Shaping dynamical neural computations using spatiotemporal constraints.

Dynamics play a critical role in computation. The principled evolution of states over time enables both biological and artificial networks to represent and integrate information to make decisions. In the past few decades, significant multidisciplinary progress has been made in bridging the gap between how we understand biological versus artificial computation, including how insights gained from one can translate to the other. Research has revealed that neurobiology is a key determinant of brain network architecture, which gives rise to spatiotemporally constrained patterns of activity that underlie computation. Here, we discuss how neural systems use dynamics for computation, and claim that the biological constraints that shape brain networks may be leveraged to improve the implementation of artificial neural networks. To formalize this discussion, we consider a natural artificial analog of the brain that has been used extensively to model neural computation: the recurrent neural network (RNN). In both the brain and the RNN, we emphasize the common computational substrate atop which dynamics occur-the connectivity between neurons-and we explore the unique computational advantages offered by biophysical constraints such as resource efficiency, spatial embedding, and neurodevelopment.

IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease.

Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ signaling in myeloid cells (Lyz-IFNγR2-/-) are protected from diet-induced insulin resistance despite fatty liver. Obesity-mediated liver inflammation is also attenuated with reduced interleukin (IL)-12, a cytokine primarily released by macrophages, and IL-12 treatment in vivo causes insulin resistance by impairing hepatic insulin signaling. Following MASH diets, Lyz-IFNγR2-/- mice are rescued from developing liver fibrosis, which is associated with reduced fibroblast growth factor (FGF) 21 levels. These results indicate critical roles for IFNγ signaling in macrophages and their release of IL-12 in modulating obesity-mediated insulin resistance and fatty liver progression to MASH. In this work, we identify the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and as potential therapeutic targets to treat MASH.

Mis-splicing of mitotic regulators sensitizes SF3B1-mutated human HSCs to CHK1 inhibition.

Splicing factor SF3B1 mutations are frequent somatic lesions in myeloid neoplasms that transform hematopoietic stem cells (HSCs) by inducing mis-splicing of target genes. However, the molecular and functional consequences of SF3B1 mutations in human HSCs remain unclear. Here, we identify the mis-splicing program in human HSCs as a targetable vulnerability by precise gene editing of SF3B1 K700E mutations in primary CD34+ cells. Mutant SF3B1 induced pervasive mis-splicing and reduced expression of genes regulating mitosis and genome maintenance leading to altered differentiation, delayed G2/M progression, and profound sensitivity to CHK1 inhibition (CHK1i). Mis-splicing or reduced expression of mitotic regulators BUBR1 and CDC27 delayed G2/M transit and promoted CHK1i sensitivity. Clinical CHK1i prexasertib selectively targeted SF3B1-mutant HSCs and abrogated engraftment in vivo. These findings identify mis-splicing of mitotic regulators in SF3B1-mutant HSCs as a targetable vulnerability engaged by pharmacological CHK1 inhibition.

Evaluating the Reliability and Quality of YouTube Videos Regarding Medial Collateral Ligament Knee Injury as a Patient Education Resource.

OBJECTIVES: The purpose of this study was to assess the educational reliability and quality of videos shared on YouTube regarding medial collateral ligament (MCL) injuries of the knee. METHODS: Using the search keywords "medial collateral ligament" on YouTube, the first 50 videos were evaluated by two independent reviewers. Video characteristics were extracted, and each video was categorized by upload source and content type. Three scoring systems were used to evaluate the videos: the Journal of the American Medical Association (JAMA) Benchmark Score to assess a video's reliability; the Global Quality Score (GQS) to assess educational quality; the novel MCL Specific Score (MCL-SS) to assess MCL-specific content quality. Linear regression analyses were conducted to explore relationships between video characteristics and scores. RESULTS: Collectively, the videos were viewed 5,759,427 times with a mean number of views per video of 115,189 ± 177,861. The mean JAMA score was 1.8, GQS was 2.1, and MCL-SS was 5.6, indicating both poor reliability and quality. Only videos uploaded by physicians showed a statistically significantly higher mean MCL-SS (P = .032) but were still of low quality with a mean MCL-SS of 9.2 ± 5.9. Multivariate linear regression revealed that videos uploaded by physicians were statistically significant predictors of greater MCL-SS (ß = 4.108; P = .029). Longer video durations were statistically significant predictors of greater GQS (ß = .001; P = .002) and MCL-SS (ß = .007; P < .001). CONCLUSIONS: YouTube videos regarding MCL injuries, despite their popularity, were found to be on average of poor overall reliability and quality as measured by JAMA, GQS, and MCL-SS. LEVEL OF EVIDENCE: III - Cross-sectional Study.

