Modelling the public health benefits of fibre fortification in the Chinese population through food reformulation.

OBJECTIVES: Various studies have highlighted how consuming adequate dietary fibre (DF) foods could confer multiple potential health benefits to humans, though data suggested that the average intake of the population is below the recommendations. The aim of this study, which involved probabilistic, mathematical and statistical modelling, was to understand, for the first time, how fibre fortification in a broad array of food categories could impact the diet and health status of Chinese consumers. DESIGN: A simulation-based approach was used to examine the potential impact of fibre fortification. The China Health and Nutrition Survey dataset was used to evaluate intakes of DF together with a dietary intake mathematical model. Commercially manufactured foods and beverages eligible for fibre fortification were identified and a total of 296 food and beverages were selected for fibre fortification calculation. Foods and beverages eligible for fibre fortification and the concentration of fibre used at intervention were identified based on Chinese legislations and regulations of nutrition label claims. Populations who meet the dietary reference values of fibre fortification have their health outcomes such as weight, cardiovascular disease (CVD) and type 2 diabetes risk quantified prefibre and postfibre reformulation as per published studies. RESULTS: The simulated fibre fortification intervention model has shown that the mean DF intake increased by 13.28%, from 12.8 g/day of baseline to 14.5 g/day, leading to an increase of 48% (from 6.85% to 10.13%) and 54% (from 14.22% to 21.84%) of the adult and children population, respectively, achieving the recommended fibre guidelines. Additionally, 234 diabetes cases per day (85 340 cases per year) as well as 73 065 deaths secondary to CVD could also potentially be averted or delayed with the increase of DF intake via fibre fortification. CONCLUSIONS: This study provides a practical application implicating the potential public health benefits that could be achieved with food product reformulation.

Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis.

PURPOSE: The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy. MATERIALS AND METHODS: A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed. The primary outcomes were stenosis recurrence and development of de novo stress urinary incontinence. Secondary outcomes were surgical complications, changes in voiding, and patient-reported satisfaction. RESULTS: Forty-five men were treated with D-BMGU for stenosis following prostatectomy and radiation. There was a total of 7 recurrences. Median follow-up in patients without recurrence was 21 months (IQR 12-24). There were no incidents of de novo incontinence, 28 patients were incontinent pre- and postoperatively, and of the 6 patients managed with suprapubic catheter preoperatively, 4 were continent after repair. Following repair, men had significant improvement in postvoid residual, uroflow, International Prostate Symptom Score, and International Prostate Symptom Score quality-of-life domain. Overall satisfaction was +2 or better in 86.6% of men on the Global Response Assessment. CONCLUSIONS: D-BMGU is a safe, feasible, and effective technique in patients with urethral stenosis after a combination of prostatectomy and radiation therapy. Although our findings suggest this technique may result in lower rates of de novo urinary incontinence compared to conventional urethral transection and excision techniques, head-to-head comparisons are needed.

Towards near-term quantum simulation of materials.

Determining the ground and excited state properties of materials is considered one of the most promising applications of quantum computers. On near-term hardware, the limiting constraint on such simulations is the requisite circuit depths and qubit numbers, which currently lie well beyond near-term capabilities. Here we develop a quantum algorithm which reduces the estimated cost of material simulations. For example, we obtain a circuit depth improvement by up to 6 orders of magnitude for a Trotter layer of time-dynamics simulation in the transition-metal oxide SrVO3 compared with the best previous quantum algorithms. We achieve this by introducing a collection of connected techniques, including highly localised and physically compact representations of materials Hamiltonians in the Wannier basis, a hybrid fermion-to-qubit mapping, and an efficient circuit compiler. Combined together, these methods leverage locality of materials Hamiltonians and result in a design that generates quantum circuits with depth independent of the system's size. Although the requisite resources for the quantum simulation of materials are still beyond current hardware, our results show that realistic simulation of specific properties may be feasible without necessarily requiring fully scalable, fault-tolerant quantum computers, providing quantum algorithm design incorporates deeper understanding of the target materials and applications.

Secondary placement of adjustable continence therapy (ProACT™) using open perineal technique: Case report of ProACT placement in a man with a devastated urethra following pelvic trauma and multiple AUS erosions.

Adjustable continence therapy (ProACT) is an underutilized treatment option in men with stress urinary incontinence. The device is placed using a perineal percutaneous tunneled approach. We demonstrate a salvage technique for ProACT placement in a man with a devastated urethra following pelvic trauma and multiple artificial urinary sphincter (AUS) erosions who failed a tunneled approach. Our novel technique has utility in those at high risk for intra-operative trocar injury to the urinary tract with a tunneled approach. An open approach may also be a viable option in high-risk patients who have failed a conventional ProACT approach, male sling, or AUS.

