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Kidney transplantation significantly improves the survival of patients with end-stage kidney disease (ESKD) compared to other forms of kidney replacement therapy. However, kidney transplant recipients' outcomes are not fully satisfactory due to increased risk of cardiovascular diseases, infections, and malignancies. Immune-related complications remain the biggest challenge in the management of kidney graft recipients. Despite the broad spectrum of immunosuppressive agents available and more detailed methods used to monitor their effectiveness, chronic allograft nephropathy remains the most common cause of kidney graft rejection. The kynurenine (KYN) pathway is the main route of tryptophan (Trp) degradation, resulting in the production of a plethora of substances with ambiguous properties. Conversion of Trp to KYN by the enzyme indoleamine 2,3-dioxygenase (IDO) is the rate-limiting step determining the formation of the next agents from the KYN pathway. IDO activity, as well as the production of subsequent metabolites of the pathway, is highly dependent on the balance between pro- and anti-inflammatory conditions. Moreover, KYN pathway products themselves possess immunomodulating properties, e.g., modify the activity of IDO and control other immune-related processes. KYN metabolites were widely studied in neurological disorders but recently gained the attention of researchers in the context of immune-mediated diseases. Evidence that this route of Trp degradation may represent a peripheral tolerogenic pathway with significant implications for transplantation further fueled this interest. Our review aimed to present recent knowledge about the role of the KYN pathway in the pathogenesis, diagnosis, monitoring, and treatment of kidney transplant recipients' complications. [ABSTRACT FROM AUTHOR]

The QuantiFERON CMV (QCMV) test evaluates specific adaptive immune system activity against CMV by measuring IFN-γ released by activated CD8+ T lymphocytes. We aimed to evaluate the QCMV test as a predictive tool for CMV manifestations and acute or chronic lung allograft rejection (AR and CLAD) in lung transplant (LTx) patients. A total of 73 patients were divided into four groups based on donor and recipient (D/R) serology for CMV and QCMV assay: group A low-risk for CMV infection and disease (D−/R−); group B and C at intermediate-risk (R+), group B with non-reactive QCMV and group C with reactive QCMV; group D at high-risk (D+/R−). Group D patients experienced higher viral replication; no differences were observed among R+ patients of groups B and C. D+/R− patients had a higher number of AR events and group C presented a lower incidence of AR. Prevalence of CLAD at 24 months was higher in group B with a higher risk of CLAD development (OR 6.33). The QCMV test allows us to identify R+ non-reactive QCMV population as the most exposed to onset of CLAD. This population had a higher, although non-significant, susceptibility to AR compared to the R+ population with reactive QCMV. [ABSTRACT FROM AUTHOR]

The proteasome generates the majority of peptides presented on MHC class I molecules. The cleavage pattern of the proteasome has been shown to be changed via the proteasome activator (PA)28 alpha beta (PA28αβ). In particular, several immunogenic peptides have been reported to be PA28αβ-dependent. In contrast, we did not observe a major impact of PA28αβ on the generation of different major histocompatibility complex (MHC) classI ligands. PA28αβ-knockout mice infected with the lymphocytic choriomeningitis virus (LCMV) or vaccinia virus showed a normal cluster of differentiation (CD) 8 response and viral clearance. However, we observed that the adoptive transfer of wild-type cells into PA28αβ-knockout mice led to graft rejection, but not vice versa. Depletion experiments showed that the observed rejection was mediated by CD8+ cytotoxic T cells. These data indicate that PA28αβ might be involved in the development of the CD8+ T cell repertoire in the thymus. Taken together, our data suggest that PA28αβ is a crucial factor determining T cell selection and, therefore, impacts graft acceptance. [ABSTRACT FROM AUTHOR]

Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and the latter's association with transplant outcomes. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR) according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and the graft outcome. Differential expression (false discovery rate (FDR) < 0.01, fold (change (FC) > 3) between normal and rejection biopsies yielded a set of 111 genes. In the protocol biopsy cohort (n = 137), 19 out of these 111 genes correlated with tacrolimus trough levels at the time of biopsy (TAC-C0), and unsupervised analysis split this cohort into two clusters. The two clusters differed in donor age and tacrolimus trough levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72–0.06, p = 0.0117) was associated with cluster 2. In a follow-up averaging 70 ± 30 months, this patient group displayed a significant decline in renal function (p = 0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function. [ABSTRACT FROM AUTHOR]

Radar Automatic Target Recognition (RATR) based on high-resolution range profile (HRRP) has received intensive attention in recent years. In practice, RATR usually needs not only to recognize in-library samples but also to reject out-of-library samples. However, most rejection methods lack a specific and accurate description of the underlying distribution of HRRP, which limits the effectiveness of the rejection task. Therefore, this paper proposes a novel rejection method for HRRP, named Deep Multi-modal Support Vector Data Description (DMMSVDD). On the one hand, it forms a more compact rejection boundary with the Gaussian mixture model in consideration of the high-dimensional and multi-modal structure of HRRP. On the other hand, it captures the global temporal information and channel-dependent information with a dual attention module to gain more discriminative structured features, which are optimized jointly with the rejection boundary. In addition, a semi-supervised extension is proposed to refine the boundary with available out-of-library samples. Experimental results based on measured data show that the proposed methods demonstrate significant improvement in the HRRP rejection performance. [ABSTRACT FROM AUTHOR]

HLA donor-specific antibodies (DSAs) pre and post transplant increase the risk of antibody-mediated rejection (AMR) and lead to poor graft survival. Increasing data exist to support the involvement of non-HLA antibodies in triggering an immunological response. The development of non-HLA antibodies specific for AT1R is associated with poor clinical outcomes in orthotopic heart transplant recipients. This case presents an investigation of non-HLA antibodies in a 56-year-old female heart transplant recipient diagnosed with AMR in the absence of DSAs. [ABSTRACT FROM AUTHOR]

Adolescent mothers experience psychological challenges, such as social withdrawal and rejection by their communities. Assuming the role of motherhood is associated with emotional and mental distress, such as fear and worry, regret and frustration, guilt and shame, and social isolation. This study adopted a qualitative critical participatory action research approach. Purposive and snowballing recruitment were employed to recruit 11 teenage mothers, and semi-structured face-to-face interviews and focus group discussions were employed to generate data. All sessions were audio recorded and transcribed verbatim. Data were analysed using qualitative thematic analysis. Teenage mothers in this study reported experiencing humiliation and being subjected to degrading remarks and judgement by schoolmates. The experience of being rejected, teased, and labelled made participants feel that they were not accepted as part of their community. It was concluded that teenage mothers experienced inconsistent support from parents and community members, which led to social isolation and feeling rejected; hence, teenage mothers lacked a sense of belonging to and acceptance by their communities. Policymakers and authorities in education and healthcare should encourage social change and transformative learning and address the issue of stigma and social isolation experienced by teenage mothers in rural communities. [ABSTRACT FROM AUTHOR]

