Alleviating nanostructural phase impurities enhances the optoelectronic properties, device performance and stability of cesium-formamidinium metal-halide perovskites.

The technique of alloying FA+ with Cs+ is often used to promote structural stabilization of the desirable α-FAPbI3 phase in halide perovskite devices. However, the precise mechanisms by which these alloying approaches improve the optoelectronic quality and enhance the stability have remained elusive. In this study, we advance that understanding by investigating the effect of cationic alloying in CsxFA1-xPbI3 perovskite thin-films and solar-cell devices. Selected-area electron diffraction patterns combined with microwave conductivity measurements reveal that fine Cs+ tuning (Cs0.15FA0.85PbI3) leads to a minimization of stacking faults and an increase in the photoconductivity of the perovskite films. Ultra-sensitive external quantum efficiency, kelvin-probe force microscopy and photoluminescence quantum yield measurements demonstrate similar Urbach energy values, comparable surface potential fluctuations and marginal impact on radiative emission yields, respectively, irrespective of Cs content. Despite this, these nanoscopic defects appear to have a detrimental impact on inter-grains'/domains' carrier transport, as evidenced by conductive-atomic force microscopy and corroborated by drastically reduced solar cell performance. Importantly, encapsulated Cs0.15FA0.85PbI3 devices show robust operational stability retaining 85% of the initial steady-state power conversion efficiency for 1400 hours under continuous 1 sun illumination at 35 °C, in open-circuit conditions. Our findings provide nuance to the famous defect tolerance of halide perovskites while providing solid evidence about the detrimental impact of these subtle structural imperfections on the long-term operational stability.

Dimeric Tubulin Modifies Mechanical Properties of Lipid Bilayer, as Probed Using Gramicidin A Channel.

Using the gramicidin A channel as a molecular probe, we show that tubulin binding to planar lipid membranes changes the channel kinetics-seen as an increase in the lifetime of the channel dimer-and thus points towards modification of the membrane's mechanical properties. The effect is more pronounced in the presence of non-lamellar lipids in the lipid mixture used for membrane formation. To interpret these findings, we propose that tubulin binding redistributes the lateral pressure of lipid packing along the membrane depth, making it closer to the profile expected for lamellar lipids. This redistribution happens because tubulin perturbs the lipid headgroup spacing to reach the membrane's hydrophobic core via its amphiphilic α-helical domain. Specifically, it increases the forces of repulsion between the lipid headgroups and reduces such forces in the hydrophobic region. We suggest that the effect is reciprocal, meaning that alterations in lipid bilayer mechanics caused by membrane remodeling during cell proliferation in disease and development may also modulate tubulin membrane binding, thus exerting regulatory functions. One of those functions includes the regulation of protein-protein interactions at the membrane surface, as exemplified by VDAC complexation with tubulin.

A Universal Perovskite/C60 Interface Modification via Atomic Layer Deposited Aluminum Oxide for Perovskite Solar Cells and Perovskite-Silicon Tandems.

The primary performance limitation in inverted perovskite-based solar cells is the interface between the fullerene-based electron transport layers and the perovskite. Atomic layer deposited thin aluminum oxide (AlOX) interlayers that reduce nonradiative recombination at the perovskite/C60 interface are developed, resulting in >60 millivolts improvement in open-circuit voltage and 1% absolute improvement in power conversion efficiency. Surface-sensitive characterizations indicate the presence of a thin, conformally deposited AlOx layer, functioning as a passivating contact. These interlayers work universally using different lead-halide-based absorbers with different compositions where the 1.55 electron volts bandgap single junction devices reach >23% power conversion efficiency. A reduction of metallic Pb0 is found and the compact layer prevents in- and egress of volatile species, synergistically improving the stability. AlOX-modified wide-bandgap perovskite absorbers as a top cell in a monolithic perovskite-silicon tandem enable a certified power conversion efficiency of 29.9% and open-circuit voltages above 1.92 volts for 1.17 square centimeters device area.

Patterns of Care for T1 Glottic Squamous Cell Carcinomas from 2004-2020.

