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This article reports on how management approaches influence methane emissions from landfills. The project team created various landfill operational scenarios for different regions of the planet with respect to waste composition, organic waste reduction and landfill gas recovery timing. These scenarios were modelled by applying a basic gas generation model according to the United Nations Intergovernmental Panel on Climate Change (IPCC) recommendations. In general, the IPCC's recommended modelling parameters and default values were used. Based on the modelling undertaken, two options stand out as being the most effective methane mitigation measures in a wide range of conditions throughout the world: (a) early gas recovery and (b) reduction of the amount of biodegradable organic waste accepted in a landfill. It is noted that reduction of organic input to any given landfill can take many years to realize. Moreover, suitable alternative processing or disposal options for the organic waste can be unaffordable for a significant percentage of the planet's population. Although effective, organic waste reduction cannot therefore be the only landfill methane mitigation measure. Early landfill gas recovery can be very effective by applying basic technologies that can be deployed relatively quickly, and at modest cost. Policymakers and regulators from around the globe can significantly reduce adverse environmental impacts from landfill gas emissions by stimulating both the early capture and flaring and/or energy recovery of landfill gas and programmes to reduce the inflow of organic waste into landfills., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Loneliness, the perception that one's social relationships do not meet the desire for social connection, is a risk factor for poor mental and physical health. Adolescents with chronic pain experience higher rates of peer loneliness which persists over time. Previous studies used a single loneliness measure, limiting our understanding of the nature of their loneliness. This study describes the types of peer loneliness (intimate, relational, and collective) experienced by these adolescents and the impact that peer loneliness has on pain-related outcomes., Methods: A cross-sectional online survey was completed by 128 Canadian adolescents aged 12-18 years who experienced pain for at least 3 months. Validated measures captured demographics, pain-related characteristics, types of peer-related loneliness, measures of social well-being, and mental and physical health outcomes., Results: Friedman's tests of z-scores indicate that participants equally experienced dyadic, relational, and collective peer loneliness. MANCOVA revealed that those who identify as Black were lonelier after controlling for socioeconomic status. Multiple regression showed that loneliness was a robust predicter of worse scores on social well-being and mental health outcomes with males and females equally impacted by loneliness. Despite moderate correlations between loneliness and pain interference and pain intensity, loneliness did not predict school absences, suggesting that loneliness' influence on physical pain outcomes may be temporally earlier (e.g. contribute to pain chronification)., Conclusions: Peer loneliness among adolescents with chronic pain negatively impacts their social well-being and mental health outcomes. Interventions addressing loneliness to target all three types of peer loneliness may be key to improving pain-related outcomes., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

We studied the intersystem crossing (ISC) property of red-light absorbing heavy atom-free dihydronaphtho[ b ]-fused Bodipy derivatives (with phenyl group attached at the lower rim via ethylene bridge, taking constrained geometry, i.e., BDP-1 and the half-oxidized product BDP-2 ) and dispiroflourene[ b ]-fused Bodipy ( BDP-3 ) that have a twisted π-conjugated framework. BDP-1 and BDP-3 show strong and sharp absorption bands (i.e., ε = 2.0 × 10 5 M -1 cm -1 at 639 nm, fwhm ∼491 cm -1 for BDP-3 ). BDP-1 is significantly twisted (φ = 21.6°), while upon mono-oxidation, BDP-2 becomes nearly planar on the oxidized side (φ = 3.5°). Interestingly, BDP-2 showed efficient ISC (triplet state quantum yield, Φ T = 40%) due to S 1 / T 2 state energy matching. Long-lived triplet excited state was observed (τ T = 212 μs in solution and 2.4 ms in polymer matrix), and ISC takes 4.0 ns. Differently, twisted BDP-1 gives weak ISC only 5%, ISC takes 7.7 ns, and the triplet state is populated only with addition of ethyl iodide. Time-resolved electron paramagnetic resonance spectra of BDP-1 revealed the coexistence of two triplet states, with drastically different zero-field splitting D parameters of -2047 MHz and -1370 MHz, respectively, along with varying sublevel population ratios. We demonstrate that the ISC is not necessarily enhanced by torsion of the π-conjugation framework; instead, S 1 / T n state energy matching is more efficient to induce ISC even in compounds that have planar molecular structures.

Background Mammographic background characteristics may stimulate human visual adaptation, allowing radiologists to detect abnormalities more effectively. However, it is unclear whether density, or another image characteristic, drives visual adaptation. Purpose To investigate whether screening performance improves when screening mammography examinations are ordered for batch reading according to mammographic characteristics that may promote visual adaptation. Materials and Methods This retrospective multireader multicase study was performed with mammograms obtained between September 2016 and May 2019. The screening examinations, each consisting of four mammograms, were interpreted by 13 radiologists in three distinct orders: randomly, by increasing volumetric breast density (VBD), and based on a self-supervised learning (SSL) encoding (examinations automatically grouped as "looking similar"). An eye tracker recorded radiologists' eye movements during interpretation. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of random-ordered readings were compared with those of VBD- and SSL-ordered readings using mixed-model analysis of variance. Reading time, fixation metrics, and perceived density were compared using Wilcoxon signed-rank tests. Results Mammography examinations (75 with breast cancer, 75 without breast cancer) from 150 women (median age, 55 years [IQR, 50-63]) were read. The examinations ordered by increasing VBD versus randomly had an increased AUC (0.93 [95% CI: 0.91, 0.96] vs 0.92 [95% CI: 0.89, 0.95]; P = .009), without evidence of a difference in specificity (89% [871 of 975] vs 86% [837 of 975], P = .04) and sensitivity (both 81% [794 of 975 vs 788 of 975], P = .78), and a reduced reading time (24.3 vs 27.9 seconds, P < .001), fixation count (47 vs 52, P < .001), and fixation time in malignant regions (3.7 vs 4.6 seconds, P < .001). For SSL-ordered readings, there was no evidence of differences in AUC (0.92 [95% CI: 0.89, 0.95]; P = .70), specificity (84% [820 of 975], P = .37), sensitivity (80% [784 of 975], P = .79), fixation count (54, P = .05), or fixation time in malignant regions (4.6 seconds, P > .99) compared with random-ordered readings. Reading times were significantly higher for SSL-ordered readings compared with random-ordered readings (28.4 seconds, P = .02). Conclusion Screening mammography examinations ordered from low to high VBD improved screening performance while reducing reading and fixation times. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

Young people's sexual and reproductive health (SRH) continues to be a major challenge in low and middle-income countries, with implications for public health now and in the future. Fortunately there is a growing array of evidence-based interventions, and commitments from governments, development partners and donors, to support programmes that aim to improve young people's SRH.However, in some situations, the technical assistance that governments feel that they need to strengthen and implement national policies and strategies, to move from words to action, is not available. The WHO Adolescent and Youth Sexual and Reproductive Health and Rights (AYSRHR) Technical Assistance (TA) Coordination Mechanism was initiated to help fill this technical assistance gap; to respond to TA requests from ministries of health in ways that are timely, efficient, effective and contribute to strengthening capacity.This paper describes the process of developing the Technical Assistance Coordination Mechanism (TA Mechanism) and the outcomes, experiences and lessons learned after three years of working. It triangulates the findings from a preliminary review of the literature and discussions with selected key informants; the outcomes from a series of structured review meetings; and the documented processes and results of the technical assistance provided to countries.The lessons learned focus on three aspects of the TA Mechanism. How it was conceptualized and designed: through listening to people who provide and receive AYSRHR TA and by reviewing and synthesizing past experiences of TA provision. What the TA Mechanism has achieved: a standardized process for TA provision, at different stages for a range of AYSRHR issues in ten countries in three geographic regions. And what worked well and what did not: which common challenges was the TA Mechanism able to address and which ones persisted despite efforts to avoid or resolve them. The paper ends with the implications of the lessons learned for future action., (© 2024. The Author(s).)