The use of intraoperative mechanical support during lung transplantation has traditionally been a controversial topic. Trends for intraoperative mechanical support strategies swing like a pendulum. Historically, cardiopulmonary bypass (CPB) was the modality of choice during transplantation. It provides full hemodynamic support including oxygenation and decarboxylation. Surgical exposure is improved by permitting the drainage of the heart and provides more permissive retraction. CPBs contain drainage reservoirs with hand-held pump suction catheters promoting blood conservation through collection and re-circulation. But CPB has its disadvantages. It is known to cause systemic inflammation and coagulopathy. CPB requires high doses of heparinization, which increases bleeding risks. As transplantation progressed, off-pump transplantation began to trend as a preferable option. ECMO, however, has many of the benefits of CPB with less of the risk. Outcomes were improved with ECMO compared to CPB. CPB has a higher blood transfusion requirement, a higher need for post-operative ECMO support, a higher re-intubation rate, high rates of kidney injury and need for hemodialysis, longer ICU stays, higher incidences of PGD grade 3, as well as overall in-hospital mortality when compared with ECMO use. The focus now shifts to using intraoperative mechanical support to protect the graft, helping to reduce ischemia-reperfusion injury and allowing for lung protective ventilator settings. Studies show that the routine use of ECMO during transplantation decreases the rate of primary graft dysfunction and many adverse outcomes including ventilator time, need for tracheostomy, renal failure, post-operative ECMO requirements, and others. As intraoperative planned ECMO is considered a safe and effective approach, with improved survival and better overall outcomes compared to both unplanned ECMO implementation and off-pump transplantation, its routine use should be taken into consideration as standard protocol. [ABSTRACT FROM AUTHOR]

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring. [ABSTRACT FROM AUTHOR]

Introduction: The optimal treatment for Secondary Pulmonary Hypertension from End-Stage Lung Disease remains controversial. Double Lung Transplantation is widely regarded as the treatment of choice as it eliminates all diseased parenchyma and introduces a large volume of physiologically normal allograft. By comparison, the role of single lung transplantation for pulmonary hypertension (PAH) is less clear. The remaining diseased lung will limit clinical improvements and permit downstream sequelae; including residual cough, recurrent infection, and continued pulmonary hypertension. But not every patient can undergo DLT. Advanced age, frailty, co-morbid conditions, and limited availability of organs will all affect surgical candidacy and can offset the benefits of double lung procedures. Studies that compare SLT and DLT do not commonly explore the utility of single lung procedures even though multiple theoretical advantages exist; including reduced waiting times, less waitlist mortality, fewer surgical complications, and lower operative mortality. Worse, multiple forms of publication and selection bias may favor DLT in registry-based studies. In this review, we present the prevailing literature on single and double lung transplants in patients with secondary pulmonary hypertension and clarify the potential utility of these procedures. Materials and Methods: A PubMed search for English-language articles exploring single and double lung transplants in the setting of secondary pulmonary hypertension was conducted from 1990 to 2023. Key words included "single lung transplant", "double lung transplant", "pulmonary hypertension", "rejection", "complications", "extracorporeal membranous oxygenation", "death", and all appropriate Boolean operators. We prioritized research from retrospective studies that evaluated clinical outcomes from single centers. Conclusions: The question is not whether DLT is better at resolving lung disease; instead, we must ask if SLT is an acceptable form of therapy in a select group of high-risk patients. Further research should focus on how best to identify recipients that may benefit from each type of procedure, and the clinical utility of perioperative VA ECMO. [ABSTRACT FROM AUTHOR]

Biological valve failure (BVF) is an inevitable condition that compromises the durability of biological heart valves (BHVs). It stems from various causes, including rejection, thrombosis, and endocarditis, leading to a critical state of valve dysfunction. Echocardiography, cardiac computed tomography, cardiac magnetic resonance, and nuclear imaging play pivotal roles in the diagnostic multimodality workup of BVF. By providing a comprehensive overview of the pathophysiology of BVF and the diagnostic approaches in different clinical scenarios, this review aims to aid clinicians in their decision-making process. The significance of early detection and appropriate management of BVF cannot be overstated, as these directly impact patients' prognosis and their overall quality of life. Ensuring timely intervention and tailored treatments will not only improve outcomes but also alleviate the burden of this condition on patients' life. By prioritizing comprehensive assessments and adopting the latest advancements in diagnostic technology, medical professionals can significantly enhance their ability to manage BVF effectively. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are emerging as a promising field of research in liver disease. EVs are small, membrane-bound vesicles that contain various bioactive molecules, such as proteins, lipids, and nucleic acids and are involved in intercellular communication. They have been implicated in numerous physiological and pathological processes, including immune modulation and tissue repair, which make their use appealing in liver transplantation (LT). This review summarizes the current state of knowledge regarding the role of EVs in LT, including their potential use as biomarkers and therapeutic agents and their role in graft rejection. By providing a comprehensive insight into this emerging topic, this research lays the groundwork for the potential application of EVs in LT. [ABSTRACT FROM AUTHOR]

Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx®) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specified time intervals by utilizing creatinine (SCr), proteinuria, donor-specific antibodies (DSAs), and dd-cfDNA. A clinically indicated biopsy sample was sent for histopathology and MMDx®. Patients were categorized into rejection (Rej) and non-rejection (NRej) groups, and further grouped according to antibody-mediated rejection (ABMR) subtypes. Rej and NRej groups included 52 and 37 biopsies, respectively. Median follow-up duration was 506 days. DSAs were positive in 53% and 22% of patients in both groups, respectively (p = 0.01). Among these groups, pre- and post-intervention median SCr, proteinuria, and dd-cfDNA at 1 month, 2 months, and at the last follow-up revealed significant difference for dd-cfDNA (all p = 0.01), however, no difference was found for SCr and proteinuria (p > 0.05). The AUC was 0.80 (95% CI: 0.69–0.91), with an optimal dd-cfDNA criterion of 2.2%. Compared to histology, MMDx® was more likely to diagnose ABMR (79% vs. 100%) with either C4d positivity or negativity and/or DSA positivity or negativity. Hence, a pre- and post-intervention allograft monitoring protocol in combination with dd-cfDNA, MMDx®, and histology has aided in early diagnosis and timely individualized intervention. [ABSTRACT FROM AUTHOR]

