Computational and systems neuroscience: The next 20 years.

Over the past 20 years, neuroscience has been propelled forward by theory-driven experimentation. We consider the future outlook for the field in the age of big neural data and powerful artificial intelligence models.

Does Prophylactic Stretching Reduce the Occurrence of Exercise-Associated Muscle Cramping? A Critically Appraised Topic.

CLINICAL SCENARIO: Exercise-associated muscle cramps (EAMC) are sudden, painful, and involuntary contractions of skeletal muscles during or after physical activity. The best treatment for EAMC is gentle static stretching until abatement. Stretching is theorized to relieve EAMC by normalizing alpha motor neuron control, specifically by increasing Golgi tendon organ activity, and physically separating contractile proteins. However, it is unclear if stretching or flexibility training prevents EAMC via the same mechanisms. Despite this, many clinicians believe prophylactic stretching prevents EAMC occurrence. CLINICAL QUESTION: Do athletes who experience EAMC during athletic activities perform less prophylactic stretching or flexibility training than athletes who do not develop EAMC during competitions? SUMMARY OF KEY FINDINGS: In 3 cohort studies and 1 case-control study, greater preevent muscle flexibility, stretching, or flexibility training (ie, duration, frequency) was not predictive of who developed EAMC during competition. In one study, athletes who developed EAMC actually stretched more often and 9 times longer (9.8 [23.8] min/wk) than noncrampers (1.1 [2.5] min/wk). CLINICAL BOTTOM LINE: There is minimal evidence that the frequency or duration of prophylactic stretching or flexibility training predicts which athletes developed EAMC during competition. To more effectively prevent EAMC, clinicians should identify athletes' unique intrinsic and extrinsic risk factors and target those risk factors with interventions. STRENGTH OF RECOMMENDATION: Minimal evidence from 3 prospective cohort studies and 1 case-control study (mostly level 3 studies) that suggests prophylactic stretching or flexibility training can predict which athletes develop EAMC during athletic competitions.

Network Polymer Properties Engineered Through Polymer Backbone Dispersity and Structure.

Dispersity (Ð or Mw/Mn) is an important parameter in material design and as such can significantly impact the properties of polymers. Here, polymer networks with independent control over the molecular weight and dispersity of the linear chains that form the material are developed. Using a RAFT polymerization approach, a library of polymers with dispersity ranging from 1.2-1.9 for backbone chain-length (DP) 100, and 1.4-3.1 for backbone chain-length 200 were developed and transformed to networks through post-polymerization crosslinking to form disulfide linkers. The tensile, swelling, and adhesive properties were explored, finding that both at DP 100 and DP 200 the swelling ratio, tensile strength, and extensibility were superior at intermediate dispersity (1.3-1.5 for DP 100 and 1.6-2.1 for DP 200) compared to materials with either substantially higher or lower dispersity. Furthermore, adhesive properties for materials with chains of intermediate dispersity at DP 200 revealed enhanced performance compared to the very low or high dispersity chains.

Evaluating instrumental learning and striatal-cortical functional connectivity in adolescent alcohol and cannabis use.

Adolescence is a vulnerable time for the acquisition of substance use disorders, potentially relating to ongoing development of neural circuits supporting instrumental learning. Striatal-cortical circuits undergo dynamic changes during instrumental learning and are implicated in contemporary addiction theory. Human studies have not yet investigated these dynamic changes in relation to adolescent substance use. Here, functional magnetic resonance imaging was used while 135 adolescents without (AUD-CUDLow ) and with significant alcohol (AUDHigh ) or cannabis use disorder symptoms (CUDHigh ) performed an instrumental learning task. We assessed how cumulative experience with instrumental cues altered cue selection preferences and functional connectivity strength between reward-sensitive striatal and cortical regions. Adolescents in AUDHigh and CUDHigh groups were slower in learning to select optimal instrumental cues relative to AUD-CUDLow adolescents. The relatively fast learning observed for AUD-CUDLow adolescents coincided with stronger functional connectivity between striatal and frontoparietal regions during early relative to later periods of task experience, whereas the slower learning for the CUDHigh group coincided with the opposite pattern. The AUDHigh group not only exhibited slower learning but also produced more instrumental choice errors relative to AUD-CUDLow adolescents. For the AUDHigh group, Bayesian analyses evidenced moderate support for no experience-related changes in striatal-frontoparietal connectivity strength during the task. Findings suggest that adolescent cannabis use is related to slowed instrumental learning and delays in peak functional connectivity strength between the striatal-frontoparietal regions that support this learning, whereas adolescent alcohol use may be more closely linked to broader impairments in instrumental learning and a general depression of the neural circuits supporting it.