Hepatobiliary infection after transjugular intrahepatic portosystemic shunt creation in patients with prior biliary intervention: A multi-institution retrospective study.

PURPOSE: To estimate the risk of hepatobiliary infection, including endoTIPSitis, liver abscesses, and cholangitis, after transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with prior biliary intervention. MATERIALS AND METHODS: This multi-institution, retrospective study identified 76 patients (n=48 males; mean age 54.9; mean model for end stage liver disease score=13.2; n=45 for ascites and n=23 for varices; n=31 with prior liver transplantation) among 2,130 undergoing TIPS (3.6%) who had prior biliary intervention (n=19 bilioenteric anastomoses, n=35 sphincterotomies, n=28 internal plastic stents, n=4 internal metal stents, and n=6 percutaneous biliary drains). The baseline risk of post-TIPS hepatobiliary infection was estimated from a control group of 1,202 TIPS procedures in patients without prior biliary intervention. RESULTS: Eleven of 76 patients (14.5%) developed hepatobiliary infection after TIPS, including 7 with endoTIPSitis, 4 with hepatic abscesses, and 2 with cholangitis. The 30-day risk of infection was 10.9% (95% CI=3.5-17.8%), significantly higher than the 0.4% risk (95% CI=0.1-0.8%) observed in patients without prior biliary intervention (hazard ratio (HR)=25.56, 95% CI=8.36-78.13, p<0.001). All types of biliary intervention were associated with increased risk of infection, with bilioenteric anastomoses conferring the highest risk. Paradoxically, among patients with prior biliary intervention, use of post-procedural antibiotic prophylaxis was associated with an increased infection risk (HR=19.85; 95% CI=2.44-161.50; p=0.005). Microbial culture data showed high rates of Enterococcus, Klebsiella, and Candida species. CONCLUSIONS: Prior biliary intervention was associated with a 10.9% risk of hepatobiliary infection, including endoTIPSitis, liver abscess, and cholangitis, within 30 days after TIPS creation.

Outcomes After Single-Stage Anatomic Multiligament Knee Reconstruction With Early Range of Motion in Adolescents.

Background: Multiligament knee injuries (MLKI), rare in adolescents, are challenging injuries that require complex surgical reconstruction. Historically, nonanatomic reconstructions have been associated with prolonged immobilization and failure to restore normal knee biomechanics, resulting in arthrofibrosis and high rates of graft failure. Purpose: To describe the clinical and patient-reported outcomes (PROs) for adolescent patients treated with single-stage anatomic multiligament knee reconstruction. Study Design: Case series; Level of evidence, 4. Methods: A single-center retrospective study was performed of patients ≤18 years old who underwent reconstruction of MLKIs by a single surgeon between 2014 and 2019 using a single-stage anatomic technique, with protected weightbearing and early range of motion. Complications were defined as infection, arthrofibrosis, deep vein thrombosis (DVT) or pulmonary embolus, and secondary surgery. PROs, including the pediatric version of the International Knee Documentation Committee (Pedi-IKDC) and the Tegner activity score, were obtained at a minimum of 2 years postoperatively. Results: Included were 30 patients (21 male, 9 female; mean age, 15.4 years). The most common ligamentous reconstruction types were anterior cruciate ligament (ACL) + fibular collateral ligament (12 patients; 40%) and ACL + medial collateral ligament (9 patients; 30%). Three patients (10%) had secondary surgeries, including irrigation and debridement of a granuloma, a staged osteochondral allograft transplantation to a lateral femoral condyle impaction fracture, and repair of a medial meniscal tear and lateral femoral condyle fracture associated with new injuries 2 years after ACL + fibular collateral ligament reconstruction. Two patients (7%) developed arthrofibrosis and 1 patient (3%) developed DVT. PRO scores obtained at a mean of 37 months postoperatively included a mean Pedi-IKDC of 87 (range, 52-92) and a median highest Tegner score at any point postoperatively of 9 (range, 5-10). Of the patients who were athletes before their injury, 70% returned to the same or higher level of sport postoperatively. Conclusion: Reconstruction of MLKI in this series of adolescents with single-stage anatomic techniques and early range of motion resulted in low rates of secondary surgery, few complications, and good knee function as well as PRO scores at mean 3-year follow-up.