Despite significant advancements in immunosuppressive therapies, kidney transplant rejection continues to pose a substantial challenge, impacting the long-term survival of grafts. This article provides an overview of the diagnosis, current therapies, and management strategies for acute T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). TCMR is diagnosed through histological examination of kidney biopsy samples, which reveal the infiltration of mononuclear cells into the allograft tissue. Corticosteroids serve as the primary treatment for TCMR, while severe or steroid-resistant cases may require T-cell-depleting agents, like Thymoglobulin. ABMR occurs due to the binding of antibodies to graft endothelial cells. The most common treatment for ABMR is plasmapheresis, although its efficacy is still a subject of debate. Other current therapies, such as intravenous immunoglobulins, anti-CD20 antibodies, complement inhibitors, and proteasome inhibitors, are also utilized to varying degrees, but their efficacy remains questionable. Management decisions for ABMR depend on the timing of the rejection episode and the presence of chronic changes. In managing both TCMR and ABMR, it is crucial to optimize immunosuppression and address adherence. However, further research is needed to explore newer therapeutics and evaluate their efficacy. [ABSTRACT FROM AUTHOR]

Complement activation by HLA antibodies is a key component of immune-mediated graft injury. We examined the clinical outcomes of kidney transplant recipients with complement-fixing de novo donor-specific antibodies (dnDSA) who were followed in our center. The C1q-binding ability was retrospectively assessed in 69 patients with dnDSA and mean fluorescence intensity (MFI) values > 2000 out of the 1325 kidney transplant recipients who were screened for DSA between 2015 and 2019. Luminex IgG single antigen beads (SAB)and C1q-SAB assays (One Lambda) were used. C1q-binding dnDSA was identified in 32/69 (46.4%) of the patients. Significantly higher MFI values were observed in C1q-positive DSA (18,978 versus 5840, p < 0.001). Renal graft biopsies were performed in 43 of the kidney transplant recipients (62.3%) with allograft dysfunction. Antibody-mediated rejection (ABMR) was detected in 29/43 (67.4%) of the patients. The incidence of ABMR was similar among patients with C1q-binding and non-C1q-binding DSA (51.7% vs. 48.3%, p = 0.523). Graft loss occurred in 30/69 (43.5%) of the patients at a median time of 82.5 months (IQR 45–135) from DSA detection. C1q-binding DSA was present in more patients who experienced graft loss (53.1% vs. 35.1%, p = 0.152). Higher MFI values and inferior clinical outcomes occurred in most of the kidney transplant recipients with C1q-binding dnDSA. [ABSTRACT FROM AUTHOR]

The risk of losing a transplanted organ is high, and non-invasive markers to warn of this phenomenon are still being sought. We investigated the impact of post-transplant microchimerism on the function of the transplanted kidney. The study included 100 kidney transplant recipients, mostly women. All transplanted organs were from opposite-sex deceased donors. Microchimerism was assessed using multiplex PCR. Male DNA was detected in all urine samples from female recipients and in 13/56 blood samples from female kidney recipients. Female DNA was found in 31/44 urine samples from male recipients, but in none of the blood samples. Microchimerism in the urine of female recipients correlated positively with blood urea (Rs = 0.45; p = 5.84 × 10−4) and K+ ions (Rs = 0.29; p = 0.03), while microchimerism in the blood of female recipients also correlated positively with blood urea (Rs = 0. 28; p = 0.04), cystatin C (Rs = 0.31; p = 0.02) and the number of incompatible HLA alleles (Rs = 0.42; p = 0.01). A history of DGF was associated with higher urinary donor DNA concentrations in female recipients.: Post-transplant microchimerism may serve as a potential marker of chronic kidney rejection. [ABSTRACT FROM AUTHOR]

Multivisceral transplant (MVTx) refers to a composite graft from a cadaveric donor, which often includes the liver, the pancreaticoduodenal complex, and small intestine transplanted en bloc. It remains rare and is performed in specialist centres. Post-transplant complications are reported at a higher rate in multivisceral transplants because of the high levels of immunosuppression used to prevent rejection of the highly immunogenic intestine. In this study, we analyzed the clinical utility of 28 18F-FDG PET/CT scans in 20 multivisceral transplant recipients in whom previous non-functional imaging was deemed clinically inconclusive. The results were compared with histopathological and clinical follow-up data. In our study, the accuracy of 18F-FDG PET/CT was determined as 66.7%, where a final diagnosis was confirmed clinically or via pathology. Of the 28 scans, 24 scans (85.7%) directly affected patient management, of which 9 were related to starting of new treatments and 6 resulted in an ongoing treatment or planned surgery being stopped. This study demonstrates that 18F-FDG PET/CT is a promising technique in identifying life-threatening pathologies in this complex group of patients. It would appear that 18F-FDG PET/CT has a good level of accuracy, including for those MVTx patients suffering from infection, post-transplant lymphoproliferative disease, and malignancy. [ABSTRACT FROM AUTHOR]

Despite the effectiveness of current vaccines in reducing the spread and severity of SARS-CoV-2 infections, many people, including migrants, refugees, and foreign workers, are hesitant to be vaccinated. This systematic review and meta-analysis (SRMA) was conducted to determine the pooled prevalence estimate of the acceptance and hesitancy rates of the COVID-19 vaccine among these populations. A comprehensive search of the peer-reviewed literature indexed in PubMed, Scopus, Science Direct, and Web of Science databases was conducted. Initially, 797 potential records were identified, of which 19 articles met the inclusion criteria. A meta-analysis of proportions using data from 14 studies revealed that the overall acceptance rate of COVID vaccination among 29,152 subjects was 56.7% (95% CI: 44.9–68.5%), while the prevalence of vaccine hesitancy among 26,154 migrants reported in 12 studies was estimated to be 31.7% (95% CI: 44.9–68.5%). The acceptance rate for the COVID-19 vaccination first declined from 77.3% in 2020 to 52.9% in 2021 and then slightly increased to 56.1% in 2022. The most frequent factors influencing vaccine hesitancy were worries about vaccine efficacy and safety. Intensive vaccination campaigns should be implemented to raise vaccination awareness among migrants, which will increase the acceptance rate for the COVID-19 vaccine and result in herd immunity. [ABSTRACT FROM AUTHOR]