Comparative study of therapy-related and de novo adult b-cell acute lymphoblastic leukaemia.

We report a comparative analysis of patients with therapy-related acute lymphoblastic leukaemia (tr-ALL) vs de novo ALL. We identified 331 patients with B-ALL; 69 (21%) were classified as tr-ALL. The most common prior malignancies were breast (23·2%) and plasma cell disorders (20·3%). Patients with tr-ALL were older (median 63·2 vs. 46·2 years, P < 0.001), more often female (66·7% vs. 43·5%, P < 0·001), and more likely to have hypodiploid cytogenetics (18·8% vs. 5·0%, P < 0·001). In multivariable analysis, patients with tr-ALL were less likely to achieve complete remission [odds ratio (OR) = 0·16, P < 0·001] and more likely to be minimal residual disease-positive (OR = 4·86, P = 0·01) but had similar OS after diagnosis and allo-haematopoietic cell transplantation.

Results of the United States Food and Drug Administration Clinical Trial of the CustomFlex Artificial Iris.

PURPOSE: To evaluate safety and efficacy of a custom-manufactured artificial iris device (CustomFlex Artificial Iris; HumanOptics AG) for the treatment of congenital and acquired iris defects. DESIGN: Multicenter, prospective, unmasked, nonrandomized, interventional clinical trial. PARTICIPANTS: Patients with photophobia, sensitivity secondary to partial or complete congenital or acquired iris defects, or both. METHODS: Eyes were implanted from November 26, 2013, to December 1, 2017, with a custom, foldable artificial iris by 1 of 4 different surgical techniques. Patients were evaluated 1 day, 1 week, and 1, 3, 6, and 12 months after surgery. At each examination, slit-lamp findings, intraocular pressure, implant position, subjective visual symptoms, and complications were recorded. Corrected distance visual acuity (CDVA) and endothelial cell density (ECD) were measured at 3, 6, or 12 months as additional safety evaluations. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to assess health-related quality of life affected by vision. The Global Aesthetic Improvement Scale was used to assess cosmetic results. MAIN OUTCOME MEASURES: Photosensitivity, glare, visual symptoms, NEI VFQ-25 score, Global Aesthetic Improvement Scale rating, prosthesis-related adverse events, intraocular lens (IOL)-related adverse events, and surgery-related adverse events 12 months after surgery. RESULTS: At the 12-month postoperative examination, a 59.7% reduction in marked to severe daytime light sensitivity (P < 0.0001), a 41.5% reduction in marked to severe nighttime light sensitivity (P < 0.0001), a 53.1% reduction in marked to severe daytime glare (P < 0.0001), and a 48.5% reduction in severe nighttime glare (P < 0.0001) were found. A 15.4-point improvement (P < 0.0001) in the NEI VFQ-25 total score was found, and 93.8% of patients reported an improvement in cosmesis as measured by the Global Aesthetic Improvement Scale 12 months after surgery. No loss of CDVA of > 2 lines related to the device was found. Median ECD loss was 5.3% at 6 months after surgery and 7.2% at 12 months after surgery. CONCLUSIONS: The artificial iris surpassed all key safety end points for adverse events related to the device, IOL, or implant surgery and met all key efficacy end points, including decreased light and glare sensitivity, improved health-related quality of life, and satisfaction with cosmesis. The device is safe and effective for the treatment of symptoms and an unacceptable cosmetic appearance created by congenital or acquired iris defects.

