentration of carbon dioxide in the atmosphere resulted in capturing increased amounts of reflected sunlight, causing serious acute and chronic environmental problems. The concentration of carbon dioxide in the atmosphere reached 421 ppm in 2022 as compared to 280 in the 1800s, this increase is attributed to the increased carbon dioxide emissions from the industrial revolution. The release of carbon dioxide into the atmosphere can be minimized by practicing carbon capture utilization and storage methods. Carbon capture utilization and storage (CCUS) has four major methods, namely, pre-combustion, post-combustion, oxyfuel combustion, and direct air capture. It has been reported that applying CCUS can capture up to 95% of the produced carbon dioxide in running power plants. However, a reported cost penalty and efficiency decrease hinder the wide applicability of CCUS. Advancements in the CCSU were made in increasing the efficiency and decreasing the cost of the sorbents. In this review, we highlight the recent developments in utilizing both physical and chemical sorbents to capture carbon. This includes amine-based sorbents, blended absorbents, ionic liquids, metal-organic framework (MOF) adsorbents, zeolites, mesoporous silica materials, alkali-metal adsorbents, carbonaceous materials, and metal oxide/metal oxide-based materials. In addition, a comparison between recently proposed kinetic and thermodynamic models was also introduced. It was concluded from the published studies that amine-based sorbents are considered assuperior carbon-capturing materials, which is attributed to their high stability, multifunctionality, rapid capture, and ability to achieve large sorption capacities. However, more work must be done to reduce their cost as it can be regarded as their main drawback.

Reprogrammed glucose metabolism is considered as the hallmark of cancer with therapeutic implications. Phytocompounds have potential to inhibit cancer metabolism. Here, we tested the ability of Withaferin A (WA), a withanolide derived from Withania somnifera, in modulating cancer metabolism. The assessed effect of WA on aerobic glycolysis in breast cancer cell lines showed that WA decreases the glucose uptake, lactate production and ATP generation by inhibiting the expression of key glycolytic enzymes i.e., GLUT1, HK2 and PKM2. We also identified that WA induced inhibition of cancer glycolysis by targeting c-myc as validated by silencing experiments followed by metabolic readouts. Decreased glycolysis resulted in reduced cell viability, biomass and colony forming ability of breast cancer cells. To further validate our in vitro findings in breast cancer patients, we analyzed 90 metabolic pathways in ~ 2000 breast tumors and observed that glycolysis is the most deregulated pathway in breast tumors. Deregulated glycolysis also predicted poor prognosis in breast cancer patients. In addition, patient data showed correlation between c-myc expression and glycolytic deregulation in breast cancer. Taken together, our results highlight the role of WA in inhibiting breast cancer metabolism via c-myc/glycolysis axis., (© 2024. The Author(s).)

Rationale & Objective: The kidney allocation system (KAS250), using circle-based distribution, attempts to address geographic disparities through broader sharing of deceased-donor kidney allografts. This study sought to evaluate the association between KAS250 and likelihood of deceased-donor kidney transplantation (DDKT) among waitlisted candidates, and whether the policy has differentially affected centers with shorter vs. longer waiting time., Study Design: Retrospective cohort study., Setting: & Participants: 160,941 candidates waitlisted at 176 transplant centers between 3/2017-3/2024., Exposure: KAS250 allocation policy., Outcome: Rate of DDKT., Analytical Approach: Multivariable Cox regression, modeling KAS250 as a time-dependent variable., Results: KAS250 was not independently associated with likelihood of DDKT overall (HR=1.01 vs. pre-KAS250, 95% C.I. 0.97-1.04). KAS250's association with likelihood of DDKT varied across centers from HR=0.18 (DDKT less likely after KAS250) to HR=17.12 (DDKT more likely) and varied even among neighboring centers. KAS250 was associated with decreased DDKT at 25.6% and increased DDKT at 18.2% of centers. Centers with previously long median waiting times (57+ months) experienced increased likelihood of DDKT after KAS250 (HR=1.20, 95% C.I. 1.15-1.26), whereas centers with previously short median waiting times (6-24mo.; HR=0.88, 0.84-0.92) experienced decreased likelihood of DDKT., Limitations: Retrospective study of allocation policy changes, confounded by multiple changes over the study timeframe., Conclusion: Association between KAS250 and DDKT varied across centers. For one-in-four centers, DDKT was less likely after KAS250 relative to pre-KAS250 trends. Candidates at centers with previously long waiting times experienced increased likelihood of DDKT after KAS250. Thus, broader distribution of kidneys may be associated with improved equity in access to DDKT, but additional strategies may be needed to minimize disparities between centers., (Copyright © 2024. Published by Elsevier Inc.)

