Search Results (299)

Porcine lymphotropic herpesviruses -1, -2, and -3 (PLHV-1, PLHV-2, and PLHV-3) are gammaherpesviruses that are widespread in pigs. These viruses are closely related to the human pathogens Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), both of which are known to cause severe diseases in humans. To date, however, no definitive association has been established between PLHVs and any disease in pigs. With the growing interest in xenotransplantation as a means to address the shortage of human organs for transplantation, the safety of using pig-derived cells, tissues, and organs is under intense investigation. In preclinical trials involving pig-to-nonhuman primate xenotransplantation, another porcine herpesvirus—porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV)—was shown to be transmissible and significantly reduced the survival time of the xenotransplants. In the present study, we examined donor pigs and their respective baboon recipients, all of which were part of preclinical pig heart xenotransplantation studies, for the presence of PLHV. PLHV-1, PLHV-2, and PLHV-3 were detected in nearly all donor pigs; however, no evidence of PLHV transmission to the baboon recipients was observed. Full article

Skeletal muscle regeneration requires a reliable source of myogenic progenitor cells capable of forming new fibers and creating a self-renewing satellite cell pool. Human induced pluripotent stem cell (hiPSC)-derived teratomas have emerged as a novel in vivo platform for generating skeletal myogenic progenitors, although in vivo studies to date have provided only an early single-time-point snapshot. In this study, we isolated a specific population of CD82⁺ ERBB3⁺ NGFR⁺ cells from human iPSC-derived teratomas and verified their long-term in vivo regenerative capacity following transplantation into NSG-mdx^4Cv mice. Transplanted cells engrafted, expanded, and generated human Dystrophin⁺ muscle fibers that increased in size over time and persisted stably long-term. A dynamic population of PAX7⁺ human satellite cells was established, initially expanding post-transplantation and declining moderately between 4 and 8 months as fibers matured. MyHC isoform analysis revealed a time-based shift from embryonic to neonatal and slow fiber types, indicating a slow progressive maturation of the graft. We further show that these progenitors can be cryopreserved and maintain their engraftment potential. Together, these findings give insight into the evolution of teratoma-derived human myogenic stem cell grafts, and highlight the long-term regenerative potential of teratoma-derived human skeletal myogenic progenitors. Full article

Background and Objectives: Glucose instability has been established to be related to postoperative morbidity and mortality in liver transplantation. To date, the impact of maintaining optimal blood glucose (BG) levels on the incidence of acute kidney injury (AKI) following liver transplantation (LT) remains unclear. This study aimed to determine the impact of optimal BG level after reperfusion (REP BG) on the incidence of AKI after living donor LT (LDLT). Materials and Methods: This study retrospectively reviewed 3331 patients who underwent LDLT between January 2008 and December 2019. Patients were divided into optimal (110 mg/dL < BG < 180 mg/dL) and non-optimal (BG < 110 mg/dL or >180 mg/dL) REP BG groups. Multivariable logistic regression analysis was performed to assess factors associated with AKI. Propensity score matching (PSM) was used to compare the incidence of AKI, AKI severity, and progression to chronic kidney disease (CKD) between the groups. Results: The incidence of AKI was 66.7%. After PSM, patients in the optimal REP BG group showed a lower incidence of AKI (66.5% vs. 70.6%, p = 0.032). Multivariable logistic regression analysis showed that the non-optimal REP BG group was independently associated with a higher risk of AKI (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.02–1.45; p = 0.037) compared to the optimal group. Similarly, the risks of severe AKI (OR, 1.32; 95% CI, 1.11–1.58; p = 0.002) and progression to CKD (OR, 1.19; 95% CI, 1.01–1.41; p = 0.039) were significantly higher in the non-optimal group after PSM. Conclusions: Maintenance of an optimal REP BG was associated with a significantly lower incidence of AKI and a reduced risk of progression to CKD within 1 year after LDLT. Full article

