Young Donors Research Articles

Anaerobutyricum hallii promotes the functional depletion of a food carcinogen in diverse healthy fecal microbiota

IntroductionAnaerobutyricum hallii is a human gut commensal that transforms the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), a carcinogen from cooked meat. The transformation mechanism involves the microbial production of acrolein from glycerol, and its conjugation with PhIP, thus blocking its mutagenic potential. A potential cancer prevention strategy could therefore involve supplementing complex human microbial communities with metabolically competent bacteria such as A. hallii that can deplete PhIP. However, it has not been established how the proportion of A. hallii in diverse healthy human gut microbial communities relates to functional capacity for PhIP transformation and, moreover, how supplementing microbiomes with A. hallii affects this function.MethodsIn this study, shotgun metagenomics was used to study taxonomic profiling, the abundance of glycerol/diol dehydratase (gdh)-harboring taxa, the proportion of resident A. hallii, and the reconstruction of A. hallii population genomes in the fecal samples of 20 healthy young adult donors. Furthermore, the influence of supplementing 106 cells/mL of A. hallii DSM 3353 with diluted fecal microbiota was characterized.Results and discussionSix microbiota were assigned to Bacteroides, nine to Prevotella, and five to Ruminococcus by enterotype-associated clustering. The total number of gdh copies in the 20 fecal microbiota expressed per 1010 bacterial cells ranged between 1.32 × 108 and 1.15 × 109. Eighteen out of the 20 donors were dominated by A. hallii, representing between 33% and 94% of the total gdh relative abundance of the samples. The microbiota with low A. hallii abundance (i.e., with a relative abundance < 1%) transformed less PhIP than the microbiota with high A. hallii abundance (i.e., with a relative abundance > 1%). Furthermore, supplementing the low-A. hallii-abundant microbiota with glycerol significantly increased the PhIP transformation capacity after 6 h while reducing total short-chain fatty acid (SCFA) levels, which is most likely due to acrolein production. Although acetate decreased in all microbiota with glycerol and with the combination of glycerol and A. hallii, for most of the microbiomes, butyrate production increased over time. Thus, for a significant number of diverse healthy human fecal microbiomes, and especially when they have little of the taxa to start with, supplementing A. hallii increases PhIP transformation. These findings suggest the need to test in vivo whether supplementing microbiomes with A. hallii reduces PhIP exposure.

The Impact of Obesity on Sperm Parameters in Young Adult Males: A Retrospective Study of Sperm Donors

To utilize a large cohort of healthy sperm bank donors to evaluate the association between body mass index and individual sperm parameters. Sperm parameters from donors across the United States were obtained between 2013 and 2022. Donors were healthy men aged 18-46years old. Semen samples were analyzed in a certified lab following guidelines by the World Health Organization. A multivariable interaction model between age, body mass index, and sperm parameters was conducted. There were 117,357 sperm donations included in our study. In our sample, 98,397 (83.84%) men were classified as young donors (ages 18-32years) and 18,960 (16.16%) were classified as old donors (ages 33-46years). We identified 1032 (0.88%) men as underweight, 76,635 (65.30%) as normal weight, 36,686 (31.26%) as overweight, and 3004 (2.56%) as obese. Participants had a median total motile sperm count (TMSC) of 186 (interquartile ranges [IQR]: 128 million), volume of 3.36 (IQR: 1.82 mL), sperm concentration of 56 (IQR: 34 million/mL) and a progressive motility of 59.84% (IQR: 16.95%). Older obese donor had lower TMSC (β = -22.98 ± 4.66, P < .001), semen volumes (β = -0.85 ± 0.06, P < .001), and progressive motility (β = -3.94 ± 0.56, P < .001) compared to younger, healthy weight donors. We observed lower TMSC, semen volumes, and progressive motility in older obese donors. Although these values are within the normal expected ranges for individual sperm parameters, our ability to detect differences within this healthy population highlights the importance of maintaining a healthy diet and exercise regimen for preserving high sperm counts.