Patterns of Acute Ischemic Stroke Treatment from 2010 to 2020: An Evolving Landscape in Stroke Management Following Thrombectomy Trials.

Background and Objectives: Population-based studies on stroke can help guide the care of patients with acute ischemic stroke (AIS) by providing health care communities with information regarding the current usage of stroke treatments. It remains unclear how rapidly new techniques, particularly endovascular stroke treatment (EST), are being adopted and whether there is any disparity in their availability. Although studies using the National Inpatient Sample (NIS) have been conducted, updated studies over a longer period may provide further insights. This study aimed to understand patterns of AIS treatment, discharge disposition, in-hospital mortality, and mean length of stay (LOS) for each modality from 2010 to 2020 using the NIS database. Methods: This retrospective longitudinal study was conducted using NIS data from 2010 to 2020. Patients were categorized into groups based on whether they received intravenous recombinant tissue plasminogen activator (rt-PA), EST, both rt-PA and EST (combined therapy), or supportive care alone. Demographic, socioeconomic, regional, insurance, and hospital data were also obtained. The primary outcome was the proportion of patients receiving each modality, whereas the secondary outcomes were in-hospital mortality, mean LOS, and discharge disposition. Results: The usage rates increased (p < 0.001) in all groups between 2010 and 2020 (rt-PA: 5.09% to 8.39%, EST: 0.31% to 4.40%, and rt-PA+EST: 0.46% to 1.09%). The highest increase in usage was observed for EST, with a thirteen-fold increase. Mortality decreased from 2010 to 2020 in all groups (rt-PA: 8.45% to 3.54%, EST: 25.22% to 12.50%, and rt-PA+EST: 21.12% in 2010 to 9.30%) (p < 0.001). Combination therapy demonstrated the greatest improvement, with an 11.2% reduction in absolute mortality. Mean LOS was reduced for patients who received rt-PA (6.8 to 4.8 days), EST (9.3 to 8.9 days), and combined therapy (10.0 to 8.3 days) (p < 0.001) over the study period. The proportion of patients discharged to home increased for rt-PA (29.01% to 41.85%), EST (14.13% to 17.70%), and combined therapy (12.89% to 24.29%) (p < 0.001). Overall, stroke treatment usage was higher among the higher income groups, regardless of race. Higher usage was also observed for Whites in the West and Hispanic ethnicities in the South and West. Regardless of income or treatment method, utilization rates were lower for Black patients. Utilization rates were lower for Black patients with Medicare, Medicaid, or self-pay than for White patients. Discussion: Our study demonstrated that endovascular stroke treatment continues to expand, leading to better outcomes for mortality, LOS, and home discharge. Despite these positive patterns, there are visible inequities across regions, income status, and races.

Visual narratives in medicine - Bridging the gap in graphic medicine with an illustrated narrative of osteoarthritis.

Objective: Visual narratives have been used in medicine to share information in the form of stories with the potential to improve understanding of conditions and change behaviours. One genre of visual narratives is "graphic medicine", which integrates comics into medical education and the delivery of healthcare. Graphic medicine can maximise the impact of research findings by presenting them in a more accessible format, which may be particularly useful in certain populations, such as those with low levels of health literacy. Those with lower health literacy levels and osteoarthritis (OA) are less likely to manage their condition with guideline recommended management strategies, experience a higher burden of disease, and have lower access to care. Our objectives were to review the current visual narratives in the field of and create a graphic medicine visual narrative based on existing research. Design: This paper summarises the current visual narratives in OA and presents a graphic medicine visual narrative to illustrate the experience of living with OA. Considerations for the dissemination of visual narratives to target audiences are also discussed. Results: The most common visual narratives in are infographics, videos, and graphic medicine. A graphic medicine visual narrative, based on previous qualitative work and informed by a framework, was created to illustrate two distinct narratives - impairment and participatory. Conclusion: Visual narratives remain an emerging field in OA but may serve as a useful resource for patients or clinicians to discuss various aspects of OA management. Future research should evaluate and validate the use of visual narratives in OA.

Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial.