The photochemistry of two representative thermally activated delayed fluorescence (TADF) emitters based on the multiple resonance effect (MRE) (DABNA-1 and DtBuCzB) was studied. No significant TADF was observed in fluid solution, although the compounds have a long-lived triplet state ( ca. 30 μs). We found that these planar boron molecules bind with Lewis bases, e.g. , 4-dimethylaminopyridine (DMAP) or an N -heterocyclic carbene (NHC). A new blue-shifted absorption band centered at 368 nm was observed for DtBuCzB upon formation of the adduct; however, the fluorescence of the adduct is the same as that of the free DtBuCzB. We propose that photo-dissociation occurs for the DtBuCzB-DMAP adduct, which is confirmed by femtosecond transient absorption spectra, implying that fluorescence originates from DtBuCzB produced by photo-dissociation; the subsequent in situ re-binding was observed with nanosecdon transient absorption spectroscopy. No photo-dissociation was observed for the NHC adduct. Time-resolved electron paramagnetic resonance (TREPR) spectra show that the triplet states of DABNA-1 and DtBuCzB have similar zero field splitting (ZFS) parameters ( D = 1450 MHz). Theoretical studies show that the slow ISC is due to small SOC and weak Herzberg-Teller coupling, although the S 1 /T 1 energy gap is small (0.14 eV), which rationalizes the lack of TADF., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Several years ago the discovery of a conical intersection offered an explanation for the ultafast photodissociation of pyrrole. Subsequently, the photodissociation of pyrrole ammonia complexes PyH*(NH 3 ) n with n ≥ 3 was studied in the gas phase as a model for a hydrogen-bond forming solvent. Two alternative mechanisms, electron coupled proton transfer (ECPT) and hydrogen atom transfer (HAT, also called the impulsive model, IM), have been proposed. The parent 1 : 1 complex was never studied, due to the short lifetime of the NH 4 radical fragment. Here we report experiments on the deuterated species PyD*(ND 3 ) n , including the 1 : 1 complex ( n = 1). The velocity distribution of the ND 4 radical is well approximated by a Maxwell-Boltzmann distribution of T ≈ 530 K, with a negative anisotropy parameter of β = -0.3. The impulsive model predicts a much narrower velocity distribution with larger negative anisotropy. The ECPT model predicts a long lived intermediate that should allow thermal equilibration of the vibrational energy but should also destroy the rotational memory of the initially excited state. The average kinetic energy agrees with the prediction of the impulsive model, whereas the wide range of kinetic energies is more in line with ECPT. Hence the mechanism seems to be more complex and requires further theoretical modelling.

Background and Objective: In contemporary Urology, the gold standard for treatment of erectile dysfunction refractory to medical therapy has been implantation with a penile prosthesis. The past 40 years has witnessed evolutions in technology and surgical techniques, which have led to increased patient satisfaction rates and decreased complication and infection rates. This review is an update to a prior review article that evaluates these advancements in the context of patient satisfaction and different rates of complications following surgeries. In addition, the review compares malleable and inflatable prostheses with regard to infection rate, mechanical failure rate, and erosion rate., Methods: A literature search was conducted using Medline and Google Scholar to examine papers from 1973 to the present day. Keywords, such as, "penile prosthesis surgery", "malleable penile prosthesis", "inflatable penile prosthesis", "two-piece Inflatable Penile Prosthesis (IPP)", and "three-piece IPP" were utilized during the search. A total of 76 papers were included, and all were in English., Key Content and Findings: Studies on the latest models of each of the three prostheses (malleable, two-piece IPP, three-piece IPP) revealed patient satisfaction ratings at or above 75%. Both types of IPPs were associated with greater satisfaction and lower erosion rates while malleable prostheses were associated with lower mechanical failure rates. Although no significant differences in infection rates were noted between the prosthesis types, a history of diabetes, obesity, and smoking were predictive of infection events., Conclusions: The three-piece IPP, if indicated for a suitable patient, is generally accepted as the best type of prosthesis given its biological mimicry to an erect human penis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-741/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Objectives: Limited research has investigated parent-targeted interventions in pediatric chronic pain, though these interventions may be an important part of family-centered care. Further, parent perspectives and feedback regarding these interventions are scant in the literature, even though they are crucial for developing, refining, and optimizing treatment options. This study aimed to understand how parents experience and perceive their participation in a cognitive-behavioral therapy-based, parent-targeted group intervention that was delivered either in-person or virtually, with a focus on the treatment components they found most important., Methods: Data from semistructured focus groups/interviews within 1week post-treatment with 32 parents (n=11 in-person, n=21 virtual) were analyzed using an inductive reflexive thematic analysis., Results: Three overarching themes were generated from the thematic analysis: building a foundation of knowledge, finding normalization and hope through connection and lived experiences, and sharing collective responsibility for pain management., Discussion: Parents perceived a range of benefits from participating in a cognitive-behavioral therapy-based, parent-targeted group intervention, both on themselves and for their youth. Overall, parent perceptions across in-person and virtual intervention delivery were consistent, except for a drawback of virtual participation for developing a deeper social connection among parents. Thus, a relatively brief parent-targeted group intervention was perceived to be a positive experience for parents, though considerations for adapting to virtual delivery and facilitating social connection among parents seem to be important., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The P450 monooxygenase CYP109A2 from Bacillus megaterium DSM319 was previously found to convert vitamin D3 (VD3) to 25-hydroxyvitamin D3. Here, we show that this enzyme is also able to convert testosterone in a highly regio- and stereoselective manner to 16β-hydroxytestosterone. To reveal the structural determinants governing the regio- and stereoselective steroid hydroxylation reactions catalyzed by CYP109A2, two crystal structures of CYP109A2 were solved in similar closed conformations, one revealing a bound testosterone in the active site pocket, albeit at a nonproductive site away from the heme-iron. To examine whether the closed crystal structures nevertheless correspond to a reactive conformation of CYP109A2, docking and molecular dynamics (MD) simulations were performed with testosterone and vitamin D3 (VD3) present in the active site. These MD simulations were analyzed for catalytically productive conformations, the relative occurrences of which were in agreement with the experimentally determined stereoselectivities if the predicted stability of each carbon-hydrogen bond was taken into account. Overall, the first-time determination and analysis of the catalytically relevant 3D conformation of CYP109A2 will allow for future small molecule ligand screening in silico, as well as enabling site-directed mutagenesis toward improved enzymatic properties of this enzyme., (© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Prostate cancer is the most common solid-organ malignancy in adult men. Early detection and treatment of prostate cancer with radical prostatectomy (RP) has improved cancer-specific survival but is associated with penile shortening and erectile dysfunction. Penile traction therapy (PTT) has been demonstrated to increase stretched penile length (SPL) prior to penile prosthesis placement and may improve erectile function (EF) in patients with Peyronie's disease. We aimed to evaluate the efficacy of PTT in preserving penile length and EF after bilateral cavernous nerve crush injury (BCNI) in a rat model., Methods: Twenty-four male Sprague-Dawley rats aged 11-13 weeks were randomly assigned to three groups (n=8, each): sham operation with no PTT (Sham), BCNI without PTT (Crush), and BCNI with PTT (Traction). PTT was started on postoperative day 3. A traction force of 1 Newton was applied to the penis for 30 minutes each day for 28 days. After 28 days of traction, the cavernous nerve was stimulated while recording the intracavernosal pressure (ICP) and the mean arterial pressure (MAP) simultaneously. Cavernosal tissue was excised, and western blot analysis for endothelial nitric oxide synthase (eNOS) was performed. Significance was determined by using ANOVA with Tukey-Kruger post-hoc testing., Results: At 4 weeks after nerve injury, the Traction group had significantly greater SPL compared to the Sham and Crush groups (30 vs. 28 and 27 mm, respectively). The Sham group had significantly greater EF (ΔICP/MAP) compared to the Crush group at 2.5, 5, and 7.5 V. The EF of the Traction group was between that of the Sham and Crush groups and was not significantly different from the Sham group at any voltages. Further downstream analysis revealed that the Traction group had significantly greater eNOS expression in cavernosal tissue compared to the Crush group, which was confirmed on western blot analysis and immunohistochemistry (IHC) staining., Conclusions: Findings from this animal study suggest that PTT has the potential to mitigate penile retraction after RP. While more studies are needed to determine the effect of PTT on preservation of EF, the increased eNOS expression observed in the Traction group offers a potential protective mechanism of action., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-53/coif). BD reports has received a grant to fund this project from the Sexual Medicine Society of North America. WJGH is an advisor for Coloplast, Boston Scientific, and a speaker for Endo. The other authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Whereas directed evolution and rational design by structural inspection are established tools for enzyme redesign, computational methods are less mature but have the potential to predict small sets of mutants with desired properties without laboratory screening of large libraries. We have explored the use of computational enzyme redesign to change the enantioselectivity of a highly thermostable alcohol dehydrogenase from Thermus thermophilus in the asymmetric reduction of ketones. The enzyme reduces acetophenone to (S)-1-phenylethanol. To invert the enantioselectivity, we used an adapted CASCO workflow which included Rosetta for enzyme design and molecular dynamics simulations for ranking. To correct for unrealistic binding modes, we used Boltzmann weighing of binding energies computed by a linear interaction energy approach. This computationally cheap method predicted four variants with inverted enantioselectivity, each with 6-8 mutations around the substrate-binding site, causing only modest reduction (2- to 7-fold) of k cat /K M values. Laboratory testing showed that three variants indeed had inverted enantioselectivity, producing (R)-alcohols with up to 99 % enantiomeric excess. The broad substrate range allowed reduction of acetophenone derivatives with full conversion to highly enantioenriched alcohols. The results demonstrate the use of computational methods to control ketoreductase stereoselectivity in asymmetric transformations with minimal experimental screening., (© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