Driver's licences for undocumented immigrants and post‐mortem organ donation

AbstractThis study examines the relationship between expanded access to driver's licences among undocumented immigrants and the number of post‐mortem organ donors, using difference‐in‐differences modelling and event study estimation techniques. Results suggest that the adoption of laws that grant driver's licences to undocumented immigrants effectively increased the population of licensed drivers by about 2.7%. These increments eventually led to subsequent increases in the number of Hispanic organ donors by 28%, and the outcome is driven mainly by young adult Hispanic donors. Moreover, DLU laws are further credited with an approximately 17% increase in organ transplants, particularly among Hispanics, although transplant waiting list addition numbers are not significantly affected. As these laws pave the way for more undocumented drivers to register as organ donors, such legislation could help to alleviate organ shortage issues and narrow the ‘ethnic waiting period gap’ for organ transplants.

External Validation of Toulouse-Rangueil eGFR12 Prediction Model After Living Donor Nephrectomy.

Decreased postdonation eGFR is associated with a higher risk of ESRD after living kidney donation, even when accounting for predonation characteristics. The Toulouse-Rangueil model (TRM) estimates 12month postdonation eGFR (eGFR12) to inform counseling of candidates for living donation. The TRM was validated in several single-center European cohorts but has not been validated in US donors. We assessed the TRM in living kidney donors in the US using SRTR data 1/2000-6/2021. We compared the 2021 CKD-EPI equation eGFR12 observed estimates to the TRM eGFR12 predictions. Median (IQR) bias was -3.4 (-9.3, 3.4) mL/min/1.73m2. Bias was higher for males vs. females (bias [IQR] -4.4 [-9.9, 1.8] vs. -2.9 [-8.8, 4.1]) and younger (31-40) vs. older donors (>50) (bias -4.9 [-10.6, 3.0] vs. -2.1 [-7.5, 4.0]). Bias was also larger for Black vs. White donors (bias (-6.7 [-12.1, -0.3], p < 0.001) vs. (-3.4 [-9.1, 3.1], p < 0.001)). Overall correlation was 0.71. In a sensitivity analysis using the 2009 CKD-EPI equation, results were generally consistent with exception to a higher overall bias (bias -4.2 [-9.8, 2.4]). The TRM overestimates postdonation renal function among US donors. Overestimation was greatest for those at higher risk for postdonation ESRD including male, Black, and younger donors. A new equation is needed to estimate postdonation renal function.

Oocyte rescue in-vitro maturation does not adversely affect chromosome segregation during the first meiotic division

Research questionDoes rescue in-vitro maturation (IVM) in the presence or absence of cumulus cells, affect the progress of meiosis I, compared with oocytes that mature in vivo? DesignThis prospective study was conducted in a university-affiliated fertility centre. Ninety-five young oocyte donors (mean age 25.57 ± 4.47) with a normal karyotype and no known fertility problems were included. A total of 390 oocytes (116 mature metaphase II [MII] and 274 immature oocytes) were analysed. The immature oocytes underwent rescue IVM in the presence of cumulus cells (CC; IVM+CC; n = 137) or without them (IVM-CC; n = 137), and IVM rate was calculated. Chromosome copy number analysis using next-generation sequencing (NGS) was performed on all rescue IVM oocytes reaching MII as well as those that were mature at the time of initial denudation (in-vivo-matured oocytes [IVO]). ResultsMaturation rates were similar in IVM+CC and IVM-CC oocytes (62.8 versus 71.5%, P = 0.16). Conclusive cytogenetic results were obtained from 65 MII oocytes from the IVM+CC group, 87 from the IVM-CC group, and 99 from the IVO group. Oocyte euploidy rates for the three groups were similar, at 75.4%, 83.9% and 80.8%, respectively (P = 0.42). ConclusionsThe results suggest that culture of germinal vesicle and metaphase I oocytes in the presence of cumulus cells does not improve rates of IVM. In general, the process of rescue IVM does not appear to alter the frequency of oocytes with a normal chromosome copy number.