Administrative claims data could provide a unique opportunity to identify acute rejection (AR) events using specific antirejection medications and to validate rejected data reported to the Organ Procurement and Transplantation Network. This retrospective cohort study examined differences in registry-reported events and those identified using claims data among adult kidney transplant recipients from 2012 to 2017 using Standard Analysis Files from the US Renal Data System. Rejection rates, survival estimates, and center-level differences were assessed using each approach. Among 45 880 first-time kidney transplant recipients, we identified 3841 AR events within 12 months of transplant reported by centers in the registry; claims data yielded 2945 events. Of all events occurring within 12 months of transplant, 48.5% were reported using registry only, 32.9% were identified using claims only, and 18.6% were identified using both approaches. A 3-year death-censored graft survival probability was 90.0%, 88.4%, and 81.2% (P < .001) for ARs identified using registry only, claims data only, and both approaches, respectively. The large discordance between registry-reported and claims-based events suggests incomplete and potentially inaccurate reporting of events in the Organ Procurement Transplant Network registry. These findings have important implications for analyses that use AR data and underscore the need for improved capture of clinically meaningful events., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose, as described by the American Journal of Transplantation. S. Mohan receives grant funding from Kidney Transplant Collaborative and the National Institute of Health (NIH, Bethesda, MD), and personal fees from Sanofi, Kidney International Reports, and the Health Services Advisory Group outside of the submitted work. The other authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Significant atrioventricular valve dysfunction can be associated with mortality or need for transplant in functionally univentricular heart patients undergoing staged palliation. The purposes of this study are to characterize the impact of concomitant atrioventricular valve intervention on outcomes at each stage of single ventricle palliation and to identify risk factors associated with poor outcomes in these patients. Methods: The Society of Thoracic Surgeons Congenital Heart Surgery Database was queried for functionally univentricular heart patients undergoing single ventricle palliation from 2013 through 2022. Separate analyses were performed on cohorts corresponding to each stage of palliation (1: initial palliation; 2: superior cavopulmonary anastomosis; 3: Fontan procedure). Bivariate analysis of demographics, diagnoses, comorbidities, preoperative risk factors, operative characteristics, and outcomes with and without concomitant atrioventricular valve intervention was performed. Multiple logistic regression was used to identify predictors associated with operative mortality or major morbidity. Results: Concomitant atrioventricular valve intervention was associated with an increased risk of operative mortality or major morbidity for each cohort (cohort 1: 62% vs 46%, P  < .001; cohort 2: 37% vs 19%, P  < .001; cohort 3: 22% vs 14%, P  < .001). Black race in cohort 1 (odds ratio [OR] 3.151, 95% CI 1.181-9.649, P  = .03) and preterm birth in cohort 2 (OR 1.776, 95% CI 1.049-3.005, P  = .032) were notable predictors of worse morbidity or mortality. Conclusions: Concomitant atrioventricular valve intervention is a risk factor for operative mortality or major morbidity at each stage of single ventricle palliation. Several risk factors are associated with these outcomes and may be useful in guiding decision-making., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Kidney transplantation with minimal or no dialysis exposure provides optimal outcomes for children with end-stage kidney disease. We sought to understand disparities in timely access to transplant waitlisting., Methods: We conducted a retrospective, registry-based cohort study of candidates ages 3 to 17 added to the US kidney transplant waitlist 2015 to 2019. We defined "preemptive waitlisting" as waitlist addition before receiving dialysis and compared demographics of candidates based on preemptive status. We used competing risk regression to determine the association between preemptive waitlisting and transplantation. We then identified waitlist additions age >18 who initiated dialysis as children, thereby missing pediatric allocation prioritization, and evaluated the association between waitlisting with pediatric prioritization and transplantation., Results: Among 4506 pediatric candidates, 48% were waitlisted preemptively. Female sex, Hispanic ethnicity, Black race, and public insurance were associated with lower adjusted relative risk of preemptive waitlisting. Preemptive listing was not associated with time from waitlist activation to transplantation (adjusted hazard ratio 0.94, 95% confidence interval 0.87-1.02). Among transplant recipients waitlisted preemptively, 68% had no pretransplant dialysis, whereas recipients listed nonpreemptively had median 1.6 years of dialysis at transplant. Among 415 candidates initiating dialysis as children but waitlisted as adults, transplant rate was lower versus nonpreemptive pediatric candidates after waitlist activation (adjusted hazard ratio 0.54, 95% confidence interval 0.44-0.66)., Conclusions: Disparities in timely waitlisting are associated with differences in pretransplant dialysis exposure despite no difference in time to transplant after waitlist activation. Young adults who experience delays may miss pediatric prioritization, highlighting an area for policy intervention., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Gallbladder cancer (GBC) is a biologically aggressive malignancy requiring appropriate biomarkers to improve its outcome. Role of ABC transporters (ABCB1 and ABCG2) has been linked to cancer aggressiveness, tumorigenesis and multidrug resistance. Herein, we studied the prognostic implication of ABCB1 and ABCG2 in GBC., Methods: Fresh tissue (tumour & normal) samples collected from 54 patients who underwent R0 resection, were analysed for mRNA and protein expression of ABCB1 and ABCG2 by quantitative Real-Time PCR and western blotting, respectively, in this prospective study. The molecular findings were correlated with clinical-pathological parameters using χ2 and fisher exact test. The molecular changes in ABCB1 and ABCG2 were analysed for predicting overall survival (OS), disease-free survival (DFS) and response to chemotherapy using Kaplan-Meier log-rank test and Cox regression multivariate analysis., Results: The mean age of the cohort was 50 ± 13.2 with 26 (48.1%) in patients having early stage gallbladder cancer (GBC). Over-expression of ABCB1 and ABCG2 was noted in 32/54 (59%) and 40/54 (74%) cases, respectively. The protein expression of ABCB1(P-glycoprotein) and ABCG2 (BCRP) was higher in 27/54 (50%) and 37/54 (59%) cases, respectively. The mean OS and DFS was 20.7 ± 11.5 and 19.3 ± 12.2 months at median follow-up of 24 months. The TNM stage, lymph node metastasis, and presence of gallstone were significant factors for predicting OS and DFS on multivariate analysis. Both ABCB1 and ABCG2 did not show any significant correlation with OS and DFS with similar incidences of late death and recurrence among over-expression and down-expression. Sub-group comparison suggests that change in expression pattern of ABCB1 and ABCG2 may not affect response to chemotherapy in GBC., Conclusion: Altered expression of ABCB1 and ABCG2 may not be a useful prognostic marker for survival or response to chemotherapy in GBC. Presently, histo-pathological characteristics and associated gallstones are the important predictors for survival and recurrence in GBC., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The etiology of recurrent miscarriage (RM) is extremely heterogeneous, encompassing genetic, immunological, anatomical, endocrine, thrombophilic, infectious, and uterine abnormalities. Thrombophilia is a major contributor to pregnancy complications, potentially harming the fetus and jeopardizing the continuation of pregnancy. Therefore, successful pregnancy outcomes depend on maintaining a delicate balance between coagulation and fibrinolytic factors, crucial for ensuring the adjustment of the basal plate to facilitate adequate placental perfusion. Despite numerous studies shedding light on the role of thrombophilic factors and genetic variations in RM, the exact pathogenesis remains unclear. It is imperative to systematically rule out thrombophilia and other related factors responsible for pregnancy disorders and RMs to guide appropriate and active management strategies. Addressing thrombophilia continues to present challenges in terms of effective treatment. The current review aims to address the heterogeneity of RM as a therapeutic challenge, emphasizing the need for standardized diagnostic tests and welldesigned multicenter research trials to gather robust, evidence-based data on thrombophilic causes of RM and provide effective treatment. The goal is to enhance the understanding of thrombophilic factors and genetic landscapes associated with RM through various approaches, including candidate gene studies, genome-wide association studies, and high-throughput sequencing. Meta-analyses have underscored the significance of genetic aberrations in RM, highlighting the necessity for identifying critical mutations implicated in the etiopathogenesis of miscarriages to pave the way for implementation of targeted clinical therapies.

