Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36.

Guanine-rich nucleic acid sequences challenge the replication, transcription, and translation machinery by spontaneously folding into G-quadruplexes, the unfolding of which requires forces greater than most polymerases can exert1,2. Eukaryotic cells contain numerous helicases that can unfold G-quadruplexes 3 . The molecular basis of the recognition and unfolding of G-quadruplexes by helicases remains poorly understood. DHX36 (also known as RHAU and G4R1), a member of the DEAH/RHA family of helicases, binds both DNA and RNA G-quadruplexes with extremely high affinity4-6, is consistently found bound to G-quadruplexes in cells7,8, and is a major source of G-quadruplex unfolding activity in HeLa cell lysates 6 . DHX36 is a multi-functional helicase that has been implicated in G-quadruplex-mediated transcriptional and post-transcriptional regulation, and is essential for heart development, haematopoiesis, and embryogenesis in mice9-12. Here we report the co-crystal structure of bovine DHX36 bound to a DNA with a G-quadruplex and a 3' single-stranded DNA segment. We show that the N-terminal DHX36-specific motif folds into a DNA-binding-induced α-helix that, together with the OB-fold-like subdomain, selectively binds parallel G-quadruplexes. Comparison with unliganded and ATP-analogue-bound DHX36 structures, together with single-molecule fluorescence resonance energy transfer (FRET) analysis, suggests that G-quadruplex binding alone induces rearrangements of the helicase core; by pulling on the single-stranded DNA tail, these rearrangements drive G-quadruplex unfolding one residue at a time.

Diversity of Chlamydia trachomatis in Trachoma-Hyperendemic Communities Treated With Azithromycin.

Prior studies have theorized that low chlamydial genetic diversity following mass azithromycin treatments for trachoma may create a population bottleneck that prevents the return of infection, but little empirical evidence exists to support this hypothesis. In this study, a single mass azithromycin distribution was administered to 21 communities in the Gurage Zone of Ethiopia in 2003. All children aged 1-5 years had conjunctival swabs performed before treatment and 2 and 6 months after treatment. All swabs positive for Chlamydia trachomatis at 2 months underwent typing of the gene encoding the major outer membrane protein (ompA) of C. trachomatis, as did the same number of swabs per community from the pretreatment and 6-month visits. Diversity of ompA types, expressed as the reciprocal of Simpson's index, was calculated for each community. In total, 15 ompA types belonging to the A and B genovars were identified. The mean diversity was 2.11 (95% confidence interval: 1.79, 2.43) before treatment and 2.16 (95% confidence interval: 1.76, 2.55) 2 months after treatment (P = 0.78, paired t test). Diversity of ompA was not associated with the prevalence of ocular chlamydia (P = 0.76) and did not predict subsequent changes in the prevalence of ocular chlamydia (P = 0.32). This study found no evidence to support the theory that ompA diversity is associated with transmission of ocular chlamydia.

Nigrostriatal Dopamine Acting on Globus Pallidus Regulates Sleep.

Lesions of the globus pallidus externa (GPe) produce a profound sleep loss (∼45%) in rats, suggesting that GPe neurons promote sleep. As GPe neuronal activity is enhanced by dopamine (DA) from the substantia nigra pars compacta (SNc), we hypothesized that SNc DA via the GPe promotes sleep. To test this hypothesis, we selectively destroyed the DA afferents to the caudoputamen (CPu) using 6-hydroxydopamine and examined changes in sleep-wake profiles in rats. Rats with 80-90% loss of SNc neurons displayed a significant 33.7% increase in wakefulness (or sleep reduction). This increase significantly correlated with the extent of SNc DA neuron loss. Furthermore, these animals exhibited sleep-wake fragmentation and reduced diurnal variability of sleep. We then optogenetic-stimulated SNc DA terminals in the CPu and found that 20-Hz stimulation from 9 to 10 PM increased total sleep by 69% with high electroencephalograph (EEG) delta power. We finally directly optogenetic-stimulated GPe neurons and found that 20-Hz stimulation of the GPe from 9 to 10 PM increased total sleep by 66% and significantly increased EEG delta power. These findings elucidate a novel circuit for DA control of sleep and the mechanisms of abnormal sleep in BG disorders such as Parkinson's disease and Huntington's disease.

Insights into the mechanism of a G-quadruplex-unwinding DEAH-box helicase.

