Search

Background & Aims: Understanding the burden of pancreatic cystic lesions (PCLs) in the general population is important for clinicians and policymakers. In this systematic review, we sought to estimate the global prevalence of PCLs using magnetic resonance imaging (MRI) and to investigate factors that contribute to its variation., Methods: We searched MEDLINE, EMBASE, and Cochrane Central, from database inception through February 2023. We included full-text articles that reported the prevalence of PCLs using MRI in the general population. A proportional meta-analysis was performed, and the prevalence of PCLs was pooled using a random-effects model., Results: Fifteen studies with 65,607 subjects were identified. The pooled prevalence of PCLs was 16% (95% confidence interval [CI], 13%-18%; I 2  = 99%), most of which were under 10 mm. Age-specific prevalence of PCLs increased from 9% (95% CI, 7%-12%) at 50 to 59 years, to 18% (95% CI, 14%-22%) at 60 to 69 years, 26% (95% CI, 20%-33%) at 70 to 79 years, and 38% at 80 years and above (95% CI, 25%-52%). There was no difference in prevalence between sexes. Subgroup analysis showed higher PCL prevalence when imaging findings were confirmed by independent radiologist(s) (25%; 95% CI, 16%-33%) than when chart review alone was used (5%; 95% CI, 4%-7%; P < .01). There was no independent association of PCL prevalence with geographic location (Europe, North America, or Asia), MRI indication (screening vs evaluation of non-pancreatic pathology), enrollment period, sample size, magnet strength (1.5 vs 3 tesla), and MRI sequence (magnetic resonance cholangiopancreatography vs no magnetic resonance cholangiopancreatography)., Conclusion: In this systematic review, the global prevalence of PCLs using a highly sensitive noninvasive imaging modality ranged between 13% and 18%., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Hispanics/Latinos of Dominican background living in United States (US) have the highest hypertension prevalence compared with other Hispanic/Latino persons., Objective: To understand cardiovascular health among Dominicans, we evaluated hypertension prevalence and risk factors among Dominicans from the US and Dominican Republic (DR) using data from Hispanic Community Health Study/ Study of Latinos [HCHS/SOL] and the Prevalencia de Hipertension Arterial y Factores de Riesgo Cardiovasculares en la República Dominicana al 2017 (ENPREFAR-HAS 17) study., Methods: Hypertension was defined as blood pressure ≥140/90 mmHg, self-reported hypertension, or antihypertensive use. Exposures included sociodemographic/socioeconomic, clinical, and lifestyle/behavioral characteristics. Weighted generalized linear models were used to estimate associations between study characteristics and hypertension prevalence (PR = prevalence ratio), age-and-sex adjusted. HCHS/SOL (n = 1,473, US Dominicans; mean age 41 years, 60.4% female) was analyzed with survey procedures, while ENPREFAR-HAS 17 (n = 2,015 DR Dominicans; mean age 40 years, 50.3% female) was analyzed with statistical analyses for simple random sampling., Results: Hypertension prevalence was 30.5% and 26.9% for DR and US Dominicans, respectively. Hypertension control was low in both cohorts (36.0% DR, 35.0% US). Alcohol use among DR Dominicans was inversely associated with hypertension prevalence (PR DR = 0.8) with no association among US Dominicans. In both settings, diabetes (PR DR = 1.4; PR US = 1.4) and obesity (PR DR = 1.8; PR US = 2.0) were associated with greater hypertension prevalence in Hispanics/Latinos of Dominican background. Physical activity was lower among US Dominicans (PR = 0.80) but higher among DR Dominicans (PR = 1.16); all p < 0.05., Conclusions: Variations in social, lifestyle/behavioral, and clinical characteristics associated with hypertension among Dominicans in the US and DR were identified, suggesting that social context and cultural factors matter among immigrant populations., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Objective: Our purpose was to synthesize evidence in the literature to determine the diagnostic accuracy of cone-beam CT (CBCT) for the detection of intracranial hemorrhage (ICH) and hemorrhage types, including intraparenchymal hemorrhage (IPH), subarachnoid hemorrhage (SAH), and intraventricular hemorrhage (IVH)., Methods: We performed a meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Our protocol was registered with International Prospective Register of Systematic Reviews (PROSPERO-CRD42021261915). Systematic searches were last performed on April 30, 2024, in EMBASE, PubMed, Web-of-Science, Scopus, and Cumulative Index to Nursing and Allied Health Literature databases. Inclusion criteria were (1) studies reporting diagnostic metrics of CBCT for ICH and (2) studies using a reference standard to determine ICH. Exclusion criteria were (1) case reports, abstracts, reviews and (2) studies without patient-level data. Pooled estimates and 95% confidence intervals (CIs) were calculated for diagnostic odds ratios (DORs), sensitivity, and specificity using random-effects and common-effects models. Mixed methods appraisal tool was used to evaluate risk of bias., Results: Seven studies were included in the meta-analysis yielding 466 patients. Mean or median age ranged from 54 to 75 years. Female patients represented 51.4% (222 of 432) in reported studies. Multidetector CT was the reference standard in all studies. DOR, pooled sensitivity, and pooled specificity for ICH were 5.28 (95% CI: 4.11-6.46), 0.88 (95% CI: 0.79-0.97), and 0.99 (95% CI: 0.98-1.0). Pooled sensitivity for IPH, SAH, and IVH was 0.98 (95% CI: 0.95-1.0), 0.82 (95% CI: 0.57-1.0), and 0.78 (95% CI: 0.55-1.0). Pooled specificity for IPH, SAH, and IVH was 0.99 (95% CI: 0.98-1.0), 0.99 (95% CI: 0.97-1.0), and 1.0 (95% CI: 0.98-1.0)., Discussion: CBCT had moderate DOR and high pooled specificity for ICH and hemorrhage types. However, pooled sensitivity varied by hemorrhage type, with the highest sensitivity for IPH, followed by SAH and IVH., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Aims: This study aimed to determine the efficacy and safety of iltamiocel investigational autologous muscle cell therapy in females with stress urinary incontinence (SUI)., Methods: Adult females were randomized 2:1 to iltamiocel (150 × 10 6  cells) or placebo and stratified by severity and prior SUI surgery. The primary objective was efficacy based on the frequency of stress incontinence episodes (SIE) recorded in a 3-day diary at 12 months posttreatment. After 12 months, placebo participants could elect to receive open-label iltamiocel. Efficacy and safety analyses were performed using all patients as treated populations., Results: The study enrolled 311 patients, 297 were randomized to either iltamiocel (n = 199) or placebo (n = 98). Of the 295 participants that completed 12 months blinded follow-up, the proportion achieving the primary endpoint of ≥ 50% SIE reduction was not statistically different between treatment groups (52% vs. 53.6%; p = 0.798). A significantly greater proportion of iltamiocel participants in the prior SUI surgery stratum group achieved ≥ 75% SIE reduction compared with placebo, (40% vs. 16%; p = 0.037). Treatment response was maintained at 24 months in 78.4% and 64.9% of iltamiocel participants who achieved ≥ 50% and ≥ 75% SIE reduction, respectively, at Month 12. Adverse events related to the treatment were reported in 19 (9.5%) iltamiocel participants and 6 (6.1%) placebo participants., Conclusion: The study did not meet its primary endpoint however, iltamiocel cell therapy is safe and may be ideally suited to female patients who have undergone prior surgery for SUI. Additional study in this group of patients with high unmet medical needs is warranted., Trial Registration: ClinicalTrials.gov identifier: NCT01893138; EudraCT number: 2014-002919-41., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Introduction: Urinary tract infections (UTIs) are a leading cause of infection in adults. The most common cause is gastrointestinal bacteria ascending the urethra into the bladder. Studies showing fecal incontinence (FI) is a risk factor for UTI have been limited to nursing home populations. Healthy patients with recurrent UTI, especially women, often receive counseling, suggesting improper personal hygiene contributes to UTIs. This advice can be stigmatizing. Given UTI prevalence, it is important to elucidate risk factors for improved diagnosis, treatment, and patient education. Our objective was to perform a hospital-centered, retrospective case-control analysis to assess the effect of FI on UTI development in ambulatory patients., Methods: Patients (n = 3035) with a diagnosis of FI were identified from a single institution and propensity score-matched with screening colonoscopy patients (n = 3035) from 2018 to 2021. Patients were matched on age, sex, race, ethnicity, body mass index, and comorbidities, for example, diabetes, vesicoureteral reflux, and urinary incontinence. The association between FI and UTI was tested using Pearson's χ 2 test., Results: Median age was 64 years with more females than males (73.81% vs. 71.20% female for case/control, p = 0.02). Patients with FI were more often to have concurrent urinary incontinence (18.62% vs. 10.25% for case/control, p < 0.001), as well as specifically urgency incontinence (13.28% vs. 11.57% for case/control, p = 0.04). There was no significant difference in the incidence of UTI between patients with FI and those presenting for screening colonoscopy (p = 0.44)., Conclusion: FI was not associated with an increased number of UTIs. Based on our results, current stigmatizing beliefs regarding the association between FI and UTI should be reevaluated., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Although chimeric antigen receptor (CAR) T cell therapies have demonstrated promising clinical outcomes, durable remissions remain limited. To extend the efficacy of CAR T cells, we develop a CAR enhancer (CAR-E), comprising a CAR T cell antigen fused to an immunomodulatory molecule. Here we demonstrate this strategy using B cell maturation antigen (BCMA) CAR T cells for the treatment of multiple myeloma, with a CAR-E consisting of the BCMA fused to a low-affinity interleukin 2 (IL-2). This selectively induces IL-2 signaling in CAR T cells upon antigen-CAR binding, enhancing T cell activation and antitumor activity while reducing IL-2-associated toxicities. We show that the BCMA CAR-E selectively binds CAR T cells and increases CAR T cell proliferation, clearance of tumor cells and development of memory CAR T cells. The memory cells retain the ability to re-expand upon restimulation, effectively controlling tumor growth upon rechallenge. Mechanistic studies reveal the involvement of both CAR and IL-2 receptor endodomains in the CAR-E mechanism of action. The CAR-E approach avoids the need for specific engineering and enables CAR T cell therapy with lower cell doses., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The tibial nerve is an established target for neuromodulation in the management of overactive bladder (OAB) and its associated symptoms, including urge urinary incontinence (UUI). Technologies are currently available to deliver tibial nerve stimulation (TNS) through percutaneous devices or through implantable devices. The benefits and safety of percutaneous TNS have led to it as a guideline-recommended therapy. However, patient compliance is limited by the burden of weekly office visits and the need for maintenance treatments. Further, insurance often only covers a limited number of lifetime visits for percutaneous TNS. These factors and others have led to the development, study, and utilization of implantable TNS devices. Implantable TNS devices deliver the same therapeutic mechanism of action for nerve stimulation with a permanent implanted device that provides at-home stimulation rather than in-office therapy delivery. Additionally, there is an added potential for dynamic and patient-centered stimulation. There is a large body of high-quality evidence published for TNS, including numerous randomized controlled trials published on percutaneous TNS which have consistently demonstrated superior efficacy to sham and similar efficacy to that of anticholinergic medications. Percutaneous TNS also performs better than conservative therapy including pelvic floor muscle training. The percutaneous and implantable approaches deliver nerve stimulation to the same target nerve, using the same mechanism of action. Therefore, data from randomized trials of percutaneous TNS are informative for implantable TNS devices. At the time of this article's publication, at least two implantable TNS devices have received marketing authorization from the Food and Drug Administration (FDA). The objective of this review is to discuss the mechanism of action for TNS and summarize the published literature from clinical trials of percutaneous TNS as a foundation of high-quality evidence for implantable devices targeting the tibial nerve., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Importance: Disparities research in Black women with pelvic floor disorders (PFDs) has primarily focused on epidemiology or surgical outcomes, but little is known about the patient perspective on seeking PFD care., Objective: To provide quality and equitable care to Black women with PFDs, we conducted a qualitative study to hear their perspectives and lived health care experiences., Study Design: Black women seeking care for PFDs at a tertiary care institution were invited to participate in qualitative interviews. Open-ended questions explored participants' knowledge, attitudes, and health care experiences. Interviews were transcribed verbatim and coded line-by-line. Inductive content analysis was performed to identify key themes, and consensus was achieved among the research team., Results: Eight Black women aged 21-83 years consented to participate. Patients noted a stigma surrounding PFDs, both among health care professionals and their community. They noted several barriers to care: financial, logistical, and racial bias. They cited difficulties in patient-health care professional communication, including not feeling heard or treated as an individual. They preferred gender and racial concordance with their physicians. These women expressed both a desire for more knowledge and to share this knowledge and advocate for other women., Conclusions: Black women expressed distinct obstacles in their PFD health care. They reported not feeling heard or treated as a unique individual. The themes derived from this study identify complex patient-centered needs that can serve as the basis for future quality improvement work and/or hypothesis-driven research. By grounding health disparities research in patient perspectives, we can improve the health care experiences of Black women., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