Background: We aimed to understand the association between cold ischemia time (CIT) and delayed graft function (DGF) after kidney transplantation and the impact of organ pumping on that association., Methods: Retrospective cohort study using US registry data. We identified kidney pairs from the same donor where both kidneys were transplanted but had a CIT difference >0 and ≤20 h. We determined the frequency of concordant (both kidneys with/without DGF) or discordant (only 1 kidney DGF) DGF outcomes. Among discordant pairs, we computed unadjusted and adjusted relative risk of DGF associated with longer-CIT status, when then repeated this analysis restricted to pairs where only the longer-CIT kidney was pumped., Results: Among 25 831 kidney pairs included, 71% had concordant DGF outcomes, 16% had only the longer-CIT kidney with DGF, and 13% had only the shorter-CIT kidney with DGF. Among discordant pairs, longer-CIT status was associated with a higher risk of DGF in unadjusted and adjusted models. Among pairs where only the longer-CIT kidney was pumped, longer-CIT kidneys that were pumped had a lower risk of DGF than their contralateral shorter-CIT kidneys that were not pumped regardless of the size of the CIT difference., Conclusions: Most kidney pairs have concordant DGF outcomes regardless of CIT difference, but even small increases in CIT raise the risk of DGF. Organ pumping may mitigate and even overcome the adverse consequences of prolonged CIT on the risk of DGF, but prospective studies are needed to better understand this relationship., Competing Interests: S.M. receives grant funding from Kidney Transplant Collaborative and the National Institutes of Health (NIH), and personal fees from Kidney International Reports, Sanofi and Health Services Advisory Group outside of the submitted work. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Organ transplantation is a life-saving treatment for end-stage organ failure patients, but the United States (US) faces a shortage of available organs. US policies incentivize identifying recipients for all recovered organs. Technological advancements have extended donor organ viability, creating new opportunities for long-distance transport and international sharing. We aimed to assess organ exports from deceased US donors to candidates abroad, a component of allocation policy allowed without suitable domestic candidates. Based on the national Scientific Registry of Transplant Recipients data from January 2014 to September 2023, 388 342 organs were recovered for transplantation, with 511 (0.13%) exported. Most exported organs were lungs (80%). Exported lung donors were older (41 vs 34 years, P < .001), more likely hepatitis C positive (22% vs 4%, P < .001), and more likely donors after circulatory death (20% vs 7%, P < .001). Lungs that were eventually exported were offered to more US potential transplant recipients (median = 65) than those kept in the US (median = 21 and 41 for lungs recovered by nonexporting and exporting organ procurement organizations, respectively; P < .001). Our study highlights the necessity for further research and clear policy initiatives to balance the benefits of cross-border sharing while considering potential opportunities for more aggressive organ allocation within the US., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. R. Lopez reports research funding from the Gift of Life Foundation and One Legacy Foundation. J. D. Schold reports consultancy for eGenesis and Sanofi Corporation; research funding from Department of Defense, Gift of Life Foundation, Kidney Transplant Collaborative, NIH/NIDDK, and One Legacy Foundation; honoraria from eGenesis and Sanofi Inc; advisory or leadership roles as Data Safety Monitoring Board Member for Bristol Myers Squibb, member of the UNOS Policy Oversight Committee, and Vice Chair of UNOS Data Advisory Committee; and speakers bureau for Sanofi. S. Mohan receives grant funding from the Kidney Transplant Collaborative and the NIH, and personal fees from Sanofi, Kidney International Reports, Specialist Direct and Health Services Advisory Group outside of the submitted work and is Chair of the UNOS Data Advisory Committee and Board Member for the Alliance for organ donation and transplantation. The other authors declare they have no financial conflicts of interest to disclose., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

The co-occurrence of active tuberculosis (TB) in patients with moderate to severe asthma presents unique therapeutic challenges, particularly with the advent of biologics like dupilumab, which targets the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways in asthma treatment. Despite the general safety of biologics, concerns about immunosuppression and susceptibility to infections like TB persist. This case report discusses a male with severe, uncontrolled type 2 allergic asthma, who experienced multiple exacerbations despite maximal bronchodilator therapy and then concomitantly developed pulmonary TB. This case demonstrates a potential clinical scenario for co-administering dupilumab with anti-TB treatment, suggesting a beneficial approach for similar clinical scenarios and contributing to the literature on this topic., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shaikh et al.)

