Decision-making preferences and regret in rectal cancer patients undergoing restorative proctectomy: A prospective cohort study.

BACKGROUND: How patients make treatment choices in rectal cancer is poorly understood and may affect long-term regret and satisfaction. The objective of this study is to characterize decision-making preferences and their effect on decisional regret in patients undergoing restorative proctectomy for rectal cancer. METHODS: A prospective cohort study was conducted in a single academic specialist rectal cancer center from October 2018 to June 2022. Adult patients who underwent restorative proctectomy at least one year prior were recruited. Health literacy was assessed using the BRIEF instrument. Decision-making preferences regarding cancer treatment were assessed using the Control Preferences Scale. Decisional regret regarding their choice of restorative proctectomy was assessed using the Decision Regret Score. Bowel dysfunction was measured using the low anterior resection syndrome score. RESULTS: Overall, 123 patients were included. Health literacy was categorized as adequate in 63%, marginal in 25%, and limited in 12%. Patients with adequate health literacy were more likely to prefer a collaborative decision-making role compared with those with low health literacy (86% vs 65%, P = .016). Patients with incongruence between preferred and actual decision-making roles were more likely to report high regret (56% vs 25%, P = .003). Patients with major low anterior resection syndrome were also more likely to experience high regret compared with patients with no/minor low anterior resection syndrome (44% vs 25%, P = .036). CONCLUSION: A significant proportion of patients with rectal cancer undergoing restorative proctectomy do not have a decision-making role that is congruent with their preferences, and these patients experience a high degree of regret.

Amphipathic Surfactant on Reconstructed Bismuth Enables Industrial-Level Electroreduction of CO2 to Formate.

Developing efficient electrocatalysts for selective formate production via the electrochemical CO2 reduction reaction (CO2RR) is challenged by high overpotential, a narrow potential window of high Faradaic efficiency (FEformate), and limited current density (Jformate). Herein, we report a hierarchical BiOBr (CT/h-BiOBr) with surface-anchored cetyltrimethylammonium bromide (CTAB) for formate-selective large-scale CO2RR electrocatalysis. CT/h-BiOBr achieves over 90% FEformate across a wide potential range (-0.5 to -1.1 V) and an industrial-level Jformate surpassing 100 mA·cm-2 at -0.7 V. In situ investigations uncover the reconstructed Bi(110) surface as the active phase, with CTAB playing a dual role: its hydrophobic alkyl chains create a CO2-enriching microenvironment, while its polar head groups fine-tune the electronic structure, fostering a highly active phase. This work provides valuable insights into the role of surfactants in electrocatalysis and guides the design of electrocatalysts for the large-scale CO2RR.

Shining New Light on Biological Systems: Luminescent Transition Metal Complexes for Bioimaging and Biosensing Applications.

Luminescence imaging is a powerful and versatile technique for investigating cell physiology and pathology in living systems, making significant contributions to life science research and clinical diagnosis. In recent years, luminescent transition metal complexes have gained significant attention for diagnostic and therapeutic applications due to their unique photophysical and photochemical properties. In this Review, we provide a comprehensive overview of the recent development of luminescent transition metal complexes for bioimaging and biosensing applications, with a focus on transition metal centers with a d6, d8, and d10 electronic configuration. We elucidate the structure-property relationships of luminescent transition metal complexes, exploring how their structural characteristics can be manipulated to control their biological behavior such as cellular uptake, localization, biocompatibility, pharmacokinetics, and biodistribution. Furthermore, we introduce the various design strategies that leverage the interesting photophysical properties of luminescent transition metal complexes for a wide variety of biological applications, including autofluorescence-free imaging, multimodal imaging, organelle imaging, biological sensing, microenvironment monitoring, bioorthogonal labeling, bacterial imaging, and cell viability assessment. Finally, we provide insights into the challenges and perspectives of luminescent transition metal complexes for bioimaging and biosensing applications, as well as their use in disease diagnosis and treatment evaluation.

How well do we measure the impact of bowel dysfunction on health-related quality of life after rectal cancer surgery?