TRAF3IP2 drives mesenchymal stem cell senescence via regulation of NAMPT-mediated NAD biosynthesis

BackgroundThe cellular senescence of mesenchymal stem cells (MSCs) limits their application in regenerative medicine. This study aimed to clarify the role of TNF receptor-associated factor 3 interacting protein 2 (TRAF3IP2), a pro-inflammatory cytoplasmic adaptor protein, in regulating MSC senescence and to explore the potential mechanisms. Methods: MSC senescence was determined by senescence-associated β-galactosidase (SA-β-gal) staining. The expression of TRAF3IP2 and senescence-related proteins was detected by Western blotting. The nicotinamide adenine dinucleotide (NAD+) level and nicotinamide phosphoribosyl transferase (NAMPT) expression in MSCs was measured. Results: Compared with that in MSCs isolated from young donors (YMSCs), the expression of TRAF3IP2 was greatly increased in MSCs derived from aged donors (AMSCs). Overexpression of TRAF3IP2 accelerated YMSC senescence whereas downregulation significantly rescued cellular senescence. The protein level of NAMPT and the level of NAD+ were significantly decreased in AMSCs compared with YMSCs. Mechanistically, TRAF3IP2 induced MSC senescence via downregulation of NAMPT expression and NAD + level by inhibiting the AMPK signaling pathway. These effects were partially reversed by treatment with an AMPK or NAMPT activator. Conclusion: We revealed that TRAF3IP2 accelerated MSC senescence via downregulation of NAMPT-mediated NAD biosynthesis by mediation of the AMPK pathway, highlighting a novel means to rejuvenate senescent MSCs.

Neuropathologic and Clinical Findings in Young Contact Sport Athletes Exposed to Repetitive Head Impacts

Young contact sport athletes may be at risk for long-term neuropathologic disorders, including chronic traumatic encephalopathy (CTE). To characterize the neuropathologic and clinical symptoms of young brain donors who were contact sport athletes. This case series analyzes findings from 152 of 156 brain donors younger than 30 years identified through the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank who donated their brains from February 1, 2008, to September 31, 2022. Neuropathologic evaluations, retrospective telephone clinical assessments, and online questionnaires with informants were performed blinded. Data analysis was conducted between August 2021 and June 2023. Repetitive head impacts from contact sports. Gross and microscopic neuropathologic assessment, including diagnosis of CTE, based on defined diagnostic criteria; and informant-reported athletic history and informant-completed scales that assess cognitive symptoms, mood disturbances, and neurobehavioral dysregulation. Among the 152 deceased contact sports participants (mean [SD] age, 22.97 [4.31] years; 141 [92.8%] male) included in the study, CTE was diagnosed in 63 (41.4%; median [IQR] age, 26 [24-27] years). Of the 63 brain donors diagnosed with CTE, 60 (95.2%) were diagnosed with mild CTE (stages I or II). Brain donors who had CTE were more likely to be older (mean difference, 3.92 years; 95% CI, 2.74-5.10 years) Of the 63 athletes with CTE, 45 (71.4%) were men who played amateur sports, including American football, ice hockey, soccer, rugby, and wrestling; 1 woman with CTE played collegiate soccer. For those who played football, duration of playing career was significantly longer in those with vs without CTE (mean difference, 2.81 years; 95% CI, 1.15-4.48 years). Athletes with CTE had more ventricular dilatation, cavum septum pellucidum, thalamic notching, and perivascular pigment-laden macrophages in the frontal white matter than those without CTE. Cognitive and neurobehavioral symptoms were frequent among all brain donors. Suicide was the most common cause of death, followed by unintentional overdose; there were no differences in cause of death or clinical symptoms based on CTE status. This case series found that young brain donors exposed to repetitive head impacts were highly symptomatic regardless of CTE status, and the causes of symptoms in this sample are likely multifactorial. Future studies that include young brain donors unexposed to repetitive head impacts are needed to clarify the association among exposure, white matter and microvascular pathologic findings, CTE, and clinical symptoms.

Overcoming the hurdles of steatotic grafts in liver transplantation: Insights into survival and prognostic factors.