The discovery that human beings may endogenously produce ethanol is not new and dates back at the end of the 19th century; recently, however, it has become clear that through the proliferation of gut microorganisms that produce ethanol from sugars or other substrates, blood alcohol level may be greater than 0, despite Homo sapiens sapiens lacking the enzymatic pathways to produce it. Very rarely this can lead to symptoms and/or to a disease, named gut fermentation syndrome or auto-brewery syndrome (ABS). The list of microorganisms (mostly bacteria and fungi) is very long and contains almost 100 different strains, and many metabolic pathways are involved. Endogenous ethanol production is a neglected entity, but it may be suspected in patients in whom ethanol consumption may be firmly excluded. Nevertheless, due to the growing prevalence of NAFLD (now renamed as MAFLD) worldwide, an ethanol-producing microorganism responsible for endogenous ethanol production such as Klebsiella pneumoniae or Saccharomices cerevisiae is increasingly sought in NAFLD patients, or in patients with metabolic diseases such as diabetes mellitus, obesity, or metabolic syndrome, at least in selected instances. In the absence of standard diagnostic and therapeutic guidelines, ABS requires a detailed patient history, including dietary habits, alcohol consumption, and gastrointestinal symptoms, and a comprehensive physical examination to detect unexplained ethanol intoxication. It has been proposed to start the diagnostic protocol with a standardized carbohydrate challenge test, followed, if positive, by the use of antifungal agents or antibiotics; indeed, fecal microbiota transplantation might be the only way to cure a patient with refractory ABS. Scientific societies should produce internationally agreed recommendations for ABS and other conditions linked to excessive endogenous ethanol production. Full article

Intergovernmental Panel on Climate Change (IPCC) guidelines have been standardized and widely used to calculate methane (CH₄) emissions from paddy fields. The emission factor (EF) is a key parameter in these guidelines, and it is different for each location globally and regionally. However, limited studies have been conducted to measure locally specific EFs (EFlocal) through on-site assessments and modeling their spatial distribution effectively. This study aims to investigate the potential of multisensor satellite data to develop a spatial model of CH₄ emission estimation on rice paddy fields under different water management practices, i.e., continuous flooding (CF) and alternate wetting and drying (AWD) in Subang, West Java, Indonesia. The model employed the national EF (EFnational) and EFlocal using the IPCC guidelines. In this study, we employed the multisensor satellite data to derive the key parameters for estimating CH₄ emission, i.e., rice cultivation area, rice age, and EF. Optical high-resolution images were used to delineate the rice cultivation area, Sentinel-1 SAR imagery was used for identifying transplanting and harvesting dates for rice age estimation, and ALOS-2/PALSAR-2 was used to map the water regime for determining the scaling factor of the EF. The closed-chamber method has been used to measure the daily CH₄ flux rate on the local sites. The results revealed spatial variability in CH₄ emissions, ranging from 1–5 kg/crop/season to 20–30 kg/crop/season, depending on the water regime. Fields under CF exhibited higher CH₄ emissions than those under AWD, underscoring the critical role of water management in mitigating CH₄ emissions. This study demonstrates the feasibility of combining remote sensing data with the IPCC model to spatially estimate CH₄ emissions, providing a robust framework for sustainable rice cultivation and greenhouse gas (GHG) mitigation strategies. Full article

Dikili Tash is a Neolithic settlement that lies next to the ruins of the ancient city of Philippi on the north-eastern part of Greece. A recent archaeological excavation has unearthed charred grapevine pips and pressings together with two-handed clay cups, jugs, and jars that date to 4300 BC. The majority of the pips were found to be Vitis vinifera ssp. sylvestris. Natural populations of this species have been localized in the valley surrounding Dikili Tash and also on Mt Pangaion and Mt Lekani, which flank the valley. Fifty-one samples from these modern populations have been analyzed using microsatellites on twenty microsatellite loci, and a dendrogram has been constructed showing the genetic closeness of the samples analyzed. Cuttings from all the vines analyzed are currently rooted and grown in the Hellenic Agricultural Organization—DIMITRA (ELGO-DIMITRA) greenhouse facilities in Lykovryssi (Athens) with the aim to, eventually, be transplanted in the grapevine, thus establishing the first V. sylvestris ex situ conservation site in Greece. Full article

Post-transplant lymphoproliferative disorders (PTLD) represent a life-threatening complication following solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in patients with relapsed or refractory (R/R) disease, where therapeutic options are limited and prognosis is poor. Among emerging strategies, adoptive cellular immunotherapy—specifically Epstein–Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)—significantly improved outcomes in this challenging patient population. EBV-CTLs restore virus-specific immunity and induce sustained remissions with minimal toxicity, even in heavily pretreated individuals. The most promising cellular product to date is tabelecleucel, an off-the-shelf, allogeneic EBV-specific T-cell therapy, which is currently the only cellular therapy approved by the European Medicines Agency (EMA) for the treatment of R/R EBV-positive PTLD following SOT or allo-HSCT. This review aims to provide an overview of PTLD treatment with a specific focus on adoptive cellular immunotherapy. We highlight the most robust clinical outcomes reported with EBV-CTLs, particularly those achieved with tabelecleucel, and explore emerging cellular approaches such as CAR T-cell therapy, which may further broaden therapeutic strategies in the near future. Full article

