Self-reported hearing loss in urban Aboriginal and Torres Strait Islander adults: unmeasured, unknown and unmanaged.

Background Effective management of hearing loss in adults is fundamental for communication, relationships, employment, and learning. This study examined the rates and management of self-reported hearing loss in urban Aboriginal and Torres Strait Islander adults. Methods A retrospective, observational study of Aboriginal and Torres Strait Islander people aged ≥15years who had annual health checks at an urban Aboriginal and Torres Strait Islander primary healthcare clinic in Inala, Queensland, was conducted to determine self-reported hearing loss rates by age and ethnic groups stratified by sex. A medical record audit of patients who self-reported hearing loss from January to June 2021 was performed to identify current management approaches, and the proportion of patients that were appropriately managed. Results Of the 1735 patients (average age 40.7years, range 15.0-88.5years, 900 [52.0%] women) who completed 3090 health checks between July 2018 and September 2021, 18.8% self-reported hearing loss. Rates did not differ between men and women. However, significant effects were noted for age, with rates increasing from 10.7% for patients aged 15-24years to 38.7% for those aged ≥65years. An audit of 73 patient medical records revealed that 39.7% of patients with self-reported hearing loss were referred to Ear, Nose and Throat/audiology or received other management. A total of 17.8% of patients owned hearing aids. Conclusions Only 40% of Aboriginal and Torres Strait Islander adults who self-reported hearing loss were referred for management. Significant changes to clinical management and government-funded referral options for hearing services are required to improve the management of self-reported hearing loss in this population.

Treatment of small as well as large declines in lung function enhances recovery to baseline in people with CF.

BACKGROUND: The benefit of antibiotic treatment of acute drops in FEV1 percent predicted (FEV1pp) has been clearly established, but data from the early 2000s showed inconsistent treatment. Further, there is no empirical evidence for what magnitude of drop is clinically significant. METHODS: We used data from the CF Foundation Patient Registry (CFFPR) from 2016 to 2019 to determine the association between treatment (any IV antibiotics, only oral or newly prescribed inhaled antibiotics, or no antibiotic therapy) following a decline of ≥5% from baseline FEV1pp and return to 100% baseline FEV1pp days using multivariable logistic regression including an interaction between the magnitude of decline and treatment category. RESULTS: Overall, 16,495 PWCF had a decline: 16.5% were treated with IV antibiotics, 25.0% non-IV antibiotics, and 58.5% received no antibiotics. Antibiotic treatment was more likely for those with lower lung function, history of a positive PA culture, older age and larger FEV1 decline (p < 0.001). Treatment with IV antibiotics or oral/inhaled antibiotics was associated with a higher odds of recovery to baseline compared to no treatment across all levels of decline, including declines of 5%-10%. CONCLUSIONS: A large proportion of acute drops in FEV1pp continue to be untreated, especially in younger patients and those with higher baseline lung function. Acute drops as small as 5% predicted are less likely to be recovered if antibiotic treatment is not prescribed. These findings suggest the need for more aggressive antimicrobial treatment of acute drops in FEV1, including those of a magnitude previously believed to be associated with self-recovery.

Pilot-scale evaluation of cascade anaerobic digestion of mixed municipal wastewater treatment sludges.

This work assessed the performance of a pilot-scale cascade anaerobic digestion (AD) system when treating mixed municipal wastewater treatment sludges. The cascade system was compared with a conventional continuous stirred tank reactor (CSTR) digester (control) in terms of process performance, stability, and digestate quality. The results showed that the cascade system achieved higher volatile solids removal (VSR) efficiencies (28-48%) than that of the reference (25-41%) when operated at the same solids residence time (SRT) in the range of 11-15 days. When the SRT of the cascade system was reduced to 8 days the VSR (32-36%) was only slightly less than that of the reference digester that was operated at a 15-day SRT (39-43%). Specific hydrolysis rates in the first stage of the cascade system were 66-152% higher than those of the reference. Additionally, the cascade system exhibited relatively stable effluent concentrations of volatile fatty acids (VFAs: 100-120 mg/l), while the corresponding concentrations in the control effluent demonstrated greater fluctuations (100-160 mg/l). The cascade system's effluent pH and VFA/alkalinity ratios were consistently maintained within the optimal range. During a dynamic test when the feed total solids concentration was doubled, total VFA concentrations (85-120 mg/l) in the cascade system were noticeably less than those (100-170 mg/l) of the control, while the pH and VFA/alkalinity levels remained in a stable range. The cascade system achieved higher total solids (TS) content in the dewatered digestate (19.4-26.8%) than the control (17.4-22.1%), and E. coli log reductions (2.0-4.1 log MPN/g TS) were considerably higher (p < 0.05) than those in the control (1.3-2.9 log MPN/g TS). Overall, operating multiple CSTRs in cascade mode at typical SRTs and mixed sludge ratios enhanced the performance, stability digesters, and digestate quality of AD. PRACTITIONER POINTS: Enhanced digestion of mixed sludge digestion with cascade system. Increased hydrolysis rates in the cascade system compared to a reference CSTR. More stable conditions for methanogen growth at both steady and dynamic states. Improved dewaterability and E. coli reduction of digestate from the cascade system.

