Interpersonal Connections Are Important for Virtual Kidney Transplant Educational Program Development.

Introduction: The Living Donor Navigator program is designed to mitigate disparities in living donor kidney transplantation, although geographic disparities in program participation were observed in the initial years of implementation. The purpose of this study was to understand participant perspectives regarding the use of a virtual option/alternative to expand program participation. Methods: Previous participants of the in-person navigator program were purposively sampled. Using the nominal group technique, a well-structured formative methodology to elicit participant perspectives, 2 meetings were conducted among transplant recipients and advocates (N = 13) to identify and prioritize responses to the question "What things would concern you about participating in a virtual and remote Living Donor Navigator program?" Findings: Mean participant age was 59.3 (9.3) years, and participants were 54% male and 62% white. Education levels varied from less than high school to master's degrees. Participants generated 70 unique responses, of which 36 (51.4%) received prioritization. The top 5 ranked responses of each nominal group technique meeting received approximately 50 percent (47.6% vs. 66.7%, respectively) of the total votes and described the potentially limited interpersonal connections, time conflicts, and differing content in a virtual navigator program compared to the in-person model. Discussion: These data suggest that previous participants were concerned with upholding the original design of the program, thus, virtual living donor kidney transplantation programs should aim to maintain interpersonal connections and consistency of content to ensure adequate programmatic engagement. Future research will focus on program fidelity independent of delivery modality.

A synthesis of recent tools and perspectives in migratory connectivity studies.

Migration movements connect breeding and non-breeding bird populations over the year. Such links, referred to as migratory connectivity, have important implications for migratory population dynamics as they dictate the consequences of localised events for the whole population network. This calls for concerted efforts to understand migration processes for large-scale conservation. Over the last 20 years, the toolbox to investigate connectivity patterns has expanded and studies now consider migratory connectivity over a broader range of species and contexts. Here, we summarise recent developments in analysing migratory connectivity, focusing on strategies and challenges to pooling various types of data to both optimise and broaden the scope of connectivity studies. We find that the different approaches used to investigate migratory connectivity still have complementary strengths and weaknesses, whether in terms of cost, spatial and temporal resolution, or challenges in obtaining large sample sizes or connectivity estimates. Certain recent developments offer particularly promising prospects: robust quantitative models for banding data, improved precision of geolocators and accessibility of telemetry tracking systems, and increasingly precise probabilistic assignments based on genomic markers or large-scale isoscapes. In parallel, studies have proposed various ways to combine the information of different datasets, from simply comparing the connectivity patterns they draw to formally integrating their analyses. Such data combinations have proven to be more accurate in estimating connectivity patterns, particularly for integrated approaches that offer promising flexibility. Given the diversity of available tools, future studies would benefit from a rigorous comparative evaluation of the different methodologies to guide data collection to complete migration atlases: where and when should data be collected during the migratory cycle to best describe connectivity patterns? Which data are most favourable to combine, and under what conditions? Are there methods for combining data that are better than others? Can combination methods be improved by adjusting the contribution of the various data in the models? How can we fully integrate connectivity with demographic and environmental data? Data integration shows strong potential to deepen our understanding of migratory connectivity as a dynamic ecological process, especially if the gaps can be bridged between connectivity, population and environmental models.

Diabetes-free survival among living kidney donors and non-donors with obesity: A longitudinal cohort study.