Female urethroplasty with dorsal onlay buccal mucosal graft: a single institution experience.

PURPOSE: Female urethral stricture disease is frequently unrecognized or misdiagnosed, with controversy in the literature regarding the definition of strictures and approach to management. The purpose of this study is to report our institutional experience with female urethroplasty and add our experience to the growing body of research. METHODS: We performed a retrospective review of patients undergoing female urethroplasty with dorsal onlay BMG at the University of Colorado between March 2015 and December 2021 performed by two surgeons (BF and JO). The primary outcome measure was surgical success, defined as no stricture recurrence. The secondary outcome measure was the incidence of de novo urinary incontinence. RESULTS: 23 patients were included in our data analysis. The median duration of lower urinary tract symptoms prior to urethroplasty was 16 years. 87% had undergone previous dilations. At a median follow-up of 12.2 months (range 1-81 months), four patients required a secondary procedure for obstruction with an overall success rate of 83%. One patient developed de novo stress urinary incontinence and one patient developed urge urinary incontinence. Subgroup analysis was performed comparing the patients that developed stricture recurrence (N = 4) to those that did not (N = 19). Those with stricture recurrence had a longer duration of symptoms and more dilations prior to urethroplasty. CONCLUSION: Female urethroplasty with BMG is effective at treating female urethral stricture disease, with excellent outcomes at over a year of follow-up and minimal risk of stress incontinence postoperatively.

Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation.

The speckle-type POZ protein (SPOP) functions in the Cullin3-RING ubiquitin ligase (CRL3) as a receptor for the recognition of substrates involved in cell growth, survival, and signaling. SPOP mutations have been attributed to the development of many types of cancers, including prostate and endometrial cancers. Prostate cancer mutations localize in the substrate-binding site of the substrate recognition (MATH) domain and reduce or prevent binding. However, most endometrial cancer mutations are dispersed in seemingly inconspicuous solvent-exposed regions of SPOP, offering no clear basis for their cancer-causing and peculiar gain-of-function properties. Herein, we present the first structure of SPOP in its oligomeric form, uncovering several new interfaces important for SPOP self-assembly and normal function. Given that many previously unaccounted-for cancer mutations are localized in these newly identified interfaces, we uncover molecular mechanisms underlying dysregulation of SPOP function, with effects ranging from gross structural changes to enhanced self-association, and heightened stability and activity.

Non-Transecting Urethroplasty for Bulbar Urethral Strictures-Narrative Review and Treatment Algorithm.

The bulbar urethra is the most common site of stricture disease for which urethroplasty remains standard of care. A decrease in trauma as an etiology in the developed world and concerns regarding sexual dysfunction related to transection of the corpus spongiosum have placed a renewed emphasis on non-transecting urethroplasty techniques. Here, we present our surgical algorithm with emphasis on non-transecting techniques for bulbar urethral stricture disease and review the current state of literature comparing transecting to non-transecting approaches in order to provide guidance to practitioners on patient selection, counseling, and technique.

Estimating the potential public health impact of fibre enrichment: a UK modelling study.

For improving human health, reformulation can be a tool as it allows individuals to consume products of choice while reducing intake of less desirable nutrients, such as sugars and fats, and potentially increasing intake of beneficial nutrients such as fibre. The potential effects of reformulating foods with increased fibre on diet and health need to be better understood. The objective of this statistical modelling study was to understand how fibre enrichment can affect the diet and health of consumers. The UK National Diet and Nutrition Survey datasets from 2014 to 2015 and 2015 to 2016 were utilised to evaluate intakes of fibre and kilocalories with a dietary intake model. Foods and beverages eligible for fibre enrichment were identified (n 915) based on EU legislation for fibre content claims. Those people who meet dietary reference values and fibre enrichment health outcomes such as weight, CVD and type 2 diabetes risk reductions were quantified pre- and post-fibre reformulation via Reynolds et al., D'Agostino et al. and QDiabetes algorithms, respectively. The fibre enrichment intervention showed a mean fibre intake of 19·9 g/d in the UK, signifying a 2·2 g/d increase from baseline. Modelling suggested that 5·9 % of subjects could achieve a weight reduction, 72·2 % a reduction in cardiovascular risk and 71·7 % a reduced risk of type 2 diabetes with fibre fortification (all Ps ≤ 0·05). This study gives a good overview of the potential public health benefits of reformulating food products using a straightforward enrichment scenario.

Disaster Behavioral Health Research Involving Military Facilities and Populations after Mass Violence: Insights from the 2013 Washington Navy Yard Shooting.

