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Code-domain signal processing techniques implemented at radio frequencies (RFs) enable simultaneous transmit and receive (STAR) applications. With direct sequence spread spectrum (DSSS) techniques and RF correlators, transmit (TX) self-interference (SI) is separated from the receive (RX) signal at the antenna interface for STAR. The processing gain inherent in the code-domain approach increases the TX SI rejection in the RF domain to relax filtering and linearity requirements of the RX. A code-domain RX demonstrates 52 dB of TX SI rejection with TX code-notch and RX code-pass filters operating at the same center frequency. The RX is tunable from 0.25 to 1.25 GHz and has a gain of 39 dB at 1 GHz while consuming 90 mW of which 40 mW are consumed in the front-end filters. The RX is implemented in a 45-nm CMOS SOI process and full-duplex operation is verified through an over-the-air demonstration.

A code-domain transceiver front end that incorporates a transmit modulator and a receive (RX) RF signal correlator is presented. An integrate-and-dump $N$ -path filter improves rejection by 8 dB. We propose an RF chopper switch with 12.1-/23.1-dBm P1dB/IIP3 for both RF correlation and filtering that rejects TX self-interference by 49.5 dB. Walsh and Barker codes are generated with fine and coarse tuning for synchronization. The RX power consumption is 18 mW, including dynamic power (1-V supply) and four analog amplifiers (1.5 V) at the operating frequency of 1 GHz and the code rate of 200 megachip-per-second (Mc/s). The TX modulator operates to RF power levels up to 34.3 dBm and consumes less than 40 mW for 300 Mc/s. Over the air testing demonstrates synchronization with Barker codes.

This article demonstrates a signal processing technique for receiving non-contiguous RF channels by concurrently mixing several RF bands to adjacent IF channels. Consequently, channel selection does not require local oscillator tuning and the proposed receiver (RX) can switch channels in less than 25 ns. The RX chip operates over a frequency range of 100 MHz–1.4 GHz and demonstrates an out-of-band rejection of 49 dB and a measured RX sensitivity of −86 dBm, which is the lowest measured for $N$ -path-based RXs. The chip was fabricated in a 45-nm RF silicon-on-insulator (SOI) CMOS process and occupies an active area of 0.55 mm2 with the power consumption of 23.1 mW when operating at 1 GHz. The chip performance is verified with over-the-air measurement of two transmitted signals 80 MHz apart that are received simultaneously with a 10-MHz analog-to-digital converter (ADC) at an error vector magnitude (EVM) around −20 dB. The measured dynamic range for EVM less than −20 dB is better than 86 dB for a QPSK constellation.

This article reports signal processing and circuit techniques for direct RF signal modulation. A pulse-encoded transition (PET) technique is introduced to reduce undesired harmonic distortion (HD) and adjacent channel leakage ratio (ACLR) generated by the direct RF modulation. To enable PET RF switching, two variations of a high-power, stacked-FET switch modulator, an 8- and 12-device stack, are designed in 45-nm silicon on insulator (SOI) CMOS. The switch design uses a tapering design to significantly improve power handling with minimal impact to switching speed. The modulators have $P_{1\,{\mathrm{ dB}}} $ values between 34 and 39 dBm while demonstrating a modulation bandwidth of nearly 500 MHz with a 1-GHz carrier. The input referred third order intercept point (IIP3) is between 46 and 61 dBm. Additionally, ACLR measurements of up to −50 dBc are demonstrated using the proposed PET technique at 30-dBm output power. To the best of our knowledge, this is record power handling and ACLR for a CMOS switch.

This paper demonstrates generalized code-selective filters for code-pass and code-reject signal processing at RF. A code-reject scheme using a quarter-wave ( $\lambda /4$ ) impedance transformation is also demonstrated to overcome tradeoffs of insertion loss (IL) and linearity compared to series band-reject $N$ -path filters. A 45-nm CMOS SOI implementation consumes a power of 9.32 mW from 1 to 1.8-V supplies at the frequency of 0.35–1.1 GHz and the chip area is 1.73 mm2. The measured transmit rejection is up to 22.6 dB with 4-dB IL. The in-band third-order-intercept point (IIP3) is up to 22.6 dBm and noise figure (NF) of 4–6 dB depending on the applied codes.