Sweat Characteristics in Individuals With Varying Susceptibilities of Exercise-Associated Muscle Cramps.

ABSTRACT: Szymanski, M, Miller, KC, O'Connor, P, Hildebrandt, L, and Umberger, L. Sweat characteristics in individuals with varying susceptibilities of exercise-associated muscle cramps. J Strength Cond Res 36(5): 1171-1176, 2022-Many medical professionals believe dehydration and electrolyte losses cause exercise-associated muscle cramping (EAMC). Unlike prior field studies, we compared sweat characteristics in crampers and noncrampers but accounted for numerous factors that affect sweat characteristics including initial hydration status, diet and fluid intake, exercise conditions, and environmental conditions. Sixteen women and 14 men (mean ± SD; age = 21 ± 2 year, body mass = 69.1 ± 11.6 kg, height = 171.4 ± 9.9 cm) self-reported either no EAMC history (n = 8), low EAMC history (n = 10), or high EAMC history (n = 12). We measured V̇o2max, and subjects recorded their diet. At least 3 days later, subjects ran at 70% of their V̇o2max for 30 minutes in the heat (39.9 ± 0.6° C, 36 ± 2% relative humidity). Dorsal forearm sweat was collected and analyzed for sweat sodium concentration ([Na+]sw), sweat potassium concentration ([K+]sw), and sweat chloride concentration ([Cl-]sw). Sweat rate (SWR) was estimated from body mass and normalized using body surface area (BSA). Dietary fluid, Na+, and K+ ingestion was estimated from a 3-day diet log. We observed no differences for any variable among the original 3 groups (p = 0.05-p = 0.73). Thus, we combined the high and low cramp groups and reanalyzed the data against the noncramping group. Again, there were no differences for [Na+]sw (p = 0.68), [K+]sw (p = 0.86), [Cl-]sw, (p = 0.69), SWR/BSA (p = 0.11), dietary Na+ (p = 0.14), dietary K+ (p = 0.66), and fluid intake (p = 0.28). Fluid and electrolyte losses may play a more minor role in EAMC genesis than previously thought.

Molecular-Driven Therapy in Advanced Thyroid Cancer.

OPINION STATEMENT: With a growing understanding of the biologic drivers of different thyroid cancers, there is an ongoing revolution in the treatment of aggressive and advanced disease variants. This includes matching patients with specific point mutations or gene fusions to targeted therapies (e.g., selective RET inhibitors), delineating patients who are likely to respond to immune checkpoint inhibition (i.e., PD-L1-positive tumors) and even priming responses to traditional therapies such as radioactive iodine (via concomitant MAPK pathway inhibition). There is also a growing role for genomics in the prognostication of thyroid tumors to aid the adjudication of appropriate treatments. Taking stock of the current state of the field, recent successes should be celebrated, but there still remains a long road ahead to improve outcomes for patients, particularly for radioactive-iodine refractory differentiated thyroid cancer and anaplastic thyroid cancer. In this review, we summarize findings from recent clinical trials and highlight promising preclinical data supporting molecular-driven therapy in advanced thyroid cancer. Ultimately, enrollment in clinical trials remains paramount to the advancement of thyroid cancer care.

Identifying Policy-relevant Indicators for Assessing Landscape Vegetation Patterns to Inform Planning and Management on Multiple-use Public Lands.