BACKGROUND: Rectal cancer surgery risks causing bowel dysfunction, which has an important impact on health-related quality of life. The validity of generic tools used to measure health-related quality of life after bowel dysfunction is unclear. This study aimed to determine the content validity of health-related quality-of-life measurement tools in rectal cancer. METHODS: This was a qualitative single-center study in which adult patients who underwent rectal cancer surgery with sphincter preservation from July 2017 to October 2020 were recruited. Patients were excluded if they developed local metastasis, required a permanent stoma, or had surgery <1 year since recruitment. Telephone-based semi-structured interviews were conducted. Bowel dysfunction was measured using the Low Anterior Resection Syndrome score. Content analysis was achieved using the International Classification of Functioning framework. RESULTS: Recurrent bowel dysfunction-related concepts included "Mental functions," "Defecation functions," "Emotional functions," "Recreation and leisure," "Intimate relationships," and "Remunerative employment." A mean of 7.5 recurrent bowel dysfunction-related concepts were identified within the health-related quality of life instruments analyzed. The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30 (n = 11) and the 36-Item Short Form Health Survey (n = 9) covered the greatest number of recurrent bowel dysfunction-related concepts. Concepts such as "Mental functions," "Urination functions," "Sexual functions," "Driving," and "Mobility" were not covered by any instrument. CONCLUSION: The content of traditional health-related quality-of-life instruments is missing important areas that represent the impact of bowel dysfunction after rectal cancer surgery on health-related quality of life. These findings could help improve patient-centered care in rectal cancer surgery.

Aetiology and epidemiology of surgical vitreoretinal presentations in an Australian paediatric population: A seven-year retrospective study.

BACKGROUND: Paediatric vitreoretinal pathology is distinct from adult cases in both presentation and surgical planning. Here we aim to report the aetiology and epidemiology in children 0-18 years requiring vitreoretinal surgery at a major tertiary paediatric hospital in Queensland, Australia. METHODS: Retrospective review of cases requiring vitreoretinal surgery between May 2015 and October 2022 was conducted. Demographics, ocular and medical history, surgical pathology, procedures performed, and epidemiology data were retrieved. Patients were grouped into three main aetiologies: traumatic, syndromic, or secondary. RESULTS: A total of 124 patients, the majority male (87, 70.2%) with a mean age of 10.3 years underwent vitreoretinal surgery. Trauma accounted for 32.3% of cases requiring surgery of which 47% were due to a penetrating eye injury. 35.5% were associated with a syndromic cause with common aetiology including coats, congenital cataract, sticklers, and retinopathy of prematurity. 32.3% developed secondary pathology and retinal detachment was the primary cause for surgery (55%). The average time from symptom onset to presentation was 30 days (SD 56.88) with patients living an average of 306.2 km (SD 558.9) away from the Queensland Children's Hospital. Older age was significantly associated with increased days to presentation in the traumatic group (p < 0.05). CONCLUSIONS: This study provides an insight into the aetiology and epidemiology of paediatric vitreoretinal presentations in Queensland, Australia.

Construction of photofunctional peptide conjugates through selective modification of N-terminal cysteine with cyclometallated iridium(III) 2-formylphenylboronic acid complexes for organelle-specific imaging, enzyme activity sensing and photodynamic therapy.

Luminescent cyclometallated iridium(III) complexes bearing a 2-formylphenylboronic acid moiety were designed; one of the complexes was utilised to modify peptides containing an N-terminal cysteine to afford luminescent conjugates with selective organelle-targeting or furin-responsive properties.

Donor Age More Than 20 Years Greater Than Recipient Age Is Associated With Worse 5 Year Survival in Young Adult Heart Transplantation.

Prior studies indicate donor age-recipient age (DA-RA) difference may be of prognostic value in adolescents, although not adults. We aim to analyze the relationship between DA-RA difference and long-term survival of young adult heart transplantation (HTx) recipients. First-time, single-organ HTx recipients aged 18-30 who underwent HTx between 2010 and 2020 were analyzed from the United Network for Organ Sharing (UNOS) registry. Four cohorts were created based on DA-RA difference. The primary outcome was 5 year post-HTx survival. Secondary outcome was post-HTx complications. One thousand eight hundred three donor-recipient pairs were divided into four groups: DA-RA < 0, 0 ≤ DA-RA < 10, 10 ≤ DA-RA < 20, and DA-RA ≥ 20 with 682 (37.8%), 651 (36.1%), 356 (19.7%), 114 (6.3%) pairs in each cohort, respectively. The estimated 5 year survival of the DA-RA ≥ 20 cohort was 66.5% compared to the other three groups at ~75%. After adjustment, DA-RA ≥ 20 was independently associated with worse survival compared to DA-RA < 0 (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.06-2.27; log-rank p = 0.008). There was no significant difference in complication incidence across cohorts. Among young adults, accepting a donor heart more than 20 years older than the recipient was associated with worse 5 year survival. We did not detect a significant difference up to 20 years. This information may help guide appropriate donor selection in the young adult population.