This paper presents a passive tunable matching network for load-modulation of a power amplifier (PA). With a set of discrete RF switches, different real impedance transformations can be realized to optimize the loadline match of the PA for output power and/or efficiency. To handle high-power, a 40-nm GaN MMIC process was used to realize three RF switches that switch across a ring impedance network. The tunable matching network realizes 15, 50, or 80Ω depending on the switch state with insertion loss (IL) between 1.7 and 3.3 dB at a center frequency of 28 GHz. The GaN devices have a high breakdown point and therefore the network P 1 dB exceeds 33 dBm. The bandwidth of the network exceeds 2.5 GHz.

Obesity is a global epidemic and coupled with the unprecedented growth of the world’s older adult population, a growing number of individuals are both old and obese. Whilst both ageing and obesity are associated with an increased prevalence of chronic health conditions and a substantial economic burden, evidence suggests that the coincident effects exacerbate negative health outcomes. A significant contributor to such detrimental effects may be the reduction in the contractile performance of skeletal muscle, given that poor muscle function is related to chronic disease, poor quality of life and all-cause mortality. Whilst the effects of ageing and obesity independently on skeletal muscle function have been investigated, the combined effects are yet to be thoroughly explored. Given the importance of skeletal muscle to whole-body health and physical function, the present study sought to provide a review of the literature to: (1) summarise the effect of obesity on the age-induced reduction in skeletal muscle contractile function; (2) understand whether obesity effects on skeletal muscle are similar in young and old muscle; (3) consider the consequences of these changes to whole-body functional performance; (4) outline important future work along with the potential for targeted intervention strategies to mitigate potential detrimental effects.

Prolonged high-fat diets (HFDs) can cause intramyocellular lipid (IMCL) accumulation that may negatively affect muscle function. We investigated the duration of a HFD required to instigate these changes, and whether the effects are muscle specific and aggravated in older age. Muscle morphology was determined in the soleus, extensor digitorum longus (EDL) and diaphragm muscles of female CD-1 mice from 5 groups: young fed a HFD for 8 weeks (YS-HFD, n=16), young fed a HFD for 16 weeks (YL-HFD, n=28) and young control (Y-Con, n=28). The young animals were 20 weeks old at the end of the experiment. Old (70 weeks) female CD-1 mice received either a normal diet (O-Con, n=30) or a HFD for 9 weeks (OS-HFD, n=30). Body mass, body mass index and intramyocellular lipid (IMCL) content increased in OS-HFD (P≤0.003). In the young mice, this increase was seen in YL-HFD and not YS-HFD (P≤0.006). The soleus and diaphragm fibre cross-sectional area (FCSA) in YL-HFD was larger than that in Y-Con (P≤0.004) while OS-HFD had a larger soleus FCSA compared with that of O-Con after only 9 weeks on a HFD (P, Summary: High-fat diet induces muscle fibre hypertrophy, an increase in oxidative capacity and accumulation of intracellular lipids, earlier in old than in young mice; these adaptations are muscle specific with the EDL being least responsive.

CMOS RF switches support watt-level RF output power while enabling signal processing with high speed. Typically, RF FET switches offer a tradeoff between a power handling and modulation bandwidth. This paper investigates the cause of compression in a FET switch, and the analysis suggests the optimization of the gate driving impedance for a stacked-FET switch. A design methodology is presented to realize watt-level power handling with high fractional bandwidth (FBW). The measurements demonstrate a BPSK modulator that can handle up to 10 W with wide FBW. The high-power, low-insertion loss, and high-modulation bandwidth demonstrate record performance.

Recent evidence has demonstrated an obesity-induced, skeletal muscle-specific reduction in contractile performance. The extent and magnitude of these changes in relation to total dose of high-fat diet consumption remains unclear. This study aimed to examine the dose–response relationship between a high-fat diet and isolated skeletal muscle contractility. 120 female CD1 mice were randomly assigned to either control group or groups receiving 2, 4, 8 or 12 weeks of a high-calorie diet (N = 24). At 20 weeks, soleus, EDL or diaphragm muscle was isolated (n = 8 in each case) and isometric force, work loop power output and fatigue resistance were measured. When analysed with respect to feeding duration, there was no effect of diet on the measured parameters prior to 8 weeks of feeding. Compared to controls, 8-week feeding caused a reduction in normalised power of the soleus, and 8- and 12-week feeding caused reduced normalised isometric force, power and fatigue resistance of the EDL. Diaphragm from the 12-week group produced lower normalised power, whereas 8- and 12-week groups produced significantly lower normalised isometric force. Correlation statistics indicated that body fat accumulation and decline in contractility will be specific to the individual and independent of the feeding duration. The data indicate that a high-fat diet causes a decline in muscle quality with specific contractile parameters being affected in each muscle. We also uniquely demonstrate that the amount of fat gain, irrespective of feeding duration, may be the main factor in reducing contractile performance.