Understanding the structure and composition of landscapes can empower agencies to effectively manage public lands for multiple uses while sustaining land health. Many landscape metrics exist, but they are not often used in public land decision-making. Our objectives were to (1) develop and (2) apply a process for identifying a core set of indicators that public land managers can use to understand landscape-level resource patterns on and around public lands. We first developed a process for identifying indicators that are grounded in policy, feasible to quantify using existing data and resources, and useful for managers. We surveyed landscape monitoring efforts by other agencies, gathered science and agency input on monitoring goals, and quantified the prevalence of potential indicators in agency land health standards to identify five landscape indicators: amount, distribution, patch size, structural connectivity, and diversity of vegetation types. We then conducted pilot applications in four bureau of land management (BLM) field offices in Arizona, California, and Colorado to refine procedures for quantifying the indicators and assess the utility of the indicators for managers. Results highlighted the dominance of upland and the limited extent of riparian/wetland vegetation communities, moderate connectivity of priority vegetation patches, and lower diversity of native vegetation types on BLM compared to non-BLM lands. Agency staff can use the indicators to inform the development of quantitative resource management objectives in land use plans, evaluate progress in meeting those objectives, quantify potential impacts of proposed actions, and as a foundation for an all-lands approach to landscape-level management across public lands.

Infrared properties of high-purity silicon.

High-purity silicon is a readily available material of utility in realizing a variety of long-wavelength optical and guided wave components. The transmittance of uncompensated for silicon is measured in the far- and mid-infrared regimes at room and cryogenic temperatures. The experimental and analysis techniques used to extract the refractive index from 100-1000cm-1 (100-10 µm) are presented, and the results are compared to the literature. An average refractive index below 300cm-1, n^(300K)=3.417+i8.9×10-5, which transitions in cooling to n^(10K)=3.389+i4.9×10-6, is observed.

Far-infrared properties of cyclic olefin copolymer.

Cyclic olefin copolymer (COC) is an amorphous thermoplastic with desirable dielectric and mechanical characteristics for optical applications. In particular, its low refractive index, overall mechanical strength, and absence of strong absorption features make it a promising substrate material for far-infrared applications, which include frequency-selective surfaces, scattering filters, and windows. The dielectric properties of selected COC formulations are surveyed from $ \approx 10 - 700\,\, {{\rm cm}^{ - 1}} $≈10-700cm-1 ($ 1000 - 14\,\, \unicode{x00B5} {\rm m} $1000-14µm), and representative usage as a thin film membrane structure in optical filters is presented.

Sweat Characteristics of Cramp-Prone and Cramp-Resistant Athletes.

Exercise-associated muscle cramps (EAMCs) are thought to be caused by dehydration and/or electrolyte losses. In this multicenter, cross-sectional study, the authors determined whether sweat rates (SRs), sweat electrolyte concentrations, or sweat electrolyte content differed in athletes with (i.e., crampers) and without (i.e., noncrampers) a history of EAMCs and whether these variables could predict EAMC-prone athletes. Male and female collegiate athletes (N = 350) from 11 sports with (n = 245) and without (n = 105) a self-reported history of EAMCs completed a typical exercise or conditioning session. SRs, calculated from body mass, and posterior forearm sweat were analyzed for sweat sodium concentration ([Na+]sw), sweat potassium concentration ([K+]sw), and sweat chloride concentration ([Cl-]sw). The authors used SRs and sweat electrolyte concentrations to calculate sweat electrolyte content lost. Within each gender, no differences in SRs (204 males, p = .92; 146 females, p = .24); [Na+]sw (191 males, p = .55; 126 females, p = .55); Na+sw content (191 males, p = .59; 126 females, p = .20); [K+]sw (192 males, p = .57; 126 females, p = .87); K+sw content (192 males, p = .49; 126 females, p = .03); [Cl-]sw (192 males, p = .94; 77 females, p = .57); and Cl-sw content (192 males, p = .55; 77 females, p = .34) occurred between crampers and noncrampers. Receiver operating characteristic curve analysis revealed that sweat electrolyte content and SRs were predictive of EAMC-prone athletes in American football (area under curve = 0.65-0.72, p ≤ .005), but not in any other sport. EAMCs may not be solely caused by fluid or electrolyte losses in most athletes. Fluid and electrolyte replacement may help American footballers. Clinicians should individualize fluid and electrolyte replacement and understand different etiologies for EAMCs.

Histone deacetylase inhibition in combination with MEK or BCL-2 inhibition in multiple myeloma.