To explore the relationship between the twisted π-conjugation framework of aromatic chromophores and the efficacy of intersystem crossing (ISC), we have studied a N , N , O , O -boron-chelated Bodipy derivative possessing a severely distorted molecular structure. Surprisingly, this chromophore is highly fluorescent, showing inefficient ISC (singlet oxygen quantum yield, Φ Δ = 12%). These features differ from those of helical aromatic hydrocarbons, where the twisted framework promotes ISC. We attribute the inefficient ISC to a large singlet-triplet energy gap (Δ E S 1 /T 1 = 0.61 eV). This postulate is tested by critical examination of a distorted Bodipy having an anthryl unit at the meso -position, for which Φ Δ is increased to 40%. The improved ISC yield is rationalized by the presence of a T 2 state, localized on the anthryl unit, with energy close to that of the S 1 state. The electron spin polarization phase pattern of the triplet state is ( e , e , e , a , a , a ), with the T z sublevel of the T 1 state overpopulated. The small zero-field splitting D parameter (-1470 MHz) indicates that the electron spin density is delocalized over the twisted framework. It is concluded that twisting of π-conjugation framework does not necessarily induce ISC, but S 1 /T n energy matching may be a generic feature for increasing ISC for a new-generation of heavy atom-free triplet photosensitizers., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Employing a qualitative content analysis of online comments made on YouTube and letters to the editor published in US newspapers, we examine the deployment and neutralization of the evil corporation master frame in debates on two distinct biotechnologies, vaccines and genetically modified organisms. This study builds on previous research by outlining three diagnostic components of the evil corporation master frame: dishonesty, greed, and the contamination of authority. It also finds that supporters of vaccines and genetically modified organisms seek to neutralize the evil corporation master frame through aggressive, defensive, endurance, and redemptive framings. This study provides ideational detail for the ways that controversial biotechnology is constructed. The particularly vexing anti-vaccine movement is not dissimilar from other challenges to mainstream science as disparate movements draw on the same master frame. It also demonstrates how defenses of genetically modified organisms and vaccines tend to reify the anti-corporate stigma that sustains challenges to scientific authority.

CYP105AS1 is a cytochrome P450 from Amycolatopsis orientalis that catalyzes monooxygenation of compactin to 6-epi-pravastatin. For fermentative production of the cholesterol-lowering drug pravastatin, the stereoselectivity of the enzyme needs to be inverted, which has been partially achieved by error-prone PCR mutagenesis and screening. In the current study, we report further optimization of the stereoselectivity by a computationally aided approach. Using the CoupledMoves protocol of Rosetta, a virtual library of mutants was designed to bind compactin in a pro-pravastatin orientation. By examining the frequency of occurrence of beneficial substitutions and rational inspection of their interactions, a small set of eight mutants was predicted to show the desired selectivity and these variants were tested experimentally. The best CYP105AS1 variant gave >99% stereoselective hydroxylation of compactin to pravastatin, with complete elimination of the unwanted 6-epi-pravastatin diastereomer. The enzyme-substrate complexes were also examined by ultrashort molecular dynamics simulations of 50 × 100 ps and 5 × 22 ns, which revealed that the frequency of occurrence of near-attack conformations agreed with the experimentally observed stereoselectivity. These results show that a combination of computational methods and rational inspection could improve CYP105AS1 stereoselectivity beyond what was obtained by directed evolution. Moreover, the work lays out a general in silico framework for specificity engineering of enzymes of known structure., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

This study aimed to answer the following question: What is the proportion of acceptance reported by parents toward pediatric behavior guidance techniques (BGTs)? Observational studies that evaluated parental acceptance of BGTs during pediatric dental visits among parents of non-special health care need (non-SHCN) and SHCN children were included. A search of the Cochrane Library, Latin American and Caribbean Health Sciences (LILACS), MedLine/PubMed, PsycINFO, Scopus, and Web of Science databases, in addition to gray literature, was performed until October 2021. The Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies was used for quality assessment. The certainty of evidence was assessed using the Recommendation, Assessment, Development, and Evaluation (Grade). Fifty-three studies with 4868 participants were included, and 42 were retained for the random-effects proportion meta-analysis. The methodological quality varied from low to high. The agreement with the BGTs varied from 85.6% (95%CI: 77.5-92.1; p < 0.001; I 2 = 93.6%; 16 studies; n = 1399) for tell-show-do to 25.7% (95%CI: 17.8-34.4; p < 0.001; I 2 = 90.4%; 12 studies; n = 1129) for passive protective stabilization among non-SHCN children's parents; meanwhile, among the parents of SHCN children, it varied from 89.1% (95%CI: 56.1-99.7; p < 0.001; I 2 = 95.7%; 3 studies; n = 454) for tell-show-do to 29.1% (95%CI: 11.8-50.0; p = 0.001; I 2 = 84.8%; 3 studies; n = 263) for general anesthesia. The effect estimates varied greatly, as substantial heterogeneity across studies was observed, thus limiting the confidence in the results. Parents were more likely to agree with basic BGTs over advanced BGTs, with very low certainty of evidence. Dentists should discuss BGT options with parents. Protocol registration: PROSPERO CRD42018103834.

Background: There is a lack of self-management tools for adolescents with cancer (AWC). This study evaluated the feasibility of Teens Taking Charge Cancer , a web-based self-management program. Methods: A pilot randomized control trial (RCT) was conducted across 4 pediatric oncology clinics. AWC (12-18 years) and their caregivers were randomized to either the intervention or control group. All were asked to complete 12 website modules over 12 weeks (at their own pace) and received monthly calls from health coaches. The intervention website was based on cognitive behavioral principals, designed as an interactive self-guided online program, while the control consisted of education and included links to 12 general cancer websites. Outcome assessments occurred at enrollment and 12 weeks post-intervention. The primary outcomes included rate of accrual and retention, adherence to the protocol, acceptability and satisfaction with intervention using questionnaire and semi-structured interviews, adverse events and engagement with the intervention. Results: Eighty-one teen-caregiver dyads were enrolled with a retention rate of 33%. In the intervention group 46% ( n  = 18) logged in at least once over the 12-week period. A mean of 2.4 of 12 modules ( SD 3.0) were completed; and no one completed the program. Thirty-three percent of caregivers in the intervention logged into the website at least once and none completed the full program. Discussion: The results from this pilot study suggest that the current design of the Teens Taking Charge Cancer RCT lacks feasiblity. Future web-based interventions for this group should include additional features to promote uptake and engagement with the program.

Three anthracene (An)-naphthalenediimide (NDI) compact electron donor-acceptor dyads were prepared. Femtosecond transient absorption (fs-TA) spectra show fast charge separation (ca. 0.9-1.7 ps) and relatively slow charge recombination (ca. 8-565 ps) upon photoexcitation; moreover, the 3 An state was observed for 9-An-NDI , whereas the final state is 3 NDI for both 9-An-Ph-NDI and 2-An-Ph-NDI , which have an intervening phenyl linker between the An and NDI units. Nanosecond transient absorption (ns-TA) spectra indicate that the lowest triplet state of all the dyads is 3 An, with triplet lifetimes of 139-354 μs. An unusually slow intramolecular triplet-triplet energy transfer (TTET) was observed for 9-An-Ph-NDI and 2-An-Ph-NDI (32-85 ns). Time-resolved electron paramagnetic resonance (TREPR) spectroscopy confirms that the intersystem crossing (ISC) mechanism is spin orbit charge transfer ISC (SOCT-ISC) for all the dyads; for 9-An-NDI , only the 3 An state was observed, while for the other two dyads, both 3 NDI and 3 An states were observed, with their relative population changing with increasing delay time, which supports TTET.