There is currently a limited amount of literature investigating the age-related changes in eccentric muscle function in vitro. The present study uniquely uses the work loop (WL) technique, to better replicate in vivo muscle function, in the assessment of the age- and muscle-specific changes in acute and sustained concentric and eccentric power and recovery. Whole soleus or extensor digitorum longus (EDL) muscles were isolated from 10-week and 78-week-old mice and acute and sustained concentric and eccentric WL power assessed. Despite an age-related increase in body and muscle mass, peak absolute power for both muscles was unaffected by age. Peak concentric power normalized to muscle mass declined significantly for each muscle, while peak normalized eccentric power declined only for soleus. Fatigue resistance and recovery for the soleus did not differ between age or contraction type. Older EDL was less resistant to concentric fatigue, but was better able to withstand sustained eccentric activity than young EDL. We have shown that age-related changes in muscle quality are more limited for eccentric function than concentric function. A greater bodily inertia is likely to further reduce in vivo locomotor performance in older animals.

Obesity affects the major metabolic and cellular processes involved in skeletal muscle contractility. Surprisingly, the effect of obesity on isolated skeletal muscle performance remains unresolved. The present study is the first to examine the muscle-specific changes in contractility following dietary-induced obesity using an isolated muscle work-loop (WL) model that more closely represents in vivo muscle performance. Following 16-wk high-calorific feeding, soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) were isolated from female (CD-1) mice, and contractile performance was compared against a lean control group. Obese SOL produced greater isometric force; however, isometric stress (force per unit muscle area), absolute WL power, and normalized WL power (watts per kilogram muscle mass) were unaffected. Maximal isometric force and absolute WL power of the EDL were similar between groups. For both EDL and DIA, isometric stress and normalized WL power were reduced in the obese groups. Obesity caused a significant reduction in fatigue resistance in all cases. Our findings demonstrate a muscle-specific reduction in contractile performance and muscle quality that is likely related to in vivo mechanical role, fiber type, and metabolic profile, which may in part be related to changes in myosin heavy chain expression and AMP-activated protein kinase activity. These results infer that, beyond the additional requirement of moving a larger body mass, functional performance and quality of life may be further limited by poor muscle function in obese individuals. As such, a reduction in muscle performance may be a substantial contributor to the negative cycle of obesity.NEW & NOTEWORTHY The effect of obesity on isolated muscle function is surprisingly underresearched. The present study is the first to examine the effects of obesity on isolated muscle performance using a method that more closely represents real-world muscle function. This work uniquely establishes a muscle-specific profile of mechanical changes in relation to underpinning mechanisms. These findings may be important to understanding the negative cycle of obesity and in designing interventions for improving weight status.

Incidence rates for glioblastoma increase exponentially with age in a sex-specific manner, with a steeper increase observed in men. This suggests that age may be a more significant factor in promoting male tumors than female tumors. Drivers in the age-related cancer increase include both the accumulation of DNA damage and microenvironment changes, specifically an increase in the number of senescent cells. Cellular senescence comprises two distinct components – a cell cycle arrest program that prevents proliferation of mutated cells and acts as a potent anti-cancer mechanism, and a paracrine signaling component that can have both pro- and anti-tumorigenic properties. The contribution of senescence to brain tumor incidence and outcome is currently unknown; additionally, no research has been done on whether there are sex differences in mechanisms of senescence induction or in the secretory phenotype of senescent cells. Using both wildtype astrocytes and a glioblastoma model, we show that female cells have a lower threshold for senescence induction in response to oxidative stress, telomere shortening, and DNA damage, and that sex differences in senescence induction in response to DNA damage are in part mediated by differences in the regulation of p21. In addition, we show that male and female senescent astrocytes differ in their secretory phenotypes. Male senescent astrocytes secrete more tumor promoting factors, and conditioned media from male but not female senescent astrocytes promotes tumor cell proliferation. These findings provide a potential explanation for sex differences in glioblastoma incidence rates. Achieving a better understanding of mechanisms of senescence and how they differ in male and female cells could advance development of senescence directed therapies and potentially improve cancer treatment for a range of tumor types.

