Outcomes of Transplantation of Single Kidneys From Pediatric Donors Into Adult Recipients.

Background Organs from extreme ages have been sought after to help increase the donor pool and alleviate transplantation wait times. There has been a growing evolution of the use of pediatric donor kidneys, including the use of en bloc kidneys (EBK), to now separating them into single kidneys (SKT), allowing for transplantation of two recipients. This study reports our outcomes utilizing SKT. Methods A retrospective review of all SKT performed from 2014 to 2022 at our center was conducted. Donors >8 years of age or >25 kg in weight were excluded. Donor and recipient characteristics and outcomes were analyzed, comparing <18 kg and ≥18 kg donor cohorts. Results Between 2014 and 2022, 81 adults received SKT. Recipients' mean age, weight, and body mass index were 49 years (22-74), 74 kg (39-136), and 26.4 mg/m2 (19.6- 39.8), respectively. Donors' mean age, weight, and kidney size were 35.7 months (8-96), 17.8 kg (8-25), and 7.2 cm (4.5-8.5), respectively. At one year post-transplant, patient survival was 100%, graft survival was 98.7%, mean serum creatinine was 1.25 mg/dL, and mean glomerular filtration rate (GFR) was 68.3 ml/min. Hyperfiltration injury was seen in 43.75% of recipients. None of the outcomes correlated with any of the donor or recipient characteristics. Conclusion Our study shows excellent short-term outcomes of single pediatric kidney transplantation in adult recipients. Exploring a lower donor weight cut-off for SKT, compared to the current Organ Procurement and Transplantation Network's (OPTN's) ≥18 kg, could expand the organ pool and lead to an increased number of transplants.

"Pre-Histologic" Antibody-Mediated Rejection Detected by Donor-Derived Cell-Free DNA and a Novel Tissue Gene Expression Assay: A Case Report.

BACKGROUND: Despite its well-characterized association with poor long-term graft outcomes, subclinical antibody-mediated rejection (ABMR) in recipients of kidney transplants continues to pose a significant diagnostic and therapeutic challenge. Specifically, its detection currently relies on invasive histologic surveillance, a relatively uncommon practice among US transplant centers. We describe a subclinical, "pre-histologic" antibody-mediated rejection identified and characterized by a combination of novel molecular tools, donor-derived cell-free DNA (dd-cfDNA), and molecular histology. CASE REPORT: A 67-year-old kidney transplant recipient was found to have a marked elevation of dd-cfDNA on routine testing at 3 months post-transplant; other laboratory parameters were stable. A biopsy was performed, demonstrating the absence of rejection by traditional histology, but evidence of rejection was seen when tissue was evaluated using a research use molecular histology assay. Four months later, in the setting of persistently elevated dd-cfDNA, the patient developed graft dysfunction and was found to have C4d-negative ABMR, which was treated with improvement in both graft function and dd-cfDNA. CONCLUSION: This case highlighted the complementary use of dd-cfDNA and molecular histology to aid in the early detection and characterization of graft injury. Hybrid approaches combining these tools may allow more expeditious therapeutic intervention, leading to improved graft and patient outcomes.

Facilitating flip-flop: Structural tuning of molecule-membrane interactions in living bacteria.

The first barrier that a small molecule must overcome before trespassing into a living cell is the lipid bilayer surrounding the intracellular content. It is imperative, therefore, to understand how the structure of a small molecule influences its fate in this region. Through the use of second harmonic generation, we show how the differing degrees of ionic headgroups, conjugated system, and branched hydrocarbon tail disparities of a series of four styryl dye molecules influence the propensity to "flip-flop" or to be further organized in the outer leaflet by the membrane. We show here that initial adsorption experiments match previous studies on model systems; however, more complex dynamics are observed over time. Aside from probe molecule structure, these dynamics also vary between cell species and can deviate from trends reported based on model membranes. Specifically, we show here that the membrane composition is an important factor to consider for headgroup-mediated small-molecule dynamics. Overall, the findings presented here on how structural variability of small molecules impacts their initial adsorption and eventual destinations within membranes in the context of living cells could have practical applications in antibiotic and drug adjuvant design.

Men Have Gender and Women Are People: A Structural Approach to Gender and Violence.

The relationship between violence and patriarchal gender systems is structural and coconstitutive; yet structural analyses that account for gender in explanations and conceptualizations of violence are often absent from violence scholarship. Additionally, there are numerous underassessed areas in more gender-nuanced, "gender-based" violence paradigms. We address the shortcomings of both types of research and propose a cohesive theoretical framework that captures the ways in which violence is patriarchy-enhancing and patriarchy-facilitated. Violence shapes and influences gender performances and structures and, concomitantly, the gender order shapes and influences violence in given contexts.