With increasing metabolic dysfunction-associated steatotic liver disease, the use of steatotic grafts in liver transplantation (LT) and their impact on postoperative graft survival (GS) needs further exploration. Analyzing adult LT recipient data (2002-2022) from the United Network for Organ Sharing database, outcomes of LT using steatotic (≥30% macrosteatosis) and nonsteatotic donor livers, donors after circulatory death, and standard-risk older donors (age 45-50) were compared. GS predictors were evaluated using Kaplan-Meier and Cox regression analyses. Of the 35,345 LT donors, 8.9% (3,155) were fatty livers. The initial 30-day postoperative period revealed significant challenges with fatty livers, demonstrating inferior GS. However, the GS discrepancy between fatty and nonfatty livers subsided over time ( p = 0.10 at 5y). Long-term GS outcomes showed comparable or even superior results in fatty livers relative to nonsteatotic livers, conditional on surviving the initial 90 postoperative days ( p = 0.90 at 1y) or 1 year ( p = 0.03 at 5y). In the multivariable Cox regression analysis, the high body surface area (BSA) ratio (≥1.1) (HR 1.42, p = 0.02), calculated as donor BSA divided by recipient BSA, long cold ischemic time (≥6.5h) (HR 1.72, p < 0.01), and recipient medical condition (intensive care unit hospitalization) (HR 2.53, p < 0.01) emerged as significant adverse prognostic factors. Young (<40y) fatty donors showed a high BSA ratio, diabetes, and intensive care unit hospitalization as significant indicators of a worse prognosis ( p < 0.01). Our study emphasizes the initial postoperative 30-day survival challenge in LT using fatty livers. However, with careful donor-recipient matching, for example, avoiding the use of steatotic donors with long cold ischemic time and high BSA ratios for recipients in the intensive care unit, it is possible to enhance immediate GS, and in a longer time, outcomes comparable to those using nonfatty livers, donors after circulatory death livers, or standard-risk older donors can be anticipated. These novel insights into decision-making criteria for steatotic liver use provide invaluable guidance for clinicians.

Characteristics of ABO Antibodies in Group O Malaysian Blood Donors.

Haemolytic transfusion reactions (HTRs) due to anti-A and anti-B antibodies in Group O blood products are rare but potentially fatal. This study aimed to identify the prevalence of high ABO antibody titre and the immunoglobulin (Ig) classes (IgM only or with IgG) and the prevalence of haemolysin antibodies in Group O blood donors. Plasma from Group O blood donors was tested by using antibody titration at room temperature. Titres ≥ 64 were considered high. The plasma was treated with 0.01 M dithiothreitol (DTT) to determine the presence of IgG antibodies and titre. IgG titres ≥ 64 were considered high. Tests for haemolysis were conducted by mixing the plasma with 3% fresh A1 and B cell suspensions and incubating at 37 °C. The haemolysis was observed macroscopically. Of 311 donors, 238 (76.5%) showed high anti-A and/or anti-B antibody titres. The highest antibody titre obtained was 256. Female and younger donors (< 40 years old) had higher anti-A and anti-B titres. The anti-B titre showed an association with gender (P < 0.001), and was high in female donors (77.8%). Males aged over 50 years old were found to have low mean titre antibodies. Most donors had both IgM and IgG ABO antibodies. The prevalence of haemolysins in our population was 3.5%. Most of our O blood donors had a high ABO antibody titre but a low prevalence of haemolysins. Males aged over 50 years old are the best O donors for preventing HTRs, particularly when mismatch transfusion is required. We recommend a transfusion unit screen for ABO antibody titre in younger female donors (< 40 years old), to prevent the transfusion of high titre O blood products into non-O recipients.

Knockdown of long noncoding RNA SAN rejuvenates aged adipose-derived stem cells via miR-143-3p/ADD3 axis

BackgroundSenescent adipose-derived stem cells (ASCs) exhibit reduced therapeutic efficacy during wound healing. Transcriptional regulation factors including long noncoding RNAs (lncRNAs) reportedly have essential roles in stem cell aging. However, the mechanisms of which lncRNAs influence mesenchymal stem cell aging and how it works need further investigation.MethodsThe expression patterns of lncRNA senescence-associated noncoding RNA (SAN) and miR-143-3p in ASCs obtained from old and young volunteer donors were detected by quantitative polymerase chain reaction. ASCs with overexpression or knockdown of SAN and γ-adducin (ADD3) were constructed by lentiviral transduction. Mimic and inhibitor were used to manipulate the cellular level of miR-143-3p in ASCs. The effects of these RNAs on ASCs proliferation, migration and cellular senescence were examined by EdU, transwell and senescence-activated β-galactosidase (SA-β-gal) staining assays. Wound scratch and tube formation assays were conducted to evaluate the capacities of ASCs in promoting fibroblasts migration and endothelial cells angiogenesis. Furthermore, dual-luciferase assays and rescue experiments were performed to identify the RNA interactions. Finally, the therapeutic effects of SAN-depleted aged ASCs were evaluated in a skin injury model.ResultsThe lncRNA SAN (NONHSAT035482.2) was upregulated in aged ASCs; it controlled cellular senescence in ASCs. lncRNA SAN knockdown in ASCs led to ASC functional enhancement and the inhibition of cellular senescence; it also promoted the effects of conditioned medium (CM) on endothelial cell tube formation and fibroblast migration. Mechanistic analysis showed that SAN serves as a sponge for miR-143-3p, thereby regulating the expression of ADD3. The application of SAN-depleted aged ASCs increased re-epithelialization, collagen deposition, neovascularization and led to accelerated skin wound closure, compared with transplantation of aged ASCs.ConclusionThe lncRNA SAN mediates ASC senescence by regulating the miR-143-3p/ADD3 pathway, providing a potential target for rejuvenation of senescent ASCs and enhancement of wound repair.