Allo- and autoimmune mechanisms are involved in kidney allograft rejection and loss. This study investigates the impact of anti-angiotensin II type-1 receptor antibodies (anti-AT1RAbs) detected alone or in association with HLA donor-specific antibodies (HLA-DSAs) on the outcome of kidney transplantation (KTx). Anti-AT1RAbs and HLA-DSAs were detected in 71 kidney transplant (KT) recipients who developed biopsy-proven acute or chronic active T-cell rejection (TCMR) (n = 51) or antibody-mediated rejection (ABMR) (n = 20), forming the rejection group (RG). The control group (CG) included 71 KTx recipients with comparable characteristics without rejection. All patients had been transplanted with negative T/B flow crossmatch (T/BFCXM). The median follow-up period was 3.7 years. Antibodies were determined pre- and periodically post-KTx by Luminex method for HLA-DSAs and enzyme-linked immunosorbent assay for anti-AT1RAbs. Before KTx, twenty-three (32.4%) patients in the RG, sixteen with TCMR and seven with ABMR, were found anti-AT1Rabs-positive (≥10 U/mL) versus eleven (15.5%) patients in the CG (p = 0.031). Simultaneous detection of preformed anti-AT1RAbs and HLA-DSAs was found in five patients of the RG versus two of the CG (p = 0.355). At the time of transplant biopsy, fifteen (21.1%) patients, four with ABMR and eleven with TCMR, were positive for anti-AT1RAbs. Anti-AT1RAbs and HLA-DSAs were detected simultaneously in 7/15 (46.7%) cases, three with ABMR and four with TCMR. During the follow-up, thirteen (18.3%) patients in the RG, eight with ABMR and five with TCMR, lost their graft compared to one patient (1.4%) in the CG (p = 0.001). Six out of thirteen (46.2%) RG patients who lost the graft were found positive for anti-AT1RAbs pretransplant. Patient survival with functioning graft did not differ significantly between anti-AT1Rabs-positive and negative KT recipients (log-rank p = 0.88). Simultaneous detection of anti-ATR1Abs and HLA-DSAs did not have a significant influence on patient survival with functioning graft (log-rank p = 0.96). Graft function at the end of the follow-up was better, but not significantly, in anti-AT1Rabs-negative patients, with serum creatinine 1.48 [1.20–1.98] mg/dL and eGFR (CKD-EPI) 48.5 [33.5–59.0] mL/min/1.73 m2, compared to anti-AT1Rabs-positive ones who had serum creatinine 1.65 [1.24–2.02] mg/dL (p = 0.394) and eGFR (CKD-EPI) 47.0 [34.8–60.3] mL/min/1.73 m2 (p = 0.966). Anti-AT1RAbs detection pretransplant characterizes KT recipients at increased risk of cellular or antibody-mediated rejection. Furthermore, anti-AT1RAbs, detected alone or simultaneously with HLA-DSAs, appear to be associated with impaired graft function, but their role in graft survival has not been documented in this study. Screening for these antibodies appears to complement pretransplant immunological risk assessment. [ABSTRACT FROM AUTHOR]

Two types of membranes, for hydrophilic and hydrophobic microfiltration, were prepared as flat sheets to treat a phenol-contaminated water solution. The membranes were fabricated using four synthetic polymers: polysulfone, polyethylene oxide, dimethylacetamide, and N-methyl-2-pyrrolidone. Scanning electron microscope measurements of the top-surface and cross-section images of the produced membranes were used to characterize them physically. Distilled water and water contaminated with phenol were used to evaluate the membrane's performance based on the flux results depending on pressure, the concentration of phenol, and temperature variables. Meanwhile, the rejection performance was evaluated using the phenol-contaminated water solution. The results show that the flux increased with increases in pressure and temperature and decreased with increases in phenol concentration. Distilled water gave far higher results than water contaminated with phenol. The flux of distilled water ranged from 52.18 to 73.15 L/m2/h for the hydrophilic type and from 72.27 to 97.46 L/m2/h for the hydrophobic type, whereas the flux of water contaminated with phenol solution ranged from 26.58 to 61.55 L/m2/h for the hydrophilic type and from 29.98 to 80.55 L/m2/h for the hydrophobic type. Meanwhile, the phenol solution's rejection was 60% when using a hydrophilic membrane, whereas it was only 45% when a hydrophobic membrane was used. The hydrophobic membrane showed high fluxes and low rejection. Thus, transport through this membrane is closer to having viscous behavior than that through the hydrophilic membrane; in contrast, the permeability through the hydrophilic membrane is less because the pore size decreases the viscous flow mechanism. [ABSTRACT FROM AUTHOR]

Kidney transplantation (KT) is the optimal therapeutic strategy for patients with end-stage renal disease. The key to post-transplantation management is careful surveillance of allograft function. Kidney injury may occur from several different causes that require different patient management approaches. However, routine clinical monitoring has several limitations and detects alterations only at a later stage of graft damage. Accurate new noninvasive biomarker molecules are clearly needed for continuous monitoring after KT in the hope that early diagnosis of allograft dysfunction will lead to an improvement in the clinical outcome. The advent of "omics sciences", and in particular of proteomic technologies, has revolutionized medical research. Proteomic technologies allow us to achieve the identification, quantification, and functional characterization of proteins/peptides in biological samples such as urine or blood through supervised or targeted analysis. Many studies have investigated proteomic techniques as potential molecular markers discriminating among or predicting allograft outcomes. Proteomic studies in KT have explored the whole transplant process: donor, organ procurement, preservation, and posttransplant surgery. The current article reviews the most recent findings on proteomic studies in the setting of renal transplantation in order to better understand the effective potential of this new diagnostic approach. [ABSTRACT FROM AUTHOR]

Islet transplantation represents an effective treatment for patients with type 1 diabetes mellitus (T1DM) and severe hypoglycaemia unawareness, capable of circumventing impaired counterregulatory pathways that no longer provide protection against low blood glucose levels. The additional beneficial effect of normalizing metabolic glycaemic control is the minimisation of further complications related to T1DM and insulin administration. However, patients require allogeneic islets from up to three donors, and the long-term insulin independence is inferior to that achieved with solid organ (whole pancreas) transplantation. This is likely due to the fragility of islets caused by the isolation process, innate immune responses following portal infusion, auto- and allo-immune-mediated destruction and β-cell exhaustion following transplantation. This review covers the specific challenges related to islet vulnerability and dysfunction that affect long-term cell survival following transplantation. [ABSTRACT FROM AUTHOR]

Dd-cfDNA is a novel biomarker with many diagnostic applications in various areas of medicine. In this review of the literature, we investigate its role in the diagnosis of many complications that occur in liver transplantations. In our review, we retrieved data from the medical databases PubMed and Scopus. In our bibliography, many areas concerning the contributions of dd-cfDNA to the field of liver transplantation, such as in the diagnosis of complications that include signsof rejection or graft injury, are mentioned. Dd-cfDNA, which are correlated with other biomarkers such as liver enzymes, can have a high diagnostic value. Measurements of Dd-cfDNA also depend on the graft's size and origin; therefore, these data should be taken into account for the estimation and explanation of dd-cfDNA values. Despite the utility of this novel diagnostic technique, it comes with some limitations and applicational exclusions, such as cases where there is a blood relation between the donor and recipient. [ABSTRACT FROM AUTHOR]