T cells play a crucial role in antitumor immune responses and the clearance of infected cells. They identify their targets through the binding of T-cell receptors (TCRs) to peptide-major histocompatibility complex (pMHC) molecules present in cancer cells, infected cells, and antigen-presenting cells. This interaction is often weak, requiring multimeric pMHC molecules to enhance the avidity for identifying antigen-specific T cells. Current exchangeable pMHC-I tetramerization methods may overlook TCRs recognizing less stable yet immunogenic peptides. In vivo applications targeting antigen-specific T cells demand the genetic synthesis of a pMHC fusion for each unique peptide antigen, which poses a significant challenge. To address these challenges, we developed a sortase and click chemistry-mediated approach for generating stable pMHC molecules. Leveraging sortase technology, we introduced an azide click-handle near the N-terminus of β2m, proximal to the MHC-peptide-binding groove. Simultaneously, the peptide was engineered with a multi glycine linker and a C-terminal alkyne click-handle. Azide-alkyne click reactions efficiently immobilized the peptide onto the MHC molecule, providing a versatile and efficient method for pMHC generation. The resulting peptide-clicked-MHC specifically binds to its cognate TCR and remains stable for over 3 months at 4 °C in the absence of any additional free peptide. The stability of the pMHC and its affinity to cognate TCRs are influenced by the linker's nature and length. Multi glycine linkers outperform poly(ethylene glycol) (PEG) linkers in this regard. This technology expands the toolkit for identifying and targeting antigen-specific T cells, enhancing our understanding of cancer-specific immune responses, and has the potential to streamline the development of personalized immunotherapies., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Background: Psychiatric disorders have been associated with higher risk for future dementia. Understanding how pre-dementia psychiatric disorders (PDPD) relate to established dementia genetic risks has implications for dementia prevention., Methods: In this retrospective cohort study, we investigated the relationships between polygenic risk scores for Alzheimer's disease (AD PRS), PDPD, alcohol use disorder (AUD), and subsequent dementia in the UK Biobank (UKB) and tested whether the relationships are consistent with different causal models., Findings: Among 502,408 participants, 9352 had dementia. As expected, AD PRS was associated with greater risk for dementia (odds ratio (OR) 1.62, 95% confidence interval (CI), 1.59-1.65). A total of 94,237 participants had PDPD, of whom 2.6% (n = 2519) developed subsequent dementia, compared to 1.7% (n = 6833) of 407,871 participants without PDPD. Accordingly, PDPD were associated with 73% greater risk of incident dementia (OR 1.73, 1.65-1.83). Among dementia subtypes, the risk increase was 1.5-fold for AD (n = 3365) (OR 1.46, 1.34-1.59) and 2-fold for vascular dementia (VaD, n = 1823) (OR 2.08, 1.87-2.32). Our data indicated that PDPD were neither a dementia prodrome nor a mediator for AD PRS. Shared factors for both PDPD and dementia likely substantially account for the observed association, while a causal role of PDPD in dementia could not be excluded. AUD could be one of the shared causes for PDPD and dementia., Interpretation: Psychiatric diagnoses were associated with subsequent dementia in UKB participants, and the association is orthogonal to established dementia genetic risks. Investigating shared causes for psychiatric disorders and dementia would shed light on this dementia pathway., Funding: US NIH (K08AG054727)., Competing Interests: Declaration of interests Dr. Goate received research funding from NIH and JPB Foundation, consulting fees from Muna Therapeutics and Genentech, payment for lectures from Biogen, Alector, and Denali Therapeutics, stock options from Cognition Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Tyrosinase-mediated protein conjugation has recently drawn attention as a site-specific protein modification tool under mild conditions. However, the tyrosinases reported to date act only on extremely exposed tyrosine residues, which limits where the target tyrosine can be located. Herein, we report a tyrosinase from Streptomyces avermitilis (SaTYR), that exhibits a much higher activity against tyrosine residues on the protein surface than other tyrosinases. We determined the crystal structure of SaTYR and revealed that the enzyme has a relatively flat and shallow substrate-binding pocket to accommodate a protein substrate. We demonstrated SaTYR-mediated fluorescence dye tagging and PEGylation of a surface tyrosine residue that was unreacted by other tyrosinases with an approximately 95.2 % conjugation yield in 1 h. We also present a structural rationale that considers the steric hindrance from adjacent residues and surrounding structures along with the extent of solvent exposure of residues, as necessary when determining the optimal positions for introducing target tyrosine residues in SaTYR-mediated protein modification. The study demonstrated that the novel tyrosinase, SaTYR, extends the scope of tyrosinase-mediated protein modification, and we propose that site-specific tyrosine conjugation using SaTYR is a promising strategy for protein bioconjugation in various applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To qualitatively analyze the knowledge, attitudes, and beliefs of women regarding genitourinary syndrome of menopause (GSM) and vaginal estrogen therapy as expressed on Reddit, a public, anonymous internet forum for discussion and information sharing., Methods: "r/menopause," a Subreddit with >30,000 subscribers, was queried for "vaginal estrogen" to collect postings related to vaginal estrogen in October 2022. Posts were analyzed qualitatively by 2 independent researchers. The principles of grounded theory were applied, and preliminary themes were generated. These themes were used to derive emergent concepts., Results: Sixty-seven unique posts with 1101 responses were analyzed. Qualitative analysis revealed 5 preliminary themes: (1) questions regarding medication usage, (2) medication side effects, (3) medication alternatives, (4) frustration with the medical system, and (5) seeking validation for symptoms and experiences. Three emergent concepts were derived: (1) women experience bothersome side effects from menopause, and they desire compassionate and effective medical treatment; (2) women are engaged and active participants in their health and health care decisions; and (3) women perceive that their concerns are not taken seriously and seek validation for their medical conditions., Conclusion: Peri- and post-menopausal women have many questions and concerns about the condition of GSM and vaginal estrogen as treatment. They also have a broad range of frustrations including access to health care and questions about the usage of vaginal estrogen. By better understanding patient perspectives, physicians can better meet women's needs and improve care for GSM., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine the perspectives, attitudes, and beliefs of the spouses of women with complications of mesh midurethral sling (MUS) surgery with the goal of increasing our understanding of the multidimensional nature of MUS surgery complications., Methods: After IRB approval, the spouses of patients who underwent surgery for MUS complications at a single tertiary care institution participated in qualitative interviews. Using an interview guide with standardized prompts, semistructured interviews were conducted. Interviews were transcribed verbatim and reviewed line-by-line by two researchers independently. Inductive content analysis was used to code the transcripts and identify themes, and consensus was achieved by the research team., Results: Seven male spouses participated in qualitative interviews, and several themes and subthemes were identified. First, spouses expressed feelings of regret. They described that their partner's dyspareunia detracted from their intimate relationship. The participants also reported the negative impact on their lives and their households. Due to the personal nature of the issue, couples would avoid involving friends and family, creating a sense of isolation. Finally, they expressed hope of finding a healthcare team experienced with mesh complications and invested in their spouse's improvement., Conclusion: Spouses of women who experience MUS complications serve as caregivers and provide support; they are impacted by adverse outcomes. It is important to acknowledge their role in patients' healthcare experiences and learn from their insights. Our study lays the foundation for future work and ultimately for improving the experiences of patients and their spouses with MUS surgery and potential complications., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: During the COVID-19 pandemic and subsequent staffing shortages there was concern about the case volume, and thus competency, of graduating trainees due to reduced surgical volumes. Elective procedures were particularly affected, which includes Female Pelvic Medicine and Reconstructive Surgery (FPMRS) cases. To understand whether FPMRS fellows were affected, we assessed their case logs for changes during the pandemic., Methods: The nationally aggregated case logs of graduating FPMRS fellows, both urology and obstetrics and gynecology (OBGYN), were obtained from the Accreditation Council for Graduate Medical Education. The available academic years (AYs) included 2018-2019, 2019-2020, and 2020-2021. Standard deviation for each index category was derived from the average and 90th percentile data. One-way analysis of variance was used to compare differences in case volumes for tracked index categories between AYs., Results: Graduating fellows logged an average of 517.4 (standard deviation [SD] 28.6) and 818.0 (SD 37.9) cases, for urology and OBGYN respectively, over their fellowship training during the examined period. No significant differences in total surgical procedures were found for either specialty between pre-COVID AY 2018-2019 and COVID-affected AYs 2019-2020 and 2020-2021. For urology fellows, gastrointestinal (GI) procedures was the only index case category with a significant difference, and it was a decrease between the two COVID-affected AYs: 2020-2021 compared to 2019-2020 (8.9 vs. 4.2, p = 0.04). For both urology and OBGYN fellows, there was a statistically significant decrease in graft/mesh augmentation procedures from COVID-affected AY 2019-2020 to AY 2020-2021. This may be attributed to the reclassification of mesh removal cases from graft/mesh augmentation procedures to genital procedures in 2020-2021. There was not a significant decrease in these procedures from pre-COVID AY 2018-2019 to the COVID-affected AYs. There were no other statistically significant differences between AYs for OBGYN fellows., Conclusions: Surgical case volumes for FPMRS urology and OBGYN fellows who trained during the COVID-19 pandemic were comparable to those of their pre-pandemic peers. No significant differences between pre-COVID and COVID-affected years were found for either total surgical procedures or index case categories. Despite disruptions in health care nationwide, FPMRS trainee case volumes were largely unaffected., (© 2023 Wiley Periodicals LLC.)