OBJECTIVE(S): Describe recent national trends in overall treatment modalities for T1 glottic squamous cell carcinomas (SCC), and identify factors associated with treatment regimens. METHODS: National Cancer Database from 2004-2020 was queried for all patients with glottic cT1N0M0 SCC. Treatment patterns over time were analyzed using the Cochran-Armitage test for trend. Multivariable logistic regressions were used to determine the factors associated with treatment regimens. RESULTS: Of the 22,414 patients identified, most patients received RT only (57%), 21% received surgery only, and 22% received dual-modality treatment ("over-treatment"). Over the time period, there was a decreasing trend in rates of over-treatment for T1 glottic SCC (p < 0.001) and an increasing trend in surgery only (p < 0.001). Treatment in 2016-2018 (OR: 1.168 [1.004 to 1.359]), 2013-2015 (OR: 1.419 [1.221 to 1.648]), 2010-2012 (OR: 1.611 [1.388 to 1.871]), 2007-2009 (OR: 1.682 [1.450 to 1.951]), or 2004-2006 (OR: 1.795 [1.548 to 2.081]) versus 2019-2020 was associated with greater likelihood of over-treatment. T1b tumors were less likely to be over-treated (OR: 0.795 [0.707 to 0.894]) versus T1a tumors, and less likely to receive surgery first (OR: 0.536 [0.485 to 0.592]) versus T1a tumors. CONCLUSION: Over-treatment for T1 glottic SCC has been declining, with increasing rates of surgery only. Year of treatment was significantly associated with the receipt of dual-modality treatment. Finally, patients with T1b disease were more likely to receive RT as the first and only treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Subcutaneous batoclimab in generalized myasthenia gravis: Results from a Phase 2a trial with an open-label extension.

OBJECTIVES: To assess the safety, tolerability, and key pharmacodynamic effects of subcutaneous batoclimab, a fully human anti-neonatal Fc receptor monoclonal antibody, in patients with generalized myasthenia gravis and anti-acetylcholine receptor antibodies. METHODS: A Phase 2a, proof-of-concept, randomized, double-blind, placebo-controlled trial is described. Eligible patients were randomized (1:1:1) to receive once-weekly subcutaneous injections of batoclimab 340 mg, batoclimab 680 mg, or matching placebo for 6 weeks. Subsequently, all patients could enter an open-label extension study where they received batoclimab 340 mg once every 2 weeks for 6 weeks. Primary endpoints were safety, tolerability, and change from baseline in total immunoglobulin G, immunoglobulin G subclasses, and anti-acetylcholine receptor antibodies at 6 weeks post-baseline. Secondary endpoints included changes from baseline to 6 weeks post-baseline for Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, Myasthenia Gravis Composite, and revised 15-item Myasthenia Gravis Quality of Life scores. RESULTS: Seventeen patients were randomized to batoclimab 680 mg (n = 6), batoclimab 340 mg (n = 5), or placebo (n = 6). Batoclimab was associated with significantly greater reductions in total immunoglobulin G and anti-acetylcholine receptor antibodies from baseline to 6 weeks post-baseline than placebo. Reductions in immunoglobulin G subclasses were generally consistent with total immunoglobulin G. While clinical measures showed directionally favorable improvements over time, the study was not powered to draw conclusions about therapeutic efficacy. No safety issues were identified. INTERPRETATION: The safety profile, pharmacodynamics, and preliminary clinical benefits observed in this study support further investigation of subcutaneous batoclimab injections as a potential patient-administered therapy for seropositive generalized myasthenia gravis.

Treatment, Management, and Otolaryngology Consultation for Epistaxis in the Emergency Room: An Institutional Experience.