The unwinding of nucleic acid secondary structures within cells is crucial to maintain genomic integrity and prevent abortive transcription and translation initiation. DHX36, also known as RHAU or G4R1, is a DEAH-box ATP-dependent helicase highly specific for DNA and RNA G-quadruplexes (G4s). A fundamental mechanistic understanding of the interaction between helicases and their G4 substrates is important to elucidate G4 biology and pave the way toward G4-targeted therapies. Here we analyze how the thermodynamic stability of G4 substrates affects binding and unwinding by DHX36. We modulated the stability of the G4 substrates by varying the sequence and the number of G-tetrads and by using small, G4-stabilizing molecules. We found an inverse correlation between the thermodynamic stability of the G4 substrates and rates of unwinding by DHX36. In stark contrast, the ATPase activity of the helicase was largely independent of substrate stability pointing toward a decoupling mechanism akin to what has been observed for many double-stranded DEAD-box RNA helicases. Our study provides the first evidence that DHX36 uses a local, non-processive mechanism to unwind G4 substrates, reminiscent of that of eukaryotic initiation factor 4A (eIF4A) on double-stranded substrates.

The anatomical, cellular and synaptic basis of motor atonia during rapid eye movement sleep.

Rapid eye movement (REM) sleep is a recurring part of the sleep-wake cycle characterized by fast, desynchronized rhythms in the electroencephalogram (EEG), hippocampal theta activity, rapid eye movements, autonomic activation and loss of postural muscle tone (atonia). The brain circuitry governing REM sleep is located in the pontine and medullary brainstem and includes ascending and descending projections that regulate the EEG and motor components of REM sleep. The descending signal for postural muscle atonia during REM sleep is thought to originate from glutamatergic neurons of the sublaterodorsal nucleus (SLD), which in turn activate glycinergic pre-motor neurons in the spinal cord and/or ventromedial medulla to inhibit motor neurons. Despite work over the past two decades on many neurotransmitter systems that regulate the SLD, gaps remain in our knowledge of the synaptic basis by which SLD REM neurons are regulated and in turn produce REM sleep atonia. Elucidating the anatomical, cellular and synaptic basis of REM sleep atonia control is a critical step for treating many sleep-related disorders including obstructive sleep apnoea (apnea), REM sleep behaviour disorder (RBD) and narcolepsy with cataplexy.

Identification of a direct GABAergic pallidocortical pathway in rodents.

Interaction between the basal ganglia and the cortex plays a critical role in a range of behaviors. Output from the basal ganglia to the cortex is thought to be relayed through the thalamus, but an intriguing alternative is that the basal ganglia may directly project to and communicate with the cortex. We explored an efferent projection from the globus pallidus externa (GPe), a key hub in the basal ganglia system, to the cortex of rats and mice. Anterograde and retrograde tracing revealed projections to the frontal premotor cortex, especially the deep projecting layers, originating from GPe neurons that receive axonal inputs from the dorsal striatum. Cre-dependent anterograde tracing in Vgat-ires-cre mice confirmed that the pallidocortical projection is GABAergic, and in vitro optogenetic stimulation in the cortex of these projections produced a fast inhibitory postsynaptic current in targeted cells that was abolished by bicuculline. The pallidocortical projections targeted GABAergic interneurons and, to a lesser extent, pyramidal neurons. This GABAergic pallidocortical pathway directly links the basal ganglia and cortex, and may play a key role in behavior and cognition in normal and disease states.

Spontaneous prebiotic formation of a ß-ribofuranoside that self-assembles with a complementary heterocycle.

The RNA World hypothesis is central to many current theories regarding the origin and early evolution of life. However, the formation of RNA by plausible prebiotic reactions remains problematic. Formidable challenges include glycosidic bond formation between ribose and the canonical nucleobases, as well as the inability of nucleosides to mutually select their pairing partners from a complex mixture of other molecules prior to polymerization. Here we report a one-pot model prebiotic reaction between a pyrimidine nucleobase (2,4,6-triaminopyrimidine, TAP) and ribose, which produces TAP-ribose conjugates in high yield (60-90%). When cyanuric acid (CA), a plausible ancestral nucleobase, is mixed with a crude TAP+ribose reaction mixture, micrometer-length supramolecular, noncovalent assemblies are formed. A major product of the TAP+ribose reaction is a ß-ribofuranoside of TAP, which we term TARC. This nucleoside is also shown to efficiently form supramolecular assemblies in water by pairing and stacking with CA. These results provide a proof-of-concept system demonstrating that several challenges associated with the prebiotic emergence of RNA, or pre-RNA polymers, may not be as problematic as widely believed.