Transmitted donor-derived glomerular diseases in the allograft kidney are rare, especially when encountered in an allograft from a living donor. To date, only individual reports of donor-derived membranous nephropathy (MN) have been described. In this report, we present a case of MN discovered in a postreperfusion biopsy of a living-donor allograft. A follow-up biopsy 3 weeks later demonstrated persistent deposits. Thirteen months posttransplant, the recipient showed mildly worsening proteinuria but stable kidney function. To further our understanding of this exceedingly rare complication, we share our experience with 7 additional in-house cases together with 6 cases described in the literature to date. A minority of the donors were living. Most donors did not exhibit significant proteinuria illustrating how predonation screening could potentially miss donor-derived MN. Reactivity for phospholipase A2 receptor and thrombospondin type 1 domain containing 7A were negative in all stained cases. On follow-up, recipients variably exhibited slow resolution of the immune deposits, variable degrees of proteinuria (mainly subnephrotic), and no significant impairment of kidney function. Donor-derived MN is rare, phospholipase A2 receptor-negative, and can still be encountered in living donors despite rigorous screening. This report provides a brief examination of the pathology, clinical, and laboratory features of such patients involved., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. I. Batal is supported by R01DK135671-01 from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Organ donation registration rates in the United States are lowest among Asian Americans. This study aimed to investigate the reasons for low organ donation registration rates among Asian Americans and develop educational material to help improve organ donation rates and awareness., Methods: We conducted a 2-phase study. In phase 1, a cross-sectional observational survey was distributed in-person on an iPad to members of the Asian community in Queens, New York, to investigate their knowledge, attitudes, and beliefs toward organ donation. Based on the results, an educational video was developed, and the efficacy of the video was assessed with an independent cohort of participants in phase 2 using a pre-/post-video comprehension assessment survey., Results: Among 514 Chinese or Korean Americans who participated in the phase 1 survey, 97 participants (19%) reported being registered organ donors. Registered donors were more likely to have previously discussed their organ donation wishes with their family (adjusted odds ratio [aOR], 4.77; 95% confidence interval [CI], 2.56-8.85; P  < 0.01), knowledge of the different registration methods (aOR, 2.57; 95% CI, 1.24-5.31; P  < 0.01), or know a registered organ donor (aOR, 2.62; 95% CI, 1.39-4.95; P  < 0.01). For the educational video efficacy assessment given pre-/post-video, the majority (90%) of the respondents reported learning something new from the video. After watching the video, there was a significant improvement in the mean knowledge score regarding organ donation (63% versus 92%; P  < 0.01) and an increase in intention to have discussion regarding organ donation with family., Conclusions: We found varies factors associated with low organ donation registration rates among Asian Americans and demonstrated the potential of our educational video to impart organ donation knowledge to viewers and instigate the intention to have family discussions regarding organ donation. Further research is needed to assess the impact of videos in motivating actual organ donation registration., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Acute kidney injury (AKI) is a common complication of pediatric heart transplant, with a subset of patients developing severe AKI requiring dialysis (AKI-D). We aimed to identify the epidemiology, risk factors, and outcomes of postoperative AKI-D in pediatric heart transplant recipients., Methods: We retrospectively identified all pediatric first-time, single-organ heart transplants at our institution from 2014 to 2022. Postoperative AKI was defined as AKI within 2 weeks of transplant. Unadjusted and adjusted logistic regression were used to identify characteristics associated with AKI-D, and unadjusted time-to-event analyses were used to determine the association between AKI-D and survival free of kidney failure., Results: Among 177 patients included, 116 (66%) developed postoperative AKI of any stage, including 13 (7%) who developed AKI-D with median time from transplant to dialysis initiation of 6 days (IQR 3-13). In adjusted models, increased cardiopulmonary bypass time (OR 1.19, 95% CI 1.04-1.37, per 15 min increase in bypass time) and higher weight at transplant were associated with higher odds of AKI-D, whereas patient demographics and pretransplant kidney function were not associated with AKI-D. AKI-D was associated with greater mortality during initial hospitalization (46% vs. 1%, p < 0.001) and a lower rate of survival free of kidney failure., Conclusions: The incidence of AKI-D after pediatric heart transplant was 7%, with extended cardiopulmonary bypass time associated with postoperative AKI-D even in adjusted models. Further research is needed to improve the prediction and management of AKI-D in this population., (© 2024 Wiley Periodicals LLC.)

Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology. Currently, there are more than 250,000 patients with a functioning kidney allograft and over 100,000 waitlisted patients awaiting kidney transplant, with a burgeoning number added to the kidney transplant wait list every year. In 2022, more than 40,000 patients were added to the kidney wait list and more than 25,000 received a kidney transplant. The Advancing American Kidney Health Initiative, passed in 2019, is aiming to double the number of kidney transplants by 2030 creating a need for additional transplant nephrologists to help care for them. Over the past decade, there has been a decline in the Nephrology-as well Transplant Nephrology-workforce due to a multitude of reasons. The American Society of Transplantation Kidney Pancreas Community of Practice created a workgroup to discuss the Transplant Nephrology workforce shortage. In this article, we discuss the scope of the problem and how the Accreditation Council for Graduate Medical Education recognition of Transplant Nephrology Fellowship could at least partly mitigate the Transplant Nephrology work force crisis., (Copyright © 2024 by the American Society of Nephrology.)

Background: C3 glomerulopathy (C3G), which encompasses C3GN and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation are limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression., Methods: We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and six DDD), who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The NanoString 770 genes PanCancer Immune Profiling Panel was used for transcriptomic analysis. Disease recurrence was the primary outcome., Results: During a median (interquartile range) follow-up period of 37 (18–56) months, C3G recurrence occurred in 16 (89%) patients (11 with C3GN and five with DDD) at a median (interquartile range) of 33 (13–141) days after transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all the allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence., Conclusions: Most of the patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played a crucial role in detecting early, subclinical recurrence of C3GN and DDD, which showed significant overlapping features.