Research on disaster behavioral health presents significant methodological challenges. Challenges are even more complex for research on mass violence events that involve military members, families, and communities, due to the cultural and logistical considerations of working with this population. The current article aims to inform and educate on this specialized area of research, by presenting a case study on the experience of designing and conducting disaster behavioral health research after a mass violence event in a military setting: the 2013 mass shooting at the Washington Navy Yard, in Washington, D.C. Using the case example, the authors explore methodological challenges and lessons learned from conducting research in this context, and provide guidance for future researchers.

Facilitating primary care non-antiretroviral drug prescribing in people living with HIV: The 'THINK ARV' initiative.

OBJECTIVES: Older people living with HIV (PLWH) have higher rates of multimorbidity, polypharmacy and an associated increased risk of potential drug-drug interactions (DDIs). We describe the development, implementation and evaluation of an intervention to increase community prescribers' access to specialist prescribing advice. METHODS: Phase One: a survey evaluating General Practitioners' (GPs') knowledge of, and confidence detecting DDIs affecting PLWH, was circulated to eight General Practices in one UK city. Phase Two: co-production was used to develop the THINK ARV intervention for prescribers in city-wide General Practices: a dedicated mobile phone and e-mail advice service staffed by HIV specialist pharmacists. Queries were audited for 6 months pre- and post-intervention. A user-satisfaction survey was emailed to enquirers. RESULTS: Phase One: 42 GPs responded, of whom 62% requested further support identifying DDIs among PLWH. Phase Two: the number of queries received increased from 25 (6 months before 'THINK ARV' launch) to 63 in the following 6 months (152% increase). 94% of the queries were specifically about DDIs. CONCLUSIONS: Increasing community prescribers' access to specialist telephone and e-mail advice resulted in increased awareness and detection of DDIs. Similar interventions could be embedded within different healthcare settings to optimise medicines and avoid potential patient harm.

Characterizing the Effects of Explosive Ordnance Disposal Operations on the Human Body While Wearing Heavy Personal Protective Equipment.

OBJECTIVE: To provide a comprehensive characterization of explosive ordnance disposal (EOD) personal protective equipment (PPE) by evaluating its effects on the human body, specifically the poses, tasks, and conditions under which EOD operations are performed. BACKGROUND: EOD PPE is designed to protect technicians from a blast. The required features of protection make EOD PPE heavy, bulky, poorly ventilated, and difficult to maneuver in. It is not clear how the EOD PPE wearer physiologically adapts to maintain physical and cognitive performance during EOD operations. METHOD: Fourteen participants performed EOD operations including mobility and inspection tasks with and without EOD PPE. Physiological measurement and kinematic data recording were used to record human physiological responses and performance. RESULTS: All physiological measures were significantly higher during the mobility and the inspection tasks when EOD PPE was worn. Participants spent significantly more time to complete the mobility tasks, whereas mixed results were found in the inspection tasks. Higher back muscle activations were seen in participants who performed object manipulation while wearing EOD PPE. CONCLUSION: EOD operations while wearing EOD PPE pose significant physical stress on the human body. The wearer's mobility is impacted by EOD PPE, resulting in decreased speed and higher muscle activations. APPLICATION: The testing and evaluation methodology in this study can be used to benchmark future EOD PPE designs. Identifying hazards posed by EOD PPE lays the groundwork for developing mitigation plans, such as exoskeletons, to reduce physical and cognitive stress caused by EOD PPE on the wearers without compromising their operational performance.

Acute management of complete bilateral ureteral transections aligned via stent through antegrade and retrograde approach.

To manage bilateral complete distal ureteral transections (CDUT) via stent placement achieved through a combination of antegrade and retrograde approaches. An antegrade wire was advanced through the nephrostomy tube. Flexible ureteroscopy was utilized via retrograde approach to identify the guidewire in the pelvis. The guidewire was grasped and withdrawn out the urethra, and bilateral stents were placed over guidewire. Patient continues to remain asymptomatic one year later, with symmetrical renal function and no evidence of obstruction. We demonstrate that a CDUT can be successfully realigned with a combined endourological approach, thereby avoiding open/laparoscopic ureteral repair.

Long-term Follow Up of Ileal Ureteral Replacement for Complex Ureteral Strictures: Single Institution Study.