EEG correlates of time-varying BOLD functional connectivity.

Recent resting-state fMRI studies have shown that the apparent functional connectivity (FC) between brain regions may undergo changes on time-scales of seconds to minutes, the basis and importance of which are largely unknown. Here, we examine the electrophysiological correlates of within-scan FC variations during a condition of eyes-closed rest. A sliding window analysis of simultaneous EEG-fMRI data was performed to examine whether temporal variations in coupling between three major networks (default mode; DMN, dorsal attention; DAN, and salience network; SN) are associated with temporal variations in mental state, as assessed from the amplitude of alpha and theta oscillations in the EEG. In our dataset, alpha power showed a significant inverse relationship with the strength of connectivity between DMN and DAN. In addition, alpha power covaried with the spatial extent of anticorrelation between DMN and DAN, with higher alpha power associated with larger anticorrelation extent. Results suggest an electrical signature of the time-varying FC between the DAN and DMN, potentially reflecting neural and state-dependent variations.

Efficient self-assembly in water of long noncovalent polymers by nucleobase analogues.

Molecular self-assembly is widely appreciated to result from a delicate balance between several noncovalent interactions and solvation effects. However, current design approaches for achieving self-assembly in water with small, synthetic molecules do not consider all aspects of the hydrophobic effect, in particular the requirement of surface areas greater than 1 nm(2) for an appreciable free energy of hydration. With the concept of a minimum hydrophobic surface area in mind, we designed a system that achieves highly cooperative self-assembly in water. Two weakly interacting low-molecular-weight monomers (cyanuric acid and a modified triaminopyrimidine) are shown to form extremely long supramolecular polymer assemblies that retain water solubility. The complete absence of intermediate assemblies means that the observed equilibrium is between free monomers and supramolecular assemblies. These observations are in excellent agreement with literature values for the free energy of nucleic acid base interactions as well as the calculated free energy penalty for the exposure of hydrophobic structures in water. The results of our study have implications for the design of new self-assembling structures and hydrogel-forming molecules and may provide insights into the origin of the first RNA-like polymers.

Neural systems approaches to understanding major depressive disorder: an intrinsic functional organization perspective.

Recent research detailing the intrinsic functional organization of the brain provides a unique and useful framework to gain a better understanding of the neural bases of Major Depressive Disorder (MDD). In this review, we first present a brief history of neuroimaging research that has increased our understanding of the functional macro-architecture of the brain. From this macro-architectural perspective, we examine the extant body of functional neuroimaging research assessing MDD with a specific emphasis on the contributions of default-mode, executive, and salience networks in this debilitating disorder. Next, we describe recent investigations conducted in our laboratory in which we explicitly adopt a neural-system perspective in examining the relations among these networks in MDD. Finally, we offer directions for future research that we believe will facilitate the development of more detailed and integrative models of neural dysfunction in depression.

Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world.

The RNA world hypothesis proposes that nucleic acids were once responsible for both information storage and chemical catalysis, before the advent of coded protein synthesis. However, it is difficult to imagine how nucleic acid polymers first appeared, as the abiotic chemical formation of long nucleic acid polymers from mononucleotides or short oligonucleotides remains elusive, and barriers to achieving this goal are substantial. One specific obstacle to abiotic nucleic acid polymerization is strand cyclization. Chemically activated short oligonucleotides cyclize efficiently, which severely impairs polymer growth. We show that intercalation, which stabilizes and rigidifies nucleic acid duplexes, almost totally eliminates strand cyclization, allowing for chemical ligation of tetranucleotides into duplex polymers of up to 100 base pairs in length. In contrast, when these reactions are performed in the absence of intercalators, almost exclusively cyclic tetra- and octanucleotides are produced. Intercalator-free polymerization is not observed, even at tetranucleotide concentrations > 10,000-fold greater than those at which intercalators enable polymerization. We also demonstrate that intercalation-mediated polymerization is most favored if the size of the intercalator matches that of the base pair; intercalators that bind to Watson-Crick base pairs promote the polymerization of oligonucleotides that form these base pairs. Additionally, we demonstrate that intercalation-mediated polymerization is possible with an alternative, non-Watson-Crick-paired duplex that selectively binds a complementary intercalator. These results support the hypothesis that intercalators (acting as 'molecular midwives') could have facilitated the polymerization of the first nucleic acids and possibly helped select the first base pairs, even if only trace amounts of suitable oligomers were available.