BACKGROUND: Epistaxis is a common reason for emergency department (ED) visits, accounting for approximately 1 of every 200 ED visits in the United States annually and up to one-third of all otolaryngology (ENT)-related ED encounters. OBJECTIVES: To detail reasons for ENT consultation for epistaxis in the ED, understand how consultation impacts patient care, assess follow-up patterns after emergency care, and study patient care after transfer or referral into the ED. METHODS: Retrospective chart review of 592 adult patients with epistaxis managed in a tertiary care ED setting between 2017 and 2018. Patients with known follow-up, ENT consult in the ED, or admission were included, while patients with trauma, recent head and neck surgery, or abnormal anatomy were excluded. RESULTS: The most common reasons for ENT consultation for epistaxis were for advanced management, referral to the ED from an outside facility or provider, and recent head and neck surgery. In total, 48.2% of patients treated for epistaxis in the ED received an ENT consultation. ENT consultation was associated with a higher likelihood of receiving absorbable or nonabsorbable packing (92.4% vs 36.1%). In total, 40.4% of patients referred into the ED from an outside facility or provider had no change in their management after receiving an ENT consult. Patients referred to the ED and White patients were significantly more likely to receive an ENT consult. Secondary analyses revealed that more White patients had an established outpatient ENT provider than patients of other races. On multivariate analysis, patients who received an ENT consult spent 75.2 min longer in the ED. CONCLUSION: The high percentage of patients referred or transferred to the ED for epistaxis management with no change in interventions after ENT consultation indicates a continued need to develop more precise clinical care pathways. Additionally, there may be gaps between White and non-White patients in access to ENT care.

The Effects of Exoskeleton Assistance at the Ankle on Sensory Integration During Standing Balance.

Exoskeleton devices can reduce metabolic cost, increase walking speed, and augment load-carrying capacity. However, little is known about the effects of powered assistance on the sensory information required to achieve these tasks. To learn how to use an assistive device, humans must integrate novel sensory information into their internal model. This process may be disrupted by challenges to the sensory systems used for posture. We investigated the exoskeleton-induced changes to balance performance and sensory integration during quiet standing. We asked 11 unimpaired adults to perform a virtual reality-based test of sensory integration in balance (VRSIB) on two days while wearing the exoskeleton either unpowered, using proportional myoelectric control, or with regular shoes. We measured postural biomechanics, muscle activity, equilibrium scores, postural control strategy, and sensory ratios. Results showed improvement in balance performance when wearing the exoskeleton on firm ground. The opposite occurred when standing on an unstable platform with eyes closed or when the visual information was non-veridical. The balance performance was equivalent when the exoskeleton was powered versus unpowered in all conditions except when both the support surface and the visual information were altered. We argue that in stable ground conditions, the passive stiffness of the device dominates the postural task. In contrast, when the ground becomes unstable the passive stiffness negatively affects balance performance. Furthermore, when the visual input to the user is non-veridical, exoskeleton assistance can magnify erroneous muscle inputs and negatively impact the user's postural control.

Survival and Enrichment Analysis of Epithelial-Mesenchymal Transition Genes in Bladder Urothelial Carcinoma.

The escalating prevalence of bladder cancer, particularly urothelial carcinoma, necessitates innovative approaches for prognosis and therapy. This study delves into the significance of genes related to epithelial-mesenchymal transition (EMT), a process inherently linked to carcinogenesis and comparatively better studied in other cancers. We examined 1184 EMT-related gene expression levels in bladder urothelial cancer cases through the TCGA dataset. Genes shown to be differentially expressed in relation to survival underwent further network and enrichment analysis to uncover how they might shape disease outcomes. Our in silico analysis revealed a subset of 32 genes, including those significantly represented in biological pathways such as VEGF signaling and bacterium response. In addition, these genes interact with genes involved in the JAK-STAT signaling pathway. Additionally, some of those 32 genes have been linked to immunomodulators such as chemokines CCL15 and CCL18, as well as to various immune cell infiltrates. Our findings highlight the prognostic utility of various EMT-related genes and identify possible modulators of their effect on survival, allowing for further targeted wet lab research and possible therapeutic intervention.

A blood biomarker test for brain amyloid impacts the clinical evaluation of cognitive impairment.

OBJECTIVE: The objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline. METHODS: The Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single-arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result on an amyloid positron emission tomography (PET) scan. The primary study outcomes were appropriateness of patient selection as well as result interpretation associated with PrecivityAD blood testing. RESULTS: A 95% (347/366) concordance rate was noted between clinicians' patient selection and the test's intended use criteria. In the final analysis including these 347 patients (median age 75 years, 56% women), prespecified test result categories incorporated 133 (38%) low APS, 162 (47%) high APS, and 52 (15%) intermediate APS patients. Clinicians' pretest and posttest AD diagnosis probability changed from 58% to 23% in low APS patients and 71% to 89% in high APS patients (p < 0.0001). Anti-AD drug therapy decreased by 46% in low APS patients (p < 0.0001) and increased by 57% in high APS patients (p < 0.0001). INTERPRETATION: These findings demonstrate the clinical utility of the PrecivityAD blood test in clinical care and may have added relevance as new AD therapies are introduced.