Human primary myoblasts derived from paraspinal muscle reflect donor age as an experimental model of sarcopenia

BackgroundLow back pain is a general phenomenon of aging, and surgery is an unavoidable choice to relieve severe back pain. The discarded surgical site during surgery is of high value for muscle and muscle-related research. This study investigated the age-dependent properties of patients' paraspinal muscles at the cellular level. MethodsTo define an association of paraspinal muscle degeneration with sarcopenia, we analyzed lumbar paraspinal muscle and myoblasts isolated from donors of various ages (25–77 years). Preoperative evaluations were performed by bioimpedance analysis using the InBody 720, magnetic resonance (MR) imaging of the lumbar spine, and lumbar extension strength using a lumbar extension dynamometer. In addition, the growth and differentiation capacity of myoblasts obtained from the donor was determined using proliferation assay and western blotting. ResultsThe cross-sectional area of the lumbar paraspinal muscle decreased with age and was also correlated with the appendicular skeletal muscle index (ASM/height2). Human primary myoblasts isolated from paraspinal muscle preserved their proliferative capacity in vitro, which tended to decrease with donor age. The age-dependent decline in myoblast proliferation was correlated with levels of cell cycle inhibitory proteins (p16INK4a, p21CIP1, and p27KIP1) associated with cellular senescence. Primary myoblasts isolated from younger donors differentiated into multinucleate myotubes earlier and at a higher rate than those from older donors in vitro. Age-dependent decline in myogenic potential of the isolated primary myoblasts was likely correlated with the inactivation of myogenic transcription factors such as MyoD, myogenin, and MEF2c. ConclusionsMyoblasts isolated from human paraspinal muscle preserve myogenic potential that correlates with donor age, providing an in vitro model of sarcopenia.

Characteristics of Kidney Transplant Recipients with Prolonged Pre-Transplant Dialysis Duration as Identified by Machine Learning Consensus Clustering: Pathway to Personalized Care.

Longer pre-transplant dialysis duration is known to be associated with worse post-transplant outcomes. Our study aimed to cluster kidney transplant recipients with prolonged dialysis duration before transplant using an unsupervised machine learning approach to better assess heterogeneity within this cohort. We performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in 5092 kidney transplant recipients who had been on dialysis ≥ 10 years prior to transplant in the OPTN/UNOS database from 2010 to 2019. We characterized each assigned cluster and compared the posttransplant outcomes. Overall, the majority of patients with ≥10 years of dialysis duration were black (52%) or Hispanic (25%), with only a small number (17.6%) being moderately sensitized. Within this cohort, three clinically distinct clusters were identified. Cluster 1 patients were younger, non-diabetic and non-sensitized, had a lower body mass index (BMI) and received a kidney transplant from younger donors. Cluster 2 recipients were older, unsensitized and had a higher BMI; they received kidney transplant from older donors. Cluster 3 recipients were more likely to be female with a higher PRA. Compared to cluster 1, cluster 2 had lower 5-year death-censored graft (HR 1.40; 95% CI 1.16-1.71) and patient survival (HR 2.98; 95% CI 2.43-3.68). Clusters 1 and 3 had comparable death-censored graft and patient survival. Unsupervised machine learning was used to characterize kidney transplant recipients with prolonged pre-transplant dialysis into three clinically distinct clusters with variable but good post-transplant outcomes. Despite a dialysis duration ≥ 10 years, excellent outcomes were observed in most recipients, including those with moderate sensitization. A disproportionate number of minority recipients were observed within this cohort, suggesting multifactorial delays in accessing kidney transplantation.