In recent years it has become evident that a healthy intestinal microbiome is beneficial for the overall health of an individual. A healthy microbiome is diverse, increasing stability and resilience and strengthening the immune system. In addition, healthy intestinal metabolisms have a beneficial effect on many physiological processes such as the brain function. Looking from the One Health perspective, which recognizes that health of humans is closely connected to the health of animals and environment, it is inherently beneficial to stimulate the health of animals for the well-being of humans. However, the intensive administration of antibiotics to livestock for prevention and cure of disease, and even stimulation of growth, disrupts a healthy microbiome. With the rapid increase of emerging zoonotic diseases, alternatives to the use of antimicrobial compounds are urgently necessary. This research analyses the development of alternatives for antibiotic use contributing to veterinary intestinal health through an in-depth patent analysis of inventions for fodder additives. In the period 1999-2020, 1269 unique patent families describing the use of probiotics, enzymes and prebiotics for swine, poultry and ruminants were identified. Innovation trends, geography, key applicants, and classification of patents were analysed. Asian industrial applicants applied for the majority of patents comprising the largest share of patents for probiotics and enzymes in combination with fodder for swine. Followed by North American and European industrial applications, applying for patents for probiotics in combination with fodder for poultry, swine, and ruminants. Overall, our results do not show a clear increase in innovations, suggesting that innovations in the use of probiotics and enzymes in animal feed appear to be stalling. While in the near future a combination of the use of antibiotics and alternatives is most likely to be implemented, the use of probiotics stands a good chance of replacing antibiotics in animal husbandry and limiting the adverse effects of antibiotic abuse., Competing Interests: OL is also Senior Manager Science at Yakult. LB is consultant for several commercial parties in the field of probiotics and life sciences; none of her advising practices are in conflict with the content of this research., (© 2022 The Authors.)

Aims: Glomerular damage indicated by proteinuria is a main symptom in diabetic nephropathy. Mineralocorticoid receptor (MR) antagonists (MRAs) are beneficial irrespective of aldosterone availability. Thus, we hypothesized an alternatively activated MR to promote glomerular damage in proteinuric diabetic nephropathy. Specifically, we aimed first to demonstrate the presence of steroid hormones serving as alternative MR targets in type II diabetic patients with proteinuric kidney disease, second whether MR selectivity was modified, third to characterize MR and glucocorticoid receptor (GR) expression and activity in glomerular cell types exposed to eu- and hyperglycemic conditions, fourth to characterize the pro-fibrotic potential of primary human renal mesangial cells (HRMC) upon stimulation with aldosterone and cortisol, and fifth to specify the involvement of the MR and/or GR in pro-fibrotic signaling., Materials and Methods: Urinary steroid hormone profiles of patients with diabetic kidney disease were analyzed by gas chromatography-mass spectrometry and compared to an age and gender matched healthy control group taken out of a population study. In both cohorts, the activity of the MR pre-receptor enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2), which inactivates cortisol to prevent it from binding to the MR, was assessed to define a change in MR selectivity. Expression of HSD11B2, MR and GR was quantified in HRMC and primary human renal glomerular endothelial cells (HRGEC). Activity of MR and GR was explored in HRMC by measuring the MR/GR down-stream signal SGK1 and the pro-fibrotic genes TGFB1, FN1 and COL1A1 in normal and high glucose conditions with the MR/GR agonists aldosterone/cortisol and the MR/GR antagonists spironolactone/RU486., Results: Patients with diabetic kidney disease excreted more tetrahydroaldosterone than the control group reaching significance in men. The excretion of MR-agonistic steroid hormones was only increased for 18-hydroxytetrahydrocorticosterone in diabetic women. The excretion of most glucocorticoids was higher in the diabetic cohort. Higher apparent systemic HSD11B2 activity suggested less activation of the MR by cortisol in diabetic patients. Both cell types, HRMC and HRGEC, lacked expression of HSD11B2. Hyperglycemic conditions did not change MR and GR expression and activity. Stimulation with both aldosterone and cortisol promoted upregulation of pro-fibrotic genes in HRMC. This effect of MR and/or GR activation was more pronounced in high glucose conditions and partially inhibited by MRAs and GR antagonists., Conclusions: In patients with diabetic kidney disease alternative MR activation is conceivable as cortisol and cortisone metabolites are increased. Systemic availability of active metabolites is counteracted via an increased HSD11B2 activity. As this cortisol deactivation is absent in HRMC and HRGEC, cortisol binding to the MR is enabled. Both, cortisol and aldosterone stimulation led to an increased expression of pro-fibrotic genes in HRMC. This mechanism was related to the MR as well as the GR and more marked in high glucose conditions linking the benefit of MRAs in diabetic kidney disease to these findings., Competing Interests: The authors have declared that no competing interests exist.

Background: Increasing evidence exists that higher levels of androgens can be found in individuals with autism. Evidence yields to a susceptible role of Cytochrome P450 17A1 (CYP17A1) with its catalyzation of the two distinct types of substrate oxidation by a hydroxylase activity (17-alpha hydroxylase) and C17/20 lyase activity. However, to what extent steps are altered in affected children with autism versus healthy controls remains to be elucidated. Methods: Urine samples from 48 boys with autism (BMI 19.1 ± 0.6 kg/m 2 , age 14.2 ± 0.5 years) and a matched cohort of 48 healthy boys (BMI 18.6 ± 0.3 kg/m 2 , 14.3 ± 0.5 years) as well as 16 girls with autism (BMI 17.5 ± 0.7 kg/m 2 , age 13.8 ± 1.0 years) and a matched cohort of 16 healthy girls (BMI 17.2 ± 0.8 kg/m 2 , age 13.2 ± 0.8 years) were analyzed for steroid hormone metabolites by gas chromatography-mass spectrometry. Results: The activity of 17-alpha Hydroxylase increased by almost 50%, whereas activity of 17/20 Lyase activity increased by around 150% in affected children with autism. Furthermore, the concentration of Cortisol was higher as compared to the average increase of the three metabolites TH-Corticosterone, 5α-TH-Corticosterone and TH-11β-DH-Corticosterone, indicating, in addition, a stimulation by the CRH-ACTH system despite a higher enzymatic activity. Discussion: As it was shown that oxidative stress increases the 17/20-lyase activity via p38α, a link between higher steroid hormone levels and oxidative stress can be established. However, as glucocorticoid as well as androgen metabolites showed higher values in subjects affected with autism as compared to healthy controls, the data indicate, despite higher CYP17A1 activity, the presence of increased substrate availability in line with the Cholesterol theory of autism.

Background: The COVID-19 pandemic health crisis has changed household and school routines leaving children and adolescents without important anchors in life. This, in turn, can influence their mental health, changing their behavioral and psychological conditions., Aims: To systematically review the literature to answer the question: "What is the worldwide prevalence of mental health effects in children and adolescents during the COVID-19 pandemic?"., Methods: Embase, Epistemonikos database, LILACS, PsycINFO, PubMed, Scopus, Web of Science, and World Health Organization Global literature on coronavirus disease were searched. Grey literature was searched on Google Scholar, Grey Literature Report, and Preprint server MedRxiv. Observational studies assessing the prevalence of mental health effects in children and adolescents during the COVID-19 pandemic were included. Four authors independently collected the information and assessed the risk of bias of the included studies., Results: From a total of 11,925 identified studies, 2873 remained after the removal of the duplicated records. Nineteen studies remained after the final selection process. The proportion of emotional symptoms and behavior changes varied from 5.7% to 68.5%; anxiety 17.6% to 43.7%, depression 6.3% to 71.5%, and stress 7% to 25%. Other outcomes such as the prevalence of post-traumatic stress disorder (85.5%) and suicidal ideation (29.7% to 31.3%) were also evaluated., Linking Evidence to Action: Overall findings showed that the proportion of children and adolescents presenting mental health effects during the COVID-19 pandemic showed a wide variation in different countries. However, there was a trend toward mental health issues. Therefore, policymakers, healthcare planners, youth mental health services, teachers, parents, and researchers need to be prepared to deal with this demand., (© 2022 Sigma Theta Tau International.)