When the skin is exposed to ultraviolet radiation (UV), it leads to the degradation of the extracellular matrix (ECM) and results in inflammation. Subsequently, melanocytes are triggered to induce tyrosinase-mediated melanin synthesis, protecting the skin. Here, we introduce a proactive approach to protect the skin from photodamage via the topical delivery of Streptomyces avermitilis -derived tyrosinase (SaTy) using single-walled carbon nanotube (SWNT). Utilizing a reverse electrodialysis (RED) battery, we facilitated the delivery of SaTy-SWNT complexes up to depths of approximately 300 μm, as analyzed by using confocal Raman microscopy. When applied to ex vivo porcine skin and in vivo albino mouse skin, SaTy-SWNT synthesized melanin, resulting in 4-fold greater UV/vis absorption at 475 nm than in mice without SaTy-SWNT. The synthesized melanin efficiently absorbed UV light and alleviated skin inflammation. In addition, the densification of dermal collagen, achieved through SaTy-mediated cross-linking, reduced photoinduced wrinkles by 66.3% in the affected area. Our findings suggest that SWNT-mediated topical protein delivery holds promise in tissue engineering applications.

Herein, we developed a bio-functionalized solution-immersed silicon (SIS) sensor at the single-cell level to identify Erwinia amylovora ( E. amylovora ), a highly infectious bacterial pathogen responsible for fire blight, which is notorious for its rapid spread and destructive impact on apple and pear orchards. This method allows for ultra-sensitive measurements without pre-amplification or labeling compared to conventional methods. To detect a single cell of E. amylovora , we used Lipopolysaccharide Transporter E (LptE), which is involved in the assembly of lipopolysaccharide (LPS) at the surface of the outer membrane of E. amylovora , as a capture agent. We confirmed that LptE interacts with E. amylovora via LPS through in-house ELISA analysis, then used it to construct the sensor chip by immobilizing the capture molecule on the sensor surface modified with 3'-Aminopropyl triethoxysilane (APTES) and glutaraldehyde (GA). The LptE-based SIS sensor exhibited the sensitive and specific detection of the target bacterial cell in real time. The dose-response curve shows a linearity (R 2 > 0.992) with wide dynamic ranges from 1 to 10 7 cells/mL for the target bacterial pathogen. The sensor showed the value change (d Ψ ) of approximately 0.008° for growing overlayer thickness induced from a single-cell E. amylovora , while no change in the control bacterial cell ( Bacillus subtilis ) was observed, or negligible change, if any. Furthermore, the bacterial sensor demonstrated a potential for the continuous detection of E. amylovora through simple surface regeneration, enabling its reusability. Taken together, our system has the potential to be applied in fields where early symptoms are not observed and where single-cell or ultra-sensitive detection is required, such as plant bacterial pathogen detection, foodborne pathogen monitoring and analysis, and pathogenic microbial diagnosis.

Percutaneous tibial neuromodulation is a medical guideline recommended therapy for treating symptoms of overactive bladder. Stimulation is delivered to the tibial nerve via a thin needle placed percutaneously for 30 min once a week for 12-weeks, and monthly thereafter. Studies have shown that this therapy can effectively relieve symptoms of overactive bladder; however, the frequent office visits present a barrier to patients and can impact therapy effectiveness. To mitigate the burden of frequent clinic visits, small implantable devices are being developed to deliver tibial neuromodulation. These devices are implanted during a single minimally invasive procedure and deliver stimulation intermittently, similar to percutaneous tibial neuromodulation. Here, we describe the implant procedure and design of a pivotal study evaluating the safety and effectiveness for an implantable tibial neuromodulation device. The Evaluation of Implantable Tibial Neuromodulation (TITAN 2) pivotal study is a prospective, multicenter, investigational device exemption study being conducted at up to 30 sites in the United States and enrolling subjects with symptoms of overactive bladder., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Una Lee: Consultant, Medtronic, Axonics, Laborie; Primary Investigator, Patient-Centered Outcomes Research Institute, Site Investigator, Cook Myosite Keith Xavier: Consultant for Medtronic Kevin Benson: Consultant for Medtronic Kimberly Burgess: Site investigator for Medtronic Sponsored study Janet Harris-Hicks: Site investigator for Medtronic Sponsored study Robert Simon: Consultant Medtronic and Axoncis Jeffrey Proctor: Site investigator for Medtronic Sponsored study J. Chris Coetzee: Consultant for Medtronic Chris Irwin, Kira Stolen, Katie Bittner, Sarah Offutt, Beth Michaud, Anne Miller and Phillip Falkner are all Employees of Medtronic, (© 2023 The Authors.)

In this study, we developed a highly sensitive and specific bimolecular fluorescence complementation (BiFC)-based influenza A virus (IAV)-sensing system by combining a galactose/glucose-binding protein (GGBP) with an N-terminal large domain (YN1-172) and a C-terminal small domain (YC173-239) made up of enhanced yellow fluorescence protein (eYFP). The GGBP-based BiFC reporter exhibits the fluorescence reconstitution as a result of conformational changes in GGBP when lactose, which was derived from 6'-silalyllactose and used as a substrate for neuraminidase (NA), binds to GGBP in the presence of IAV. The system showed a linear dynamic range extending from 1 × 10 0 to 1 × 10 7 TCID 50 /mL, and it had a detection limit of 1.1 × 10 0 TCID 50 /mL for IAV (H1N1), demonstrating ultra-high sensitivity. Our system exhibited fluorescence intensity enhancements in the presence of IAV, while it displayed weak fluorescence signals when exposed to NA-deficient viruses, such as RSV A, RSV B, adenovirus and rhinovirus, thereby indicating selective responses for IAV detection. Overall, our system provides a simple, highly sensitive and specific IAV detection platform based on BiFC that is capable of detecting ligand-induced protein conformational changes, obviating the need for virus culture or RNA extraction processes.

Objective: To characterize instances of censorship of the word "vagina" to better understand perceptions and behaviors surrounding the word., Methods: Internet and relevant database (PubMed, Academic OneFile, Proquest, Health Business Elite, etc) searches were conducted for the words "vagina," "censor," and related wildcard terms. Search results were filtered by three independent reviewers for relevance. Related articles were summarized and reviewed for common themes. In addition, interviews were conducted with three people who have personal experience with censorship of the word "vagina." Interviews were transcribed and also reviewed for common themes., Results: Examples of censorship of the word "vagina" were compiled, and several themes were identified: (1) Policies surrounding censorship are unclear; (2) Policies appear highly variable; (3) There are differing standards between references to male and female genitalia; and (4) Objections often call the use of "vagina" overtly sexual, profane, or unprofessional., Conclusion: The word "vagina" is censored across multiple platforms and policies regarding censorship are inconsistent and unclear. Pervasive censorship of the word "vagina" perpetuates a culture of ignorance and shame about women's bodies. Until we normalize the word "vagina," we cannot make progress on women's pelvic health., Competing Interests: DECLARATION OF COMPETING INTEREST None declared., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To determine the prevalence and determinants of electronic nicotine delivery systems (ENDS) use among Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)., Methods: Cross-sectional data collected between the years 2015-2017 were analyzed to assess ENDS use (ever (current: use ≤ past 30 days; former: use > past 30 days) and never) among 11,623 adults (mean age 47 years±0.3 years; 52% women). Weighted prevalence estimates were reported, and age-adjusted logistic regression models were used to examine associations between sociodemographic and clinical exposures with ENDS use., Results: The prevalence of current and former ENDS use was 2.0% and 10.4%, respectively. Having ever used ENDS was associated with prevalent coronary artery disease. Current ENDS use was higher in males and associated with higher education, English language preference, and Puerto Rican background compared with nonsmokers and cigarette-only smokers (all p <0.05)., Conclusions: Hispanic/Latino individuals who are young adults, male, US-born, and have high acculturation were more likely to report current ENDS use. These findings could inform preventive and regulatory interventions targeted to Hispanics/Latinos., Competing Interests: Declaration of Competing Interest Dr. Rodriguez has received research support from and participated on an Advisory Board for Amgen. All other authors have no conflicts of interest to disclose.