The aim of this study is to contribute new knowledge about interactions of power and social pedagogical recognition in narratives of students who use alcohol and drugs in an upper secondary school context. In this context, the student narratives create and re-create a series of images of varied treatment by professional actors (e.g., teachers, student coordinators, counsellors). The reproduced power interactions in narratives describing the practices of professional actors are significant for student learning, teaching, nurturing, inclusion, change, discipline, and identity creation. The social pedagogical recognition of the "other party" in the pupil–professional actor relationship is especially important for achieving the aims of including pupils who use alcohol and drugs in a learning context and enacting positive change through the creation and re-creation of social pedagogical identities (e.g., successful pupil identity) in the upper secondary school context. [ABSTRACT FROM AUTHOR]

There are subtypes within blood type A, termed non-A1, that have reduced expression of A antigen on cell surfaces. This can result in the development of anti-A1 antibodies. There is limited information regarding the impact of this in heart transplant (HTx) recipients. We conducted a single-center cohort study of 142 Type A HTx recipients in which we compared outcomes of a match group (an A1/O heart into an A1 recipient or a non-A1/O heart into a non-A1 recipient) with a mismatch group (an A1 heart into a non-A1 recipient or a non-A1 heart into an A1 recipient). At one year post-transplant, there were no differences between the groups in survival, freedom from non-fatal major adverse cardiovascular events, freedom from any treated rejection, or freedom from cardiac allograft vasculopathy. There was an increased hospital length of stay in the mismatch group (13.5 vs. 17.1 days, p = 0.04). Our study showed that A1 mismatch was not associated with worse outcomes at one year post-HTx. [ABSTRACT FROM AUTHOR]

Simple Summary: Heart transplantation is the gold standard in selected patients with end-stage heart failure. However, immune responses to the transplanted heart can lead to major complications and graft failure, limiting long-term survival. It has been shown that antibodies targeting the heart are elevated in end-stage heart failure patients and before transplantation of the donor heart. We aimed to determine whether elevated antibody levels before heart transplantation are associated with a poor outcome after transplantation. We measured four general subtypes of antibodies (IgM, IgG1, IgG2, IgG3) in the blood of patients just before the transplantation was performed. We observe that patients with higher levels of IgG1 and IgG2 antibodies tend to reject the transplanted heart more often compared to patients with lower levels of these antibodies. In addition, we observe that IgG1 and IgG2 levels in these patients remain elevated after transplantation. Together our data suggest that a more active adaptive, antibody-mediated, immune system can lead to graft-related complications in cardiac transplant patients. This implies that a subpopulation of heart transplant patients might benefit from expanded immunosuppressive therapy, which includes medications targeting antibody-producing cells. Cardiac allograft vasculopathy (CAV) and antibody-mediated rejection are immune-mediated, long-term complications that jeopardize graft survival after heart transplantation (HTx). Interestingly, increased plasma levels of immunoglobulins have been found in end-stage heart failure (HF) patients prior to HTx. In this study, we aimed to determine whether increased circulating immunoglobulin levels prior to transplantation are associated with poor post-HTx survival. Pre-and post-HTx plasma samples of 36 cardiac transplant recipient patients were used to determine circulating immunoglobulin levels. In addition, epicardial tissue was collected to determine immunoglobulin deposition in cardiac tissue and assess signs and severity of graft rejection. High levels of IgG1 and IgG2 prior to HTx were associated with a shorter survival post-HTx. Immunoglobulin deposition in cardiac tissue was significantly elevated in patients with a survival of less than 3 years. Patients with high plasma IgG levels pre-HTx also had significantly higher plasma levels after HTx. Furthermore, high pre-HTX levels of IgG1 and IgG2 levels were also significantly increased in patients with inflammatory infiltrate in CAV lesions. Altogether the results of this proof-of-concept study suggest that an activated immune response prior to transplantation negatively affects graft survival. [ABSTRACT FROM AUTHOR]

Investigations on mate choice in humans frequently report preferences, but there is little knowledge about what is important for rejection by a potential mate. The present study aims to verify if facial asymmetry and facial disharmony have an influence on mate rejection by men. We hypothesized that more asymmetric and disharmonious faces would be more rejected. For this purpose, photographs of women's faces were presented in pairs by self-declared heterosexual men. It was requested they reject one of the faces as a potential mate for a long-term relationship. Women's faces were also analyzed to measure facial asymmetry and facial disharmony. We used a linear mixed model to evaluate the effect of the cited metrics on each face's number of rejections. We found that the female metrics influenced mate rejection only if associated with male age and income. The older participants rejected female partners with asymmetric faces. We suggest that aging makes men more demanding in mate choices, at least considering facial asymmetry. We concluded that rejection could be a key variable in mate choice studies, but further research is needed to clarify its effects. [ABSTRACT FROM AUTHOR]

Background: The current gold standard to diagnose T-cell-mediated acute rejection (TCMR) requires liver histology. Using data from the ChilSFree study on immune response after paediatric liver transplantation (pLT), we aimed to assess whether soluble cytokines can serve as an alternative diagnostic tool in children suspected to have TCMR. Methods: A total of n = 53 blood samples obtained on the day of or up to 3 days before liver biopsy performed for suspected TCMR at median 18 days (range 7–427) after pLT in n = 50 children (38% female, age at pLT 1.8 (0.5–17.5) years) were analysed for circulating cytokine levels using Luminex-based Multiplex technology. Diagnostic accuracy of cytokine concentrations was assessed using a multivariable model based on elastic net regression and gradient boosting machine analysis. Results: TCMR was present in 68% of biopsies. There was strong evidence that patients with TCMR had increased levels of soluble CXCL8, CXCL9, CXCL10, IL-16, IL-18, HGF, CCL4, MIF, SCGF-β, and HGF before biopsy. There was some evidence for increased levels of sCD25, ICAM-1, IL-6, IL-3, and CCL11. Diagnostic value of both single cytokine levels and a combination of cytokines and clinical markers was poor, with AUROCs not exceeding 0.7. Conclusion: Patients with TCMR showed raised levels of cytokines and chemokines reflective of T-cell activation and chemotaxis. Despite giving insight into the mechanisms of TCMR, the diagnostic value of soluble cytokines for the confirmation of TCMR in a clinical scenario of suspected TCMR is poor. [ABSTRACT FROM AUTHOR]