Nonenzymatic ligation of DNA with a reversible step and a final linkage that can be used in PCR.

Nonenzymatic DNA ligation chemistries containing a reversible step allow thermodynamic control of product formation, but they are not necessarily compatible with polymerase enzymes. We report a ligation system that uses commercially available reagents, includes a reversible step, and results in a linkage that can function as a template for PCR amplification with accurate sequence transfer.

Gender specific pelvic pain severity in neurogenic cystitis.

PURPOSE: Interstitial cystitis/painful bladder syndrome is a chronic bladder inflammatory disease of unknown etiology that is often regarded as neurogenic cystitis. The condition is associated with focal inflammation, urothelial lesions, voiding dysfunction and pain in the pelvic/perineal area. Approximately 90% of patients with the condition are women, suggesting the possibility of hormonal involvement in interstitial cystitis/painful bladder syndrome symptoms. We examined the basis of gender specific pelvic pain in a murine model of neurogenic cystitis that recapitulates features of interstitial cystitis/painful bladder syndrome and in which pelvic pain is mediated by mast cell histamine. MATERIALS AND METHODS: Murine neurogenic cystitis was induced by tail base inoculation of C57BL/6 or BALB/c mice with the Bartha strain of pseudorabies virus. Pelvic pain behavior was assessed by quantifying tactile allodynia in response to mechanical stimulation with von Frey filaments. Bladder mast cells were quantified by flow cytometry. RESULTS: Female mice of each genetic background showed significantly greater pelvic pain behavior than males, although responses were greater in BALB/c females. Gender specific pelvic pain behavior did not correspond to increased bladder inflammation or barrier dysfunction. Modulating reproductive hormonal status by ovariectomy and subsequent estrogen replacement had no effect on the magnitude of pseudorabies virus induced pain. The number of mast cells was associated with pelvic pain severity in female mice but it did not correlate with gender specific pelvic pain. CONCLUSIONS: These data suggest that pelvic pain in mice with murine neurogenic cystitis is mediated by gender specific responsiveness to mast cells while pelvic pain severity is modulated by genetic factors.

Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder.

OBJECTIVES: A range of prefrontal and subcortical volumetric abnormalities have been found in adults and adolescents with bipolar disorder. It is unclear, however, if these deficits are present early in the onset of mania or are a consequence of multiple mood episodes or prolonged exposure to medication. The goal of this study was to examine whether youth with bipolar I disorder who recently experienced their first episode of mania are characterized by brain volumetric abnormalities. METHODS: Anatomical images from magnetic resonance imaging of 26 13- to 18-year-old adolescents with bipolar I disorder and 24 age-comparable healthy controls with no personal or family history of psychopathology were analyzed using whole-brain voxel-based morphometry (VBM). RESULTS: Compared with healthy controls, adolescents with bipolar I disorder had significantly less gray matter volume in the left subgenual cingulate cortex [p<0.05, family-wise error (FWE)-corrected]. CONCLUSIONS: Adolescents with a recent single episode of mania have smaller subgenual cingulate cortex volume than do their healthy counterparts, suggesting that this anomaly occurs early in the onset of, or may predate the disorder. Longitudinal studies are needed to examine the impact of this volumetric reduction on the course and outcome of this disorder.

Reduced sleep quality in healthy girls at risk for depression.

Depression is characterized by sleep difficulties, but the extent to which subjective and objective sleep disturbances precede depression are unclear. This study was designed to examine perceptions of sleep quality in addition to actigraphy- and diary-measured sleep variables in healthy girls at low and high familial risk for major depressive disorder. Forty-four healthy daughters and their mothers completed a week of daily sleep diary and actigraphy; 24 girls had mothers with no history of psychopathology (low risk, mean age 14.92 years), and 20 girls had mothers with recurrent depression during the daughter's lifetime (high risk, mean age 14.12 years). All daughters had no current or past psychopathology. High-risk girls reported significantly poorer subjective sleep quality than did low-risk girls (P = 0.001). The two groups of participants did not differ in actigraphy- or diary-measured sleep duration, onset latency or snooze duration. Healthy girls at high familial risk for depression report poorer sleep quality than do girls at low risk for depression, despite the absence of group differences in objective sleep disturbances as measured by actigraphy or daily diary. This pattern of findings may reflect a broader cognitive or physiological phenotype of risk for depression.