Purpose of Review: There is a growing interest in nonantibiotic prevention strategies for recurrent urinary tract infections (rUTIs). Our objective is to provide a focused, pragmatic review of the latest evidence., Recent Findings: Vaginal estrogen is well tolerated and effective for preventing rUTI in postmenopausal women. Cranberry supplements at sufficient doses are effective in preventing uncomplicated rUTI. Methenamine, d -mannose, and increased hydration all have evidence to support their use, although the evidence is of somewhat variable quality., Summary: There is sufficient evidence to recommend vaginal estrogen and cranberry as first-line rUTI prevention strategies, particularly in postmenopausal women. Prevention strategies can be used in series or in tandem, based on patient preference and tolerance for side effects, to create effective nonantibiotic rUTI prevention strategies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To re-examine and improve the cystoscopy process for women based on patient input. While cystoscopy is a common urological procedure, women perceive it as invasive, personal, and fear-inducing. Patients want to be treated as individuals and not just another "procedure.", Methods: Women's perspectives on cystoscopy were collected using experience-based design. Observations and timings, emotion word lists, debrief forms, patient surveys, simulation, and interviews were used. A structured 2-day quality improvement event included both in-person and virtual patient participation to gain a deeper understanding of patients' perspectives. Ideas for process improvements were generated using brainstorming, creativity exercises, and prioritization. These changes were implemented and refined using an iterative process based on feedback., Results: Patients who reported feeling grateful for the positive impact of their care tended to minimize procedure-associated wait times, inconvenience, and discomfort. Women in the evaluation phase of their treatment and those who were unhappy with their symptoms tended to magnify the negative emotions associated with their procedure. Patient feedback and areas for improvement specific to women's needs were identified. Actionable changes were implemented including engaging clinic staff, updating the cystoscopy workflow, and physical changes to enhance patient privacy., Conclusion: Identifying and addressing the needs of women undergoing cystoscopy improves satisfaction as their emotional, physical, and knowledge-based needs are addressed. Active participation in the health care process empowers patients to have a voice in their care. An extraordinary experience with cystoscopy may decrease anxiety of the unknown and help patients have control over the experience., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Virtual non-contrast (VNC) coronary artery calcium scoring (CAC) may obviate the need for traditional non-contrast (TNC) CAC. There is no data on the influence of body mass index (BMI) on VNC reliability. We aimed to evaluate the influence of BMI on VNC CAC agreement with TNC., Materials and Methods: All patients who underwent sequential CAC and coronary CT angiography (CCTA) using spectral CT with TNC CAC > 0 between August 2020 and December 2021 were included. Agatston CAC scores were calculated manually by 2 blinded readers from VNC scans. A correction factor was calculated from the slope of the linear regression using the method of least squares and applied to the VNC scores. Bland-Altman plots and Cohen's weighted Kappa were utilized., Results: We included 174 patients (57.5% female). Mean BMI was 32.6 ± 7.02 kg/m 2 [BMI < 30 (39.7%); BMI 30-40 (45.4%); and BMI > 40 kg/m 2 (14.9%)]. Mean TNC CAC was 177.8 ± 316.86 and mean VNC CAC after applying the correction factor 149.34 ± 296.73. The TNC value strongly correlated with VNC (r = 0.94; p < 0.0001). As BMI increased there was a progressive reduction in signal-to-noise ratio, contrast-to-noise ratio and coronary enhancement (p < 0.05). The degree of agreement between VNC and TNC CAC decreased as BMI increased (agreement = 91.79 (weighted Kappa = 0.72), 91.14 (weighted Kappa = 0.58) and 88.46% (weighted Kappa = 0.48) (all P values < 0.001) for BMI < 30; 30-40 and > 40 kg/m 2 , respectively)., Conclusion: BMI has a significant influence on the accuracy of VNC CAC. VNC CAC shows substantial agreement in non-obese patients but performs poorly in BMI > 40 kg/m 2 . This is the first study to evaluate the influence of body mass index (BMI) on virtual non-contrast (VNC) coronary artery calcium scoring (CAC) as compared to traditional non-contrast (TNC). We retrospectively evaluated 174 patients with TNC CAC and two blinded reviewers manually calculated the VNC CAC. All cases were included without specific selection for quality. The ratio between the two directly proportional values was determined using the slope from the linear regression through the method of least squares. This correction factor of 2.65 was applied to the calcium scores obtained from VNC images. We found that VNC CAC shows substantial risk-class agreement with TNC in non-obese patients (agreement = 91.79 and weighted Kappa = 0.72) but performs poorly in BMI > 40 kg/m 2 (agreement: 88.46% and weighted Kappa = 0.48). These findings show the potential use of VNC CAC to avoid additional radiation in non-obese patients. However, further research on potential improvement strategies for VNC CAC in obese patients is needed., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Polyphenols are bioactive molecules that are used in therapeutics. Polyphenol hydroxylation and glycosylation have been shown to increase their bioavailability, solubility, bioactivity, and stability for use in various applications. Ortho-hydroxylation of polyphenols using tyrosinase allows high selectivity and yield without requiring a cofactor, while meta- and para-hydroxylation of polyphenols are mediated by site-specific hydroxylases and cytochrome P450s, although these processes are somewhat rare. O-glycosylation of polyphenols proceeds further after hydroxylation. The O-glycosylation reaction typically requires nucleotide diphosphate (NDP) sugar. However, amylosucrase (AS) has emerged as a promising enzyme for polyphenol glycosylation in large-scale production without requiring NDP-sugar. Overall, this review describes recent findings on the enzymatic mechanisms, enzyme engineering, and applications of enzymatic reactions., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

MicroRNAs (miRNAs) are short non-coding RNAs that play an important role in regulating gene expression. Since miRNAs are abnormally expressed in various cancers, they are considered to be promising biomarkers for early cancer diagnosis. However, the short length and strong sequence similarity among miRNAs make their reliable quantification very challenging. We developed a highly selective amplification-free miRNA detection method based on Förster resonance energy transfer (FRET)-aided single-molecule counting. miRNAs were selectively labeled with FRET probes using splinted ligation. When imaged with a single-molecule FRET setup, the miRNA molecules were accurately identified by the probe's FRET. miRNA concentrations were estimated from the count of molecules. The high sensitivity of the method in finding sparse molecules enabled us to achieve a limit of detection of 31-56 amol for miR-125b, miR-100, and miR-99a. Single nucleotide mismatch could be discriminated with a very high target-to-mismatch ratio. The method accurately measured the high expression of miR-125b in gastric cancer cells, which agreed well with previous reports. The high sensitivity and accuracy of this technique demonstrated its clinical potential as a robust miRNA detection method.

Objective: To describe and assess the quality and accuracy of the most highly viewed YouTube and TikTok posts related to urinary tract infections (UTIs). Social media is increasingly a resource for health information. YouTube and TikTok videos are highly utilized and are potentially a source of helpful information or misinformation., Methods: During January 2021, "UTI" was searched within YouTube and TikTok and the most relevant videos were identified and analyzed for their content. Accuracy of scientific information, possible misinformation, and credibility of the videos was rated independently by three reviewers. Posts were categorized as educational/informational, shared experience, humor/entertainment, and home remedies/alternative therapies., Results and Conclusions: In 50 YouTube and 50 TikTok videos respectively, the median number of views was 49K and 1.4M, the median number of likes was 296 and 58K, and the median number of comments was 50 and 616. The proportion of female to male presenters was equal for YouTube videos while 94% of those from TikTok were female. Overall, YouTube videos had higher median scores for scientific information, credibility, and less misinformation compared to TikTok. YouTube videos with more views, likes, and comments tended to have lower scores in all categories and more misinformation. More presenters were medical professionals on YouTube videos than those on TikTok. While videos from both platforms contained misinformation, none promoted misinformation that would cause harm to health. Healthcare providers should be aware of the potential influence of social media as patients are getting health information from many sources., Competing Interests: Conflict of Interest Disclosures None., (Copyright © 2022. Published by Elsevier Inc.)

Background: The developmental toxicity potential (dTP) concentration from the devTOX quickPredict (devTOX qP ) assay, a metabolomics-based human induced pluripotent stem cell assay, predicts a chemical's developmental toxicity potency. Here, in vitro to in vivo extrapolation (IVIVE) approaches were applied to address whether the devTOX qP assay could quantitatively predict in vivo developmental toxicity lowest effect levels (LELs) for the prototypical teratogen valproic acid (VPA) and a group of structural analogues., Methods: VPA and a series of structural analogues were tested with the devTOX qP assay to determine dTP concentration and we estimated the equivalent administered doses (EADs) that would lead to plasma concentrations equivalent to the in vitro dTP concentrations. The EADs were compared to the LELs in rat developmental toxicity studies, human clinical doses, and EADs reported using other in vitro assays. To evaluate the impact of different pharmacokinetic (PK) models on IVIVE outcomes, we compared EADs predicted using various open-source and commercially available PK and physiologically based PK (PBPK) models. To evaluate the effect of in vitro kinetics, an equilibrium distribution model was applied to translate dTP concentrations to free medium concentrations before subsequent IVIVE analyses., Results: The EAD estimates for the VPA analogues based on different PK/PBPK models were quantitatively similar to in vivo data from both rats and humans, where available, and the derived rank order of the chemicals was consistent with observed in vivo developmental toxicity. Different models were identified that provided accurate predictions for rat prenatal LELs and conservative estimates of human safe exposure. The impact of in vitro kinetics on EAD estimates is chemical-dependent. EADs from this study were within range of predicted doses from other in vitro and model organism data., Conclusions: This study highlights the importance of pharmacokinetic considerations when using in vitro assays and demonstrates the utility of the devTOX qP human stem cell-based platform to quantitatively assess a chemical's developmental toxicity potency., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Birth Defects Research published by Wiley Periodicals LLC.)