Choosing Between Older Matched Sibling Donor and Younger Matched Unrelated Donor in Allogeneic Hematopoietic Cell Transplantation: Comparison of Clinical Outcomes in Acute Myeloid Leukemia and Myelodysplastic Syndrome

The choice between an older matched sibling donor (MSD) and a younger matched unrelated donor (MUD) in allogeneic hematopoietic cell transplantation (HCT) remains a subject of ongoing debate. In this single-center retrospective study of 377 patients who received peripheral blood stem cell (PBSC) transplants for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), we compared outcomes of 85 patients who received grafts from MSDs age >60 years and 292 patients who received grafts from MUDs age <30 years. Compared to recipients of MSD transplants, recipients of MUD transplants were younger and more likely to receive dual T cell depletion (TCD), a higher CD34+ cell dose, and a fresh graft. Recipients of MSD transplants were maintained on immunosuppressive therapy longer than those who received MUD grafts. We found no differences in overall survival, relapse-free survival, graft-versus-host disease (GVHD)-free and relapse-free survival, nonrelapse mortality, relapse, engraftment, graft failure, and acute GVHD between recipients of MSD grafts and recipients of MUD grafts. We report a higher 30-day incidence, but not 1-year incidence, of bloodstream infections among recipients of MUD transplants compared to subjects who received their grafts from a MSD. The incidence of moderate-severe chronic GVHD was higher in MSD graft recipients compared with MUD graft recipients in univariate analysis, but not in multivariate analysis. Although this difference could reflect the greater use of dual TCD, known to be associated with very low rates of chronic GVHD in MUD transplant recipients, the incidence of moderate-severe chronic GVHD was no different between MSD and MUD transplant recipients following propensity score matching, suggesting that other variables could be responsible. Taken together, our data suggest that in patients with AML or MDS who receive PBSC transplants, such factors as convenience, ease of access, and costs should be considered when selecting an older MSD over a younger MUD.

Anti-aging mechanism of different age donor-matched adipose-derived stem cells

BackgroundAdipose-derived stem cells (ASCs) have anti-aging and anti-obesity effects in aged animals, but the underlying molecular mechanism remains unknown.MethodsIn the present study, we evaluated the in vivo transplantation effects of different age donor-matched ASCs on natural aging and leptin knockout mice (ob−/ob− mice). The multi-omics expression profiles of young and aged mouse donor-derived ASCs were also analyzed.ResultsThe results revealed that ASCs from young donors induced weight and abdominal fat loss for older recipients but not for young or ob−/ob−mice. The young and aged mouse donor ASCs displayed significant phenotypic differences, contributing to the distinguished weight loss and anti-aging effects in aged mice.ConclusionsOur data suggest an underlying molecular mechanism by which young-donor ASCs reduce immune cells and inflammation in aged mice via secreted immune factors. These findings point to a general anti-aging mechanism of stem cells, which may provide new insights into age-related disturbances of stem cell plasticity in healthy aging and age-related diseases.

Donor utilization in heart transplant with donation after circulatory death in the United States

Heart transplantation using donation after circulatory death (DCD) was recently adopted in the United States. This study aimed to characterize organ yield from adult (≥18 years) DCD heart donors in the United States using the United Network for Organ Sharing registry. The registry does not identify potential donors who do not progress to circulatory death, and only those who progressed to death were included for analysis. Outcomes included organ recovery from the donor operating room and organ utilization for transplant. Multiple logistic regression was used to identify predictors of heart recovery and utilization. Among 558 DCD procurements, recovery occurred in 89.6%, and 92.5% of recovered hearts were utilized for transplant. Of 506 DCD procurements with available data, 65.0% were classified as direct procurement and perfusion and 35.0% were classified as normothermic regional perfusion (NRP). Logistic regression identified that NRP, shorter agonal time, younger donor age, and highest volume of organ procurement organizations were independently associated with increased odds for heart recovery. NRP independently predicted heart utilization after recovery. DCD heart utilization in the United States is satisfactory and consistent with international experience. NRP procurements have a higher yield for DCD heart transplantation compared with direct procurement and perfusion, which may reflect differences in donor assessment and acceptance criteria.