BACKGROUND: Doravirine and islatravir is an investigational, once-daily, single-tablet regimen with high antiviral potency, favourable safety and tolerability, and low propensity for resistance. We report week 48 results from a phase 3 trial evaluating switch from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (0·75 mg). METHODS: This phase 3, multicentre, randomised, active-controlled, open-label, non-inferiority trial was conducted at 77 research, community, and hospital-based clinics in 15 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL on any oral, two-drug or three-drug ART regimen for at least 3 months, and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation schedule to switch to doravirine (100 mg) and islatravir (0·75 mg) or to continue their baseline ART regimen. Block randomisation was based on a block size of four, and randomisation was stratified by baseline regimen (ie, protease inhibitor, integrase inhibitor, or other). Participants in the doravirine and islatravir group were instructed to take one tablet at approximately the same time each day, and participants in the baseline ART group continued to take the medication according to the locally approved label. HIV-1 RNA and safety evaluations were done at baseline and weeks 4, 12, 24, 36, and 48. CD4 cell counts were measured at baseline, week 24, and week 48. The primary endpoint was proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug) using the US Food and Drug Administration snapshot approach and prespecified non-inferiority margin of 4%. This study is registered with ClinicalTrials.gov (NCT04223778) and is completed. FINDINGS: Between Feb 18 and Oct 2, 2020, 740 individuals were screened for eligibility, of whom 672 (90·8%) participants (249 [37·1%] women and 423 [62·9%] men; median CD4 count of 678 cells per µL [IQR 496-868]) were randomly assigned to doravirine (100 mg) and islatravir (0·75 mg; n=336) or to continue baseline ART (n=336). The last follow-up visit occurred on Sept 8, 2021. At week 48, zero of 336 participants in the doravirine and islatravir group versus five (1·5%) of 336 participants in the baseline ART group had greater than or equal to 50 HIV-1 RNA copies per mL (difference -1·5, 95% CI -3·4 to -0·3). The per-protocol analysis showed consistent results. Headache was the most common adverse event in both groups (35 [10·4%] of 336 participants in the doravirine and islatravir group, 16 [4·8%] of 336 in the baseline ART group), infection rates were similar (113 [33·6%] in both groups), and discontinuations due to adverse events were low (seven [2·1%] vs one [0·3%]). 66 (19·6%) of 336 participants had treatment-related adverse events in the doravirine and islatravir group compared with 30 (8·9%) of 336 in the baseline ART group. In the islatravir and doravirine group, CD4 cell counts (mean change -30·3 cells per µL) and total lymphocyte counts (mean change -0·26 × 109/L) were decreased at 48 weeks. INTERPRETATION: Switching to single-tablet doravirine (100 mg) and islatravir (0·75 mg) maintained viral suppression up to week 48 and was non-inferior to antiretroviral combinations used in clinical practice for adults with HIV-1; however, decreases in CD4 cell and total lymphocyte counts do not support further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Quality and Reliability Analysis of YouTube as a Source for Patient Education on Dupuytren's Contracture.

Purpose: This study seeks to assess the quality and reliability of YouTube videos on Dupuytren's contracture. Methods: The first 50 unique videos on Dupuytren's contracture were evaluated by searching YouTube for Dupuytren's contracture. Video metrics, source, and content type were recorded. Video reliability was assessed using the Journal of American Medical Association (JAMA) Benchmark criteria. Video educational quality was assessed using the Global Quality Score (GQS) and a Dupuytren's Contracture-Specific Score (DC-SS). Results: The total number of views for all 50 videos evaluated was 1,908,608 (mean, 38,172.16 ± 5,502.45 views). The mean reliability (JAMA) score was 2.21 ± 0.69 (range 0-4), the mean educational quality (GQS) score was 2.80 ± 1.28 (range 1-5), and the mean disease-specific (DC-SS) score was 6.05 ± 2.17 (range 0-15). Nonphysician health care professionals had the most popular videos, but the lowest DC-SS. GQS varied based on the video source, with physician-uploaded videos having the highest average quality scores. Physician source was an independent positive predictor of higher quality (GQS) (ß = 0.477). Conclusions: Videos on Dupuytren's contracture were frequently viewed on YouTube but had overall low educational quality and reliability. Of the videos that discussed collagenase as a treatment option, 40% failed to mention percutaneous needle aponeurotomy. Patients may be exposed to an incomplete set of treatment options. Educational content on YouTube should be interpreted cautiously and proper in-office education and high-quality resources for Dupuytren's contracture should be provided by physicians. Type of Study/Level of Evidence: Therapeutic IV.