Mitochondria-targeting biocompatible fluorescent BODIPY probes.

An increase in the mitochondrial membrane potential (MMP) is a characteristic feature of cancer and cardiovascular disease. Therefore, it remains of crucial importance to develop new and improved fluorescent probes that are sensitive to the MMP, to report on mitochondrial health and function. Reported here are the design, synthesis, photophysical properties and biological characterisation of a series of BODIPY dyes, BODIPY-Mito-n, for mitochondria-targeted fluorescence imaging applications. Six BODIPY-Mito-n analogues were synthesised under mild conditions, and displayed excellent fluorescence quantum yields of between 0.59 and 0.72 in aqueous environments at physiological pH (pH = 7.4). The incorporation of poly(ethylene glycol) (PEG) chains to the triarylphosphonium cation moiety significantly improved the biocompatibility of the probes (BODIPY-Mito-6, IC50 > 50 µM). All BODIPY-Mito-n compounds demonstrated a high MMP-sensitive localisation in the mitochondria, with Pearson's correlation coefficients (PCC) of between 0.76 and 0.96. Compounds BODIPY-Mito-2 and BODIPY-Mito-6 revealed the highest sensitivity to the MMP, with a decrease in the emission intensity of 62% and 75%, respectively following MMP depolarisation. It is anticipated that the highest MMP sensitivity and enhanced biocompatibility of BODIPY-Mito-6 could lead to the development of new probes for mitochondrial imaging in the future.

Optimized Transition Metal Phosphides for Direct Seawater Electrolysis: Current Trends.

Seawater electrolysis presents a viable route for sustainable large-scale hydrogen production, yet its practical application is hindered by several technical challenges. These include the sluggish kinetics of hydrogen evolution, poor stability, cation deposition at the cathode, electrode corrosion, and competing chloride oxidation at the anode. To overcome these obstacles, the development of innovative electrocatalysts is crucial. Transition metal phosphides (TMPs) have emerged as promising candidates owing to their superior catalytic performance and tunable structural properties. This review provides a comprehensive analysis of recent progress in the structural engineering of TMPs tailored for efficient seawater electrolysis. We delve into the catalytic mechanisms underpinning hydrogen and oxygen evolution reactions in different pH conditions, along with the detrimental side reactions that impede hydrogen production efficiency. Several methods to prepare TMPs are then introduced. Additionally, detailed discussions on structural modifications and interface engineering tactics are presented, showcasing strategies to enhance the activity and durability of TMP electrocatalysts. By analyzing current research findings, our review aims to inform ongoing research endeavors and foster advancements in seawater electrolysis for practical and ecologically sound hydrogen generation.

Spatial engineering of single-atom Fe adjacent to Cu-assisted nanozymes for biomimetic O2 activation.

The precise design of single-atom nanozymes (SAzymes) and understanding of their biocatalytic mechanisms hold great promise for developing ideal bio-enzyme substitutes. While considerable efforts have been directed towards mimicking partial bio-inspired structures, the integration of heterogeneous SAzymes configurations and homogeneous enzyme-like mechanism remains an enormous challenge. Here, we show a spatial engineering strategy to fabricate dual-sites SAzymes with atomic Fe active center and adjacent Cu sites. Compared to planar Fe-Cu dual-atomic sites, vertically stacked Fe-Cu geometry in FePc@2D-Cu-N-C possesses highly optimized scaffolds, favorable substrate affinity, and fast electron transfer. These characteristics of FePc@2D-Cu-N-C SAzyme induces biomimetic O2 activation through homogenous enzymatic pathway, resembling functional and mechanistic similarity to natural cytochrome c oxidase. Furthermore, it presents an appealing alternative of cytochrome P450 3A4 for drug metabolism and drug-drug interaction. These findings are expected to deepen the fundamental understanding of atomic-level design in next-generation bio-inspired nanozymes.

Surface-Reconstructed Ru-Doped Nickel/Iron Oxyhydroxide Arrays for Efficient Oxygen Evolution.