The Luminex multiplex assay for the definition of HLA antibodies was introduced 20 years ago. To date, although the assay is simple and straightforward, the interpretation of the results remains a conundrum. Making use of the so-called mean fluorescence value only does not help since this value is relative, the day-to-day variation is significantly large, and the user variation is beyond acceptable ranges. Within the same range of problems, the cutoff value used to classify HLA-specific antibodies as being either present or absent varies between laboratories. This threshold influences clinical decision-making. In addition, the readout value is used to diagnose the amount of HLA-specific antibodies after treatments like absorption, plasmapheresis, or transplantation, overlooking the relative nature of the value. In this study, we show bead variability for HLA class I and HLA class II based on negatively defined bead reactions with a mean fluorescence value below 1500 and self-antigens. In an effort to circumvent the assay’s inherent problems, we introduced the term ratio. For each serum sample, a paired sample from before the treatment is run in parallel. The ratio of post-treatment to pre-treatment can then be used to characterize antibody dynamics: a ratio above 1 reflects increased antibody production and a ratio below 1 indicates a decrease in antibodies in the serum. This value may offer the possibility to make more informed and adaptive treatment decisions. Full article

Background: The potential therapeutic role of fecal microbiota transplantation (FMT) in various diseases has been thoroughly studied over the last few decades. However, the majority of studies focus on the adult population, therefore, conclusions regarding the application of FMT in the pediatric population are much less clear. This systematic review aims to summarize the research conducted so far on the efficacy and safety of FMT in the pediatric population, assess the quality of the evidence of its effectiveness, and outline the most promising areas for future research. Methods: We performed a systematic literature search from the index date to 8 June 2024 on the Embase, PubMed, and Web of Science databases. One author screened the resulting 121 articles. Eventually, 35 eligible studies that reported FMT use in seven different diseases were identified. Results: All of the studies assessed FMT as a safe procedure without many serious adverse effects. The best-documented application, which is the only one recommended in official guidelines, is recurrent Clostridioides difficile infection. Other disease entities in which the use of FMT has been studied with good clinical effects are inflammatory bowel disease, allergic colitis, autism, Tourette syndrome, and colonization with multi-drug-resistant organisms. However, it should be noted that the majority of studies are cohort and case-control studies, without randomization, which translates into low evidence quality. In one randomized, controlled trial focusing on the effect of FMT on weight loss in obese individuals, a lack of effect was found. Conclusions: While FMT and subsequent iterations of gut microbiota-targeted interventions hold promising therapeutic potential for various disease entities in the pediatric population, the current evidence behind this conclusion is of low quality. Based on current studies, these methods appear to be both effective and safe. However, further randomized clinical trials are necessary, especially within the pediatric population, for which such studies remain scarce. Full article

Premature white matter injury (PWMI) represents the principal form of brain injury in preterm infants, and effective therapies remain elusive. Transplantation of oligodendrocyte precursor cells (OPCs) emerges as a potential treatment for PWMI, yet the injury-induced inflammatory response may impact these cells’ functionality. To date, no studies have explored the influence of inflammatory factors on the functionality of human (h) OPCs. The predominant inflammatory cytokines identified in PWMI lesions are tumor necrosis factor (TNF)-α and interleukin (IL)-1β. This study investigates the impact of these cytokines on hOPC migration, proliferation, and differentiation using the human adult neural stem cell amplification and differentiation system in vitro. Results indicate that IL-1β significantly impedes hOPC migration, while both TNF-α and IL-1β hinder proliferation and differentiation. In summary, inflammatory factors overexpressed following PWMI impede OPCs from realizing their regenerative potential. These findings underscore the necessity of modulating the post-PWMI inflammatory milieu to enhance the efficacy of transplanted cells concerning migration, proliferation, and differentiation. Full article

Background/Objectives: Although kidney transplant recipients (KTRs) who are immune-compromised have been shown to be at high risk of adverse acute COVID-19 outcomes (i.e., mortality and critical illness), the long-term outcomes of KTRs with a history of SARS-CoV-2 infection are unknown. We aimed to compare long-term outcomes of KTRs with and without exposure to SARS-CoV-2. Methods: This study retrospectively evaluated 1815 KTRs in the Montefiore Health System from 4 January 2001 to 31 January 2024. The final cohorts consisted of KTRs who survived COVID-19 (n = 510) and matched KTRs without COVID-19 (n = 510, controls). Outcomes were defined as all-cause mortality and changes in estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (UPCR) from 30 days up to four years post index date. Kaplan–Meier survival analysis and Cox proportional modeling were performed for mortality. Generalized estimating equations were used to analyze changes in eGFR and UPCR across time. Results: There was no significant group difference in long-term all-cause mortality (adjusted hazard ratio = 0.66, [0.43, 1.01] p = 0.057). eGFR in controls and COVID-19 patients before infection similarly decreased −0.98 units/year [−1.50, −0.46]. By contrast, eGFR declined at a significantly greater rate (−1.80 units/year [−2.45, −1.15]) in KTRs after COVID-19 compared to KTRs without COVID-19. This association was only seen among male and not female KTRs. COVID-19 status was not significantly associated with rate of change in UPCR or acute kidney rejection rate. Conclusions: SARS-CoV-2 infection was associated with an accelerated decline in eGFR up to four years post infection, suggesting potential long-term implications for graft health. These findings underscore the importance of vigilant monitoring and management of kidney function post SARS-CoV-2 infection in this vulnerable population. Full article