BACKGROUND: Approval of living kidney donors (LKD) with end-stage kidney disease (ESKD) risk factors, such as obesity, has increased. While lifetime ESKD development data are lacking, the study of intermediate outcomes such as diabetes is critical for LKD safety. Donation-attributable diabetes risk among persons with obesity remains unknown. The purpose of this study was to evaluate 10-year diabetes-free survival among LKDs and non-donors with obesity. METHODS: This longitudinal cohort study identified adult, LKDs (1976-2020) from 42 US transplant centers and non-donors from the Coronary Artery Risk Development in Young Adults (1985-1986) and the Atherosclerosis Risk in Communities (1987-1989) studies with body mass index ≥30 kg/m2. LKDs were matched to non-donors on baseline characteristics (age, sex, race, body mass index, systolic and diastolic blood pressure) plus diabetes-specific risk factors (family history of diabetes, impaired fasting glucose, smoking history). Accelerated failure time models were utilized to evaluate 10-year diabetes-free survival. FINDINGS: Among 3464 participants, 1119 (32%) were LKDs and 2345 (68%) were non-donors. After matching on baseline characteristics plus diabetes-specific risk factors, 4% (7/165) LKDs and 9% (15/165) non-donors developed diabetes (median follow-up time 8.5 (IQR: 5.6-10.0) and 9.1 (IQR: 5.9-10.0) years, respectively). While not significant, LKDs were estimated to live diabetes-free 2 times longer than non-donors (estimate 1.91; 95% CI: 0.79-4.64, p = 0.15). CONCLUSIONS: LKDs with obesity trended toward living longer diabetes-free than non-donors with obesity, suggesting within the decade following donation there was no increased diabetes risk among LKDs. Further work is needed to evaluate donation-attributable diabetes risk long-term.

Decellularized Spinach Biomaterials Support Physiologically Relevant Mechanical Cyclic Strain and Prompt a Stretch-Induced Cellular Response.

Recently, decellularized plant biomaterials have been explored for their use as tissue engineered substitutes. Herein, we expanded upon the investigation of the mechanical properties of these materials to explore their elasticity as many anatomical areas of the body require biomechanical dynamism. We first constructed a device to secure the scaffold and induce a strain within the physiological range of the normal human adult lung during breathing (12-20 movements/min; 10-20% elongation). Results showed that decellularized spinach leaves can support cyclic strain for 24 h and displayed heterogeneous local strain values (7.76-15.88%) as well as a Poisson's ratio (0.12) similar to that of mammalian lungs (10.67-19.67%; 0.01), as opposed to an incompressible homogeneous standard polymer (such as PDMS (10.85-12.71%; 0.4)). Imaging and mechanical testing showed that the vegetal scaffold exhibited strain hardening but maintained its structural architecture and water retention capacity, suggesting an unaltered porosity. Interestingly, we also showed that cells seeded on the scaffold can also sense the mechanical strain as demonstrated by a nuclear reorientation perpendicular to strain direction (63.3° compared to 41.2° for nonstretched cells), a nuclear location of YAP and increased expression of YAP target genes, a high cytoplasmic calcium level, and an elevated expression level of collagen genes (COL1A1, COL3A1, COL4A1, and COL6A) with an increased collagen secretion at the protein level. Taken together, these data demonstrated that decellularized plant leaf tissues have an inherent elastic property similar to that found in the mammalian system to which cells can sense and respond.

COVID-19 Vaccination and Remdesivir are Associated With Protection From New or Increased Levels of Donor-Specific Antibodies Among Kidney Transplant Recipients Hospitalized With COVID-19.

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.

Greater community vulnerability is associated with poor living donor navigator program fidelity.