Transplantation of gut microbiota from old mice into young healthy mice reduces lean mass but not bone mass

ABSTRACT Aging is associated with low bone and lean mass as well as alterations in the gut microbiota (GM). In this study, we determined whether the reduced bone mass and relative lean mass observed in old mice could be transferred to healthy young mice by GM transplantation (GMT). GM from old (21-month-old) and young adult (5-month-old) donors was used to colonize germ-free (GF) mice in three separate studies involving still growing 5- or 11-week-old recipients and 17-week-old recipients with minimal bone growth. The GM of the recipient mice was similar to that of the donors, demonstrating successful GMT. GM from old mice did not have statistically significant effects on bone mass or bone strength, but significantly reduced the lean mass percentage of still growing recipient mice when compared with recipients of GM from young adult mice. The levels of propionate in the cecum of mice receiving old donor GM were significantly lower than those in mice receiving young adult donor GM. Bacteroides ovatus was enriched in the microbiota of recipient mice harboring GM from young adult donors. The presence of B. ovatus was not only significantly associated with high lean mass percentage in mice, but also with lean mass adjusted for fat mass in the large human HUNT cohort. In conclusion, GM from old mice reduces lean mass percentage but not bone mass in young, healthy, still growing recipient mice. Future studies are warranted to determine whether GM from young mice improves the musculoskeletal phenotype of frail elderly recipient mice.

Aging: silencing the PKA and AkT/PKB signaling pathways alters the antioxidant capacity of resveratrol.

One of the theories related to aging is the increase in oxidative stress. Given this, the objective of the study is to evaluate the cellular mechanisms responsible for the resveratrol antioxidant effect on leukocytes from donors aged between 20 and 80years old. For this, leukocytes from donors of three age groups (20-39, 40-59 and 60-80) were isolated. Image-iT™LIVE Green Reactive Oxygen Species (ROS) Kit was used. Reactive Nitrogen Species (RNS) analysis was performed by measuring nitric oxide and peroxynitrite. The PKA, Akt/PKB and p38-MAPK were evaluated by chemiluminescence. The statistical analysis between age and treatments were performed by Pearson correlation (*p < 0.05). It was possible to observe the antioxidant effect of resveratrol in all age groups. The correlation results show loss of resveratrol effect in decreasing ROS in leukocytes from older donors. We observed an active antioxidant effect of p38-MAPK in all ages, with resveratrol acting on it. The PKA and Akt/PKB were active in leukocytes from donors aged 20-59. In cells from donors older than 60, these pathways are silenced, and an effect is also not observed in cells treated with resveratrol. Therefore, resveratrol showed antioxidant effect in all age, although it was more pronounced in leukocytes from younger. One of resveratrol's mechanisms is due to the activation of the PKA and Akt/PKB, which were activated in younger donor cells.

Prediction tool for renal adaptation after living kidney donation using interpretable machine learning.

Post-donation renal outcomes are a crucial issue for living kidney donors considering young donors' high life expectancy and elderly donors' comorbidities that affect kidney function. We developed a prediction model for renal adaptation after living kidney donation using interpretable machine learning. The study included 823 living kidney donors who underwent nephrectomy in 2009-2020. AutoScore, a machine learning-based score generator, was used to develop a prediction model. Fair and good renal adaptation were defined as post-donation estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m2 and ≥ 65% of the pre-donation values, respectively. The mean age was 45.2 years; 51.6% were female. The model included pre-donation demographic and laboratory variables, GFR measured by diethylenetriamine pentaacetate scan, and computed tomography kidney volume/body weight of both kidneys and the remaining kidney. The areas under the receiver operating characteristic curve were 0.846 (95% confidence interval, 0.762-0.930) and 0.626 (0.541-0.712), while the areas under the precision-recall curve were 0.965 (0.944-0.978) and 0.709 (0.647-0.788) for fair and good renal adaptation, respectively. An interactive clinical decision support system was developed. The prediction tool for post-donation renal adaptation showed good predictive capability and may help clinical decisions through an easy-to-use web-based application.