Exercise-induced BDNF promotes PPARδ-dependent reprogramming of lipid metabolism in skeletal muscle during exercise recovery.

Post-exercise recovery is essential to resolve metabolic perturbations and promote long-term cellular remodeling in response to exercise. Here, we report that muscle-generated brain-derived neurotrophic factor (BDNF) elicits post-exercise recovery and metabolic reprogramming in skeletal muscle. BDNF increased the post-exercise expression of the gene encoding PPARδ (peroxisome proliferator-activated receptor δ), a transcription factor that is a master regulator of lipid metabolism. After exercise, mice with muscle-specific Bdnf knockout (MBKO) exhibited impairments in PPARδ-regulated metabolic gene expression, decreased intramuscular lipid content, reduced ß-oxidation, and dysregulated mitochondrial dynamics. Moreover, MBKO mice required a longer period to recover from a bout of exercise and did not show increases in exercise-induced endurance capacity. Feeding naïve mice with the bioavailable BDNF mimetic 7,8-dihydroxyflavone resulted in effects that mimicked exercise-induced adaptations, including improved exercise capacity. Together, our findings reveal that BDNF is an essential myokine for exercise-induced metabolic recovery and remodeling in skeletal muscle.

Shifts in patient preference of third-line overactive bladder therapy after introduction of the implantable tibial nerve stimulator.

INTRODUCTION: Third-line therapies for overactive bladder (OAB) that are currently recommended include intravesical Onabotulinumtoxin-A injections (BTX-A), percutaneous tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The implantable tibial nerve stimulator (ITNS) is a novel therapy that is now available to patients with OAB. OBJECTIVE: The objective of this study was to analyze shifts in patient preference of third-line therapies for OAB after introducing ITNS as an option among the previously established therapies for non-neurogenic OAB. METHODS: A survey was designed and distributed via SurveyMonkey to the platform's audience of U.S. adults of age 18 and older. Screening questions were asked to include only subjects who reported symptoms of OAB. Descriptions of current AUA/SUFU guideline-approved third-line therapies (BTX-A, PTNS, and SNM) were provided, and participants were asked to rank these therapies in order of preference (stage A). Subsequently, ITNS was introduced with a description, and participants were then asked to rank their preferences amongst current guideline-approved therapies and ITNS (stage B). Absolute and relative changes in therapy preferences between stage A and stage B were calculated. Associations between ultimate therapy choice in stage B and participant characteristics were analyzed. RESULTS: A total of 485 participants completed the survey (62.5% female). The mean age was 49.1 ± 36.5 years (SD). The most common OAB symptoms reported were urgency urinary incontinence (UUI) (73.0%) and urinary urgency (68.0%). 29.2% of patients had tried medication for OAB in the past, and 8.0%-10.3% of patients were previously treated with a third-line therapy for OAB. In stage A, participants ranked their first choice of third-line therapy as follows: 28% BTX-A, 27% PTNS, and 13.8% SNM. 26.6% of participants chose no therapy, and 4.5% chose all three equally. In stage B, participants ranked their first choice as follows: 27.6% BTX-A, 19.2% PTNS, 7.8% SNM, and 19.2% ITNS. 21.9% of participants chose no therapy and 4.3% chose all four equally as their first choice. There were both absolute and relative declines in proportions of patients interested in BTX-A, SNM, and PTNS as their first choice of third-line therapy with the introduction of ITNS. Patients originally interested in PTNS in stage A had the greatest absolute change after the introduction of ITNS with 7.8% of participants opting for ITNS in stage B. Those interested in SNM in stage A had the largest relative change in interest, with 43.5% of those originally interested in SNM opting for ITNS in stage B. Finally, with the introduction of ITNS, the number of participants initially not interested in any third-line therapy declined by an absolute change of 4.7% and relative change of 17.6%. Participants experiencing concurrent stress urinary incontinence (SUI) symptoms were more likely to choose a current guideline-approved third-line therapy than ITNS or no therapy at all (p = 0.047). Those who had prior experience with third-line therapies were more likely to choose a third-line therapy other than ITNS as their ultimate choice of therapy in stage B. Of those who had chosen a guideline-approved third-line therapy in stage B (not ITNS), 13.6% had prior experience with BTX-A, 14.7% with PTNS, and 32 (11.2%) with SNM (p < 0.001, p < 0.001, p = 0.009, respectively). CONCLUSION: From our study, it appears that ITNS may attract a subset of patients who would not have otherwise pursued current guideline-approved third-line therapies for OAB. When patients are provided with descriptions of third-line OAB therapies including ITNS as an option, ITNS appears to compete with SNM and PTNS. It is possible that ITNS will provide patients with a different phenotype of neuromodulation therapy that can appeal to a niche OAB population. Given that ITNS devices have been introduced relatively recently to the market, their application will largely depend on cost and payer coverage, provider bias, and patient comorbidities. Further study is needed to understand how these factors interact with and influence patient preference of advanced OAB therapy to understand which patients will most benefit from this treatment modality.