This paper demonstrates a code-domain transceiver that incorporates a transmit (TX) modulator and receive (RX) RF signal correlator. We propose a transmission gate switch with 12.1-dBm/23.1-dBm P1dB/IIP3 for both RF correlation and filtering and rejects TX self-interference by 49.5 dB. An integrate-and-dump N-path filter improves rejection by 8 dB. The RX power consumption is 18 mW at 1 GHz. The TX modulator operates to RF power levels up to 34.3 dBm and consumes less than 40 mW for 300 Megachip-per-second (Mc/s). Over the air testing demonstrates synchronization with Barker codes.

This work reports a high-power modulator implemented in 45-nm CMOS SOI for signal processing after the power amplifier. Two stacked switch variations, a 12 stack and 8 stack, were designed in 45-nm SOI CMOS and tested for trade-offs in insertion loss and power handling. These switches use a novel tapering technique to significantly improve switch linearity. The modulators have P 1dB values between 34 dBm and 39 dBm while demonstrating a modulation bandwidth of nearly 500 MHz with a 1 GHz carrier. The IIP3 is between 46 dBm and 61 dBm.

Objective Pharmacokinetics (PK) of antiseizure drugs differ considerably between rats and humans. Rodents require larger and more frequent doses to maintain therapeutic drug levels. This study uses the antiseizure drug (ASD) carbamazepine (CBZ) to validate the application of a previously described automated drug delivery system for delivering chronic oral medication to rats. Methods Treatment-naive, male Sprague-Dawley rats were treated with oral CBZ, 75 mg/kg every 6 hours for 10 days, via the automated feeder. Blood samples were collected on day 0 (acute), day 2 (steady-state), and day 9 (chronic) and used to measure plasma CBZ and carbamazepine-10,11-epoxide (CBZ-E) concentrations via high-performance liquid chromatography. The PK of CBZ and CBZ-E were modeled using Monolix v2018R1. The acute and chronic tolerability of CBZ was evaluated using the open field test. Results CBZ and CBZ-E concentrations were best described by a one-compartment parent-metabolite model with first-order absorption and elimination kinetics. Observed and predicted CBZ concentrations were maintained within the therapeutic window (4-12 μg/mL) for the duration of the study. There was no change in open-field test activity following acute or chronic oral dosing of 75 mg/kg CBZ compared to a pretreatment baseline (P > 0.4). Significance Oral administration of CBZ dosed q.i.d. in rats using an automated drug delivery system results in therapeutic concentrations of CBZ and its active metabolite. This study represents the first PK validation for this previously described preclinical drug delivery system.

Sex differences in incidence and outcome are consistently observed in cancer, including in the most common malignant brain tumor – glioblastoma (GBM). Women are less likely to develop GBM and have a survival advantage compared to men. Previous research from our lab identified the proteins Rb, p16, and p21 as key mediators of female protection against cellular transformation. Strikingly, these proteins are all primary components of the senescence response, a potent cell-intrinsic anti-cancer mechanism that results in permanent cell cycle arrest, preventing proliferation of damaged cells. We hypothesized that sex differences in GBM incidence and outcome are mediated by differences in senescence induction after DNA damage in male and female cells. Using both wildtype astrocytes and a GBM model, we found that females have a lower threshold for senescence induction in response to oxidative stress, telomere shortening, and treatment with chemotherapy or radiation. Following irradiation, female GBM model cells had higher levels of p21 expression, and p21 levels correlated with the percentage of senescent cells. Knocking out p21 eliminated sex differences in the senescence response following irradiation. Achieving a better understanding of mechanisms of senescence and how they differ in male and female cells could advance development of senescence-directed therapies and potentially improve treatment for brain tumors.