Chronic pain affects 1 in 5 youth, many of whom manage their pain using a biopsychosocial approach. The COVID-19 pandemic has impacted the way that healthcare is delivered. As part of a larger program of research, this study aimed to understand the impact of the pandemic on pediatric chronic pain care delivery including impact on patients' outcomes, from the perspective of pediatric healthcare providers. A qualitative descriptive study design was used and 21 healthcare providers from various professional roles, clinical settings, and geographic locations across Canada were interviewed. Using a reflexive thematic analysis approach 3 themes were developed: (1) duality of pandemic impact on youth with chronic pain (i.e., how the pandemic influenced self-management while also exacerbating existing socioeconomic inequalities); (2) changes to the healthcare system and clinical practices (i.e., triaging and access to care); (3) shift to virtual care (i.e., role of institutions and hybrid models of care). These findings outline provider perspectives on the positive and negative impacts of the pandemic on youth with chronic pain and highlight the role of socioeconomic status and access to care in relation to chronic pain management during the pandemic in a high-income country with a publicly funded healthcare system.

Introduction: Electronic cigarettes (e-cigs) have increased in popularity as a potentially less harmful alternative to tobacco smoking; however, the literature suggests "vaping" can cause endothelial damage, which can adversely affect erectile function. While there is a known link between smoking cigarettes and erectile dysfunction (ED), the effect of e-cigs on erectile function has been understudied., Objectives: To review the evidence for e-cig use causing endothelial dysfunction, to explore endothelial dysfunction as a potential mechanism for ED, and to determine if there is literature to support e-cigs as a cause of ED., Methods: A literature review was performed to identify publications pertaining to e-cig consumption and ED. Publications regarding e-cig consumption and vascular or endothelial damage were also included. The search was conducted through PubMed, MEDLINE database, the Cochrane Library Central Search, Web of Science, and Google Scholar. We identified 40+ publications for review, including 6 clinical trials and 3 basic science studies., Results: The literature suggests that e-cig use induces oxidative stress, including the direct formation of reactive oxygen species and hydroxyl radicals, leading to endothelial damage. Endothelial dysfunction is a potential mechanism for ED, but there is a paucity of studies evaluating the relationship between e-cig use and ED., Conclusion: E-cig use may cause ED in men, but more studies, specifically clinical trials, are needed to establish a relationship between e-cigs and ED. E-cig-induced endothelial dysfunction is a potential mechanism for ED that is worth exploring further. Pincus J, Sandoval V, Dick B, et al. E-Cigarette-Associated Endothelial Damage: A Potential Mechanism for Erectile Dysfunction. Sex Med Rev 2022;10:168-173., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

ω-Transaminases (ω-TAs) catalyze the conversion of ketones to chiral amines, often with high enantioselectivity and specificity, which makes them attractive for industrial production of chiral amines. Tailoring ω-TAs to accept non-natural substrates is necessary because of their limited substrate range. We present a computational protocol for predicting the enantioselectivity and catalytic selectivity of an ω-TA from Vibrio fluvialis with different substrates and benchmark it against 62 compounds gathered from the literature. Rosetta-generated complexes containing an external aldimine intermediate of the transamination reaction are used as starting conformations for multiple short independent molecular dynamics (MD) simulations. The combination of molecular docking and MD simulations ensures sufficient and accurate sampling of the relevant conformational space. Based on the frequency of near-attack conformations observed during the MD trajectories, enantioselectivities can be quantitatively predicted. The predicted enantioselectivities are in agreement with a benchmark dataset of experimentally determined ee % values. The substrate-range predictions can be based on the docking score of the external aldimine intermediate. The low computational cost required to run the presented framework makes it feasible for use in enzyme design to screen thousands of enzyme variants.

Objective: To review the literature about children's and parent's perceptions on surgical attire., Data Source: A systematic search was conducted in the databases EMBASE, Latin American and Caribbean Health Sciences (LILACS), PubMed, PsycINFO, Scopus and Web of Science. Grey literature was searched on Google Scholar, Open Grey and ProQuest Dissertations, and Theses Database., Data Synthesis: A total of 2,567 papers were identified. After a two-phase selection, 15 studies were included in narrative synthesis. Children favored wearing white coats in five of the nine included studies (55.5% [95%CI 48.3-62.7]; p=1.00). With respect to parents' preferences, results of vote counting showed that in 11 of 15 included studies, they favored physicians wearing white coats (73.3% [95%CI 67.9-78.6]; p=0.11)., Conclusions: Children and parents have preferred physicians to wear a white coat with a very low certainty of evidence.

Introduction: There is an increased prevalence of erectile dysfunction in patients with solid organ transplant (SOT) compared with the general population. Many of these patients may become refractory to medical treatment of erectile dysfunction and penile prosthesis (PP) is often recommended. Concerns regarding the safety of PP in patients with SOT are due to their immunosuppressed state., Objective: We aim to review all current literature on the outcomes of patients with SOT who have received PP., Methods: A PubMed search was performed to identify articles pertaining to the outcomes of PP in patients with SOT., Results: We identified and included 14 studies that report on outcomes of PP placement in 143 patients with SOT and 191 non-SOT controls from interval period from 1979 to 2019. Studies included retrospective cohort studies, case series, and case reports. Compared with non-SOT controls who had PP, aggregate analysis demonstrated that patients with SOT who had PP did not develop significantly increased overall complications. However, they were significantly more likely to experience future surgical complications., Conclusion: Our aggregate analysis demonstrated that patients with SOT are not at a significantly increased risk of overall complications when receiving a PP. Nevertheless, there is an increased risk of experiencing PP injury during subsequent surgeries, which may be mitigated by the earlier involvement of a urologist. Given the lack of recent data, large studies are prerequisite to further evaluate the safety and overall outcome of PP surgery in patients with SOT. Dick B, Greenberg JW, Polchert M, et al. A Systematic Review of Penile Prosthesis Surgery in Organ Transplant Recipients. Sex Med Rev 2021;9:636-640., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

ω-Transaminases (ω-TA) are attractive biocatalysts for the production of chiral amines from prochiral ketones via asymmetric synthesis. However, the substrate scope of ω-TAs is usually limited due to steric hindrance at the active site pockets. We explored a protein engineering strategy using computational design to expand the substrate scope of an ( S )-selective ω-TA from Pseudomonas jessenii ( Pj TA-R6) toward the production of bulky amines. Pj TA-R6 is attractive for use in applied biocatalysis due to its thermostability, tolerance to organic solvents, and acceptance of high concentrations of isopropylamine as amino donor. Pj TA-R6 showed no detectable activity for the synthesis of six bicyclic or bulky amines targeted in this study. Six small libraries composed of 7-18 variants each were separately designed via computational methods and tested in the laboratory for ketone to amine conversion. In each library, the vast majority of the variants displayed the desired activity, and of the 40 different designs, 38 produced the target amine in good yield with >99% enantiomeric excess. This shows that the substrate scope and enantioselectivity of Pj TA mutants could be predicted in silico with high accuracy. The single mutant W58G showed the best performance in the synthesis of five structurally similar bulky amines containing the indan and tetralin moieties. The best variant for the other bulky amine, 1-phenylbutylamine, was the triple mutant W58M + F86L + R417L, indicating that Trp58 is a key residue in the large binding pocket for Pj TA-R6 redesign. Crystal structures of the two best variants confirmed the computationally predicted structures. The results show that computational design can be an efficient approach to rapidly expand the substrate scope of ω-TAs to produce enantiopure bulky amines., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Caprolactamase is the first enzyme in the caprolactam degradation pathway of Pseudomonas jessenii. It is composed of two subunits (CapA and CapB) and sequence-related to other ATP-dependent enzymes involved in lactam hydrolysis, like 5-oxoprolinases and hydantoinases. Low sequence similarity also exists with ATP-dependent acetone- and acetophenone carboxylases. The caprolactamase was produced in Escherichia coli, isolated by His-tag affinity chromatography, and subjected to functional and structural studies. Activity toward caprolactam required ATP and was dependent on the presence of bicarbonate in the assay buffer. The hydrolysis product was identified as 6-aminocaproic acid. Quantum mechanical modeling indicated that the hydrolysis of caprolactam was highly disfavored (ΔG 0 '= 23 kJ/mol), which explained the ATP dependence. A crystal structure showed that the enzyme exists as an (αβ) 2 tetramer and revealed an ATP-binding site in CapA and a Zn-coordinating site in CapB. Mutations in the ATP-binding site of CapA (D11A and D295A) significantly reduced product formation. Mutants with substitutions in the metal binding site of CapB (D41A, H99A, D101A, and H124A) were inactive and less thermostable than the wild-type enzyme. These residues proved to be essential for activity and on basis of the experimental findings we propose possible mechanisms for ATP-dependent lactam hydrolysis., (© 2021 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