A Randomized Phase 1 Evaluation of Deupirfenidone, a Novel Deuterium-Containing Drug Candidate for Interstitial Lung Disease and Other Inflammatory and Fibrotic Diseases.

LYT-100 (deupirfenidone) is a selectively deuterated form of pirfenidone under development for the treatment of inflammatory and fibrotic diseases, including interstitial lung disease. Adverse events associated with antifibrotics can be a barrier to adoption and persistence in patients with interstitial lung diseases, most of whom are not on standard-of-care therapy. LYT-100 is designed to have a differentiated pharmacokinetic (PK) profile from pirfenidone and could offer a differentiated safety profile compared to current standard-of-care drugs while retaining the biochemical potency and specificity of pirfenidone. We conducted a phase 1b study to ascertain the safety, tolerability, steady-state PK profile, and food effect of LYT-100. This was a 2-part study. Part 1 assessed multiple ascending doses of LYT-100 from 100, 250, 500, 750, and 1000 mg twice daily given over 5 days without titration. Part 2 assessed the effects of fed vs fasting conditions on the PK profile of a single 500-mg dose of LYT-100. All doses up to 1000 mg were well tolerated, with adverse events being mild and transient. Exposure was slightly lower in the fed condition. LYT-100 was well tolerated and has a dose-proportional PK profile. The ratio of parent to major metabolite concentration was higher than reported with pirfenidone, which is consistent with an effect of deuteration on metabolism. No maximum tolerated dose was identified up to 1000 mg twice-daily dosing. These results support further clinical development of LYT-100, particularly considering the adverse event profile of current standard-of-care drugs.

Characterization and factors associated with sleep quality in adolescents with bipolar I disorder.

Sleep disturbance is an early marker for bipolar disorder (BD) onset in youth. We characterized sleep quality in adolescents experiencing mania within the last 6-12 months. We examined the association between mood and sleep in 27 adolescents with BD and 24 matched healthy controls (HC). Subjects were assessed by parent and teen report of sleep, a semi-structured clinical interview, the Young Mania Rating Scale (YMRS), and the Childhood Depression Rating Scale (CDRS-R). Average BD youth YMRS (mean 20.3 ± 7.3) and CDRS-R (mean 42.4 ± 14.1) scores indicated they were still ill at time of assessment. Compared to HCs, adolescents with BD have distinct patterns of prolonged sleep onset latency, frequent nighttime awakenings, and increased total time awake. Mood symptoms, specifically excessive guilt, self-injurious behavior, and worsening evening mood, interfered with sleep. Further studies are needed to determine whether early regulation of sleep would improve long-term outcome in BD youth.

Characteristics Associated With New Patient Appointment No-Shows at an Academic Ophthalmology Department in the United States.

PURPOSE: This study aimed to identify patient and appointment characteristics associated with no-shows to new patient appointments at a US academic ophthalmology department. DESIGN: Cross-sectional study. METHODS: This was a study of all adult patients with new patient appointments scheduled with an attending ophthalmologist at Penn State Eye Center between January 1st and December 31st of 2019. A multiple logistic regression model was used to assess the association between characteristics and no-show status. RESULTS: Of 4,628 patients, 759 (16.4%) were no-shows. From the multiple logistic regression model, characteristics associated with no-shows were age (Odds Ratio (OR) for 18-40 years vs. >60 years: 3.41, 95% Confidence Interval (CI) 2.57, 4.51, p <0.001 and OR for 41-60 years vs. >60 years: 2.14, 95% CI 1.67, 2.74, p<0.001), median household income (OR for <$35,667 vs. >$59,445: 1.59, 95% CI 1.08, 2.34, p<0.001), insurance (OR for None vs. Medicare: 6.92, 95% CI 4.41, 10.86, p<0.001 and OR for Medicaid vs. Medicare: 1.54, 95% CI 1.18, 2.01, p=0.002), race (OR for Black vs. White: 2.62, 95% CI 2.00, 3.43, p<0.001 and OR for Other vs. White: 2.02, 95% CI 1.58, 2.59, p<0.001), and commute distance (OR for 5-10 mi vs. ≤5 mi: 1.73, 95% CI 1.17, 2.55, p=0.006). Appointments with longer lead times and scheduled with glaucoma or retina specialists were also significantly associated with greater no-shows. CONCLUSION: Certain patient and appointment characteristics were associated with no-show status. These findings may assist in the development of targeted interventions at the patient, practice, and health system levels to improve appointment attendance.