OBJECTIVE Medication nonadherence directly contributes to poor seizure control. A lack of emphasis on correcting poor adherence and failures in patient adherence can result in unwarranted alterations to a patient's drug regimen. We have modeled nonadherent patients in an animal model of epilepsy to study how alterations to pharmacotherapy, made without consideration of a patient's adherence, result in changes to seizure control. METHODS Newly diagnosed rats with epilepsy were treated with carbamazepine (CBZ) during a 4-week baseline period to establish their baseline seizure rate in the presence of 50% adherence. Next, animals were randomized to one of three treatment interventions and monitored for 6 weeks. Groups included: (1) no change in therapy-rats continued the 50% adherent paradigm; (2) dose escalation-the dose of CBZ was doubled, and the 50% adherent paradigm continued; and (3) nonadherence corrected-rats continued the initial dose of CBZ, but the adherence rate was adjusted to 100% (ie, fully adherent). RESULTS The rats in the no change in therapy arm displayed a 61% increase in seizure burden over the 6-week intervention phase. Similarly, rats in the dose escalation arm had a 66% worsening of their daily seizure burden. In contrast, rats in the nonadherence corrected arm displayed a 33% reduction in their daily seizure burden; a significant improvement when compared to the normalized seizure burden scores of rats in the other two treatment arms (P

This paper demonstrates transmit rejection with a quarter-wave $(\lambda/4)$ transformer that inverts the response of a shunt $N$ -path filter to break the inherent $N$ -path trade-offs between switch resistance and rejection. A 45-nm CMOS SOI filter supports both frequency and code selective filtering modes. The chip consumes a power of 9.37 mW from I-V and 1.8-V supplies at frequency of 0.9-1.1 GHz and the chip area is 1.77mm2. The transmit rejection is 21.9 dB with 3.3 dB insertion loss. The in-band third-order-intercept point (IIP3) is 22.6 dBm.

This paper reports a Watt-level power handling modulator using a stacked-FET switch for signal processing at the antenna. Two design approaches are compared in this paper: a resistive gate termination and an inductive gate termination. The stacked switches are implemented in 45-nm CMOS SOI. Measured performance of these stacked switches shows the benefit of an inductive termination: power handling capabilities of $> 30\ \mathbf{dBm}$ with modulation speeds of up to 300 MHz. The IIP3 is demonstrated to exceed 45 dBm.

The purpose of this study is to describe our technique for pericatheter retrograde urethrogram (pcRUG) and to evaluate the utility of a pcRUG to detect a clinically significant leak after urethral reconstruction. We retrospectively reviewed our prospective IRB-approved database of patients undergoing urethral reconstruction. pcRUG was performed at 3–4 weeks after surgery, in standardized fashion. Patients were placed in oblique position, and with the penis stretched, diluted contrast was instilled via an angiocatheter alongside the indwelling urethral catheter under dynamic fluoroscopy. The image was then evaluated for the presence of any contrast extravasation. Patient with and without extravasation seen on initial pcRUG were compared. From September 2012 through February 2017, 144 pericatheter retrograde urethrograms were performed on 130 patients. 115 patients (88.5%) had no extravasation on pcRUG. Fifteen patients (11.5%) demonstrated extravasation, with 13 of those patients (10%) undergoing a repeat pcRUG. Patients with extravasation seen on initial pcRUG were more likely to have strictures that were panurethral (36 vs. 9%, p = 0.029) and ≥10 cm (43 vs. 11%, p = 0.016). One patient (0.8%) presented with urinary leak and scrotal abscess after a urethra was assessed as sufficiently healed at the initial pcRUG and the catheter removed. There were otherwise no infectious or procedural complications related to pericatheter retrograde urethrogram. Our pericatheter retrograde urethrogram technique is a safe and reproducible technique to effectively assess urethral healing after urethroplasty and determine timing of catheter removal. The pcRUG is minimally invasive and is comparable in accuracy and sensitivity to voiding cystourethrography and retrograde urethrography that have traditionally been used to assess healing after urethroplasty.

Ageing and obesity independently have been shown to significantly impair isolated muscle contractile properties, though their synergistic effects are poorly understood. We uniquely examined the effects of 9 weeks of a high-fat diet (HFD) on isometric force, work loop power output (PO) across a range of contractile velocities, and fatigability of 79-week-old soleus, extensor digitorum longus (EDL) and diaphragm compared with age-matched lean controls. The dietary intervention resulted in a significant increase in body mass and gonadal fat pad mass compared to the control group. Despite increased muscle mass for HFD soleus and EDL, absolute isometric force, isometric stress (force/CSA), PO normalised to muscle mass and fatigability was unchanged, although absolute PO was significantly greater. Obesity did not cause an alteration in the contractile velocity that elicited maximal PO. In the obese group, normalised diaphragm PO was significantly reduced, with a tendency for reduced isometric stress and fatigability was unchanged. HFD soleus isolated from larger animals produced lower maximal PO which may relate to impaired balance in older, larger adults. The increase in absolute PO is smaller than the magnitude of weight gain, meaning in vivo locomotor function is likely to be impaired in old obese adults, with an association between greater body mass and poorer normalised power output for the soleus. An obesity-induced reduction in diaphragm contractility will likely impair in vivo respiratory function and consequently contribute further to the negative cycle of obesity.