Tylophora indica (Burm f.) Merrill, belong to family Asclepiadaceae, is considered to be a natural remedy with high medicinal benefits. The objective of this work is to assess the metabolomic profile of T. indica leaves enriched in alkaloids, as well as to evaluate the in vitro cytotoxicity of these leaves using the MTT assay on human breast MCF-7 and liver HepG2 cancer cell lines. Dried leaves of T. indica were extracted by sonication, using methanol containing 2 % (v/v) of acetic acid and obtained fraction was characterized by HPTLC and UPLC-MS. The UPLC-MS study yielded a preliminary identification of 32 metabolites, with tylophorine, tylophorine B, tylophorinine, and tylophorinidine being the predominant metabolites. The cytotoxicity of the extract of T. indica was evaluated on HepG2 and MCF-7 cell lines, yielding inhibitory concentration (IC 50 ) values of 75.71 μg/mL and 69.60 μg/mL, respectively. Data suggested that the phytochemical screening clearly showed presence of numerous secondary metabolites with moderate cytotoxic efficacy. In conclusion, the future prospects of T. indica appear promising for the advancement of phytopharmaceutical-based anticancer medications, as well as for the design of contemporary pharmaceuticals in the field of cancer chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Among heart transplantation (HT) recipients, the accuracy of serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) may be limited by fluctuations in muscle mass. Cystatin C (cysC) is less influenced by muscle mass, but its levels may increase with obesity and steroid use. Herein, we (1) longitudinally compared eGFRcysC and eGFRsCr among HT recipients; (2) investigated the association of body mass index (BMI), steroid use, and muscle mass with discrepancies between eGFRs; and (3) explored the implications of eGFRcysC use on valganciclovir (VGC) dosing., Methods: cysC and sCr were measured in 294 blood samples obtained from 80 subjects. Intraindividual differences between eGFRs (eGFRdiff cysC-sCr ) were calculated with negative values corresponding to eGFRsCr > eGFRcysC and positive values to eGFRcysC > eGFRsCr. In a patient subset (n = 21), pectoralis muscle measures were obtained., Results: Marked differences between eGFRcysC and eGFRsCr were observed, particularly early post-HT (1-week post-HT, median eGFRdiff cysC-sCr -28 ml/min/1.73 m 2 ). eGFRcysC demonstrated stability following a transient postoperative decline, while eGFRsCr decreased in the first year post-HT. Lower BMI and higher prednisone dose displayed a modest association with more negative eGFRdiff cysC-sCr values. Pectoralis muscle measures indicative of greater muscle mass and better tissue quality exhibited a stronger association with more positive eGFRdiff cysC-sCr values. The use of eGFRcysC would have led to VGC dose adjustment in 46% of samples, predominantly resulting in dose reduction., Conclusions: Among HT recipients, eGFRcysC and eGFRsCr markedly differ with implications for VGC dosing. The observed discrepancies may reflect changes in body composition and steroid use., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: For neonates and infants with aortic valve pathology, the Ross procedure historically has been associated with high rates of morbidity and mortality. Data regarding long-term durability are lacking., Methods: The international, multi-institutional Ross Collaborative included 6 tertiary care centers. Infants who underwent a Ross operation between 1996 and 2016 (allowing a minimum 5 years of follow-up) were retrospectively identified. Serial echocardiograms were examined to study evolution in neoaortic size and function., Results: Primary diagnoses for the 133 patients (n = 30 neonates) included isolated aortic stenosis (14%, n = 19), Shone complex (14%, n = 19), and aortic stenosis plus other (excluding Shone complex; n = 95, 71%), including arch obstruction (n = 55), left ventricular hypoplasia (n = 9), and mitral disease (moderate or greater stenosis or regurgitation, n = 31). At the time of the Ross procedure, median age was 96 days (interquartile range, 36-186), and median weight was 4.4 kg (3.6-6.5). In-hospital mortality occurred in 13 of 133 patients (10%) (4/30 [13%] neonates). Postdischarge mortality occurred in 10 of 120 patients (8%) at a median of 298 days post-Ross. Post-Ross neoaortic dilatation occurred, peaking at 4 to 5 SDs above normal at 2 to 3 years before returning to near-baseline z-score at a median follow-up of 11.5 [6.4-17.4] years. Autograft/left ventricular outflow tract reintervention was required in 5 of 120 patients (4%) at a median of 10.3 [4.1-12.8] years. Freedom from moderate or greater neoaortic regurgitation was 86% at 15 years., Conclusions: Neonates and infants experience excellent postdischarge survival and long-term freedom from autograft reintervention and aortic regurgitation after the Ross. Neoaortic dilatation normalizes in this population in the long-term. Increased consideration should be given to Ross in neonates and infants with aortic valve disease., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease, infection, malignancy, and thromboembolism are major causes of morbidity and mortality in kidney transplant recipients (KTR). Prospectively identifying monogenic conditions associated with post-transplant complications may enable personalized management. Therefore, we developed a transplant morbidity panel (355 genes) associated with major post-transplant complications including cardiometabolic disorders, immunodeficiency, malignancy, and thrombophilia. This gene panel was then evaluated using exome sequencing data from 1590 KTR. Additionally, genes associated with monogenic kidney and genitourinary disorders along with American College of Medical Genetics (ACMG) secondary findings v3.2 were annotated. Altogether, diagnostic variants in 37 genes associated with Mendelian kidney and genitourinary disorders were detected in 9.9% (158/1590) of KTR; 25.9% (41/158) had not been clinically diagnosed. Moreover, the transplant morbidity gene panel detected diagnostic variants for 56 monogenic disorders in 9.1% KTRs (144/1590). Cardiovascular disease, malignancy, immunodeficiency, and thrombophilia variants were detected in 5.1% (81), 2.1% (34), 1.8% (29) and 0.2% (3) among 1590 KTRs, respectively. Concordant phenotypes were present in half of these cases. Reviewing implications for transplant care, these genetic findings would have allowed physicians to set specific risk factor targets in 6.3% (9/144), arrange intensive surveillance in 97.2% (140/144), utilize preventive measures in 13.2% (19/144), guide disease-specific therapy in 63.9% (92/144), initiate specialty referral in 90.3% (130/144) and alter immunosuppression in 56.9% (82/144). Thus, beyond diagnostic testing for kidney disorders, sequence