Purpose: In 2019 the American Urological Association (AUA) released the evidence-based guideline "Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline." Information supporting the guideline came from a 2019 systematic evidence review prepared for the AUA by the Pacific Northwest Evidence-based Practice Center (EPC). The AUA used evidence found for 11 Key Questions (Appendix C) in the EPC's report to derive 16 Guideline Statements. In 2021 the EPC conducted an Update Literature Review (ULR) assessing abstracts from new studies published since the 2019 systematic review. The AUA asked the EPC to further assess a subset of studies included in the ULR report, to support potential changes to the 2019 guideline., Materials/methods: A systematic-review utilized research from the Oregon Health & Science University. Pacific Northwest EPC was used to update the 2019 AUA Guideline on rUTI in women with new evidence published through 2021., Results: Updates were made to reflect changes in literature since 2019. Updates include recent publications on antibiotic prophylaxis, non-antibiotic prophylaxis, and estrogen therapy., Conclusion: The presence of rUTI is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand. .

Objective: To assess the national case logs of the first graduating urologic resident cohorts to have trained during the COVID-19 pandemic for effects on surgical volumes., Methods: The nationally aggregated Accreditation Council for Graduate Medical Education urology resident case logs were obtained for graduates of academic years (AYs) 2015-2016 through 2020-2021. Case volume differences for tracked index categories were compared between AYs with a 1-way analysis of variance. Data were then combined into pre-COVID and COVID-affected resident cohorts and differences in average cases logged were analyzed with 2-tailed student's t-tests., Results: Graduating urology residents logged an average of 1322 (SD 24.8) cases over their residency during the examined period. Total cases had multiple statistical differences between AYs but the only index category with a statistically significant decrease for a COVID-affected AY compared to pre-COVID AY was pediatric majors: AY 2020-2021 logged fewer cases than AY 2015-2016 (53.9 vs 63.0, P = .004) and AY 2018-2019 (53.9 vs 61.2, P = .04). When aggregated into pre- and COVID-affected cohorts, both pediatric minor (123.4 vs 117.5, P = .049) and pediatric major (61.4 vs 56.8, P = .003) case averages decreased for the COVID-affected cohort of residents, but no adult index category decreased., Conclusion: National graduating urology resident surgical volume for adult index categories was maintained through the pandemic. Pediatric cases saw a statistical decrease in volume of questionable clinical significance. This does not eliminate concern that individuals may have experienced a detrimental impact on their resident education., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To assess whether a multimodal opioid-limiting protocol and patient education intervention can reduce postoperative opioid use following transurethral resection of the prostate., Methods: This prospective, non-blinded, single-institution, randomized controlled trial (NCT04102566) assigned 50 patients undergoing a transurethral resection of the prostate to either a standard of care control (SOC) or multimodal experimental group (MMG). The intervention included adding ibuprofen to the postoperative pain regimen, promoting appropriate opioid use while hospitalized, an educational intervention, and discharging without opioid prescription. Data regarding demographics, operative data, opioid use, pain scores, and patient satisfaction were compared., Results: A total of 47 patients were included, n = 23 (MMG) and n = 24 (SOC). Demographic and operative findings were similar. Statistical analysis for noninferiority demonstrated non-inferior inpatient pain control (mean pain score 2.5 MMG vs 2.4 SOC, P = 0.0003). The multimodal group used significantly fewer morphine milligram equivalents after discharge (0 vs 4.1, P = 0.04). Inpatient use was reduced but did not reach statistical significance (6.0 vs 9.8, P = 0.2). Mean satisfaction scores with pain control were similar (9.6 MMG vs 9.2 SOC, P = 0.32). No opioid prescriptions were requested after discharge. Adverse events and medication side effects were infrequent and largely similar between groups., Conclusion: Implementation of an opioid-limiting postoperative pain protocol and patient education resulted in no outpatient opioid use while maintaining patient satisfaction with pain control. Eliminating opioids following a common urologic procedure will decrease risk of opioid-related adverse events and have a positive downstream impact., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Race and ethnicity are major considerations in the incidence, management, and long-term outcome of ST-elevation myocardial infarction (STEMI) in the United States, but there is limited existing comparative data., Methods: We assembled a registry in a health system serving Bronx, NY of STEMI patients from 2008-2014 and analyzed differences in presentation, treatment and mortality between Hispanic/Latino (H/L), non-Hispanic Black (NHB) and non-Hispanic White (NHW). Upon discharge post-treatment for STEMI, all patients were followed for a median of 4.4 years (interquartile range 2.5, 6.0). Out of 966 STEMI patients, mean age was 61 years, 46% were H/L and 65% were male. H/Ls and NHBs had a higher prevalence of hypertension and diabetes mellitus than their NHW counterparts, coinciding with a lower socioeconomic status (SES)., Results: The number of critically diseased vessels found at cardiac catheterization and mean troponin levels did not vary by race-ethnicity; neither did the adjusted hazard ratios (HR) for death. However, age-sex adjusted rates of general hospital readmission were higher in NHBs vs NHWs (HR 1.30, P=.03). Age-sex adjusted cardiovascular readmissions rates were higher in H/Ls than NHWs (HR 1.42, P=.03). Age-sex adjusted heart failure readmissions were increased for both H/Ls (HR 2.14, P=.01) and NHBs (HR 2.12, P=.02) over NHWs., Conclusions: Among STEMI patients, a higher prevalence of modifiable cardiovascular risk factors and a lower SES was seen among NHBs and H/Ls compared to NHWs. Despite similar coronary disease severity and in-hospital death, NHBs and H/Ls had a greater risk of general, cardiovascular and heart failure readmissions post-STEMI compared to NHWs., Competing Interests: Competing Interests: None declared., (Copyright © 2022, Ethnicity & Disease, Inc.)

Melanin nanoparticles (MNPs) used for biomedical applications are often synthesized via the chemical auto-oxidation of catecholic monomers such as dopamine and 3,4-dihydroxyphenylalanine (DOPA) under alkaline conditions. However, the synthetic method for the chemical synthesis of MNP (cMNP) is relatively straightforward and more robust to control their homogenous particle size and morphology than the corresponding enzymatic synthetic methods. In this study, we demonstrated that the simple enzymatic synthesis of MNPs (eMNPs) with homogenous and soluble (<20 nm diameter) properties is possible using dopamine and Burkholderia cepacia tyrosinase ( Bc Ty) under acidic conditions ( i.e. , pH 3.0). Bc Ty was highly reactive under pH 5.0, where the natural and chemical oxidation of catechol is complex, and thus melanin was synthesized via the hydroxylation of phenolic substrates. The detailed chemical analysis and characterization of the physical properties of the eMNPs confirmed the higher preservation of the catechol and primary amine moieties in the monomer substrate such as dopamine under acidic conditions. The eMNPs showed enhanced antioxidant activity and conferred stickiness to the formed hydrogel compared to the chemical auto-oxidation method owing to the large number of hydroxyl groups remaining such as catechol and quinone moieties. Because of these advantages and characteristics, the synthesis of MNPs using Bc Ty under acidic conditions can open a new path for their biomedical applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Several regiospecific enantiomers of hydroxy-( S )-equol (HE) were enzymatically synthesized from daidzein and genistein using consecutive reduction (four daidzein-to-equol-converting reductases) and oxidation (4-hydroxyphenylacetate 3-monooxygenase, HpaBC). Despite the natural occurrence of several HEs, most of them had not been studied owing to the lack of their preparation methods. Herein, the one-pot synthesis pathway of 6-hydroxyequol (6HE) was developed using HpaBC ( Ec HpaB) from Escherichia coli and ( S )-equol-producing E. coli , previously developed by our group. Based on docking analysis of the substrate or products, a potential active site and several key residues for substrate binding were predicted to interpret the ( S )-equol hydroxylation regioselectivity of Ec HpaB. Through investigating mutations on the key residues, the T292A variant was verified to display specific mono- ortho -hydroxylation activity at C6 without further 3'-hydroxylation. In the consecutive oxidoreductive bioconversion using T292A, 0.95 mM 6HE could be synthesized from 1 mM daidzein, while 5HE and 3'HE were also prepared from genistein and 3'-hydroxydaidzein (3'HD or 3'-ODI), respectively. In the following efficacy tests, 3'HE and 6HE showed about 30∼200-fold higher EC 50 than ( S )-equol in both ER α and ER β , and they did not have significant SERM efficacy except 6HE showing 10% lower β/α ratio response than that of 17β-estradiol. In DPPH radical scavenging assay, 3'HE showed the highest antioxidative activity among the examined isoflavone derivatives: more than 40% higher than the well-known 3'HD. In conclusion, we demonstrated that HEs could be produced efficiently and regioselectively through the one-pot bioconversion platform and evaluated estrogenic and antioxidative activities of each HE regio-isomer for the first time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Song, Lee, Kim, Kim, Lee, Kim, Lee, Kim, Kim and Kim.)