We recently discovered that forebrain activation of the IL-1 receptor/Toll-like receptor (IL-1R1/TLR4) innate immunity signal plays a pivotal role in neuronal hyperexcitability underlying seizures in rodents. Since this pathway is activated in neurons and glia in human epileptogenic foci, it represents a potential target for developing drugs interfering with the mechanisms of epileptogenesis that lead to spontaneous seizures. The lack of such drugs represents a major unmet clinical need. We tested therefore novel therapies inhibiting the IL-1R1/TLR4 signaling in an established murine model of acquired epilepsy. We used an epigenetic approach by injecting a synthetic mimic of micro(mi)RNA-146a that impairs IL1R1/TLR4 signal transduction, or we blocked receptor activation with antiinflammatory drugs. Both interventions when transiently applied to mice after epilepsy onset, prevented disease progression and dramatically reduced chronic seizure recurrence, while the anticonvulsant drug carbamazepine was ineffective. We conclude that IL-1R1/TLR4 is a novel potential therapeutic target for attaining disease-modifications in patients with diagnosed epilepsy. (C) 2016 Elsevier Inc. All rights reserved

A hollow-core waveguide structure for on-chip atomic spectroscopy is presented. The devices are based on Anti-Resonant Reflecting Optical Waveguides and may be used for a wide variety of applications which rely on the interaction of light with gases and vapors. The designs presented here feature short delivery paths of the atomic vapor into the hollow waveguide. They also have excellent environmental stability by incorporating buried solid-core waveguides to deliver light to the hollow cores. Completed chips were packaged with an Rb source and the F = 3 ≥ F′ = 2, 3, 4 transitions of the D2 line in 85Rb were monitored for optical absorption. Maximum absorption peak depths of 9% were measured.

This paper presents an approach to quantifying the diffusion rate of rubidium in glass microchannels. These types of microchannels are often used in integrated systems (chip and fiber based) which utilize light and rubidium vapor interactions to produce quantum interference phenomena such as slow light. The test platforms reported here were made using glass capillaries connected to larger glass chambers through glassblowing. Rubidium diffusion was monitored in two different ways. First, fluorescence measurements were taken over time at different points down the length of the capillary. Second, optical absorption measurements were taken through the large glass chambers on either side of the capillaries. Results indicate that reaching measurable atomic densities in microscale geometries can take many days or even weeks.

We established the physiological relevance of LL-37 induced bladder inflammation. We hypothesized that 1) human urinary LL-37 is increased in pediatric patients with spina bifida, 2) LL-37 induced inflammation occurs in our mouse model via urothelial binding and is dose dependent and 3) LL-37 induced inflammation involves mast cells.To test our first hypothesis, we obtained urine samples from 56 pediatric patients with spina bifida and 22 normal patients. LL-37 was measured by enzyme-linked immunosorbent assay. Our second hypothesis was tested in C57Bl/6 mice challenged with 7 LL-37 concentrations intravesically for 1 hour. At 24 hours tissues were examined histologically and myeloperoxidase assay was done to quantitate inflammation. In separate experiments fluorescent LL-37 was instilled and tissues were obtained immediately (time = 0) and at 24 hours (time = 24). To test our final hypothesis, we performed immunohistochemistry for mast cell tryptase and evaluated 5 high power fields per bladder to determine the mean number of mast cells per mm(2).Urinary LL-37 was 89-fold higher in patients with spina bifida. Mouse LL-37 dose escalation experiments revealed increased inflammation at higher LL-37 concentrations. Fluorescent LL-37 demonstrated global urothelial binding at time = 0 but was not visible at time = 24. Immunohistochemistry for tryptase revealed mast cell infiltration in all tissue layers. At higher concentrations the LL-37 challenge led to significantly greater mast cell infiltration.Urinary LL-37 was significantly increased in pediatric patients with spina bifida. To our knowledge we report for the first time that LL-37 can elicit profound, dose dependent bladder inflammation involving the urothelium. Finally, inflammation propagation involves mast cells.