Breaking reflection symmetry: evolving long dynamical cycles in Boolean systems.

In interacting dynamical systems, specific local interaction rules for system components give rise to diverse and complex global dynamics. Long dynamical cycles are a key feature of many natural interacting systems, especially in biology. Examples of dynamical cycles range from circadian rhythms regulating sleep to cell cycles regulating reproductive behavior. Despite the crucial role of cycles in nature, the properties of network structure that give rise to cycles still need to be better understood. Here, we use a Boolean interaction network model to study the relationships between network structure and cyclic dynamics. We identify particular structural motifs that support cycles, and other motifs that suppress them. More generally, we show that the presence of dynamical reflection symmetry in the interaction network enhances cyclic behavior. In simulating an artificial evolutionary process, we find that motifs that break reflection symmetry are discarded. We further show that dynamical reflection symmetries are over-represented in Boolean models of natural biological systems. Altogether, our results demonstrate a link between symmetry and functionality for interacting dynamical systems, and they provide evidence for symmetry's causal role in evolving dynamical functionality.

Fluid intake behavior in women with refractory overactive bladder undergoing third line therapy.

INTRODUCTION AND OBJECTIVES: Fluid intake has been shown to be related to urinary symptoms, but no studies to date have investigated the effect of fluid intake on urinary symptoms in women with refractory overactive bladder (OAB). As this group of women are considered to have a possible unique pathophysiologic mechanism of OAB, we investigated the relationship between fluid intake, fluid intake behavior, and urinary symptoms in women with refractory OAB. METHODS: A prospective cross-sectional study of women with refractory OAB was conducted by assessing the relationship between fluid intake and lower urinary tract symptoms (LUTS) in women undergoing third line OAB therapies. Fluid intake and behavior were measured by the questionnaire based voiding diary and urinary symptoms were measured by the International Consultation on Incontinence Questionnaire for Female Lower Urinary Tract Symptoms (ICIQ-FLUTS). The relationship between fluid intake and symptom severity was assessed using Spearman's rank correlation and χ2  tests. RESULTS: Of the 126 individuals undergoing third line therapy for OAB, 60 (48%) underwent intradetrusor onabotulinumtoxinA injection (BTX) injection, 42 (33%) peripheral tibial nerve stimulation, and 24 (19%) sacral neuromodulation. The mean total daily fluid intake was 2567.0 ± SD 1292.4 mL and did not differ significantly across treatment groups. Total fluid intake was weakly correlated with worse filling-type LUTS (r = 0.241, p = 0.007), and there was no relationship between LUTS and caffeinated fluid intake. Half (52%) of the subjects reported current fluid restricting behavior to control urinary symptoms, but this behavior was not correlated with LUTS severity (all p > 0.05). Patients that currently use tobacco have greater LUTS (current = 25.8 ± SD 9.5, former = 14.8 ± SD 6.1, never = 15.0 ± SD 6.1; p < 0.001). BMI was also positively correlated with worse incontinence symptoms (r = 0.351, p < 0.001). CONCLUSIONS: Fluid intake along with other lifestyle factors, including tobacco use and weight, are minimally related to the symptomatology seen in women with refractory OAB. Further studies are needed to assess if behaviors change during treatment with third line therapies, and if these behavioral changes may affect treatment response.

New approach to testing treatments for osteoarthritis: FastOA.