annotation identified monogenic disorders associated with common post-transplant complications in 9.1% of KTR, with important clinical implications. Incorporating genetic diagnostics for transplant morbidities would enable personalized management in pre- and post-transplant care., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The increase of multiple drug resistance bacteria significantly diminishes the effectiveness of antibiotic armory and subsequently exaggerates the level of therapeutic failure. Phytoconstituents are exceptional substitutes for resistance-modifying vehicles. The plants appear to be a deep well for the discovery of novel antibacterial compounds. This is owing to the numerous enticing characteristics of plants, they are easily accessible and inexpensive, extracts or chemicals derived from plants typically have significant levels of action against infections, and they rarely cause serious adverse effects. The enormous selection of phytochemicals offers very distinct chemical structures that may provide both novel mechanisms of antimicrobial activity and deliver us with different targets in the interior of the bacterial cell. They can directly affect bacteria or act together with the crucial events of pathogenicity, in this manner decreasing the aptitude of bacteria to create resistance. Abundant phytoconstituents demonstrate various mechanisms of action toward multi drug resistance bacteria. Overall, this comprehensive review will provide insights into the potential of phytoconstituents as alternative treatments for bacterial infections, particularly those caused by multi drug resistance strains. By examining the current state of research in this area, the review will shed light on potential future directions for the development of new antimicrobial therapies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Anemia occurs before and after kidney transplantation. Determining the impact of perioperative transfusion on post-transplant outcomes can help determine best management of anemia., Project Aim: The current study aims to describe clinical outcomes associated with packed red blood cell transfusions in the peri-operative management of anemia after transplantation., Design: This was a single-center, retrospective study of adult kidney recipients with anemia at the time of transplantation. 1271 patients were stratified by donor-type due to the potential variability in underlying recipient and transplant characteristics; living donor (n = 698, 62%) or deceased donor (n = 573, 38%)., Results: Living donor recipients that received blood during the index hospitalization were more likely to experience rejection within 30 days (18% vs. 10%, p = 0.008) and 1 year of transplant (32% vs. 16%, p = 0.038). In multivariate analysis, receiving both blood and darbepoetin (HR: 1.89 [1.20,3.00], p = 0.006), age at transplant (HR: 0.98 [0.97, 0.99], p = 0.02), number of HLA mismatches (HR: 1.17 [1.05,1.30], p = 0.003), and whether the case was a repeat transplant (HR: 2.77 [1.93,3.97], p < 0.01) were significantly associated with hazard of rejection. For deceased donor recipients, there were no differences in acute rejection, graft failure or mortality at 30 days or 1 year. When analyzing hazard of rejection in a multivariate model, treatment received was not found to be significantly associated with rejection., Conclusion: Our findings suggest there may be a role for more aggressive pre-transplant treatment of anemia for those patients undergoing living donor transplants., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Though belatacept is administered with a weight-based dosing schema, there has been higher clearance reported in obese patients. Therefore, we evaluated the association between body mass index (BMI) and transplant outcomes in kidney transplant recipients who were randomized to cyclosporine- or belatacept-based immunosuppression in the BENEFIT and BENEFIT-EXT randomized clinical trials. A total of 666 and 543 patients underwent randomization and transplantation in BENEFIT and BENEFIT-EXT, respectively, of which 1056 had complete data and were included in this analysis. Patients were grouped categorically according to BMI: <25, 25 to <30, and ≥30 kg/m 2 . BMI did influence both the incidence and severity of acute rejection. Obese patients with BMI >30 kg/m 2 in the low intensity belatacept group experienced significantly more rejection at 12 months than did patients with BMI <25 kg/m 2 or BMI 25 to <30 kg/m 2 . In both the moderate intensity belatacept and low intensity belatacept groups, obese patients with BMI >30 kg/m 2 experienced significantly more severe acute rejection than did patients with BMI < 25 kg/m 2 or BMI 25 to <30 kg/m 2 . These results suggest that obese kidney transplant recipients are at an increased risk for acute rejection when under belatacept-based immunosuppression when compared to nonobese patients., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

For centuries, plants have been serving as sources of potential therapeutic agents. In recent years, there has been a growing interest in investigating the effects of plant-derived compounds on epigenetic processes, a novel and captivating Frontier in the field of epigenetics research. Epigenetic changes encompass modifications to DNA, histones, and microRNAs that can influence gene expression. Aberrant epigenetic changes can perturb key cellular processes, including cell cycle control, intercellular communication, DNA repair, inflammation, stress response, and apoptosis. Such disruptions can contribute to cancer development by altering the expression of genes involved in tumorigenesis. However, these modifications are reversible, offering a unique avenue for therapeutic intervention. Plant secondary compounds, including terpenes, phenolics, terpenoids, and sulfur-containing compounds are widely found in grains, vegetables, spices, fruits, and medicinal plants. Numerous plant-derived compounds have demonstrated the potential to target these abnormal epigenetic modifications, including apigenin (histone acetylation), berberine (DNA methylation), curcumin (histone acetylation and epi-miRs), genistein (histone acetylation and DNA methylation), lycopene (epi-miRs), quercetin (DNA methylation and epi-miRs), etc. This comprehensive review highlights these abnormal epigenetic alterations and discusses the promising efficacy of plant-derived compounds in mitigating these deleterious epigenetic signatures in human cancer. Furthermore, it addresses ongoing clinical investigations to evaluate the therapeutic potential of these phytocompounds in cancer treatment, along with their limitations and challenges., 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., (Copyright © 2024 Khan, Khan, Khan, Malik, Massey, Parveen, Mustafa, Shamsi and Husain.)