Heavy atom-free triplet photosensitizers (PSs) are particularly of interest concerning both fundamental photochemistry study and practical applications. However, achieving efficient intersystem crossing (ISC) in planar heavy atom-free aromatic organic compounds is challenging. Herein, we demonstrate that two perylenebisimide (PBI) derivatives with anthryl and carbazole moieties fused at the bay position, showing twisted π-conjugation frameworks and red-shifted UV-vis absorption as compared to the native PBI chromophore (by 75-1610 cm -1 ), possess efficient ISC (singlet oxygen quantum yield: Φ Δ = 85%) and a long-lived triplet excited state (τ T = 382 μs in fluid solution and τ T = 4.28 ms in solid polymer film). Femtosecond transient absorption revealed ultrafast intramolecular charge-transfer (ICT) process in the twisted PBI derivatives (0.9 ps), and the ISC takes 3.7 ns. Pulsed laser excited time-resolved electron paramagnetic resonance (TREPR) spectra indicate that the triplet-state wave function of the twisted PBIs is mainly confined on the PBI core, demonstrated by the zero-field-splitting D parameter. Accordingly, the twisted derivatives have higher T 1 energy ( E T 1 = 1.48-1.56 eV) as compared to the native PBI chromophore (1.20 eV), which is an advantage for the application of the derivatives as triplet PSs. Theoretical computation of the Franck-Condon density of states, based on excited-state dynamics methods, shows that the efficient ISC in the twisted PBI derivatives is due to the increased spin-orbit coupling matrix elements for the S 1 -T 1 and S 1 -T 2 states [spin-orbit coupling matrix element (SOCME): 0.11-0.44 cm -1 . SOCME is zero for native PBI], as well as the Herzberg-Teller vibronic coupling. For the planar benzoPBI, the moderate ISC is due to S 1 → T 2 transition (SOCME: 0.03 cm -1 . The two states share a similar energy, ca. 2.5 eV).

Objective Painful experiences are common, distressing, and salient in childhood. Parent-child reminiscing about past painful experiences is an untapped opportunity to process pain-related distress and, similar to reminiscing about other distressing experiences, promotes children's broader development. Previous research has documented the role of parent-child reminiscing about past pain in children's pain-related cognitions (i.e., memories for pain), but no study to date has examined the association between parent-child reminiscing about past painful experiences and children's broader cognitive skills. Design and Methods One hundred and ten typically developing four-year-old children and one of their parents reminisced about a past painful autobiographical event. Children then completed two tasks from the NIH Toolbox Cognitive Battery, the Flanker Inhibitory Control & Attention Test and the Picture Sequence Memory Test, to measure their executive function and episodic memory, respectively. Results Results indicated that the relation between parental reminiscing style and children's executive function was moderated by child sex, such that less frequent parental use of yes-no repetition questions was associated with boys' but not girls', greater performance on the executive function task. Children displayed greater episodic memory performance when their parents reminisced using more explanations. Conclusions The current study demonstrates the key role of parent-child reminiscing about pain in children's broader development and supports the merging of developmental and pediatric psychology fields. Future longitudinal research should examine the directionality of the relation between parent-child reminiscing about past pain and children's developmental outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Diagnostic ratios calculated from urinary steroid hormone metabolites are used as a measure for the relative activity of steroidogenic enzymes or pathways in the clinical investigation of steroid metabolism disorders. However, population-based sex- and age-specific reference intervals and day-night differences in adults are lacking., Methods: Sixty-five diagnostic ratios were calculated from steroid metabolites measured by GC-MS in day- and night-time and in 24-hour urine from 1128 adults recruited within the Swiss Kidney Project on Genes in Hypertension (SKIPOGH), a population-based, multicenter cohort study. Differences related to sex, age and day- and night-time were evaluated and reference curves in function of age and sex were modelled by multivariable linear mixed regression for diagnostic ratios and were compared to values from the literature., Results: Most ratios had sex- and age-specific relationships. For each ratio, percentiles were plotted in function of age and sex in order to create reference curves and sex- and age-specific reference intervals derived from 2.5th and 97.5th percentiles were obtained. Most ratios reflected a higher enzyme activity during the day compared to the night., Conclusions: Sex- and age-specific references for 24 hours, day and night urine steroid metabolite ratios may help distinguishing between health and disease when investigating human disorders affecting steroid synthesis and metabolism. The day-night differences observed for most of the diagnostic ratios suggest a circadian rhythm for enzymes involved in human steroid hormones metabolism., Competing Interests: The authors have declared that no competing interests exist.

The electronic structure and photophysical properties of a series of N-methyl and N-acetyl substituted alloxazines (AZs) were investigated with extensive density functional theory (DFT) and time-dependent density functional theory (TD-DFT) based calculations. We showed that non-radiative decays from the lowest singlet and triplet excited states of these AZs are dominant over their radiative counterparts. The fast non-radiative decays of the excited AZs can be attributed to the energy consumption (Ereorg) through structural reorganization facilitated by the intrinsic normal modes of the alloxazine framework, as well as their coupling with those of the functional groups. Substitution with functional groups may lead to further perturbation of the electronic structure of the AZ chromophore, which may enhance intersystem crossing with the ππ* states of the AZs. Due to the different bonding of N1 and N3 within the alloxazine framework, substitution may result in AZs with different photophysical properties. Specifically, functionalization at N1 may help in maintaining or even reducing Ereorg and would promote the absorption and radiative decay from the excited AZs. However, the strong coupling of the vibrational modes of acetyl at N3 with the intrinsic normal modes of the alloxazine framework would contribute significantly to Ereorg, and benefit the non-radiative decay of the excited AZs. We expect that the findings would pave the way for rational design of novel AZs with extraordinary photophysical properties.

Over the past 40 years, the technological and surgical advancements in penile prostheses have led to increased patient satisfaction rates and decreased complication and infection rates. In cis males with erectile dysfunction (ED), these technological improvements tremendously improve quality of life. In female to male transgender patients, prostheses provide the ability to engage in penetrative intercourse and to urinate standing. This review evaluates technological and surgical advancements in penile prosthetics in the context of documented patient satisfaction and complication rates from prosthesis surgeries. Retrospective studies of penile implant usage in female to male gender-affirming surgeries report that infection and complication rates are higher than those seen in cis males. There are newer prostheses developed specifically for female to male reassignment surgeries, but outcome data is limited. Continued research and development are needed to develop more efficacious penile implantation options for gender affirmation surgery., Competing Interests: Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-1279). The series “Controversies and Considerations of Penile Surgery” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Purpose: To evaluate stability and performance of a new monofocal anterior capsulotomy-fixated intraocular lens (IOL) (FEMTIS; Teleon Surgical B.V., Spankeren, Netherlands) after femtosecond laser-assisted cataract surgery (FLACS)., Design: Prospective, multicenter, interventional, noncomparative case series., Methods: FLACS with FEMTIS IOL was performed in 336 eyes of 183 cataract patients with fixation of the IOL to the anterior capsulotomy followed up for 12 months. Examination included uncorrected distance visual acuity (UDVA), best-corrected visual acuity (CDVA), subjective refraction, IOL centration, posterior capsule opacification (PCO), and investigators' satisfaction questionnaire., Results: At 12 months, mean IOL rotation was 1.50 ± 1.76 degrees and decentration 0.14 ± 0.14 mm from baseline (day of surgery). Mean horizontal IOL tilt was 0.70 ± 0.60 degrees and vertical 1.15 ± 1.06 degrees relative to the baseline (crystalline lens). Mean distance between IOL and iris was 0.32 mm to 0.36 mm for all measured meridians. Mean UDVA was 0.12 ± 0.14 logMAR (range -0.20 to 0.54 logMAR), mean CDVA -0.01 ± 0.09 logMAR (range -0.30 to 0.20 logMAR). Mean spherical equivalent was 0.35 ± 0.53 diopter (D) and 98% of eyes (n = 235) were within ±1.0 D. Median PCO score was 1 with an Nd:YAG laser rate of 3.1% after 12 months. Most surgeons were very satisfied (median score: 1) with surgery and implanted IOL., Conclusions: Implantation of FEMTIS IOL provided excellent visual and stable refractive outcomes. IOL decentration was very low compared to other published studies and showed an exceptional high in-the-bag stability over a 12-month period. This lens benefits from femtosecond laser capsulotomies. It can be positioned very predictably and offers an optimal platform for toric and multifocal IOL optics., (Copyright © 2020. Published by Elsevier Inc.)