Interface passivation for 31.25%-efficient perovskite/silicon tandem solar cells.

Silicon solar cells are approaching their theoretical efficiency limit of 29%. This limitation can be exceeded with advanced device architectures, where two or more solar cells are stacked to improve the harvesting of solar energy. In this work, we devise a tandem device with a perovskite layer conformally coated on a silicon bottom cell featuring micrometric pyramids-the industry standard-to improve its photocurrent. Using an additive in the processing sequence, we regulate the perovskite crystallization process and alleviate recombination losses occurring at the perovskite top surface interfacing the electron-selective contact [buckminsterfullerene (C60)]. We demonstrate a device with an active area of 1.17 square centimeters, reaching a certified power conversion efficiency of 31.25%.

Hyperbaric oxygenation improve red blood cell deformability in patients with acute or chronic inflammation.

INTRODUCTION: Red blood cells (RBC) are one of the key elements of the microcirculation. Their ability to pass through capillaries and to deliver oxygen to cells is due to their large degree of deformability linked to the characteristics of the RBC membrane. Alterations in RBC deformability as a result of membrane damage, linked in part to increased synthesis of reactive oxygen species (ROS), can be observed in several diseases, such as sepsis, and may contribute to the altered microcirculation observed in these pathologies. Hyperbaric oxygen therapy (HBOT), with inhalation of 100 % oxygen, has been proposed in several acute or chronic pathologies, including carbon monoxide poisoning. OBJECTIVE: We investigated the effects of HBOT on oxidative stress from ROS produced by myeloperoxidase (MPO) and on RBC deformability in patients with acute or chronic inflammation (n = 10), in patients with acute carbon monoxide poisoning (n = 10), and in healthy volunteers (n = 10). METHODS: RBC deformability was evaluated before and after HBOT in the various populations using the ektacytometry technique (Laser-assisted Optical Rotational Red Cell Analyzer - LORRCA). Deformability was determined by the elongation index (EI) in relation to the shear stress (SS) over a range of 0.3 to 50 Pa. Oxidative stress was estimated through changes in proteins (chlorotyrosine and homocitrulline) induced by MPO activity measured by liquid chromatography-tandem mass spectrometry analysis. RESULTS: Before HBOT, EI was significantly lower in patients with acute or chronic inflammation than in healthy volunteers and patients with acute carbon monoxide poisoning for the majority of SS values studied. After one session of HBOT, the EI was significantly higher than before HBOT for SS values of 1.93 Pa or higher in patients with acute or chronic inflammation. This effect remains constant after 10 sessions. There were no differences before and after HBOT in protein or amino acid oxidation due to ROS generation mediated by MPO in the three populations. CONCLUSIONS: Our results confirm altered RBC deformability in patients with acute and chronic conditions associated with an underlying inflammatory process. HBOT improves deformability only after one session and therefore may improve microcirculation in this population. According to our results, this improvement does not seem mediated by the ROS pathway via MPO. These results need to be confirmed in a larger population.

Deep-Learning Electron Diffractive Imaging.

We report the development of deep-learning coherent electron diffractive imaging at subangstrom resolution using convolutional neural networks (CNNs) trained with only simulated data. We experimentally demonstrate this method by applying the trained CNNs to recover the phase images from electron diffraction patterns of twisted hexagonal boron nitride, monolayer graphene, and a gold nanoparticle with comparable quality to those reconstructed by a conventional ptychographic algorithm. Fourier ring correlation between the CNN and ptychographic images indicates the achievement of a resolution in the range of 0.70 and 0.55 Å. We further develop CNNs to recover the probe function from the experimental data. The ability to replace iterative algorithms with CNNs and perform real-time atomic imaging from coherent diffraction patterns is expected to find applications in the physical and biological sciences.

Associations of selenoprotein expression and gene methylation with the outcome of clear cell renal carcinoma.