BACKGROUND: Community-level factors contribute to living donor kidney transplantation disparities but may also influence the interventions aimed to mitigate these disparities. The Living Donor Navigator Program was designed to separate the advocacy role from the patient in need of transplantation-friends/family are encouraged to participate as the patients' advocates to identify living donors, though some of the patients participate alone as self-advocates. Self-advocates have a lower living donor kidney transplantation likelihood compared to the patients with an advocate. We sought to evaluate the relationship between the patients' community-level vulnerability and living donor navigator self-advocacy as a surrogate for program fidelity. METHODS: This single-center, retrospective study included 110 Living Donor Navigator participants (April 2017-June 2019). Program fidelity was assessed using the participants' advocacy status. Measures of community vulnerability were obtained from the Centers for Disease Control and Prevention Social Vulnerability Index. Modified Poisson regression was used to evaluate the association between community-level vulnerability and living donor navigator self-advocacy. RESULTS: Of the 110 participants, 19% (n = 21) were self-advocates. For every 10% increase in community-level vulnerability, patients had 17% higher risk of self-advocacy (adjusted relative risk 1.17, 95% confidence interval: 1.03-1.32, P = .01). Living in areas with greater unemployment (adjusted relative risk: 1.18, 95% confidence interval: 1.04-1.33, P = .01), single-parent households (adjusted relative risk: 1.23, 95% confidence interval: 1.06-1.42, P = .006), minority population (adjusted relative risk: 1.30, 95% confidence interval: 1.04-1.55, P = .02), or no-vehicle households (adjusted relative risk: 1.17, 95% confidence interval: 1.02-1.35, P = .02) were associated with increased risk of self-advocacy. CONCLUSION: Having a greater community-level vulnerability was associated with poor Living Donor Navigator Program fidelity. The potential barriers identified using the Social Vulnerability Index may direct resource allocation and program refinement to optimize program fidelity and efficacy for all participants.

Donor-reported barriers to living kidney donor follow-up.

BACKGROUND: Despite regulations mandating follow-up laboratory testing for living kidney donors, less than half of transplant centers are in compliance. We sought to understand barriers to follow-up testing from the donors' perspective. METHODS: We surveyed our center's living kidney donors. Binary logistic regression was used to assess factors associated with follow-up testing completion. RESULTS: Of 185 living kidney donors, 110 (59.4%) participated. Among them, 82 (74.5%) completed 6-month laboratory testing, 76 (69.1%) completed 12-month testing, 68 (61.8%) completed both, and 21 (19.0%) completed neither. Six-month testing completion was strongly associated with 12-month testing completion (OR 9.74, 95%CI: 2.23-42.50; p = .002). Those who disagreed with the statements, "Getting labs checked wasn't a priority for me," (OR for completing 6-month testing: 15.05, 95%CI: 3.70-61.18; p < .001; OR for completing 12-month testing: 5.85, 95%CI: 1.94-17.63; p = .002); and, "I forgot to get labs drawn [until I was reminded]" (OR for completing 6-month testing: 6.93, 95%CI: 1.59-30.08; p = .01; OR for completing 12-month testing: 6.55, 95%CI: 1.98-21.63; p = .002) were more likely to complete testing. CONCLUSIONS: To our knowledge, this is the only study providing perspective on donor insights regarding the need for follow-up testing post donation. Interventions to influence living donor attitudes toward follow-up testing may improve follow-up.

First clinical-grade porcine kidney xenotransplant using a human decedent model.

A radical solution is needed for the organ supply crisis, and the domestic pig is a promising organ source. In preparation for a clinical trial of xenotransplantation, we developed an in vivo pre-clinical human model to test safety and feasibility tenets established in animal models. After performance of a novel, prospective compatible crossmatch, we performed bilateral native nephrectomies in a human brain-dead decedent and subsequently transplanted two kidneys from a pig genetically engineered for human xenotransplantation. The decedent was hemodynamically stable through reperfusion, and vascular integrity was maintained despite the exposure of the xenografts to human blood pressure. No hyperacute rejection was observed, and the kidneys remained viable until termination 74 h later. No chimerism or transmission of porcine retroviruses was detected. Longitudinal biopsies revealed thrombotic microangiopathy that did not progress in severity, without evidence of cellular rejection or deposition of antibody or complement proteins. Although the xenografts produced variable amounts of urine, creatinine clearance did not recover. Whether renal recovery was impacted by the milieu of brain death and/or microvascular injury remains unknown. In summary, our study suggests that major barriers to human xenotransplantation have been surmounted and identifies where new knowledge is needed to optimize xenotransplantation outcomes in humans.

Evaluation of Community-Level Vulnerability and Racial Disparities in Living Donor Kidney Transplant.