Background: The presence of parents during the dental appointment can affect the child's behaviour and, consequently, the success of the treatment., Aim: This systematic review aimed to evaluate whether parents' presence in the operatory room influences children's behaviour, anxiety and fear during dental treatment., Design: EMBASE, Cochrane Library, LILACS, PubMed, PsycINFO, Scopus, Web of Science, Google Scholar, OpenGrey and ProQuest Dissertations and Theses Databases were searched. Randomized and non-randomized clinical trials in which some measure assessing children's behaviour and/or anxiety and fear during dental treatment with the presence and absence of parents were included. Two reviewers assessed studies for selection, extracted data, evaluated bias (Joanna Briggs Institute) and graded the certainty of evidence (Grading of Recommendations, Assessment, Development and Evaluation). Random-effects meta-analyses using mean difference (MD) and narrative synthesis were performed., Results: A total of 2846 papers were identified, and after a 2-phase selection, sixteen studies were included (five in meta-analyses). There was no difference in children's behaviour in the presence or absence of parents (P = .23, P = .40, P = .60 and P = .89, respectively). The presence or absence of parents did not influence children's anxiety (P = .94 and P = .97) or fear (DM: -0.08; CI:-0.34-0.19, P = .24). All included studies presented a high risk of bias, and the certainty of evidence was considered to be very low., Conclusion: It is concluded that parents' presence in the operation room does not influence children's (up to 12 years old) behaviour, anxiety and fear during dental treatment with very low certainty of evidence. Methodological limitations of included studies, however, suggest that better designed trials are needed to adequately understand this issue., (© 2020 BSPD, IAPD and John Wiley & Sons Ltd.)

Introduction: Although telemedicine (TM) has been available for several decades, the recent increase in its acceptance due to the COVID-19 pandemic has emerged as a valuable solution for the delivery of health care that provides easy, affordable, and convenient communication with urologic patients., Objectives: The objective of this study was to highlight limiting factors and provide successful practical solutions to assist urologists in incorporating and maintaining TM in their practices., Methods: A thorough literature review was conducted utilizing PubMed, Cochrane library, clinicaltrials.gov, Google Scholar, and Web of Science. Search terms and keywords included "telemedicine" and "urology." Only articles written or translated into the English language were included., Results: A total of 12 peer-reviewed articles were identified that discussed barriers for incorporation of TM in urology. Articles exclusive to the use of TM during the COVID-19 pandemic were also included, as well as American Urological Association and European Urological Association guidelines and Centers for Medicare & Medicaid Services statements and policies regarding TM pertinent to urological practice., Conclusion: TM is currently a viable option and fills an unmet need for most practicing urologists, especially during the COVID-19 pandemic, offering insight to the relative ease of transition to online clinical practice. OA Raheem, S Brimley, C Natale, et al. The Emerging Critical Role of Telemedicine in the Urology Clinic: A Practical Guide. Sex Med Rev 2021;9:289-295., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To propose a new model outlining a hypothesized cyclical relation between executive functioning, emotional regulation, and chronic pain in adolescence and to highlight the likely importance of such a relation for self-management behavior and pain-related disability., Methods: A review of the existing literature that critically explores the role of executive functioning in understanding chronic pain experiences and self-management in adolescence in order to develop the Cyclical model Of Pain, Executive function, emotion regulation, and Self-management (COPES)., Results: Growing evidence points towards a potential cyclical relation between chronic pain and impaired executive functioning, which forms the basis of COPES. The COPES model proposes that the relative immaturity of executive functioning in adolescence negatively influences their ability to engage with self-management, which in turn increases adolescents' disability due to pain and contributes to the maintenance of chronic pain, which perpetuates the reduced capacity of executive functioning. The moderating influence of flexible parental support is hypothesized to offset some of these influences. However, the available evidence is limited due to methodological shortcomings such as large variety in executive functioning operationalization, reliance on self-report and cross-sectional designs., Conclusions: It is anticipated that the COPES model will stimulate more systematic, theory-driven research to further our understanding of the links between executive functioning, chronic pain, self-management, and wellbeing. Such enhanced understanding has the potential to drive forward intervention development and refinement aimed at improving self-management uptake and adherence amongst adolescents with chronic pain., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure-function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation., (© 2020 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

The mycobacterial PQS dioxygenase AqdC, a cofactor-less protein with an α/β-hydrolase fold, inactivates the virulence-associated quorum-sensing signal molecule 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) produced by the opportunistic pathogen Pseudomonas aeruginosa and is therefore a potential anti-virulence tool. We have used computational library design to predict stabilizing amino acid replacements in AqdC. While 57 out of 91 tested single substitutions throughout the protein led to stabilization, as judged by increases in T app m of >2 °C, they all impaired catalytic activity. Combining substitutions, the proteins AqdC-G40K-A134L-G220D-Y238W and AqdC-G40K-G220D-Y238W showed extended half-lives and the best trade-off between stability and activity, with increases in T app m of 11.8 and 6.1 °C and relative activities of 22 and 72 %, respectively, compared to AqdC. Molecular dynamics simulations and principal component analysis suggested that stabilized proteins are less flexible than AqdC, and the loss of catalytic activity likely correlates with an inability to effectively open the entrance to the active site., (© 2020 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Diaminopimelate decarboxylases (DAPDCs) are highly selective enzymes that catalyze the common final step in different lysine biosynthetic pathways, i.e. the conversion of meso-diaminopimelate (DAP) to L-lysine. We examined the modification of the substrate specificity of the thermostable decarboxylase from Thermotoga maritima with the aim to introduce activity with 2-aminopimelic acid (2-APA) since its decarboxylation leads to 6-aminocaproic acid (6-ACA), a building block for the synthesis of nylon-6. Structure-based mutagenesis of the distal carboxylate binding site resulted in a set of enzyme variants with new activities toward different D-amino acids. One of the mutants (E315T) had lost most of its activity toward DAP and primarily acted as a 2-APA decarboxylase. We next used computational modeling to explain the observed shift in catalytic activities of the mutants. The results suggest that predictive computational protocols can support the redesign of the catalytic properties of this class of decarboxylating PLP-dependent enzymes., (© The Author(s) 2021. Published by Oxford University Press.)

Omniligase-1 is a broadly applicable enzyme for peptide bond formation between an activated acyl donor peptide and a non-protected acyl acceptor peptide. The enzyme is derived from an earlier subtilisin variant called peptiligase by several rounds of protein engineering aimed at increasing synthetic yields and substrate range. To examine the contribution of individual mutations on S/H ratio and substrate scope in peptide synthesis, we selected peptiligase variant M222P/L217H as a starting enzyme and introduced successive mutations. Mutation A225N in the S1' pocket and F189W of the S2' pocket increased the synthesis to hydrolysis (S/H) ratio and overall coupling efficiency, whereas the I107V mutation was added to S4 pocket to increase the reaction rate. The final omniligase variants appeared to have a very broad substrate range, coupling more than 250 peptides in a 400-member library of acyl acceptors, as indicated by a high-throughput FRET assay. Crystal structures and computational modelling could rationalize the exceptional properties of omniligase-1 in peptide synthesis., Competing Interests: AT, TN, RdV, LKMM are employees of EnzyPep and some of EnzyPep’s products are (enzymatically synthesized) peptides., (© 2021 The Authors.)