Although a few registry-based studies have shown associations between receiving kidney allografts from Black donors and shorter allograft survival, detailed, large, single-center studies accounting for common confounding factors are lacking. Furthermore, pathologic alterations underlying this potential disparity have not been systematically studied. We performed a retrospective clinical-pathological study of kidney transplant recipients who received kidney allografts from either Black ( n  = 407) or White ( n  = 1,494) donors at Columbia University Irving Medical Center from 2005 to 2018, with median follow-up of 4.5 years post-transplantation. Black donor race was independently associated with allograft failure (adjusted HR = 1.34, p = 0.02) and recipients of kidney allografts from Black donors had a higher incidence of collapsing glomerulopathy [7.4% vs. 1.9%, OR = 4.17, p < 0.001]. When causes of allograft failure were examined, only allograft failure following development of collapsing glomerulopathy was more frequent in recipients of allografts from Black donors [15% vs. 5%, OR = 3.16, p  = 0.004]. Notably, when patients who developed collapsing glomerulopathy were excluded from analysis, receiving kidney allografts from Black donors was not independently associated with allograft failure (adjusted HR = 1.24, p  = 0.10). These findings revealed that, compared with recipients of kidney allografts from White donors, recipients of kidneys from Black donors have modestly shorter allograft survival and a higher probability of developing collapsing glomerulopathy, which negatively impacts allograft outcome. Identification of collapsing glomerulopathy risk factors may help decrease this complication and improve allograft survival, which optimally may reduce racial disparities post-transplantation., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 DiFranza, Daniel, Serban, Thomas, Santoriello, Ratner, D’Agati, Vasilescu, Husain and Batal.)

The XVIth Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from September 19 to 23, 2022, as a joint meeting with the Canadian Society of Transplantation. In addition to a key focus on the impact of microvascular inflammation and biopsy-based transcript analysis on the Banff Classification, further sessions were devoted to other aspects of kidney transplant pathology, in particular T cell-mediated rejection, activity and chronicity indices, digital pathology, xenotransplantation, clinical trials, and surrogate endpoints. Although the output of these sessions has not led to any changes in the classification, the key role of Banff Working Groups in phrasing unanswered questions, and coordinating and disseminating results of investigations addressing these unanswered questions was emphasized. This paper summarizes the key Banff Meeting 2022 sessions not covered in the Banff Kidney Meeting 2022 Report paper and also provides an update on other Banff Working Group activities relevant to kidney allografts., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Some living donor kidneys are found to have biopsy evidence of chronic scarring and/or glomerular disease at implantation, but it is unclear if these biopsy findings help predict donor kidney recovery or allograft outcomes. Our objective was to identify the prevalence of chronic histological changes and glomerular disease in donor kidneys, and their association with donor and recipient outcomes., Study Design: Retrospective cohort study., Setting & Participants: Single center, living donor kidney transplants from January 2010 to July 2022., Exposure: Chronic histological changes, glomerular disease in donor kidney implantation biopsies., Outcome: For donors, single-kidney estimated glomerular filtration rate (eGFR) increase, percent total eGFR loss, ≥40% eGFR decline from predonation baseline, and eGFR<60mL/min/1.73m 2 at 6 months after donation; for recipients, death-censored allograft survival., Analytical Approach: Biopsies were classified as having possible glomerular disease by pathologist diagnosis or chronic changes based on the percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease. We used logistic regression to identify factors associated with the presence of chronic changes, linear regression to identify the association between chronic changes and single-kidney estimated glomerular filtration rate (eGFR) recovery, and time-to-event analyses to identify the relationship between abnormal biopsy findings and allograft outcomes., Results: Among 1,104 living donor kidneys, 155 (14%) had advanced chronic changes on implantation biopsy, and 12 (1%) had findings suggestive of possible donor glomerular disease. Adjusted logistic regression showed that age (odds ratio [OR], 2.44 per 10 years [95% CI, 1.98-3.01), Hispanic ethnicity (OR, 1.87 [95% CI, 1.15-3.05), and hypertension (OR, 1.92 [95% CI, 1.01-3.64), were associated with higher odds of chronic changes on implantation biopsy. Adjusted linear regression showed no association of advanced chronic changes with single-kidney eGFR increase or relative risk of eGFR<60mL/min/1.73m 2 . There were no differences in time-to-death-censored allograft failure in unadjusted or adjusted Cox proportional hazards models when comparing kidneys with chronic changes to kidneys without histological abnormalities., Limitations: Retrospective, absence of measured GFR., Conclusions: Approximately 1 in 7 living donor kidneys had chronic changes on implantation biopsy, primarily in the form of moderate vascular disease, and 1% had possible donor glomerular disease. Abnormal implantation biopsy findings were not significantly associated with 6-month donor eGFR outcomes or allograft survival., Plain-Language Summary: Kidney biopsies are the gold standard test to identify the presence or absence of kidney disease. However, kidneys donated by healthy living donors-who are extensively screened for any evidence of kidney disease before donation-occasionally show findings that might be considered "abnormal," including the presence of scarring in the kidney or findings suggestive of a primary kidney disease. We studied the frequency of abnormal kidney biopsy findings among living donors at our center. We found that about 14% of kidneys had chronic abnormalities and 1% had findings suggesting possible glomerular kidney disease, but the presence of abnormal biopsy findings was not associated with worse outcomes for the donors or their recipients., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Herbal drugs when used in combination with chemotherapeutic drugs can reduce the side effects and increase the efficacy by acting on multiple targets. Andrographolide (AG), a diterpene lactone isolated from Andrographis paniculata Nees, is a bioactive compound with anticancer potential, and 5-fluorouracil (FU), a pyrimidine