Human cytomegalovirus (HCMV) is a critical pathogen in immunocompromised populations, such as organ transplant recipients as well as congenitally infected neonates with immature immune systems. Despite decades of research and the growing financial burden associated with the management of HCMV, there is no licensed vaccine to date. In this review, we aim to outline the complexity of HCMV and the antigens it presents and the journey and challenges of developing an effective HCMV vaccine, as well as further highlight the recent analyses of the most successful vaccine candidate so far—gB/MF59. Full article

Breastfeeding after kidney transplantation remains a complex and underexplored topic, primarily due to concerns regarding the safety of immunosuppressive therapies during lactation. Individuals who have received kidney transplants face a higher likelihood of delivering preterm infants and giving birth to babies with a low birth weight when compared with the general population. In this context, breastfeeding is increasingly important because of its advantages for preterm infants. Despite the well-established benefits of breastfeeding for both the mother and infant, the traditional recommendation has been to avoid nursing due to potential drug transmission through breast milk. However, emerging evidence suggests that certain immunosuppressants may be compatible with breastfeeding, challenging long-standing clinical guidelines. In this review, we examine the current literature on the pharmacokinetics, safety profiles, and clinical outcomes associated with key immunosuppressive agents, including cyclosporine, tacrolimus, everolimus, azathioprine, corticosteroids, and belatacept. Our work highlights that all published reports to date on the studied treatments indicate that the amount of the drug reaching breast milk is considered safe for the child’s health. These conclusions, however, are derived from very short-term measurements and small numbers of patients. Therefore, we emphasize the need to design structured prospective studies to assess safety in the medium and long term. Our review aims to equip clinicians with the most up-to-date evidence on this topic, enabling them to make informed decisions regarding the compatibility of post-kidney transplant treatments with breastfeeding. Full article

There is still an unmet need for the treatment of high-risk hematological malignancies. To date, allogeneic stem cell transplantation remains the only chance of cure. Most patients suffering from high-risk hematological malignancies are of an older age and often present with comorbidities. Moreover, patients achieving remission often suffer from early relapse. Amongst the different treatment options, sequential conditioning has yet to prove its value against other conditioning regimens. Sequential conditioning relies on a short course of intensive chemotherapy that is quickly followed by immunosuppressive conditioning before allogeneic stem cell transplantation. Here, we will try to determine which patients can benefit from sequential conditioning. Amongst the different sequential regimens, we will also try to assess if one regimen is better than all the others. Despite the several studies conducted on sequential conditioning, very few are prospective work and head-to-head comparisons are almost inexistant. Sequential conditioning also relies on the use of prophylactic donor lymphocyte infusion post-transplantation. Hence, limiting non-relapse complications is of primary importance to the allow administration of post-transplant treatment. In the era of new targeting therapies, is there still a place for sequential conditioning? Can patients benefit from an association of new therapeutic agents and sequential conditioning? Full article

Cardiovascular disease (CVD) remains the leading cause of death globally, with myocardial infarction (MI) being a major contributor. The current therapeutic approaches are limited in effectively regenerating damaged cardiac tissue. Up-to-date strategies for heart regeneration/reconstitution aim at cardiac remodeling through repairing the damaged tissue with an external cell source or by stimulating the existing cells to proliferate and repopulate the compromised area. Cell reprogramming is addressed to this challenge as a promising solution, converting fibroblasts and other cell types into functional cardiomyocytes, either by reverting cells to a pluripotent state or by directly switching cell lineage. Several strategies such as gene editing and the application of miRNA and small molecules have been explored for their potential to enhance cardiac regeneration. Those strategies take advantage of cell plasticity by introducing reprogramming factors that regress cell maturity in vitro, allowing for their later differentiation and thus endorsing cell transplantation, or promote in situ cell proliferation, leveraged by scaffolds embedded with pro-regenerative factors promoting efficient heart restoration. Despite notable advancements, important challenges persist, including low reprogramming efficiency, cell maturation limitations, and safety concerns in clinical applications. Nonetheless, integrating these innovative approaches offers a promising alternative for restoring cardiac function and reducing the dependency on full heart transplants. Full article