Objective: To improve women's experiences with mesh mid-urethral sling (MUS) surgery for treatment of stress urinary incontinence (SUI), we sought to qualitatively examine patient perspectives of MUS surgery, organize resulting patient-derived themes, and present our findings as potential springboards for future research and quality improvement efforts., Methods: We conducted semi-structured focus groups and interviews of patients who had undergone mesh MUS surgery at a single tertiary referral institution. Discussions were recorded, transcribed, de-identified, and analyzed using deductive and inductive content analysis. Two researchers independently performed line-by-line coding which was verified by two additional researchers., Results: Eleven women participated. Most sought SUI care after becoming frustrated with their symptoms. However, some participants experienced barriers to care or dismissal of their symptoms by their physicians. While participants expected improvements in SUI symptoms after MUS surgery, some expected improvement or resolution of other pelvic floor-related issues such as bowel symptoms. Despite having improved SUI symptoms, participants described non-SUI symptoms as negative outcomes from their MUS surgery. Overall, participants wished SUI-associated embarrassment could be lessened and suggested public service announcements to help normalize discussion of SUI symptoms., Conclusion: Obtaining first-hand information from SUI patients who have undergone MUS surgery provides insights into what matters to patients. Information from this study can help support further investigation into barriers to care for SUI patients and further study into improving counseling on goals and expectations of MUS surgery. The themes complement the current knowledge on MUS by providing insights that can only be collected through open-ended inquiry., (Copyright © 2021. Published by Elsevier Inc.)

Tyrosinase-mediated melanin synthesis is an essential biological process that can protect skin from UV radiation and radical species. This work reports on in situ biosynthesis of artificial melanin in native skin using photoactivatable tyrosinase (PaTy). The I41Y mutant of Streptomyces avermitilis tyrosinase (SaTy) shows enzymatic activity comparable to that of wild-type SaTy. This Y41 is replaced with photocleavable o-nitrobenzyl tyrosine (ONBY) using the introduction of amber codon and ONBY-tRNA synthetase/tRNA pairs. The ONBY efficiently blocks the active site and tyrosinase activity is rapidly recovered by the photo-cleavage of ONBY. The activated PaTy successfully oxidizes L-tyrosine and tyramine-conjugated hyaluronic acid (HA&#95;T) to synthesize melanin particles and hydrogel, respectively. To produce artificial melanin in living tissues, PaTy is encapsulated into lipid nanoparticles as an artificial melanosome. Using liposomes containing PaTy (PaTy&#95;Lip), PaTy is transdermally delivered into ex vivo porcine skin and in vivo mouse skin tissues, thus achieving the in situ biosynthesis of artificial melanin for skin tissue protection under UV irradiation. The results of this study demonstrate that this biomimetic system can recapitulate the biosynthetic analogs of naturally occurring melanin. It should therefore be considered to be a promising strategy for producing protective biological molecules within living systems for tissue protection., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Introduction: Onabotulinumtoxin A (BTX-A) is an effective therapy for overactive bladder (OAB), however, adverse events may prevent patients from initiating therapy. The study objective was to report real-world rates of incomplete emptying and urinary tract infection (UTI) in men and women undergoing BTX-A for OAB., Methods: Eleven clinical sites performed a retrospective study of adults undergoing first-time BTX-A injection (100 units) for idiopathic OAB in 2016. Exclusions included: postvoid residual (PVR) > 150 ml, prior BTX-A, pelvic radiation, or need for preprocedure catheterization. Primary outcomes at 6 months were incomplete emptying (clean intermittent catheterization [CIC] or PVR ≥ 300 ml without the need for CIC); and UTI (symptoms with either positive culture or urinalysis or empiric treatment). We compared rates of incomplete emptying and UTI within and between sexes, using univariate and multivariable models., Results: 278 patients (48 men and 230 women) met inclusion criteria. Mean age was 65.5 years (range: 24-95). 35% of men and 17% of women had incomplete emptying. Men had 2.4 (95% CI: 1.04-5.49) higher odds of incomplete emptying than women. 17% of men and 23.5% of women had ≥1 UTI, the majority of which occurred within the first month following injection. The strongest predictor of UTI was a history of prior UTI (OR: 4.2 [95% CI: 1.7-10.3])., Conclusions: In this multicenter retrospective study, rates of incomplete emptying and UTI were higher than many previously published studies. Men were at particular risk for incomplete emptying. Prior UTI was the primary risk factor for postprocedure UTI., (© 2022 Wiley Periodicals LLC.)

Purpose: The objective of this study was to obtain the perspectives of surgeons who treat female stress urinary incontinence (SUI) and better understand their range of experiences with mesh mid urethral sling (MUS) surgery., Materials and Methods: This qualitative study recruited gynecologic and urological surgeons who treat SUI. Surgeons were interviewed by phone and in person using a standardized interview guide. Interviews were transcribed, de-identified, and analyzed by 2 independent researchers. The transcripts were coded and summarized using the principles of thematic analysis. The research team came to consensus that a saturation of ideas representing a diverse demographic of surgeons had been achieved., Results: Twenty-four interviews of surgeons from diverse geographic locations and practice types were performed. Many surgeons described MUS surgery as rewarding and favorably impactful for women with SUI, while others grappled with the serious risks associated with MUS surgery. Those who had treated women with life-altering pain after MUS recounted impactful patient stories. Many stated that recognition, acknowledgement, and appropriate referral of complications were fundamental to responsible and ethical care. Some surgeons expressed frustration and concern about the raised level of controversy and anxiety regarding the MUS landscape. All participants expressed that there was substantial room for improvement in multiple domains. Participants also shared their optimal strategies relevant to MUS surgery., Conclusions: Despite diverse views regarding the role of the MUS, there was agreement among surgeons that the surgeon-patient relationship, thorough informed consent and patient counseling, and accountability are essential when implanting MUSs.

Bio-based polyurethane (PU) has recently drawn our attention due to the increasing interest in sustainability and the risks involved with petroleum depletion. Herein, bio-based self-healing PU with a novel polyol, i.e. , eugenol glycol dimer (EGD), was synthesized and characterized for the first time. EGD was designed to have pairs of primary, secondary, and aromatic alcohols, which all are able to be involved in urethane bond formation and to show self-healing and antioxidant effects. EGD was incorporated into a mixture of the prepolymer of polyol (tetramethylene ether glycol) and 4,4'-methylene diphenyl diisocyanate to synthesize PU. EGD-PU showed excellent self-healing properties (99.84%), and it maintained its high self-healing property (84.71%) even after three repeated tests. This dramatic self-healing was induced through transcarbamoylation by the pendant hydroxyl groups of EGD-PU. The excellent antioxidant effect of EGD-PU was confirmed by 2,2-diphenyl-1-picrylhydrazyl analysis. Eugenol-based EGD is a promising polyol chain extender that is required in the production of bio-based, self-healing, and recyclable polyurethane; therefore, EGD-PU can be applied to bio-based self-healable films or coating materials as a substitute for petroleum-based PU., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Tyrosinase is generally known as a melanin-forming enzyme, facilitating monooxygenation of phenols, oxidation of catechols into quinones, and finally generating biological melanin. As a homologous form of tyrosinase in plants, plant polyphenol oxidases perform the same oxidation reactions specifically toward plant polyphenols. Recent studies reported synthetic strategies for large scale preparation of hydroxylated plant polyphenols, using bacterial tyrosinases rather than plant polyphenol oxidase or other monooxygenases, by leveraging its robust monophenolase activity and broad substrate specificity. Herein, we report a novel synthesis of functional plant polyphenols, especially quercetin and myricetin from kaempferol, using screened bacterial tyrosinases. The critical bottleneck of the biocatalysis was identified as instability of the catechol and gallol under neutral and basic conditions. To overcome such instability of the products, the tyrosinase reaction proceeded under acidic conditions. Under mild acidic conditions supplemented with reducing agents, a bacterial tyrosinase from Bacillus megaterium ( Bm Ty) displayed efficient consecutive two-step monophenolase activities producing quercetin and myricetin from kaempferol. Furthermore, the broad substrate specificity of Bm Ty toward diverse polyphenols enabled us to achieve the first biosynthesis of tricetin and 3'-hydroxyeriodictyol from apigenin and naringenin, respectively. These results suggest that microbial tyrosinase is a useful biocatalyst to prepare plant polyphenolic catechols and gallols with high productivity, which were hardly achieved by using other monooxygenases such as cytochrome P450s.