Importance: Living donor kidney transplant (LDKT) is the ideal treatment for end-stage kidney disease, but racial disparities in LDKT have increased over the last 2 decades. Recipient clinical and social factors do not account for LDKT racial inequities, although comprehensive measures of community-level vulnerability have not been assessed. Objective: To determine if racial disparities persist in LDKT independent of community-level vulnerability. Design, Setting, and Participants: This retrospective, multicenter, cross-sectional study included data from 19 287 adult kidney-only transplant recipients in the Scientific Registry of Transplant Recipients. The study included individuals who underwent transplant between January 1 and December 31, 2018. Exposures: Recipient race and the 2018 US Centers for Disease Control and Prevention Social Vulnerability Index (SVI). Census tract-level SVI data were linked to census tracts within each recipient zip code. The median SVI measure among the census tracts within a zip code was used to describe community-level vulnerability. Main Outcomes and Measures: Kidney transplant donor type (deceased vs living). Modified Poisson regression was used to evaluate the association between SVI and LDKT, and to estimate LDKT likelihood among races, independent of community-level vulnerability and recipient-level characteristics. Results: Among 19 287 kidney transplant recipients, 6080 (32%) received LDKT. A total of 11 582 (60%) were male, and the median (interquartile range) age was 54 (43-63) years. There were 760 Black LDKT recipients (13%), 4865 White LDKT recipients (80%), and 455 LDKT recipients of other races (7%; American Indian, Asian, multiracial, and Pacific Islander). Recipients who lived in communities with higher SVI (ie, more vulnerable) had lower likelihood of LDKT compared with recipients who lived in communities with lower SVI (ie, less vulnerable) (adjusted relative risk [aRR], 0.97; 95% CI, 0.96-0.98; P < .001). Independent of community-level vulnerability, compared with White recipients, Black recipients had 37% lower likelihood (aRR, 0.63; 95% CI, 0.59-0.67; P < .001) and recipients of other races had 24% lower likelihood (aRR, 0.76; 95% CI, 0.70-0.82; P < .001) of LDKT. The interaction between SVI and race was significant among Black recipients, such that the disparity in LDKT between Black and White recipients increased with greater community-level vulnerability (ratio of aRRs, 0.67; 95% CI, 0.51-0.87; P = .003). Conclusions and Relevance: Community-level vulnerability is associated with access to LDKT but only partially explains LDKT racial disparities. The adverse effects of living in more vulnerable communities were worse for Black recipients. The interaction of these constructs is worrisome and suggests evaluation of other health system factors that may contribute to LDKT racial disparities is needed.

Obesity as an isolated contraindication to kidney transplantation in the end-stage renal disease population: A cohort study.

OBJECTIVE: The aim of this study was to characterize end-stage renal disease (ESRD) patients with obesity as their only contraindication to listing and to quantify wait-list and transplant access. METHODS: Using the US Renal Data System, a retrospective cohort study of incident dialysis cases (2012 to 2014) was performed. The primary outcomes were time to wait-listing and time to transplantation. RESULTS: Of 157,572 dialysis patients not already listed, 39,844 had BMI as their only demonstrable transplant contraindication. They tended to be younger, female, and Black. Compared with patients with BMI < 35, those with BMI 35 to 39.9, 40 to 44.9, and ≥45 were, respectively, 15% (adjusted hazard ratio [aHR] 0.85; 95% CI: 0.83-0.88; p < 0.001), 45% (aHR 0.55; 95% CI: 0.52-0.57; p < 0.001), and 71% (aHR 0.29; 95% CI: 0.27-0.31; p < 0.001) less likely to be wait-listed. Wait-listed patients with BMI 35 to 39.9 were 24% less likely to achieve transplant (aHR 0.76; 95% CI: 0.72-0.80; p < 0.0001), BMI 40 to 44.9 were 21% less likely (aHR 0.79; 95% CI: 0.72-0.86; p < 0.0001), and BMI ≥ 45 were 15% less likely (aHR 0.85; 95% CI: 0.75-0.95; p = 0.004) compared with patients with BMI < 35. CONCLUSIONS: Obesity was the sole contraindication to wait-listing for 40,000 dialysis patients. They were less likely to be wait-listed. For those who were, they had a lower likelihood of transplant. Aggressive weight-loss interventions may help this population achieve wait-listing and transplant.