Animal models of post traumatic osteoarthritis have shown many promising treatments for disease, but human trials have mostly failed to identify effective treatments. This viewpoint suggests that the frequent failure of drug and treatment development in osteoarthritis is due, in part, to the advanced stage of disease of patients in trials and suggests that mirroring the animal model approach might be more successful. It suggests a path forward by enriching trial enrollees with those likely to develop post traumatic OA quickly.

Barriers to Healthcare: Non-English Speaking and Elderly Patients More Likely to Have Retained Ureteral Stents.

OBJECTIVE: To identify factors for retained ureteral stents in our institution of patients receiving de novo ureteral stents. Ureteral stent placement, a commonly performed urologic procedure, is a temporary measure and requires timely removal. Retained ureteral stents may result in significant morbidities and need for additional procedures. MATERIALS AND METHODS: We queried for all de novo ureteral stents indicated for calculi at our institution between July 2019-June 2021. Retained ureteral stents were defined as stents that remained indwelling for a period greater than 90days. Patients with metallic stents, stents on strings, pediatric patients, and planned therapy outside 90days were excluded. Patient demographic information including gender, race, age, insurance status, non-English speaking status as well as clinical data including location of presentation and indication were collected. Characteristics of patients with retained stents were compared to those without. RESULTS: Four hundred fifty-seven de novo stent patients meeting study criteria were identified, of which 61 (13%) patients had retained stents. The median duration of retention was 24days +/- 32days (IQR). Patients with retained stents were older than those with stents removed within 90days (62.1 vs 57.2years, P = .03). Retained stents were more common among non-English-speaking patients (13% vs 5%, P = .012). CONCLUSION: Stent retention was found to be associated with non-English speaking status and older age. Healthcare barriers in language and age may lead to increased morbidity due to stent retention.

National analysis of over and under-triage rates in relation to trauma population risk factors and associated outcomes across various levels trauma centers.

INTRODUCTION: Over and under-triage represent a misallocation of resources that can affect patient outcomes. The purpose of this study is to evaluate over and under-triage rates in relation to risk factors and associated outcomes of trauma patients nationwide. METHODS: A retrospective cohort study using the Trauma Quality Improvement Program from 2017 to 2020. Multivariable regression models were used to assess predictors of over-triage (activation when unnecessary) and under-triage (limited activation when full activation was necessary). RESULTS: 22.2 % (32,782) of the study population were over-triaged and 20.3 % (29,996) were under-triaged. Most over-triaged patients were Black, with Medicaid, or had a penetrating injury, whereas most under-triaged patients were White, with private/commercial insurance, or had a blunt injury. With covariates adjusted for, Pacific Islander (p = 0.024) and American Indian patients (p = 0.015) were associated with higher odds of over-triage, and Hispanic patients had higher odds of under-triage (p<0.001). Patients with Medicare (p<0.001) had higher odds of over-triage, and patients with private/commercial insurance (p<0.001) had higher odds of under-triage compared to Medicaid patients. Patients in level II (p<0.001) and level III (p<0.001) trauma hospitals were associated with higher odds of over-triage. CONCLUSION: Pacific Islander and American Indian patients, Medicare, and level II and III trauma centers are at increased risk of over-triage rates, while Hispanic and privately insured trauma patients had a higher risk for under-triage. Future studies should further investigate factors contributing to poor outcomes linked to under-triage practices and methods to improve consistency and standardization of triage tools across various levels of trauma centers.

Shaping dynamical neural computations using spatiotemporal constraints.

Dynamics play a critical role in computation. The principled evolution of states over time enables both biological and artificial networks to represent and integrate information to make decisions. In the past few decades, significant multidisciplinary progress has been made in bridging the gap between how we understand biological versus artificial computation, including how insights gained from one can translate to the other. Research has revealed that neurobiology is a key determinant of brain network architecture, which gives rise to spatiotemporally constrained patterns of activity that underlie computation. Here, we discuss how neural systems use dynamics for computation, and claim that the biological constraints that shape brain networks may be leveraged to improve the implementation of artificial neural networks. To formalize this discussion, we consider a natural artificial analog of the brain that has been used extensively to model neural computation: the recurrent neural network (RNN). In both the brain and the RNN, we emphasize the common computational substrate atop which dynamics occur-the connectivity between neurons-and we explore the unique computational advantages offered by biophysical constraints such as resource efficiency, spatial embedding, and neurodevelopment.