Pediatric acute liver failure (PALF) is a common cause of liver transplantation (LT) but showed poor post-LT outcomes. We reviewed 36 PALF patients and 120 BA patients who underwent LT in our institution. The cause of PALF was unknown in 66.7%. PALF patients were older (6.2 vs. 2.9 years) with higher PELD scores (31.5 vs. 24.4) and shorter waitlist time (15.7 vs. 256.1 days) (p < 0.01). PALF patients showed higher rates of post-transplant renal replacement therapy (RRT) (13.9% vs. 4.2%) and hepatic artery complications (13.9% vs. 0.8%), while portal vein complications rates were lower (0% vs. 10.8%), (p < 0.05). Although PALF patients showed lower 5-year survival rates (77.8% vs. 95.0 %, p < 0.01), the 5-year survival rates of patients who lived beyond the first year were comparable (96.6% vs. 98.3%, p = 0.516). The most common cause of deaths within one year was graft failure (75.0%) in PALF patients, but infection (67.7%) in BA patients. In multivariate analysis, lower body weight, hepatic artery complications and post-transplant RRT were associated with worse survival outcomes (p < 0.05). In conclusion, physicians should be alert to monitor the immediate postoperative graft dysfunction and hepatic artery complications and patients on post-transplant RRT in order to improve survival outcomes in PALF patients. [ABSTRACT FROM AUTHOR]

Verapamil hydrochloride, a calcium channel-blocking agent, is detectable in receiving water bodies and affects the well-being of aquatic organisms. Membrane filtration could be effective in removing such pharmaceutical contaminants. However, limited studies have employed commercial membranes, such as polyvinylidene fluoride (PVDF), in removing verapamil from water sources, owing to their low solution fluxes, poor antibacterial properties, and high surface hydrophobicity. Efforts are needed to create the PVDF membrane suitable for removing verapamil from water sources. In this study, PVDF composite membranes incorporated with from 0 to 0.10 wt% silver-doped graphene oxide quantum dots (Ag−GOQD) were evaluated in terms of their morphological structures, elemental composition, surface roughness, hydrophilicity, verapamil rejection capability, anti-fouling, and antibacterial capabilities. The pure PVDF membrane showed the lowest verapamil rejection (73.66 ± 2.45%), highest surface roughness (mean surface roughness, Sa = 123.80 nm), and least hydrophilic membrane surface (contact angle = 79.06 ± 4.53°) when compared to other membranes incorporated with nanocomposites. However, the membrane incorporated with 0.10 wt% Ag−GOQD showed the smoothest and the most hydrophilic membrane surface (Sa = 13.10 nm and contact angle = 53.60 ± 4.75°, respectively), associated with the highest verapamil rejection (96.04 ± 1.82%). A clear inhibition zone was spotted in the agar plate containing the membrane incorporated with Ag−GOQD, showing the antibacterial capability of the membrane. The overall improvement in morphological structures, surface smoothness, surface hydrophilicities, permeabilities, verapamil rejection abilities, and anti-fouling and antibacterial capabilities indicated a great potential to incorporate Ag−GOQD in PVDF membrane fabrication. [ABSTRACT FROM AUTHOR]

Background. Delayed graft function is a frequent complication of kidney transplantation that requires dialysis in the first week posttransplant. Materials and Methods. We searched for the most relevant articles in the National Institutes of Health library of medicine, as well as in transplantation, pharmacologic, and nephrological journals. Results. The main factors that may influence the development of delayed graft function (DGF) are ischemia–reperfusion injury, the source and the quality of the donated kidney, and the clinical management of the recipient. The pathophysiology of ischemia–reperfusion injury is complex and involves kidney hypoxia related to the duration of warm and cold ischemia, as well as the harmful effects of blood reperfusion on tubular epithelial cells and endothelial cells. Ischemia–reperfusion injury is more frequent and severe in kidneys from deceased donors than in those from living donors. Of great importance is the quality and function of the donated kidney. Kidneys from living donors and those with normal function can provide better results. In the peri-operative management of the recipient, great attention should be paid to hemodynamic stability and blood pressure; nephrotoxic medicaments should be avoided. Over time, patients with DGF may present lower graft function and survival compared to transplant recipients without DGF. Maladaptation repair, mitochondrial dysfunction, and acute rejection may explain the worse long-term outcome in patients with DGF. Many different strategies meant to prevent DGF have been evaluated, but only prolonged perfusion of dopamine and hypothermic machine perfusion have proven to be of some benefit. Whenever possible, a preemptive transplant from living donor should be preferred. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are antibodies that target and block immune checkpoints. These biologics were initially approved by the United States Food and Drug Administration (US FDA) in 2011 for the management of melanoma. Since then, the use of ICI therapy has increased, with many new medications on the market that treat approximately 50 types of cancers. Patients receiving this therapy are at an increased risk for transplant rejection, including corneal rejection. Ophthalmologists must be aware of individuals receiving ICI therapy as it may be a relative contraindication for patients with a history of corneal transplantation. Patients on ICIs may also experience ocular side effects, including uveitis, dry eye, and inflammation, while on checkpoint inhibitor therapy. This commentary discusses the current understanding of immune checkpoint inhibitors, their mechanism of action, their ocular side effects, and their role in corneal transplant rejection. [ABSTRACT FROM AUTHOR]

Recently, there has been a special research focus on the bioconversion of glycerol to 1,3-propanediol (1,3-PD) due to its significance in the chemical industry. However, the treatment and separation of fermentation broths is a great challenge. Currently, the reverse osmosis (RO) process is a reliable state-of-the-art technique for separation of biological solutions. This study (as the first to do so) investigated the feasibility of separation of 1,3-PD broths with the use of cellulose acetate (CA) membrane by the RO process. The experiments were carried out using the installation equipped with the plate module, under the transmembrane pressure (TMP) and temperature of 1 MPa and 298 K, respectively. It was found that the used membrane was suitable for broth separation. Indeed, it was noted that 1,3-PD, as a target product, migrated through the membrane; meanwhile, other broth components were rejected in various degrees. Moreover, it was proven that retention of carboxylic acids tended to increase with increasing molecular weight, according to the following order: succinic acid > lactic acid > acetic acid > formic acid. With regards to ions, retention degree increased with the increase of ionic radius and decrease of diffusion coefficient. Finally, it was demonstrated that the CA membrane is resistant to irreversible fouling, which has a positive effect on the economic viability of the process. [ABSTRACT FROM AUTHOR]

Kidney transplantation is unquestionably the most advantageous and preferred treatment when patients with end-stage renal disease are considered. It does have a substantially positive influence on both the quality and expectancy of their lives. Thus, it is quintessential to extend the survival rate of kidney grafts. On account of T-cell-focused treatment, this is being exponentially achieved. The kynurenine pathway, as an immunosuppressive apparatus, and indoleamine 2,3-dioxygenase (IDO1), as its main regulator, are yet to be exhaustively explored. This review presents the recognised role of IDO1 and its influence on the kynurenine pathway, with emphasis on immunosuppression in kidney transplant protection. [ABSTRACT FROM AUTHOR]