Impact of Protease Inhibitor-Based Antiretroviral Therapy on Tacrolimus Intrapatient Variability in HIV-Positive Kidney Transplant Recipients.

BACKGROUND: Human immunodeficiency virus (HIV)-positive kidney transplant (KT) recipients have been shown to experience higher rejection rates due in part to drug-drug interactions between antiretroviral therapy (ART) and immunosuppression regimens. High tacrolimus (FK) intrapatient variability (IPV) is associated with inferior outcomes in KT. The purpose of this study was to determine the impact of protease inhibitor (PI)-based ART on FK IPV and graft outcomes. METHODS: We performed a single-center review of HIV-positive KT recipients from 2007 to 2017. Percentage coefficient of variation (%CV = (σ/µ) × 100; σ, median; µ, standard deviation) was calculated for FK IPV. FK IPV at 6 and 12 months, graft function, and immune outcomes in PI-based vs non-PI-based KT recipients were compared. RESULTS: A total of 23 HIV-positive KT patients were identified, of whom 10 were maintained on PI-based ART. Median IPV for the entire cohort at 6 and 12 months was 35.8% and 41%, respectively. Patients on PI-based regimens were proportionally more likely to experience high IPV at both time points. Median FK IPV was numerically higher at 6 months (37.3% vs 26.8%, P = .11) and significantly higher at 12 months (57.8% vs 30.9%, P = .01) for patients on PI-based regimens. Lastly, inferior graft function was observed in PI-based patients. CONCLUSION: Our data suggest that PI-based ART is associated with a higher degree of FK IPV, which may contribute to worsening graft function. Larger studies are warranted to determine the impact of PI-based ART on FK IPV and graft outcomes in this population.

Brevibacillus Laterosporus Bacteremia in an Adult.

Brevibacillus laterosporus (B. laterosporus) is an aerobic gram-positive bacillus that is rarely associated with human infection. A review of multiple online databases revealed no other cases of bacteremia in an adult involving this organism. Historically, this "canoe-shaped" microbe has been characterized as a pathogen in invertebrates, and information regarding human infection is scarce. We present a clinical vignette of what we believe to be the first reported case of B. laterosporus bacteremia in an adult human subject.

Dialysis Disequilibrium Syndrome and Cerebellar Herniation with Successful Reversal Using Mannitol.

Dialysis disequilibrium syndrome (DDS) is a morbid but rare complication of dialysis. Feared sequalae of this diagnosis are brain herniation and death. This report presents a patient who was diagnosed with DDS with subsequent tonsillar herniation shown on imaging with complete resolution of clinical signs and symptoms, as well as imaging findings of herniation after prompt initiation of intravenous mannitol. This is the first known case of reversal and survival of DDS-induced tonsillar herniation using mannitol.

Sample exchange by beam scanning with applications to noncollinear pump-probe spectroscopy at kilohertz repetition rates.

In laser spectroscopy, high photon flux can perturb the sample away from thermal equilibrium, altering its spectroscopic properties. Here, we describe an optical beam scanning apparatus that minimizes repetitive sample excitation while providing shot-to-shot sample exchange for samples such as cryostats, films, and air-tight cuvettes. In this apparatus, the beam crossing point is moved within the focal plane inside the sample by scanning both tilt angles of a flat mirror. A space-filling spiral scan pattern was designed that efficiently utilizes the sample area and mirror scanning bandwidth. Scanning beams along a spiral path is shown to increase the average number of laser shots that can be sampled before a spot on the sample cell is resampled by the laser to ∼1700 (out of the maximum possible 2500 for the sample area and laser spot size) while ensuring minimal shot-to-shot spatial overlap. Both an all-refractive version and an all-reflective version of the apparatus are demonstrated. The beam scanning apparatus does not measurably alter the time delay (less than the 0.4 fs measurement uncertainty), the laser focal spot size (less than the 2 µm measurement uncertainty), or the beam overlap (less than the 3.3% measurement uncertainty), leading to pump-probe and autocorrelation signal transients that accurately characterize the equilibrium sample.

Communication: uncovering molecule-TiO2 interactions with nonlinear spectroscopy.

Femtosecond transient grating experiments are used to investigate electronic structures and transport mechanisms in dye-sensitized nanocrystalline TiO(2) films. This study examines two molecular sensitizers spanning the weak (a phosphonated Ruthenium complex) and strong (catechol) molecule-TiO(2) coupling regimes. It is shown that strong molecule-TiO(2) interactions give rise to photoinduced vibrational coherences at the interface between species. We suggest that the amplitudes of these coherences reflect the molecule-TiO(2) coupling strength and signify the delocalization of excited state wavefunctions.