The generation of an active phase through dynamic surface reconstruction is a promising strategy for improving the activity of electrocatalysts. However, studies investigating the reconstruction process and its impact on the intrinsic properties of the catalysts are scarce. Herein, the surface reconstruction of NiFe2 O4 interfaced with NiMoO4 (Ru-NFO/NMO) facilitated by Ru doping is reported. The electrochemical and material characterizations demonstrate that Ru doping can regulate the electronic structure of NFO/NMO and induce the high-valence state of Ni3.6+ δ , facilitating the surface reconstruction to highly active Ru-doped NiFeOOH/NiOOH (SR-Ru-NFO/NMO). The optimized SR-Ru-NFO/NMO exhibits promising performance in the oxygen evolution reaction, displaying a low overpotential of 229 mV at 10 mA cm-2 and good stability at varying current densities for 80 h. Density functional theory calculations indicate that Ru doping can increase the electron density and optimize intermediate adsorption by shifting the d-band center downward. This work provides valuable insights into the tuning of electrocatalysts by surface reconstruction and offers a rational design strategy for the development of highly active oxygen evolution reaction electrocatalysts.

Does a multimodal prehabilitation program improve sleep quality and duration in patients undergoing colorectal resection for cancer? Pilot randomized control trial.

Sleep difficulties are a common symptom in cancer patients at different stages of treatment trajectory and may lead to numerous negative consequences for which management is required. This pilot Randomized Controlled Trial (RCT) aims to assess the potential effectiveness of home-based prehabilitation intervention (prehab) on sleep quality and parameters compared to standard care (SOC) in colorectal cancer patients during the preoperative period and up to 8 weeks after the surgery. One hundred two participants (48.3% female, mean age 65 years) scheduled for elective resection of colorectal cancer were randomized to the prehab (n = 50) or the SOC (n = 52) groups. Recruitment and retention rates were 54% and 72%, respectively. Measures were completed at the baseline and preoperative, 4- and 8-week after-surgery follow-ups. Our mixed models' analyses revealed no significant differences between groups observed over time for all subjective and objective sleep parameters. A small positive change was observed in the perceived sleep quality only at the preoperative time point for the prehabilitation group compared to the SOC group, with an effect size d = 0.11 and a confidence interval (CI) between - 2.1 and - 0.1, p = .048. Prehab group patients with high anxiety showed a significant improvement in the rate of change of sleep duration over time compared to the SOC group, with a difference of 110 min between baseline and 8 weeks after surgery (d = 0.51, 95% CI: 92.3 to 127.7, p = .02). Multimodal prehabilitation intervention is feasible in colorectal cancer patients and may improve sleep duration for patients with high anxiety symptoms. Future large-scale RCTs are needed to confirm our results.

Predictive Factors for Successful Same-Day Discharge After Minimally Invasive Colectomy and Stoma Reversal.