Selenoproteins are a ubiquitous class of proteins defined by having a selenocysteine amino acid residue. While many of the selenoproteins have been well characterized with important roles in oxidation-reduction reactions and hormone synthesis among others, there exist some whose biological roles are not as well understood as denoted by the "SELENO" root. In this study, we explored associations between the reported RNA levels of "SELENO" proteins and clear cell renal cell carcinoma (ccRCC), the most common subtype of renal carcinoma in the US. Utilizing The Cancer Genome Atlas (TCGA) alongside other in silico tools, we discovered higher mRNA expression of Selenoprotein I, T, and P was associated with better overall survival outcomes and differential expression of other selenoproteins based on tumor stage. Additionally, we uncovered relative hypomethylation among selenoproteins in primary ccRCC tumor samples compared to normal tissue. Network and enrichment analysis showed numerous genes through which selenoproteins may modulate cancer progression and outcomes such as DERL1, PNPLA2/3, MIEN1, and FOXO1 which have been well-described in other cancers. In light of our findings highlighting an association of selenoprotein methylation and expression patterns with ccRCC outcome, further wet lab research is warranted.

Implementation and Usability of an Electronic Medical Record-based Ureteral Stent Tracker.

OBJECTIVE: To design and implement a simple electronic medical record-based ureteral stent tracker. To assess its impact on stent dwell time and stent-related complications. METHODS: Patients with stents placed 12 months before and 6 months after stent tracker implementation were identified at 3 urban hospitals. Those with stents-on-strings and intentional chronic indwelling stents (greater than 90 days) were excluded. Patient demographics, stent characteristics (eg, indication, string, dwell time), and clinical outcomes (eg, positive urine cultures, complications) were reviewed and compared between pre- and posttracker cohorts. A 12-question usability survey was administered to surgical nurses to assess usability. RESULTS: A total of 323 stents (173 pre- and 150 posttracker) were placed in 217 patients. The prestent tracker cohort had a longer mean dwell time (pre: 40.9 ± 59.1 days vs post: 28.8 ± 22.0 days, P = .02) and a higher retention rate >90 days (pre: 8.1% [14/173] vs post: 1.3% [2/150], P = .005). The 2 cohorts had no significant differences in positive urine culture rates, patient phone calls to providers, stent-related emergency department visits, or hospitalizations. The usability survey showed that 86.4% of surgical nurses found the tracker to be user-friendly and 95.5% reported that it added less than 1 minute of work per procedure. CONCLUSION: Implementation of an electronic medical record-based ureteral stent tracker decreased average stent dwell time and frequency of retained stents. Surgical nurses reported the tracker to be user-friendly and convenient. Stent trackers can improve the efficiency of postoperative removal of indwelling ureteral stents.

Restricting α-synuclein transport into mitochondria by inhibition of α-synuclein-VDAC complexation as a potential therapeutic target for Parkinson's disease treatment.

Involvement of alpha-synuclein (αSyn) in Parkinson's disease (PD) is complicated and difficult to trace on cellular and molecular levels. Recently, we established that αSyn can regulate mitochondrial function by voltage-activated complexation with the voltage-dependent anion channel (VDAC) on the mitochondrial outer membrane. When complexed with αSyn, the VDAC pore is partially blocked, reducing the transport of ATP/ADP and other metabolites. Further, αSyn can translocate into the mitochondria through VDAC, where it interferes with mitochondrial respiration. Recruitment of αSyn to the VDAC-containing lipid membrane appears to be a crucial prerequisite for both the blockage and translocation processes. Here we report an inhibitory effect of HK2p, a small membrane-binding peptide from the mitochondria-targeting N-terminus of hexokinase 2, on αSyn membrane binding, and hence on αSyn complex formation with VDAC and translocation through it. In electrophysiology experiments, the addition of HK2p at micromolar concentrations to the same side of the membrane as αSyn results in a dramatic reduction of the frequency of blockage events in a concentration-dependent manner, reporting on complexation inhibition. Using two complementary methods of measuring protein-membrane binding, bilayer overtone analysis and fluorescence correlation spectroscopy, we found that HK2p induces detachment of αSyn from lipid membranes. Experiments with HeLa cells using proximity ligation assay confirmed that HK2p impedes αSyn entry into mitochondria. Our results demonstrate that it is possible to regulate αSyn-VDAC complexation by a rationally designed peptide, thus suggesting new avenues in the search for peptide therapeutics to alleviate αSyn mitochondrial toxicity in PD and other synucleinopathies.