Sex Differences in Academic Rank, Scholarly Productivity, National Institutes of Health Funding, and Industry Ties Among Academic Cornea Specialists in the United States.

PURPOSE: This study analyzed sex differences among cornea specialists with regards to academic rank, scholarly productivity, National Institutes of Health (NIH) funding, and industry partnerships. DESIGN: Cross-sectional study. METHODS: This was a study of faculty at 113 US academic programs. Sex, residency graduation year, and academic rank were collected from institutional websites between January and March 2019. H-indices and m-quotients were collected from the Scopus database. The NIH Research Portfolio Online Reporting Tool and Centers for Medicare and Medicaid Services databases were queried for data on NIH funding and industry partnerships. RESULTS: Of the 440 cornea specialists identified, 131 (29.8%) were female. The proportions of females and males at each academic rank (assistant 69.5% vs 41.8%; associate 17.6% vs 21.0%; full professor 13.0% vs 37.2%) were not significant after adjusting for career duration (P = .083, .459, and .113, respectively). Females had significantly lower median h-indices (4.0 [interquartile range {IQR} 7.0] vs 11.0 [IQR 17.0], P < .001) and shorter median career duration (12.0 [IQR 11.0] vs. 25.0 [IQR 20.0] years, P < .001) than males but similar median m-quotients (0.5 [IQR 0.8] vs 0.5 [IQR 0.8], P = 1.00). Sex differences in h-indices were not seen at each academic rank or career duration interval. Among NIH-funded investigators, the median grant funding was $1.6M (IQR $2.2M) for females and $1.2M (IQR $4.6M, P = .853) for males. Overall, 25.5% of females and 58.6% of males (P = .600) had industry partnerships. CONCLUSION: Sex differences within academic ranks and h-indices are likely due to a smaller proportion of females with advanced career duration.

Neoadjuvant Leuprolide Therapy with Radical Prostatectomy: Long-term Effects on Health-related Quality of Life.

BACKGROUND: Neoadjuvant androgen ablation (neoadjuvant androgen deprivation therapy [NADT]) is used prior to radical prostatectomy, contrary to guidelines, but its long-term effects on quality of life is unknown. OBJECTIVE: To determine the effect of NADT on patient's long-term recovery following surgery. DESIGN, SETTING, AND PARTICIPANTS: From March 2011 to August 2013, 5808 men with newly diagnosed prostate were followed up to 24 mo. A cohort of men who received NADT prior to robotic-assisted laparoscopic prostatectomy (RALP; n=51) was compared 1:3 with a matched group that underwent RALP only (n=153). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were matched on Charlson comorbidities, biopsy Gleason score, and node status on final pathology. The Kruskall-Wallis test was used to compare the groups on their bowel, urinary, sexual, and hormonal domains of the 26-item Expanded Prostate Cancer Index Composite at baseline and at 1, 3, 6, 12, 18, and 24 mo postoperatively. RESULTS AND LIMITATIONS: The urinary irritative, urinary incontinence, and bowel domains were similar in the two groups during the 24 mo (p=0.832, 0.901, and 0.732, respectively). In the hormonal domain, the NADT group did worse (p<0.001). The sexual domain was also worse for the NADT group. However, when accounting for nerve sparing, there was no significant difference in sexual outcomes between the two groups (p=0.069). CONCLUSIONS: Patients who received NADT prior to RALP do not have worse sexual function, but have worse hormonal scores for up to 2yr after surgery. PATIENT SUMMARY: Neoadjuvant androgen deprivation therapy (NADT) is administered prior to robotic-assisted laparoscopic prostatectomy (RALP), contrary to clinical guidelines. NADT may not have worse sexual function outcomes up to 2yr after RALP.