Reaching critically short telomeres induces cellular senescence and ultimately cell death. Cellular senescence contributes to the loss of tissue function. We aimed to determine the association between variants within genes involved in telomere length maintenance, posttransplant events, and aortic telomere length in heart transplant patients. DNA was isolated from paired aortic samples of 383 heart recipients (age 50.7 ± 11.9 years) and corresponding donors (age 38.7 ± 12.0 years). Variants within the TERC (rs12696304), TERF2IP (rs3784929 and rs8053257), and OBCF1 (rs4387287) genes were genotyped, and telomere length was measured using qPCR. We identified similar frequencies of genotypes in heart donors and recipients. Antibody-mediated rejection (AMR) was more common (p < 0.05) in carriers of at least one G allele within the TERF2IP locus (rs3784929). Chronic graft dysfunction (CGD) was associated with the TERC (rs12696304) GG donor genotype (p = 0.05). The genetic risk score did not determine posttransplant complication risk prediction. No associations between the analyzed polymorphisms and telomere length were detected in either donor or recipient DNA. In conclusion, possible associations between donor TERF2IP (rs3784929) and AMR and between TERC (rs12696304) and CGD were found. SNPs within the examined genes were not associated with telomere length in transplanted patients. [ABSTRACT FROM AUTHOR]

Introduction: Heart transplant (HT) survival has barely improved in the last decades, which is unsatisfactory for many HT recipients. The development of anti-human leukocyte antigen (anti-HLA) antibodies in HT patients is associated with a cardiac allograft dysfunction. The mechanisms leading to this damage are unclear. The Multimodality Evaluation Of Antibody-Mediated Injury In Heart Transplantation (LEONE-HT) study aimed to thoroughly describe the damage inflicted on the myocardium by anti-HLA antibodies. Methods and analysis: The LEONE-HT study is a cohort study with a cross-sectional approach in which HT patients with positive anti-HLA antibodies are compared with coetaneous HT patients with negative anti-HLA antibodies. All patients will undergo a state-of-the-art multimodal assessment, including imaging techniques, coronary anatomy and physiology evaluations and histological and immunological analyses. The individual and combined primary outcomes of structural graft injuries and longitudinal secondary outcomes are to be compared between the exposed and non-exposed groups with univariate and multivariable descriptive analyses. Ethics and dissemination: The LEONE-HT study is carried out in accordance with the principles set out in the Declaration of Helsinki and the International Conference on Harmonization guidelines for good clinical practice and following national laws and regulations. The study design, objectives and participant centers have been communicated to clinicaltrials.gov (NCT05184426). The LEONE-HT study counts on the support of patient associations to disseminate the objectives and results of the research. This study was funded by the Spanish Ministry of Science and Innovation and the Spanish Society of Cardiology. [ABSTRACT FROM AUTHOR]

Our aim was to investigate the role of left atrial longitudinal strain (LALS) in the non-invasive diagnosis of acute cellular rejection (ACR) episodes in heart transplant (HTx) recipients. Methods: We performed successive echocardiographic exams in 18 consecutive adult HTx recipients in their first year after HTx within 3 h of the routine surveillance endomyocardial biopsies (EMB) in a single center. LALS parameters were analyzed with two different software. We investigated LALS association with ACR presence, as well as inter-vendor variability in comparable LALS values. Results: A total of 147 pairs of EMB and echo exams were carried out. Lower values of LALS were significantly associated with any grade of ACR presence. Peak atrial longitudinal strain (PALS) offered the best diagnostic value for any grade of ACR, with a C statistic of 0.77 using one software (95% CI 0.68–0.84, p < 0.0005) and 0.64 with the other (95% CI 0.54–0.73, p = 0.013) (p = 0.02 for comparison between both curves). Reproducibility between comparable LALS parameters was poor (intraclass correlation coefficients were 0.60 for PALS, 95% CI 0.42–0.73, p < 0.0005; and 0.42 for PALS rate, 95% CI −0.13–0.68, p < 0.0005). Conclusions: LALS variables might be a sensitive marker of ACR in HTx recipients, principally discriminating between those studies without rejection and those with any grade of ACR. Inter-vendor variability was significant. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) in kidney transplant (KT) recipients is an important opportunistic infection with higher incidence and prevalence than in the general population and is associated with important morbidity and mortality. We performed an extensive literature review of articles published between 1 January 2000 and 15 June 2022 to provide an evidence-based review of epidemiology, pathogenesis, diagnosis, treatment and outcomes of TB in KT recipients. We included all studies which reported epidemiological and/or outcome data regarding active TB in KT, and we approached the diagnostic and treatment challenges according to the current guidelines. Prevalence of active TB in KT recipients ranges between 0.3–15.2%. KT recipients with active TB could have a rejection rate up to 55.6%, a rate of graft loss that varies from 2.2% to 66.6% and a mortality rate up to 60%. Understanding the epidemiological risk, risk factors, transmission modalities, diagnosis and treatment challenges is critical for clinicians in providing an appropriate management for KT with TB. Among diagnostic challenges, which are at the same time associated with delay in management, the following should be considered: atypical clinical presentation, association with co-infections, decreased predictive values of screening tests, diverse radiological aspects and particular diagnostic methods. Regarding treatment challenges in KT recipients with TB, drug interactions, drug toxicities and therapeutical adherence must be considered. [ABSTRACT FROM AUTHOR]

Background: Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event that leads to the cascade of events that result in rejection of a transplanted organ. Objectives: To describe the results of a systematic review for solid organ rejections following SARS-CoV-2 vaccination or COVID-19 infection. Methods: For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines for studies on the incidence of solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection, published from 1 December 2019 to 31 May 2022, with English language restriction. Results: One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). The median or mean patient age ranged from 23 to 94 years across the studies. The majority of the patients were male (n = 51, 53.1%) and were of White (Caucasian) (n = 51, 53.7%) and Hispanic (n = 15, 15.8%) ethnicity. A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination [Pfizer-BioNTech (n = 31), Moderna (n = 14), Oxford Uni-AstraZeneca (n = 10) and Sinovac-CoronaVac (n = 1)]. The median time from SARS-CoV-2 vaccination to organ rejection was 13.5 h (IQR, 3.2–17.2), while the median time from COVID-19 infection to organ rejection was 14 h (IQR, 5–21). Most patients were easily treated without any serious complications, recovered and did not require long-term allograft rejection therapy [graft success (n = 70, 85.4%), graft failure (n = 12, 14.6%), survived (n = 90, 95.7%) and died (n = 4, 4.3%)]. Conclusion: The reported evidence of solid organ rejections post-SARS-CoV-2 vaccination or COIVD-19 infection should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively small in relation to the hundreds of millions of vaccinations that have occurred, and the protective benefits offered by SARS-CoV-2 vaccination far outweigh the risks. [ABSTRACT FROM AUTHOR]