Ankle Exoskeleton Assistance can Affect Step Regulation during Self-Paced Walking.

Exoskeleton assistance can reduce metabolic cost and increase preferred walking speed in unimpaired and impaired groups, but individual outcomes are highly variable. Assistance may influence step regulation, leading to individual modulation of gait variability, energetic cost, and balance control. In this study, we aimed to understand the effects of a powered ankle exoskeleton on step regulation and its relationship to self-selected walking speed, cost of transport, and gait variability. We asked 12 unimpaired young adults to walk at their comfortable walking speed on a self-paced treadmill in their regular shoes, with the exoskeleton tracking zero torque, and in two trials using proportional myoelectric control. We measured preferred walking speed, cost of transport (COT), mean and standard deviation of gait parameters, (step length, step time, and step width) and computed long-term correlations via detrended fluctuation analysis (DFA). In all exoskeleton trials, subjects walked significantly slower than in their shoes. However, the COT was equivalent between shoes and both proportional myoelectric control trials. Subjects also increased medio-lateral balance control by increasing their mean step width and reducing both short-term variability and long-term auto-correlation for this parameter. In the second powered trial subjects returned to the levels of control over step width exhibited during regular shoe walking. During the unpowered condition subjects showed a significant association between step width regulation, walking speed, and COT. However, these parameters were not significantly associated when the assistance was turned on. Together, these results demonstrate that the response to assistance is closely related to the stepping strategy, especially in the initial stages of learning.

Merkel Cell Carcinoma: Changing Practice Patterns and Impact on Recurrence-Free and Overall Survival at a Single Institution and Nationally.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. Our report describes the evolution of management and characteristics associated with recurrence, disease-specific survival (DSS) and overall survival (OS) in the treatment of MCC. METHODS: A single institution retrospective review of MCC and SEER data to determine factors associated with RFS, DSS, and OS using a multivariable Cox regression on inverse-probability weighted cohorts. RESULTS: One hundred fifty-nine patients were identified with a median age of 75. Of these, 96% were Caucasian and 60% male. Fifty-eight out of 159 (36%) of all patients were deceased with 21/58 (36%) dead from MCC with a median follow-up of 3.1 years. Institutionally, trends over time demonstrated an increased use of immunotherapy with a concomitant decrease in chemotherapy and decreased use of radiotherapy alone. Institutionally and nationally, there has been increased surgical nodal staging. Institutionally, factors associated with shorter DSS included advanced age, active cigarette smoker (p = 0.002), cT2 disease (p = 0.007), and MCC with unknown primary (p < 0.001). Institutionally, factors associated with shorter OS included ages ≥ 75 years (p < 0.001), an immunocompromised state (p < 0.001), truncal primary site (p = 0.002), and cT2 disease (HR 9.59, p < 0.001). CONCLUSION: Changing practice patterns in MCC management have been driven by the adoption of immunotherapy. Our study highlights that competing risks of mortality in MCC patients likely prevents OS from being an accurate surrogate outcome measure to understand factors associated with DSS.

Nasal oxytocin for the treatment of psychiatric disorders and pain: achieving meaningful brain concentrations.

There is evidence of the therapeutic potential of intranasal oxytocin for the treatment of pain and various psychiatric disorders, however, there is scant evidence that oxytocin reaches the brain. We quantified the concentration and distribution pattern of [125I]-radiolabeled oxytocin in the brains and peripheral tissues of rats after intranasal delivery using gamma counting and autoradiography, respectively. Radiolabel was detected in high concentrations in the trigeminal and olfactory nerves as well as in brain regions along their trajectories. Considerable concentrations were observed in the blood, however, relatively low levels of radiolabel were measured in peripheral tissues. The addition of a mucoadhesive did not enhance brain concentrations. These results provide support for intranasal OT reaching the brain via the olfactory and trigeminal neural pathways. These findings will inform the design and interpretation of clinical studies with intranasal oxytocin.