OBJECTIVE: To report our 16-year experience with ileal ureter interposition for complex ureteral stricture. Ureteral reconstruction continues to evolve to include less invasive techniques to successfully manage ureteral stricture. However, long, complex, obliterative and especially radiated ureteral strictures are not amenable to less invasive techniques and may require Ileal ureter interposition. MATERIALS AND METHODS: Retrospective review of a single institution's ureteral reconstruction database was performed. Demographics, operative details, success rate, complication rate, and length of follow-up were noted. Unilateral replacements utilized ileal ureteral interposition. Success rate was defined as no need for further open intervention. RESULTS: Between 2003 and 2019, 188 ureteral reconstructions were performed, of which 46 required ileal ureter interposition. Of these 46 patients, 10 required bilateral reconstruction. Average age was 53 years, 26 (57%) were female. The average stricture length was 9.1 cm (2-20 cm). Stricture etiology included iatrogenic causes (n = 24, 52%), radiation causes (n = 12; 26%), vascular disease (n = 3; 7%), and idiopathic retroperitoneal fibrosis (n = 3; 7%). Forty-three surgeries were performed by open abdominal approach; 3 were performed robotically. The average length of operation was 412 minutes, blood loss 417 mL and LOS was 10 days. At mean follow up of 4.4 years (1-16 years), overall success rate was 83%, with 17% (n = 8) patients requiring subsequent major surgery (5 successful ureteral revision, 3 nephrectomy) and 11 (24%) patients experiencing a major complication. CONCLUSION: In our long-term follow up of over 4 years, ileal ureteral interposition remains a successful option for complex ureteral strictures in properly selected patients.

Enhancing Psychological Sustainment & Promoting Resilience in Healthcare Workers During COVID-19 & Beyond: Adapting Crisis Interventions From High-Risk Occupations.

COVID-19 is a unique disaster, which has placed extreme stress on Healthcare Workers (HCWs) and the systems in which they work. Eradicating the pandemic requires sustainment of the healthcare workforce through actions that mitigate stress, promote resilience, and enhance performance. A major barrier is the lack of organizational practices and procedures designed to sustain HCWs during prolonged crisis events, such as COVID-19. Adapting existing best practices from other high-risk occupations allows for a more rapid, efficient response to optimize workforce well-being and preserve healthcare organizational functioning. This paper discusses current and emerging literature on the unique impacts of COVID-19 on HCWs and provides actionable, evidence-informed recommendations for individuals, teams, and leaders to enhance sustainment of HCWs that is critical to the preservation of national and global health security.

The role of liquid-liquid phase separation in regulating enzyme activity.

Liquid-liquid phase separation (LLPS) is now recognized as a common mechanism underlying regulation of enzyme activity in cells. Insights from studies in cells are complemented by in vitro studies aimed at developing a better understanding of mechanisms underlying such control. These mechanisms are often based on the influence of LLPS on the physicochemical properties of the enzyme's environment. Biochemical mechanisms underlying such regulation include the potential for concentrating reactants together, tuning reaction rates, and controlling competing metabolic pathways. LLPS is thus a powerful tool with extensive utilities at the cell's disposal, e.g. for consolidating cell survival under stress or rerouting metabolic pathways in response to the energy state of the cell. Here, we examin the evidence for how LLPS affects enzyme catalysis and begin to understand emerging concepts and expand our understanding of enzyme catalysis in living cells.

A multi-institutional critical assessment of dorsal onlay urethroplasty for post-radiation urethral stenosis.

PURPOSE: To critically evaluate a multi-institutional patient cohort undergoing Dorsal-Onlay Buccal Mucosal Graft Urethroplasty (D-BMGU) for recurrent post-radiation posterior urethral stenosis. METHODS: Retrospective multi-institutional review of patients with posterior urethral stenosis from 10 institutions between 2010-2019 was performed. Patients with at least 1-year follow-up were assessed. Patient demographics, stenosis characteristics, peri-operative outcomes, and post-operative clinical and patient-reported outcomes were analyzed. The primary outcomes were stenosis recurrence and de-novo stress urinary incontinence (SUI). Secondary outcomes were changes in voiding, sexual function, and patient-reported satisfaction. RESULTS: Seventy-nine men with post-radiation urethral stenosis treated with D-BMGU met inclusion criteria. Median age and stenosis length were 72 years, (IQR 66-75), and 3.0 cm (IQR 2.5-4 cm), respectively. Radiation modalities included: 36 (45.6%) external beam radiotherapy (EBRT), 13 (16.5%) brachytherapy (BT), 10 (12.7%) combination EBRT/BT, and 20 (25.3%) EBRT/radical prostatectomy. At a median follow-up of 21 months (IQR 13-40), 14 patients (17.7%) had stenosis recurrence. Among 37 preoperatively-continent patients, 3 men (8.1%) developed de-novo SUI following dorsal onlay urethroplasty. Of 29 patients with preoperative SUI all but one remained incontinent post-operatively (96.6%). Following repair, patients experienced significant improvement in PVR (92.5 to 26 cc, p = 0.001) and Uroflow (4.6 to 15.9 cc/s, p = 0.001), and high overall satisfaction, with 91.9% reporting a GRA of + 2 or better). CONCLUSION: Dorsal onlay buccal mucosa graft urethroplasty is a safe and feasible technique in patients with post-radiation posterior urethral stenosis. This non-transecting approach may confer low rates of de-novo SUI. Further research is needed to compare this technique with excisional urethroplasty.