Self-advocacy is associated with lower likelihood of living donor kidney transplantation.

BACKGROUND: The Living Donor Navigator (LDN) Program pairs kidney transplant candidates (TC) with a friend or family member for advocacy training to help identify donors and achieve living donor kidney transplantation (LDKT). However, some TCs participate alone as self-advocates. METHODS: In this retrospective cohort study of TCs in the LDN program (04/2017-06/2019), we evaluated the likelihood of LDKT using Cox proportional hazards regression and rate of donor screenings using ordered events conditional models by advocate type. RESULTS: Self-advocates (25/127) had lower likelihood of LDKT compared to patients with an advocate (adjusted hazard ratio (aHR): 0.22, 95% confidence interval (CI): 0.03-1.66, p = 0.14). After LDN enrollment, rate of donor screenings increased 2.5-fold for self-advocates (aHR: 2.48, 95%CI: 1.26-4.90, p = 0.009) and 3.4-fold for TCs with an advocate (aHR: 3.39, 95%CI: 2.20-5.24, p < 0.0001). CONCLUSIONS: Advocacy training was beneficial for self-advocates, but having an independent advocate may increase the likelihood of LDKT.

The Living Donor Navigator Program Provides Support Tools for Caregivers.

INTRODUCTION: The Living Donor Navigator (LDN) program is one of several initiatives designed to help transplant candidates identify living donors with the help of a friend or family member advocate to speak on their behalf. More than half of advocates in the LDN program were the spouse or parent of the candidate and served in a caregiving role. Caregivers for patients awaiting transplantation have reported poorer quality of life than the general population, suggesting more support is needed for this vulnerable group. The purpose of this study was to understand whether the LDN program met the needs of advocates who were also caregivers for the transplant candidate. METHODS: We performed a supplementary secondary qualitative analysis of a parent study conducted December 2017-January 2018 with 9 advocates who participated in the LDN program. Transcripts were reanalyzed from focus group discussions, concentrating on comments about caregiving or made by caregivers. Using manual coding and reflexive thematic analysis, we identified broad codes and major themes. FINDINGS: Our re-analysis revealed one theme overlapping with our previous analysis (Support) and 2 new themes specific to caregiver advocates: Quality of Life and Fear. Caregivers agreed that the LDN program equipped them with tools to address these areas and best serve their simultaneous caregiver/advocate roles. DISCUSSION: These analyses demonstrated that those who served as advocate and caregiver derived a benefit from the LDN program but had distinct needs from other advocates. These findings can inform continued refinement of the program and expansion to support needs of caregiver.

When psychiatric symptoms reflect medical conditions.

The brain dysfunction associated with certain medical and neurological conditions can produce essentially any psychiatric symptom. This means there is always a chance that presentations thought to be 'psychiatric' are actually explained by unidentified medical pathology. This paper aims to outline an approach to minimise these missed diagnoses.

Genome-wide association analyses reveal complex genetic architecture underlying natural variation for flowering time in canola.

Optimum flowering time is the key to maximize canola production in order to meet global demand of vegetable oil, biodiesel and canola-meal. We reveal extensive variation in flowering time across diverse genotypes of canola under field, glasshouse and controlled environmental conditions. We conduct a genome-wide association study and identify 69 single nucleotide polymorphism (SNP) markers associated with flowering time, which are repeatedly detected across experiments. Several associated SNPs occur in clusters across the canola genome; seven of them were detected within 20 Kb regions of a priori candidate genes; FLOWERING LOCUS T, FRUITFUL, FLOWERING LOCUS C, CONSTANS, FRIGIDA, PHYTOCHROME B and an additional five SNPs were localized within 14 Kb of a previously identified quantitative trait loci for flowering time. Expression analyses showed that among FLC paralogs, BnFLC.A2 accounts for ~23% of natural variation in diverse accessions. Genome-wide association analysis for FLC expression levels mapped not only BnFLC.C2 but also other loci that contribute to variation in FLC expression. In addition to revealing the complex genetic architecture of flowering time variation, we demonstrate that the identified SNPs can be modelled to predict flowering time in diverse canola germplasm accurately and hence are suitable for genomic selection of adaptative traits in canola improvement programmes.