BACKGROUND: Same-day discharge after minimally invasive colorectal surgery is a safe, effective practice in specific patients that can enhance the efficiency of enhanced recovery pathways. OBJECTIVE: To identify predictive factors associated with success or failure of same-day discharge. DESIGN: Prospective cohort study from January 2020 to March 2023. SETTINGS: Tertiary colorectal center. PATIENTS: Adult patients eligible for same-day discharge with remote postdischarge follow-up included those with minimal comorbidities, residing near the hospital, having sufficient home support, and owning a mobile device. INTERVENTIONS: Patients were discharged on the day of surgery upon meeting specific criteria, including adequate pain control, tolerance of oral intake, independent mobility, urination, and the absence of complications. Successful same-day discharge was defined as discharge on the day of surgery without unplanned visits in the first 72 hours. MAIN OUTCOME MEASURES: Factors associated with successful or failed same-day discharge after minimally invasive colorectal surgery. RESULTS: A total of 175 patients (85.3%) were discharged on the day of surgery, with 14 patients (8%) having an unplanned visit within 72 hours. Overall, 161 patients (78.5%) were categorized as same-day discharge success and 44 patients (21.5%) as same-day discharge failure. The same-day discharge failure group had a higher Charlson Comorbidity Index (3.7 vs 2.8, p = 0.03). Mean length of stay (0.8 vs 3.0, p = 0.00), 30-day complications (10% vs 48%, p = 0.00), and readmissions (8% vs 27%, p = 0.00) were higher in the same-day discharge failure group. Regression analysis showed that failed same-day discharge was associated with higher comorbidities (OR 0.79; 95% CI, 0.66-0.95) and prolonged postanesthesia care unit time (OR 0.99; 95% CI, 0.99-0.99). Individuals who received a regional nerve block (OR 4.1; 95% CI, 1.2-14) and those who did not consume postoperative opioids (OR 4.6; 95% CI, 1-21) were more likely to have successful same-day discharge. LIMITATIONS: Single-center study. CONCLUSIONS: Our findings indicate that comorbidities and prolonged postanesthesia care unit stays were associated with same-day discharge failure, whereas regional nerve blocks and minimal postoperative opioids were related to success. These factors may inform future research aiming to enhance colorectal surgery recovery protocols. See Video Abstract . FACTORES PREDICTIVOS PARA UN ALTA EXITOSA EL MISMO DA DESPUS DE UNA COLECTOMA MNIMAMENTE INVASIVA Y REVERSIN DEL ESTOMA: ANTECEDENTES:El alta el mismo día después de una cirugía colorrectal mínimamente invasiva es una práctica segura y eficaz en pacientes específicos que puede mejorar la eficiencia de las vías de recuperación mejoradas.OBJETIVO:Identificar factores predictivos asociados con el éxito o fracaso del alta el mismo día.DISEÑO:Estudio de cohorte prospectivo del 01/2020 al 03/2023.AJUSTES:Centro colorrectal terciario.PACIENTES:Los pacientes adultos elegibles para el alta el mismo día con seguimiento remoto posterior al alta incluyeron aquellos con comorbilidades mínimas, que residían cerca del hospital, tenían suficiente apoyo en el hogar y poseían un dispositivo móvil.INTERVENCIONES:Los pacientes fueron dados de alta el día de la cirugía al cumplir con criterios específicos, incluido un control adecuado del dolor, tolerancia a la ingesta oral, movilidad independiente, micción y ausencia de complicaciones. El alta exitosa el mismo día se definió como el alta el día de la cirugía sin visitas no planificadas en las primeras 72 horas.PRINCIPALES MEDIDAS DE RESULTADO:Factores asociados con el alta exitosa o fallida el mismo día después de una cirugía colorrectal mínimamente invasiva.RESULTADOS:Un total de 175 (85,3%) pacientes fueron dados de alta el día de la cirugía y 14 (8%) pacientes tuvieron una visita no planificada dentro de las 72 horas. En total, 161 (78,5%) pacientes se clasificaron como éxito del alta el mismo día y 44 (21,5%) pacientes como fracaso del alta el mismo día. El grupo de fracaso del alta el mismo día tuvo un índice de comorbilidad de Charlson más alto (3,7, 2,8, p = 0,03). La duración media de la estancia hospitalaria (0,8, 3,0, p = 0,00), las complicaciones a los 30 días (10%, 48%, p = 0,00) y los reingresos (8%, 27%, p = 0,00) fueron mayores en el mismo día grupo de fallo de descarga. El análisis de regresión mostró que el alta fallida el mismo día se asoció con mayores comorbilidades (OR 0,79; IC del 95 %: 0,66; 0,95) y tiempo prolongado en la unidad de cuidados postanestésicos (OR 0,99; IC del 95 %: 0,99; 0,99). Las personas que recibieron un bloqueo nervioso regional (OR 4,1; IC del 95 %: 1,2, 14) y aquellos que no consumieron opioides posoperatorios (OR 4,6, IC del 95 %: 1-21) tuvieron más probabilidades de tener éxito en el mismo día -descarga.LIMITACIONES:Estudio unicéntrico.CONCLUSIONES:Nuestros hallazgos indican que las comorbilidades y las estancias prolongadas en la unidad de cuidados postanestésicos se asociaron con el fracaso del alta el mismo día, mientras que los bloqueos nerviosos regionales y los opioides postoperatorios mínimos se relacionaron con el éxito. Estos factores pueden informar investigaciones futuras destinadas a mejorar los protocolos de recuperación de la cirugía colorrectal. (Traducción-Yesenia Rojas-Khalil ).

The impact of patient activation on the effectiveness of digital health remote post-discharge follow-up and same-day-discharge after elective colorectal surgery.