Faecal microbiota transplantation from young rats attenuates age-related sarcopenia revealed by multiomics analysis.

Gut microbiota plays a key role in the development of sarcopenia via the 'gut-muscle' axis, and probiotics-based therapy might be a strategy for sarcopenia. Fecal microbiota transplantation from young donors (yFMT) has attracted much attention because of its probiotic function. However, whether or not yFMT is effective for sarcopenia in old recipients is largely unknown. Thus, we aimed to investigate the effect and mechanism of yFMT on age-related sarcopenia. The fecal microbiota of either young (12weeks) or old (88weeks) donor rats was transplanted into aged recipient rats for 8weeks. Then, muscle mass, muscle strength, muscle function, muscle atrophy, and muscle regeneration capacity were measured. Analysis of fecal 16s rRNA, serum non-targeted metabolomic, gut barrier integrity, and muscle transcriptome was conducted to elucidate the interaction between gut microbiota and skeletal muscles. As evaluated by magnetic resonance imaging examination, grip strength test (P<0.01), rotarod test (P<0.05), and exhaustive running test (P<0.05), we found that yFMT mitigated muscle mass loss, muscle strength weakness, and muscle function impairment in aged rats. yFMT also countered age-related atrophy and poor regeneration capacity in fast- and slow-switch muscles, which were manifested by the decrease in slow-switch myofibres (both P<0.01) and muscle interstitial fibrosis (both P<0.05) and the increase in the cross-section area of myofibres (both P<0.001), fast-switch myofibres (both P<0.01), and muscle satellite cells (both P<0.001). In addition, yFMT ameliorated age-related dysbiosis of gut microbiota and metabolites by promoting the production of beneficial bacteria and metabolites-Akkermansia, Lactococcus, Lactobacillus, γ-glutamyltyrosine, 3R-hydroxy-butanoic acid, and methoxyacetic acid and inhibiting the production of deleterious bacteria and metabolites-Family_XIII_AD3011_group, Collinsella, indoxyl sulfate, indole-3-carboxilic acid-O-sulphate, and trimethylamine N-oxide. Also, yFMT prevented age-related destruction of gut barrier integrity by increasing the density of goblet cells (P<0.0001) and the expression levels of mucin-2 (P<0.0001) and tight junctional proteins (all P<0.05). Meanwhile, yFMT attenuated age-related impairment of mitochondrial biogenesis and function in fast- and slow-switch muscles. Correlation analysis revealed that yFMT-induced alterations of gut microbiota and metabolites might be closely related to mitochondria-related genes and sarcopenia-related phenotypes. yFMT could reshape the dysbiosis of gut microbiota and metabolites, maintain gut barrier integrity, and improve muscle mitochondrial dysfunction, eventually alleviating sarcopenia in aged rats. yFMT might be a new therapeutic strategy for age-related sarcopenia.

Booster vaccinations and Omicron: the effects on SARS-CoV-2 antibodies in Dutch blood donors

IntroductionThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) booster vaccination campaign and the emergence of SARS-CoV-2 Omicron variants impact the prevalence and levels of SARS-CoV-2 antibodies in the Netherlands. In this study we determined antibody levels across age groups, the impact of Omicron variant infections, and the effect of booster vaccinations on antibody levels.MethodsIn September and December 2021 and in February 2022, over 2000 Dutch blood donors were tested for presence of SARS-CoV-2 antibodies. Donations were selected based on age, sex, and region of residence, to provide an optimal coverage and representation of the Dutch population.ResultsLevels of vaccination-induced spike antibodies decreased over time in all age groups. Donors vaccinated with Janssen or AstraZeneca had significantly lower antibody levels than donors vaccinated with Pfizer or Moderna vaccine. Boostering with an mRNA vaccine elevated antibody levels in all age-groups irrespective of the initial vaccine. In donors aged < 56 years, the proportion of infected donors almost doubled between December 2021 and February 2022.ConclusionThe booster vaccination campaign increased antibody levels in all age-groups. After a booster vaccination, donors initially vaccinated with AstraZeneca or Janssen vaccine showed antibody levels similar to donors initially vaccinated with an mRNA vaccine. The emergence of the SARS-CoV-2 Omicron variant in the Netherlands caused a substantial increase in donors with infection-induced antibodies, especially among younger donors.