Objectives: Preliminary research in youth with chronic pain suggests differences in attention and working memory, which has been similarly demonstrated in adults with chronic pain. There has been little research on other aspects of executive functioning (EF) in this population despite its critical role in problem solving, school functioning, and coping. This study aimed to examine differences in several aspects of EF between youth with chronic pain and a nonchronic pain comparison group using performance-based neuropsychological tests and a behavior rating scale., Materials and Methods: Participants completed ratings of pain; physical, emotional, social, and school functioning; sleep quality; medication; and a general intelligence screener. Standardized neuropsychological tests were used to examine EF with a focus on working memory, divided and alternating attention, inhibition, flexibility, incidental memory, and planning. A parent-report and self-report behavior rating of EF was also administered., Results: Recruitment from 2 tertiary-care pain clinics resulted in a sample of 26 youth with chronic pain (80.8% girls) and their parents. A comparison group of 30 youth without chronic pain and their parents were recruited from the community. Participants with chronic pain had significantly lower scores on several performance-based tests of working memory/divided attention, inhibition, and flexibility/alternating attention than the comparison group. Statistically significant group differences were also found on behavior ratings of emotion control, shifting, task initiation and completion, working memory, planning and organization, overall emotion and cognitive regulation as well as global EF. Covariate analysis was conducted in all analyses where there were significant group differences and several observed group differences remained., Discussion: This study is one of few multidimensional examinations of EF in youth with chronic pain, using a comprehensive neuropsychological test battery combined with behavior ratings. Our findings suggest EF differences in youth with chronic pain, across a variety of domains and may suggest risk for specific cognitive processing weaknesses in this population. Medical and educational teams should work toward identification, treatment, and compensatory support for EF within individualized pain management for youth., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Although available treatments for erectile dysfunction (ED) have expanded, there has been a concomitant shift in the treatment paradigm. Newer treatment options focus on disease modification and improving overall erectile function., Objective: The objective of this study is to review the evidence of 3 promising novel ED treatments., Methods: A thorough review of the literature was divided into sections corresponding to low-intensity extracorporeal shockwave therapy (Li-ESWT), stem cell therapy (SCT), and platelet-rich plasma (PRP). Search terms included "erectile dysfunction" or "ED" plus "extracorporeal shockwave therapy", "stem cell therapy" or "platelet rich plasma". International Index of Erectile Function (IIEF) scores were the primary outcome measure. Secondary outcome measures included peak systolic velocity and intracorporeal pressure., Results: Li-ESWT section includes 1 randomized controlled study, 2 prospective studies, 1 animal study, and 2 meta-analyses. IIEF score improvement was 3.54 (range 1.99-6.40). Authors concluded statistically significant short-term effect and improvement in erectile function (EF) with Li-ESWT. SCT section included 4 case series and 1 open-label study. Intraperitoneal, venous, and cavernosal SCT injections improved EF in animal models. 3 studies (n = 6-8) demonstrated 83-100% and 29-50% of patients regained erection and penetration ability, respectively. 2 studies (n = 12-16) found that all patients improved IIEF scores after SCT. Literature review for PRP yielded 3 animal, 1 retrospective, and 1 prospective study. Animal studies have shown that rats sustaining crush cavernosal injuries treated with PRP significantly improved EF and preservation of cavernous nerve axons. One retrospective analysis on humans showed mean improvement by 4.14 in IIEF scores. One prospective study on humans (n = 75) demonstrated improved peak systolic velocity (P = .005) and IIEF scores (P = .046) with PRP therapy., Conclusions: This review reveals limited published evidence on current novel ED treatment options. Further research on Li-ESWT, SCT, and PRP therapy is necessary to elucidate the role of these therapies in ED treatment regimens. Raheem OA, Natale C, Dick B, et al. Novel Treatments of Erectile Dysfunction: Review of the Current Literature. Sex Med Rev 2021;9:123-132., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The past 2 decades have witnessed an increased amount of research into botulinum neurotoxin (BoNT) as a treatment for various forms of sexual dysfunction and pain syndromes refractory to other medical therapy. BoNT is postulated to reduce pain sensation by inhibiting neuropeptide release in the presynaptic neuron. Dyspareunia, vaginismus, vestibulodynia, and persistent genital arousal disorder are female sexual dysfunctions with cryptic pathophysiology and limited treatment options. BoNT has emerged as a potential treatment for many of these afflictions in women., Objectives: To review the literature regarding BoNT as a treatment for female sexual and genitourinary dysfunction., Methods: A PubMed search for English-language articles was performed using the following terms: "Botox," "botulinum toxin," "botulinum toxin A," "Onabotulinum A," "Abobutlinum A," "BoNT," and "BoNT-A." The main outcomes measured by each study were resolution of dysfunction. This entailed reduction of pain with intercourse for dyspareunia, reduction of pain for vestibulodynia, decreased arousal for persistent genital arousal disorder, and ability to tolerate penetration for vaginismus., Results: A total of 12 human studies that evaluated BoNT as a treatment for female sexual disorders were included. Study types included prospective, retrospective, cohort, pilot, and open-label., Conclusion: There is growing evidence suggesting that BoNT is a safe and efficacious treatment option for female patients suffering from various sexual and genitourinary disorders. However, more research is needed to develop a better understanding of the mechanisms through which BoNT treats these disorders. Dick B, Natale C, Reddy A, et al. Application of Botulinum Neurotoxin in Female Sexual and Genitourinary Dysfunction: A Review of Current Practices. Sex Med 2021;9:57-63., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

The triplet state lifetimes of organic chromophores are crucial for fundamental photochemistry studies as well as applications as photosensitizers in photocatalysis, photovoltaics, photodynamic therapy and photon upconversion. It is noteworthy that the triplet state lifetime of a chromophore can vary significantly for its analogues, while the exact reason was rarely studied. Herein with a few exemplars of typical BODIPY derivatives, which show triplet lifetimes varying up to 110-fold (1.4-160 μs), we found that for these derivatives with short triplet state lifetimes ( ca. 1-3 μs), the electron spin polarization (ESP) pattern of the time-resolved electron paramagnetic resonance (TREPR) spectra of the triplet state is inverted at a longer delay time after laser pulse excitation, as a consequence of a strong anisotropy in the decay rates of the zero-field state sublevel of the triplet state. For the derivatives showing longer triplet state lifetimes (>50 μs), no such ESP inversion was observed. The observed fast decay of one sublevel is responsible for the short triplet state lifetime; theoretical computations indicate that it is due to a strong coupling between the T z sublevel and the ground state mediated by the spin-orbit interaction. Another finding is that the heavy atom effect on the shortening of the triplet state lifetime is more significant for the T 1 states with lower energy. To the best of our knowledge, this is the first systematic study to rationalize the short triplet state lifetime of visible-light-harvesting organic chromophores. Our results are useful for fundamental photochemistry and the design of photosensitizers showing long-lived triplet states., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

α-Amylase from Bacillus paralicheniformis (BliAmy), belonging to GH13&#95;5 subfamily of glycoside hydrolases, was proven to be a highly efficient raw starch digesting enzyme. The ability of some α-amylases to hydrolyze raw starch is related to the existence of surface binding sites (SBSs) for polysaccharides that can be distant from the active site. Crystallographic studies performed on BliAmy in the apo form and of enzyme bound with different oligosaccharides and oligosaccharide precursors revealed binding of these ligands to one SBS with two amino acids F257 and Y358 mainly involved in complex formation. The role of this SBS in starch binding and degradation was probed by designing enzyme variants mutated in this region (F257A and Y358A). Kinetic studies with different substrates show that starch binding through the SBS is disrupted in the mutants and that F257 and Y358 contributed cumulatively to binding and hydrolysis. Mutation of both sites (F257A/Y358A) resulted in a 5-fold lower efficacy with raw starch as substrate and at least 5.5-fold weaker binding compared to the wild type BliAmy, suggesting that the ability of BliAmy to hydrolyze raw starch with high efficiency is related to the level of its adsorption onto starch granules., (Copyright © 2020 Elsevier B.V. All rights reserved.)