analogue, is used in the treatment of cancer. Both drugs are used to formulate combination nanoformulation to increase absorption, thereby increasing their oral bioavailability., Objective: The study aimed to develop and validate stability indicating simultaneous HPTLC method for quantification of FU and AG in combination nanoformulation along with in silico docking and network pharmacology analysis to understand the interaction between the drugs and cancer targets., Methods: Chromatographic separation was performed using mobile phase chloroform: methanol: formic acid (9: 0.5: 0.5, v/v/v) on HPTLC silica plates 60 F254 as a stationary phase using UV-Vis detector and HPTLC scanner at 254 nm. Further, in silico docking analysis was performed to predict the binding affinity of AG and FU with different proteins and network pharmacology to find out the exact biomolecular relationship of AG and FU in alleviating cancer., Results: The data from the calibration curve showed a good linear regression relationship with r² = 0.9981 (FU) and r² = 0.9977 (AG) in the concentration range of 0.1-2.0 μg/mL. The developed method was validated according to the ICH guidelines. Stability studies showed changes in peak patterns and areas. Bioinformatic and network pharmacology analyses of AG and FU with target proteins and genes associated with cancer play a multimechanistic role in alleviating cancer., Conclusion: The developed method has been concluded to be robust, simple, precise, reproducible, accurate, and stability indicating for simultaneous quantification of AG and FU, and the molecular interaction studies have further indicated that the combination nanoformulation of AG and FU could be effective against cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Incidental kidneys cysts are typically considered benign, but the presence of cysts is more frequent in individuals with other early markers of kidney disease. We studied the association of donor kidney cysts with donor and recipient outcomes after living donor kidney transplantation., Methods: We retrospective identified 860 living donor transplants at our center (1/1/2011-7/31/2022) without missing data. Donor cysts were identified by review of pre-donation CT scan reports. We used linear regression to study the association between donor cysts and 6-month single-kidney estimated glomerular filtration rate (eGFR) increase, and time-to-event analyses to study the association between donor cysts and recipient death-censored graft failure., Results: Among donors, 77% donors had no kidney cysts, 13% had ≥1 cyst on the kidney not donated, and 11% only had cysts on the donated kidney. In adjusted linear regression, cysts on the donated kidney and kidney not donated were not significantly associated with 6-month single-kidney eGFR increase. Among transplants, 17% used a transplanted kidney with a cyst and 6% were from donors with cysts only on the kidney not transplanted. There was no association between donor cyst group and post-transplant death-censored graft survival. Results were similar in sensitivity analyses comparing transplants using kidneys with no cysts versus 1-2 cysts versus ≥3 cysts., Conclusions: Kidney cysts in living kidney donors were not associated with donor kidney recovery or recipient allograft longevity, suggesting incidental kidney cysts need not be taken into account when determining living donor candidate suitability or the laterality of planned donor nephrectomy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Chart review as the current gold standard for phenotype evaluation cannot support observational research on electronic health records and claims data sources at scale. We aimed to evaluate the ability of structured data to support efficient and interpretable phenotype evaluation as an alternative to chart review., Materials and Methods: We developed Knowledge-Enhanced Electronic Profile Review (KEEPER) as a phenotype evaluation tool that extracts patient's structured data elements relevant to a phenotype and presents them in a standardized fashion following clinical reasoning principles. We evaluated its performance (interrater agreement, intermethod agreement, accuracy, and review time) compared to manual chart review for 4 conditions using randomized 2-period, 2-sequence crossover design., Results: Case ascertainment with KEEPER was twice as fast compared to manual chart review. 88.1% of the patients were classified concordantly using charts and KEEPER, but agreement varied depending on the condition. Missing data and differences in interpretation accounted for most of the discrepancies. Pairs of clinicians agreed in case ascertainment in 91.2% of the cases when using KEEPER compared to 76.3% when using charts. Patient classification aligned with the gold standard in 88.1% and 86.9% of the cases respectively., Conclusion: Structured data can be used for efficient and interpretable phenotype evaluation if they are limited to relevant subset and organized according to the clinical reasoning principles. A system that implements these principles can achieve noninferior performance compared to chart review at a fraction of time., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains., (Copyright © 2023 [Author/Employing Institution]. Published by Elsevier Inc. All rights reserved.)

Cervical cancer (Cacx) is the second and endometrial cancer (Ec) is the third most common gynecological cancer worldwide. The present study aims to understand the complex and unexplored conditions occurring in cervix and endometrium of the female genital tract caused due to the infection of the human papilloma viruses (HPVs) and Chlamydia trachomatis (CT). A total of 300 tissue biopsy samples of cervix and endometrium were included in the present study and tested for the presence of HPV and CT deoxyribonucleic acid (DNA) by using polymerase chain reaction (PCR) technique. The odds ratios and 95% confidence interval were considered for the calculation of the association of HPV and CT infection with the risk of cervical or Ec. Among endometrial patients, samples were 5% positive for HPV and 5% positive for CT infection. Among endometrial control group, no sample was found positive for either HPV or CT infection. Among cervical patients, 72% samples were positive for only HPV infection and 1% samples were positive for only CT infection. Among control group, 7% of samples were positive for only HPV infection and 3% were positive for only CT infection. The co-infection of CT with HPV in 9% of Cacx cases and in 2% of cervical control samples was also observed. This is the first study in Indian women to detect the prevalence of HPV and CT infections in endometrium cases and control. An updated estimate regarding the HPV and CT prevalence in cervix cases and control samples was also provided.