Despite recent advances in the treatment of multiple myeloma, patients with this disease still inevitably relapse and become refractory to existing therapies. Mutations in K-RAS, N-RAS and B-RAF are common in multiple myeloma, affecting 50% of patients at diagnosis and >70% at relapse. However, targeting mutated RAS/RAF via MEK inhibition is merely cytostatic in myeloma and largely ineffective in the clinic. We examined mechanisms mediating this resistance and identified histone deacetylase inhibitors as potent synergistic partners. Combining the MEK inhibitor AZD6244 (selumetinib) with the pan-histone deacetylase inhibitor LBH589 (panobinostat) induced synergistic apoptosis in RAS/RAF mutated multiple myeloma cell lines. Interestingly, this synergy was dependent on the pro-apoptotic protein BIM. We determined that while single-agent MEK inhibition increased BIM levels, the protein remained sequestered by antiapoptotic BCL-2 family members. LBH589 dissociated BIM from MCL-1 and BCL-XL, which allowed it to bind BAX/BAK and thereby initiate apoptosis. The AZD6244/LBH589 combination was specifically active in cell lines with more BIM:MCL-1 complexes at baseline; resistant cell lines had more BIM:BCL-2 complexes. Those resistant cell lines were synergistically killed by combining the BH3 mimetic ABT-199 (venetoclax) with LBH589. Using more specific histone deacetylase inhibitors, i.e. MS275 (entinostat) and FK228 (romidepsin), and genetic methods, we determined that concomitant inhibition of histone deacetylases 1 and 2 was sufficient to synergize with either MEK or BCL-2 inhibition. Furthermore, these drug combinations effectively killed plasma cells from myeloma patients ex vivo Given the preponderance of RAS/RAF mutations, and the fact that ABT-199 has demonstrated clinical efficacy in relapsed/refractory multiple myeloma, these drug combinations hold prom ise as biomarker-driven therapies.

Precooling's Effect on American Football Skills.

Bradley, LJ, Miller, KC, Wiese, BW, and Novak, JR. Precooling's effect on American football skills. J Strength Cond Res 33(10): 2616-2621, 2019-Precooling (i.e., cooling before exercise) may reduce the risk of exertional heatstroke (EHS) in American football athletes. However, implementation of precooling by coaches or medical staff would likely be poor if it impaired performance. We investigated whether precooling impacted American football skill performance in this randomized, crossover, counterbalanced study. Twelve men (24 ± 2 years, mass = 85.5 ± 6.3 kg, height = 181.8 ± 8.1 cm) completed a familiarization day to practice each skill and then 2 testing days. On testing days (wet-bulb globe temperature = 19.3 ± 4.1° C), subjects were either precooled for 15 minutes using cold-water immersion (10.1 ± 0.3° C) or not (control). Then, they donned an American football uniform and completed several bouts of 8 different football skills. Rectal temperature (Trec) was measured before, during, and after skill testing. Precooling did not affect vertical jump, broad jump, agility, dynamic or stationary catching, or maximum throwing distance (p ≥ 0.13). Precooling impaired 40-yard dash time (precooling = 5.72 ± 0.53 seconds, control = 5.31 ± 0.34 seconds; p = 0.03, effect size = 1.2) and throwing accuracy (precooling = 4 ± 1 points, control = 7 ± 2 points; p = 0.001, effect size = 1.4). On average, Trec was 0.58 ± 0.35° C lower during skills testing after precooling and statistically differed from control from minute 10 to the end of testing (∼35 minutes; p < 0.05, effect size ≥ 1.2). Precooling may be a useful EHS prevention strategy in American football players because it lowered Trec without impacting most skills. By lowering Trec, precooling would prolong the time it would take for an athlete's Trec to become dangerous (i.e., >40.5° C). If precooling is implemented, coaches should alter practice so that throwing accuracy and speed drills occur after an athlete's Trec returns to normal (i.e., >35 minutes).

Does Precooling With Whole-Body Immersion Affect Thermal Sensation or Perceived Exertion? A Critically Appraised Topic.