Cognitive behavioural therapy for depression: systematic review of imaging studies.

OBJECTIVE: Although cognitive behavioural therapy (CBT) has been shown to be an effective treatment for depression, the biological mechanisms underpinning it are less clear. This review examines if it is associated with changes identifiable with current brain imaging technologies. METHODS: To better understand the mechanisms by which CBT exerts its effects, we undertook a systematic review of studies examining brain imaging changes associated with CBT treatment of depression. RESULTS: Ten studies were identified, five applying functional magnetic resonance imaging, three positron emission tomography, one single photon emission computer tomography, and one magnetic resonance spectroscopy. No studies used structural MRI. Eight studies included a comparator group; in only one of these studies was there randomised allocation to another treatment. CBT-associated changes were most commonly observed in the anterior cingulate cortex (ACC), posterior cingulate, ventromedial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC) and amygdala/hippocampus. DISCUSSION: The evidence, such as it is, suggests resting state activity in the dorsal ACC is decreased by CBT. It has previously been suggested that treatment with CBT may result in increased efficiency of a putative 'dorsal cognitive circuit', important in cognitive control and effortful regulation of emotion. It is speculated this results in an increased capacity for 'top-down' emotion regulation, which is employed when skills taught in CBT are engaged. Though changes in activity of the dorsal ACC could be seen as in-keeping with this model, the data are currently insufficient to make definitive statements about how CBT exerts its effects. Data do support the contention that CBT is associated with biological brain changes detectable with current imaging technologies.

Catalytic wittig reactions of semi- and nonstabilized ylides enabled by ylide tuning.

The first examples of catalytic Wittig reactions with semistabilized and nonstabilized ylides are reported. These reactions were enabled by utilization of a masked base, sodium tert-butyl carbonate, and/or ylide tuning. The acidity of the ylide-forming proton was tuned by varying the electron density at the phosphorus center in the precatalyst, thus facilitating the use of relatively mild bases. Steric modification of the precatalyst structure resulted in significant enhancement of E selectivity up to >95:5, E/Z.

Brain structure in adolescents and young adults with alcohol problems: systematic review of imaging studies.

AIMS: Alcohol-dependent people who are middle-aged or older have a widespread loss of cortical grey and white matter, particularly in the prefrontal cortex (PFC). We examine if brain abnormalities are detectable in alcohol use disorders before the fifth decade (i.e., <40), and the brain structural differences associated with alcohol abuse/dependence in adolescence. METHODS: Case-control studies comparing brain structure in alcohol-abusing/-dependent individuals with normal controls in which the mean age of participants was <40 were identified using Medline, EMBASE and PsychInfo. Studies in which mean age was over and under 21 were considered separately. RESULTS: Twelve papers fulfilled inclusion criteria, five in the adolescent (14-21) and seven in the young adult age range. Two independent groups reported hippocampal and prefrontal volume reductions in adolescents, although this was consistently observed only in females. In young adults (aged 21-40), there were grey matter deficits in the PFC in both sexes. Adult women appeared to, particularly, exhibit white matter differences, evident as reduced area of the corpus callosum. Hippocampal volume reduction was observed in one study of young adults study but not another. CONCLUSION: The available data suggest that quantitative structural abnormalities of the brain are detectable in young alcohol abusers. There is overlap between the abnormalities seen in adolescents and young adults, although hippocampal volume loss is most consistently seen in the former group. The adolescent hippocampus may be particularly susceptible to alcohol, potentially because of an interaction between adolescent brain development and alcohol exposure.