Immune cell invasion after the transplantation of solid organs is directed by chemokines binding to glycosaminoglycans (GAGs), creating gradients that guide immune cell infiltration. Renal transplant is the preferred treatment for end stage renal failure, but organ supply is limited and allografts are often injured during transport, surgery or by cytokine storm in deceased donors. While treatment for adaptive immune responses during rejection is excellent, treatment for early inflammatory damage is less effective. Viruses have developed highly active chemokine inhibitors as a means to evade host responses. The myxoma virus-derived M-T7 protein blocks chemokine: GAG binding. We have investigated M-T7 and also antisense (ASO) as pre-treatments to modify chemokine: GAG interactions to reduce donor organ damage. Immediate pre-treatment of donor kidneys with M-T7 to block chemokine: GAG binding significantly reduced the inflammation and scarring in subcapsular and subcutaneous allografts. Antisense to N-deacetylase N-sulfotransferase1 (ASONdst1) that modifies heparan sulfate, was less effective with immediate pre-treatment, but reduced scarring and C4d staining with donor pre-treatment for 7 days before transplantation. Grafts with conditional Ndst1 deficiency had reduced inflammation. Local inhibition of chemokine: GAG binding in donor organs immediately prior to transplant provides a new approach to reduce transplant damage and graft loss. [ABSTRACT FROM AUTHOR]

Challenges exist in the wastewater treatment of dyes produced by the world's growing textiles industry. Common problems facing traditional wastewater treatments include low retention values and breaking the chemical bonds of some dye molecules, which in some cases can release byproducts that can be more harmful than the original dye. This research illustrates that track-etched polycarbonate filtration membranes with 100-nanometer diameter holes can be functionalized with azo dye direct red 80 at 1000 µM, creating a filter that can then be used to remove the entire negatively charged azo dye molecule for a 50 µM solution of the same dye, with a rejection value of 96.4 ± 1.4%, at a stable flow rate of 114 ± 5 µL/min post-functionalization. Post-functionalization, Na+ and NO3− ions had on average 17.9%, 26.0%, and 31.1% rejection for 750, 500, and 250 µM sodium nitrate solutions, respectively, at an average flow rate of 177 ± 5 µL/min. Post-functionalization, similar 50 µM azo dyes had increases in rejection from 26.3% to 53.2%. Rejection measurements were made using ultraviolet visible-light spectroscopy for dyes, and concentration meters using ion selective electrodes for Na+ and NO3− ions. [ABSTRACT FROM AUTHOR]

An increasing number of AB0-incompatible (AB0i) liver transplantations (LT) are being undertaken internationally in recent years due to organ shortages and the need for urgent transplantation. The aim of our study was establish the value of ABOi LT from available retrospective results of AB0i pediatric liver transplantations performed in European reference centers now belonging to the TransplantChild, European Reference Network (ERN). Data from medical records were analyzed, including demographic data, diagnosis, urgency of transplantation, time on the waiting list, PELD/MELD score, desensitization procedures, immunosuppression, selected post-transplant complications, and patient and graft survival. A total of 142 patients (pts) with transplants between 1986 and 2018 in 8 European transplant centers were included in the study. The indications for liver transplantation were: cholestatic diseases in 62 pts, acute liver failure in 42 pts, and other conditions in the remaining 38 pts. Sixty-six patients received grafts from living donors, and seventy-six received grafts from deceased donors. Both patient and graft survival were significantly affected by deceased donor type, urgent transplantation, and the development of vascular complications. In the multi-variate analysis, vascular complications had a negative impact on patient and graft survival, while a longer time from the first AB0i LT in the study showed better results, suggesting an international learning experience. In conclusion, we believe that AB0i LT in children is now a safe procedure that may be adopted more readily in children. [ABSTRACT FROM AUTHOR]

Forward osmosis (FO) membranes have gained interest in several disciplines for the rejection and concentration of various molecules. One application area for FO membranes that is becoming increasingly popular is the use of the membranes to concentrate or dilute high value compound solutions such as pharmaceuticals. It is crucial in such settings to control the transport over the membrane to avoid losses of valuable compounds, but little is known about the rejection and transport mechanisms of larger biomolecules with often flexible conformations. In this study, transport of two chemically similar peptides with molecular weight (Mw) of 375 and 692 Da across a thin film composite Aquaporin Inside™ Membrane (AIM) FO membrane was investigated. Despite the relative large size, both peptides were able to permeate the dense active layer of the AIM membrane and the transport mechanism was determined to be diffusion-based. Interestingly, the membrane permeability increased 3.65 times for the 692 Da peptide (1.39 x 10-12 m2·s-1) compared to the 375 Da peptide (0.38 x 10-12 m2·s-1). This increase thus occurs for an 85% increase in Mw but only for a 34% increase in peptide radius of gyration (Rg) as determined from molecular dynamics (MD) simulations. This suggests that Rg is a strong influencing factor for membrane permeability. Thus, an increased Rg reflects the larger peptide chains ability to sample a larger conformational space when interacting with the nanostructured active layer increasing the likelihood for permeation. [ABSTRACT FROM AUTHOR]

In this paper, two axiomatic theories T- and T' are constructed, which are dual to Tarski's theory T+ (1930) of deductive systems based on classical propositional calculus. While in Tarski's theory T+ the primitive notion is the classical consequence function (entailment) Cn+, in the dual theory T- it is replaced by the notion of Słupecki's rejection consequence Cn- and in the dual theory T' it is replaced by the notion of the family Incons of inconsistent sets. The author has proved that the theories T+, T-, and T' are equivalent. [ABSTRACT FROM AUTHOR]

Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) and antibody-mediated rejection are immune-mediated, long-term complications that jeopardize graft survival after heart transplantation (HTx). Interestingly, increased plasma levels of immunoglobulins have been found in end-stage heart failure (HF) patients prior to HTx. In this study, we aimed to determine whether increased circulating immunoglobulin levels prior to transplantation are associated with poor post-HTx survival. Pre-and post-HTx plasma samples of 36 cardiac transplant recipient patients were used to determine circulating immunoglobulin levels. In addition, epicardial tissue was collected to determine immunoglobulin deposition in cardiac tissue and assess signs and severity of graft rejection. High levels of IgG1 and IgG2 prior to HTx were associated with a shorter survival post-HTx. Immunoglobulin deposition in cardiac tissue was significantly elevated in patients with a survival of less than 3 years. Patients with high plasma IgG levels pre-HTx also had significantly higher plasma levels after HTx. Furthermore, high pre-HTX levels of IgG1 and IgG2 levels were also significantly increased in patients with inflammatory infiltrate in CAV lesions. Altogether the results of this proof-of-concept study suggest that an activated immune response prior to transplantation negatively affects graft survival.