Clinical Scenario: Exertional heat stroke (EHS) is a potentially deadly heat illness and poses a significant health risk to athletes; EHS survival rates are near 100% if properly recognized and treated. Whole-body cold water immersion (CWI) is the most effective method for lowering body core temperature. Precooling (PC) with CWI before exercise may prevent severe hyperthermia or EHS by increasing the body's overall heat storage capacity. However, PC may also alter athletes' perception of how hot they feel or how hard they are exercising. Consequently, they may be unable to accurately perceive their body core temperature or how hard they are working, which may predispose them to severe hyperthermia or EHS. Clinical Question: Does PC with whole-body CWI affect thermal sensation (TS) or rating of perceived exertion (RPE) during exercise in the heat? Summary of Key Findings: In 4 studies, RPE during exercise ranged from 12 (2.0) to 20 (3.0), with no clinically meaningful differences between PC and control trials. TS scores ranged from 2 (1.0) to 8 (0.5) in control trials and from 2 (1.0) to 7.5 (0.5) during PC trials. Clinical Bottom Line: PC did not cause clinically meaningful differences in RPE or TS during exercise. It is unlikely that PC would predispose athletes to EHS by altering perceptions of exercise intensity or body core temperature. Strength of Recommendation: None of the reviewed studies (all level-2 studies with Physiotherapy Evidence Database scores ≥ 5) suggest that PC with CWI influences RPE or TS in exercising males.

Does Gender Affect Rectal Temperature Cooling Rates? A Critically Appraised Topic.

Clinical Scenario: Exertional heat stroke (EHS) is a medical emergency characterized by body core temperatures >40.5°C and central nervous system dysfunction. An EHS diagnosis should be immediately followed by cold-water immersion (CWI). Ideally, EHS victims cool at a rate >0.15°C/min until their temperature reaches 38.9°C. While generally accepted, these EHS treatment recommendations often stem from research that examined only males. Since gender differences exist in anthropomorphics (eg, body surface area, lean body mass) and anthropomorphics impact CWI cooling rates, it is possible that CWI cooling rates may differ between genders. Clinical Question: Do CWI rectal temperature (Trec) cooling rates differ between hyperthermic males and females? Summary of Findings: The average Trec cooling rate across all examined studies for males and females was 0.18 (0.05) and 0.24 (0.03)°C/min, respectively. Hyperthermic females cooled ∼33% faster than males. Clinical Bottom Line: Hyperthermic females cooled faster than males, most likely because of higher body surface area to mass ratios and less lean body mass. Regardless of gender, CWI is highly effective at lowering Trec. Clinicians must be able to treat all EHS victims, regardless of gender, with CWI, given its high survival rate when implemented appropriately. Strength of Recommendation: Moderate evidence (2 level 3 studies) suggests that females cool faster than males when treated with CWI following severe hyperthermia. Despite gender differences, cooling rates exceeded cooling rate recommendations for EHS victims (ie, 0.15°C/min).

Dielectric properties of conductively loaded polyimides in the far infrared.

The dielectric properties of selected conductively-loaded polyimide samples are characterized in the microwave through far-infrared wavebands. These materials, belonging to the Vespel family, are more readily formed by direct machining than their ceramic-loaded epoxy counterparts and present an interesting solution for realizing absorptive optical control structures. Measurements spanning a spectral range from 1 to 600 cm-1 (0.03-18 THz) were performed and used in parametrization of the media's dielectric function at frequencies below ≈3 THz.

Prophylactic stretching does not reduce cramp susceptibility.