BACKGROUND: Low patient activation (PA) is associated with worse postoperative outcomes, however, its impact on the effectiveness of digital health interventions is unknown. We sought to determine the impact of PA on the effectiveness of digital health application for remote post-discharge follow-up for patients undergoing elective colectomy. METHODS: Data analysis included a control cohort (CC) of patients undergoing elective colorectal surgery from 10/2017 to 04/2018 without the digital health intervention and a digital application cohort (DAC) that received a smart phone application for remote post-discharge follow-up from 03/2021 to 08/2022, including a subset of same-day discharge (SDD) patients. PA was measured using the Patient Activation Measure (PAM; score 0-100) and categorized into low (< 55.1) and high (≥ 55.1). The PAM was administered 4-6 weeks before surgery in the DAC group and on postoperative day (POD) 1 in the CC group. The main outcome measure was 30-day emergency department (ED) visits. RESULTS: A total of 164 patients were included (89DAC with 50 SDD, 75CC), with no differences in patient characteristics other than more stoma closures in the DAC group. Overall, 77% of patients had high PA level, with no difference between CC and DAC (77% vs. 81%, p = 0.25). There was no difference in ED visits between CC and DAC (19% vs. 18%, p = 0.90). Overall, low PA was associated more ED visits (29% vs 14%, p = 0.04). In the SDD subgroup, low PA patients had more ED visits (38% vs. 7%, p = 0.015). PA level did not affect app usage metrics. On multiple regression, only low PA remained independently associated with ED visits (OR 3.42, 95%CI 1.27, 9.24). CONCLUSION: Low PA remains an important predictor of surgical outcomes after elective colorectal surgery regardless of the use of a digital health application for remote post-discharge follow-up. This suggests that improving PA levels may improve postoperative outcomes.

Bioorthogonal dissociative rhenium(i) photosensitisers for controlled immunogenic cell death induction.

Photosensitisers for photoimmunotherapy with high spatiotemporal controllability are rare. In this work, we designed rhenium(i) polypyridine complexes modified with a tetrazine unit via a bioorthogonally activatable carbamate linker as bioorthogonally dissociative photosensitisers for the controlled induction of immunogenic cell death (ICD). The complexes displayed increased emission intensities and singlet oxygen (1O2) generation efficiencies upon reaction with trans-cyclooct-4-enol (TCO-OH) due to the separation of the quenching tetrazine unit from the rhenium(i) polypyridine core. One of the complexes containing a poly(ethylene glycol) (PEG) group exhibited negligible dark cytotoxicity but showed greatly enhanced (photo)cytotoxic activity towards TCO-OH-pretreated cells upon light irradiation. The reason is that TCO-OH allowed the synergistic release of the more cytotoxic rhenium(i) aminomethylpyridine complex and increased 1O2 generation. Importantly, the treatment induced a cascade of events, including lysosomal dysfunction, autophagy suppression and ICD. To the best of our knowledge, this is the very first example of using bioorthogonal dissociation reactions as a trigger to realise photoinduced ICD, opening up new avenues for the development of innovative photoimmunotherapeutic agents.

An emerging direction for nanozyme design: from single-atom to dual-atomic-site catalysts.

Nanozymes, a new class of functional nanomaterials with enzyme-like characteristics, have recently made great achievements and have become potential substitutes for natural enzymes. In particular, single-atomic nanozymes (Sazymes) have received intense research focus on account of their versatile enzyme-like performances and well-defined spatial configurations of single-atomic sites. More recently, dual-atomic-site catalysts (DACs) containing two neighboring single-atomic sites have been explored as next-generation nanozymes, thanks to the flexibility in tuning active sites by various combinations of two single-atomic sites. This minireview outlines the research progress of DACs in their synthetic approaches and the latest characterization techniques highlighting a series of representative examples of DAC-based nanozymes. In the final remarks, we provide current challenges and perspectives for developing DAC-based nanozymes as a guide for researchers who would be interested in this exciting field.

Light-Activated Assembly of DNA Origami into Dissipative Fibrils.

Hierarchical DNA nanostructures offer programmable functions at scale, but making these structures dynamic, while keeping individual components intact, is challenging. Here we show that the DNA A-motif-protonated, self-complementary poly(adenine) sequences-can propagate DNA origami into one-dimensional, micron-length fibrils. When coupled to a small molecule pH regulator, visible light can activate the hierarchical assembly of our DNA origami into dissipative fibrils. This system is recyclable and does not require DNA modification. By employing a modular and waste-free strategy to assemble and disassemble hierarchical structures built from DNA origami, we offer a facile and accessible route to developing well-defined, dynamic, and large DNA assemblies with temporal control. As a general tool, we envision that coupling the A-motif to cycles of dissipative protonation will allow the transient construction of diverse DNA nanostructures, finding broad applications in dynamic and non-equilibrium nanotechnology.