Purpose: Frailty has emerged as a significant predictor of morbidity in urological surgery, but its impact on outcomes of sling surgery for stress incontinence remains unclear. The purpose of this study is to describe the prevalence of frailty among women undergoing sling surgery and determine the association of frailty with 30-day postoperative outcomes., Materials and Methods: We analyzed data from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP®) in 2013-2016 to identify patients undergoing sling placement using Current Procedural Terminology, 10th edition, code 57288. Patients were categorized into 2 groups based on whether they underwent isolated sling placement or had a sling with concomitant prolapse surgery. Frailty was assessed using the 5-factor Modified Frailty Index (mFI-5) developed for use with the NSQIP data set. Patients were considered frail if 2 or more factors from the mFI-5 were present. Outcomes and complications within 30 days were captured from the NSQIP data and logistic regression models used to adjust for age, race/ethnicity, body mass index and frailty., Results: We identified 25,887 women who underwent sling placement, 15,087 of whom underwent isolated sling placement (Group 1) and 10,800 of whom underwent sling with concomitant prolapse repair surgery (Group 2). Frailty was present in 9.3% of patients in Group 1 and 10.2% of patients in Group 2 (p=0.0122). Among those who underwent isolated sling placement, frailty was associated with increased length of hospital stay (OR 1.2, 95% CI 1.1-1.4, p=0.0008) and 30-day hospital readmission (OR 1.7, 95% CI 1.1-2.5, p=0.0093). Older patients undergoing isolated sling placement were more likely to have longer operation time (OR 1.2, 95% CI 1.1-1.3, p <0.0001) and hospital length of stay (OR 1.3, 95% CI 1.2-1.4, p <0.0001). Frailty was also associated with increased 30-day hospital readmission in patients who underwent sling with concomitant prolapse repair (OR 1.8, 95% CI 1.3-2.6, p=0.0003), while age was not (OR 0.9, 95% CI 0.7-1.1, p=0.29)., Conclusions: We found that frailty was present in relatively few patients undergoing sling surgery. Adverse postoperative outcomes and complications were low overall. Increased age and frailty were both associated with longer length of stay. Frailty, but not age, was significantly associated with increased likelihood of hospital readmission within 30 days following surgery. Our findings provide insight into the preoperative characteristics of women undergoing sling surgery in a large national sample, suggesting the need for preoperative identification of the frail patient.

The incidence of colorectal cancer (CRC) has increased in Korea, a newly- industrialized Asian country, with the dramatic increase of meat intake. To assess the risks of red or processed meat consumption on CRC, we performed a case-control study with biological monitoring of urinary1-OHP, PhIP, and MeIQx for the meat exposure; dG-C8 MeIQx and dG-C8 PhIP for HCA-induced DNA adducts; and homocysteine and C-reactive protein (CRP) in blood as well as malondialdehyde (MDA) and 31fatty acids in urine for inflammation and lipid alteration. We further analyzed global DNA methylation and expression of 15 CRC-related genes. As a result, the consumption of red or processed meat was not higher in the cases than in the controls. However, urinary MeIQx and PhIP were associated with the intake of red meat and urinary 1-OHP. MDA and multiple fatty acids were related to the exposure biomarkers. Most of the 31 fatty acids and multiple saturated fatty acids were higher in the cases than in the controls. Finally, the cases showed upregulation of PTGS2 , which is related to pro-inflammatory fatty acids. This study describes indirect mechanisms of CRC via lipid alteration with a series of processes including exposure to red meat, alteration of fatty acids, and relevant gene expression.

Pancreatic β cell therapy for type 1 diabetes is limited by low cell survival rate owing to physical stress and aggressive host immune response. In this study, we demonstrate a multilayer hydrogel nanofilm caging strategy capable of protecting cells from high shear stress and reducing immune response by interfering cell-cell interaction. Hydrogel nanofilm is fabricated by monophenol-modified glycol chitosan and hyaluronic acid that cross-link each other to form a nanothin hydrogel film on the cell surface via tyrosinase-mediated reactions. Furthermore, hydrogel nanofilm formation was conducted on mouse β cell spheroids for the islet transplantation application. The cytoprotective effect against physical stress and the immune protective effect were evaluated. Last, caged mouse β cell spheroids were transplanted into the type 1 diabetes mouse model and successfully regulated its blood glucose level. Overall, our enzymatic cross-linking-based hydrogel nanofilm caging method will provide a new platform for clinical applications of cell-based therapies., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background Although tobacco product use and transitions have been characterized in the general population, few studies have focused on individuals with established cardiovascular disease (CVD) in a population-based sample. Methods and Results We examined tobacco use prevalence and longitudinal patterns of tobacco product transitions in adults (≥18 years) of the nationally representative PATH (Population Assessment of Tobacco and Health) study, from 2013 to 2014 (Wave 1) through 2016 to 2018 (Wave 4). Prevalent CVD was classified through self-report of having had a heart attack, heart failure, stroke, or other heart condition. Factors associated with tobacco product use and transitions were investigated using survey logistic regression. We examined 2615 participants with self-reported CVD at Wave 1. Overall, 28.9% reported current tobacco use, equating to ≈6.2 million adults in the United States with prevalent CVD and current tobacco use. Among adults with CVD who are current tobacco users, the most commonly used product was cigarettes (82.8%), followed by any type of cigar (23.7%), and e-cigarette use (23.3%). E-cigarette use without concurrent cigarette use among participants with prevalent CVD was uncommon (1.1%). Factors associated with tobacco use were younger age, male sex, had lower education level, and lack of knowledge about the association between smoking and CVD. Men with prevalent CVD were less likely to use e-cigarettes compared with women (odds ratio [OR], 0.7; 95% CI, 0.5-0.9). Among cigarette users with CVD, transition rates between Waves 1 and 4 demonstrated <5% decrease in cigarette, with a 0.5% increase in e-cigarette use. Only ≈10% were in formal tobacco cessation programs. Conclusions Despite known harmful cardiovascular effects, over one fourth of adults with prevalent CVD use tobacco products and few quit smoking over the 4 waves of the PATH data set.

Purpose: Urinary incontinence is frequently underreported and underdiagnosed in the clinical setting. We analyzed 12 years of data from a large, nationally representative sample of women in the United States to assess the prevalence, severity, and daily impact of urinary incontinence and its subtypes at the population level., Materials and Methods: We analyzed data from 15,003 women aged ≥20 years who participated in the 2005-2016 National Health and Nutrition Examination Survey. We estimated the prevalence of urinary incontinence in the prior year, overall and by subtype (stress, urgency or mixed). Among women with urinary incontinence, we additionally assessed symptom severity using the validated 4-level Incontinence Severity Index, as well as impact on daily activities., Results: The 2005-2016 prevalence of any urinary incontinence was 53%; 16% of women had mixed urinary incontinence, 26% had stress only and 10% had urgency only. While urgency urinary incontinence and mixed urinary incontinence were highest among women aged ≥60 years, stress urinary incontinence was highest among women aged 40-59 years. NonHispanic Black women had higher prevalence of urgency urinary incontinence and lower prevalence of stress urinary incontinence compared to other racial/ethnic groups. Of women with urinary incontinence, 30% reported moderate or severe symptoms, which were more common among older than younger women. In addition, 24% of women with urinary incontinence reported that the condition affected their daily activities., Conclusions: Our study demonstrates a high prevalence of urinary incontinence among a nationally representative population of women in the United States, with many reporting that urinary incontinence affected their daily activities. Age and racial/ethnic trends varied by urinary incontinence subtype.