INTRODUCTION: Some clinicians advocate stretching to prevent muscle cramps. It is unknown whether static or proprioceptive neuromuscular facilitation (PNF) stretching increases cramp threshold frequency (TFc ), a quantitative measure of cramp susceptibility. METHODS: Fifteen individuals completed this randomized, counterbalanced, cross-over study. We measured passive hallux range of motion (ROM) and then performed 3 minutes of either static stretching, PNF stretching (hold-relax-with agonist contraction), or no stretching. ROM was reassessed and TFc was measured. RESULTS: PNF stretching increased hallux extension (pre-PNF 81 ± 11°, post-PNF 90 ± 10°; P < 0.05) but not hallux flexion (pre-PNF 40 ± 7°, post-PNF 40 ± 7°; P > 0.05). Static stretching increased hallux extension (pre-static 80 ± 11°, post-static 88 ± 9°; P < 0.05) but not hallux flexion (pre-static 38 ± 9°, post-static 39 ± 8°; P > 0.05). No ROM changes occurred with no stretching (P > 0.05). TFc was unaffected by stretching (no stretching 18 ± 7 Hz, PNF 16 ± 4 Hz, static 16 ± 5 Hz; P = 0.37). DISCUSSION: Static and PNF stretching increased hallux extension, but neither increased TFc . Acute stretching may not prevent muscle cramping. Muscle Nerve 57: 473-477, 2018.

Randomized controlled trial of belladonna and opiate suppository during intravesical onabotulinum toxin A injection.

BACKGROUND: Intravesical injection with onabotulinum toxin A injection can be performed in-office under local anesthesia. Rectally administered pain medication presents a potentially feasible and previously uninvestigated adjunct to office-based anesthesia protocols. OBJECTIVE: The primary aim of this study was to determine whether adding a belladonna and opiate suppository to standard lidocaine instillation resulted in reduction of bladder injection pain during onabotulinum toxin A injection procedure. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study of patients undergoing onabotulinum toxin A bladder injection at a single clinic. Patients age ≥18 years, who met clinical criteria for invasive treatment of refractory urinary symptoms, had previously documented postvoid residual volumes <150 mL, and elected for in-office intravesical onabotulinum toxin A injection were eligible to participate. Participants were randomized by computer-generated block randomization to receive a belladonna and opiate (belladonna alkaloid with morphine 16.2/7.5 mg) or placebo suppository. Suppositories were placed immediately prior to lidocaine-based anesthesia, which all participants received. All participants underwent a standardized injection procedure using the same rigid cystoscope, needle type, and injection pattern (20 injections total). A 0-10 numeric rating scale was used to assess pain intensity before anesthesia and suppository, 40 minutes after administration of anesthesia and suppository, after first 10 bladder injections, and immediately after completion of 20 injections. Pain increase during procedure was calculated using the difference between score 40 minutes after administration of anesthesia and suppository and score after first 10 bladder injections. Postvoid residual were measured immediately postprocedure and 2 weeks later. Patient satisfaction with pain control was measured using a Likert scale. Our primary outcome was change in pain level from anesthetic baseline to midprocedure (score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository). A final sample size of 26 patients was needed to have 80% power (alpha = 0.05) to detect a 50% reduction in bladder injection pain during the procedure as defined by our primary outcome. An intent-to-treat approach was used for all analyses. RESULTS: In all, 26 participants were enrolled and randomized with 13 in each study arm. Participants in the treatment group were slightly older than in the placebo group (P = .05); there were no statistically significant differences in medical comorbidities. Median score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository for the placebo group and treatment group was 4 (range 1-10) and 5 (range 0,9), respectively (P = .94). Median scores immediately after completion of 20 injections for the placebo group and treatment group were 3 (range 0-10) and 2 (range 0,8), respectively (P = .29). There were no significant differences in preinjection pain scores reported before anesthesia and suppository and at 40 minutes after administration of anesthesia and suppository. Postprocedure postvoid residual >200 mL was noted in 5 (38%) of the placebo group and 3 (23%) of the treatment group (P = .67). Two-week postprocedure postvoid residual >200 mL was noted in 3 (25%) of the placebo group and 2 (15%) of the treatment group (P = .64) for an overall rate of 20%. Eleven (84%) participants in each group reported being "mostly satisfied" or "very much satisfied" with pain control. CONCLUSION: Belladonna and opiate suppository use did not significantly reduce bladder injection pain, or increase risk of urinary retention immediately postprocedure or 2 weeks later. Satisfaction with pain control among onabotulinum toxin A injection patients is high.