Two-year interim safety and efficacy of pegvaliase in Japanese adults with phenylketonuria.

Phenylketonuria (PKU) is an inborn error of metabolism caused by deficiency of phenylalanine hydroxylase, resulting in high blood phenylalanine (Phe) concentrations with potential for impaired neurocognition. Pegvaliase, a pegylated recombinant phenylalanine ammonia lyase that metabolizes Phe, is approved for use in adults with PKU and high blood Phe despite prior management. In the Phase 3 PRISM studies conducted in the United States, pegvaliase induction/titration/maintenance dosing led to clinically meaningful and statistically significant blood Phe reductions versus placebo, with a manageable safety profile. Here we report the primary endpoint, change in blood Phe levels from baseline to Week 52, and 2-year interim efficacy and safety results (to Week 144; data cut-off March 31, 2022) of an ongoing, open-label study in a Japanese PKU population (JapicCTI-194,642). Participants were 12 adults with PKU from Japan aged 18-70 years with blood Phe levels >600 µmol/L. In Part 1, participants received subcutaneous 2.5 mg pegvaliase once weekly for 4 weeks (induction), followed by titration up to 20 mg/day, then dose adjustment to a maximum 40 mg/day to achieve blood Phe efficacy (≤360 µmol/L); this maintenance dose was continued to Week 52. In Part 2, participants continued pegvaliase with dose adjustments up to a maximum 60 mg/day for up to 168 weeks. Among 11 participants evaluable for efficacy, mean (standard deviation) blood Phe concentration decreased from 1025.9 (172.7) µmol/L at baseline to 448.3 (458.8) µmol/L at Week 52 (mean 57.5% decrease). Up to Week 104, all 11 (100%) efficacy-evaluable participants achieved blood Phe levels ≤600 µmol/L, 9 (81.8%) achieved ≤360 µmol/L, and 8 (72.7%) achieved ≤120 µmol/L. All 12 participants reported ≥1 adverse event (AE), most commonly injection site erythema and injection site swelling (n = 10, 83.3% each). The pegvaliase exposure-adjusted AE rate was 23.5 per person-years overall, 41.2 per person-years during induction/titration, and 13.5 per person-years during maintenance. All participants developed pegvaliase-induced antibody responses. There were no AEs leading to discontinuation, no deaths, and no anaphylaxis events. Although interim, these results support the use of pegvaliase in Japanese adults with PKU with elevated blood Phe levels and are consistent with results from the Phase 3 PRISM studies.

Outcomes of hyperbaric oxygen treatment for central and branch retinal artery occlusion at a major Australian referral hospital.

Introduction: This study analysed the treatment outcomes of patients that received hyperbaric oxygen treatment (HBOT) for retinal artery occlusion (RAO) at the Royal Brisbane and Women's Hospital in Brisbane, Australia between 2015 and 2021. Methods: Retrospective study from patient records including 22 eyes from 22 patients that received HBOT for either central RAO (17 patients) or branch RAO (five patients). Patients received the Royal Brisbane and Women's Hospital RAO protocol for their HBOT. Analysis included best corrected visual acuity pre- and post-treatment, subjective improvements, side effects and patient risk factors were also recorded. Results: Improvement in best corrected visual acuity was LogMAR -0.2 for central RAO on average with 8/17 (47%) experiencing objective improvement, 5/17 (29%) experienced no change and 4/22 (24%) experienced a reduction in best corrected visual acuity. Subjective improvement (colour perception or visual fields) was reported in an additional 4/17 patients, resulting in 12/17 (71%) reporting improvement either in visual acuity or subjectively. There was no improvement in the best corrected visual acuity of any of the five patients suffering from branch RAO. Cardiovascular risk factors present in the cohort included hypertension, hypercholesterolaemia, previous cardiovascular events, cardiac disease and smoking. Limited side effects were experienced by this patient cohort with no recorded irreversible side effects. Conclusions: Hyperbaric oxygen treatment appears a safe, beneficial treatment for central RAO. No benefit was demonstrated in branch RAO although numbers were small. Increased awareness of HBOT for RAO resulting in streamlined referrals and transfers and greater uptake of this intervention may further improve patient outcomes.