Normothermic Machine Perfusion and Normothermic Regional Perfusion of DCD Kidneys Before Transplantation: A Systematic Review.

BACKGROUND: To overcome organ shortages, donation after circulatory death (DCD) kidneys are being increasingly used for transplantation. Prior research suggests that DCD kidneys have inferior outcomes compared with kidneys donated after brain death. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) may enhance the preservation of DCD kidneys and improve transplant outcomes. This study aimed to review the evidence surrounding NMP and NRP in DCD kidney transplantation. METHODS: Two independent reviewers conducted searches for all publications reporting outcomes for NMP and NRP-controlled DCD kidneys, focusing on delayed graft function, primary nonfunction, graft function, graft survival, and graft utilization. Weighted means were calculated for all relevant outcomes and controls. Formal meta-analyses could not be conducted because of significant heterogeneity. RESULTS: Twenty studies were included for review (6 NMP studies and 14 NRP studies). Delayed graft function rates seemed to be lower for NRP kidneys (24.6%) compared with NMP kidneys (54.3%). Both modalities yielded similar outcomes with respect to primary nonfunction (NMP 3.3% and NRP 5.6%), graft function (12-mo creatinine 149.3 µmol/L for NMP and 129.9 µmol/L for NRP), and graft utilization (NMP 83.3% and NRP 89%). Although no direct comparisons exist, our evidence suggests that both modalities have good short- and medium-term graft outcomes and high graft survival rates. CONCLUSIONS: Current literature demonstrates that both NMP and NRP are feasible strategies that may increase donor organ utilization while maintaining acceptable transplant outcomes and likely improved outcomes compared with cold-stored DCD kidneys. Further research is needed to directly compare NRP and NMP outcomes.

Oxidative Stress-Associated Male Infertility: Current Diagnostic and Therapeutic Approaches.

Infertility is a prevalent global issue affecting approximately 17.5% of adults, with sole male factor contributing to 20-30% of cases. Oxidative stress (OS) is a critical factor in male infertility, disrupting the balance between reactive oxygen species (ROS) and antioxidants. This imbalance detrimentally affects sperm function and viability, ultimately impairing fertility. OS also triggers molecular changes in sperm, including DNA damage, lipid peroxidation, and alterations in protein expression, further compromising sperm functionality and potential fertilization. Diagnostic tools discussed in this review offer insights into OS markers, antioxidant levels, and intracellular ROS concentrations. By accurately assessing these parameters, clinicians can diagnose male infertility more effectively and thus tailor treatment plans to individual patients. Additionally, this review explores various treatment options for males with OS-associated infertility, such as empirical drugs, antioxidants, nanoantioxidants, and lifestyle modifications. By addressing the root causes of male infertility and implementing targeted interventions, clinicians can optimize treatment outcomes and enhance the chances of conception for couples struggling with infertility.

Medicolegal death investigations on tribal lands-underrepresented or underserved?

Death investigation on tribal lands and of American Indian/Alaska Native (AIAN) people is complex and not well documented. An analysis of data from the 2018 Census of Medical Examiner and Coroner Offices (CMEC) provides a timely update on the extent of medicolegal death investigations (MDIs) on federal and state-recognized tribal lands. An estimated 150 MEC offices serve tribal lands, however, 44 % of these offices (i.e., 4 % of MEC offices) do not track cases from tribal lands separately. MEC offices with a population of 25,000 to 250,000 that serve tribal lands had more resources and access to information to perform MDIs than all other MEC offices. Analysis also indicates that the median number of unidentified human remains cases from MECs serving tribal lands is 6 times higher than that of jurisdictions not serving tribal lands. This analysis begins to elucidate gaps in the nation's understanding of MDI on tribal lands.

FEV1 Variability Predicts Lung Transplant or Mortality in Cystic Fibrosis Patients in the US.

RATIONALE: Declines in percent predicted Forced Expiratory Volume in 1 Second (ppFEV1) are an important marker of clinical progression of Cystic Fibrosis (CF). OBJECTIVES: We examined ppFEV1 variability on a combined outcome of lung transplant or death. METHODS: We estimated the association between ppFEV1 variability and the combined outcome of lung transplant or death. We included children ages 8 years and above with CF and two prior years of ppFEV1 data before baseline between 2005 and 2021. We defined ppFEV1 increased variability as any relative increase or decrease of at least 10% in ppFEV1 from a two-year averaged baseline. A marginal structural Cox proportional hazards model was used. We examined a cumulative measure of ppFEV1 variability, defined as the cumulative proportion of visits with ppFEV1 variability at each visit. Kaplan-Meier survival curves were generated based upon quartiles of the cumulative distribution of ppFEV1 variability. MEASUREMENTS AND MAIN RESULTS: We included 9,706 CF patients in our cohort. Median age at cohort entry was 8.3 (IQR 8.2 - 8.4) years, 50% of patients were female, 94% white, and median baseline ppFEV1 was 94.4 (IQR 81.6 - 106.1). The unadjusted HR for increased ppFEV1 variability on lung transplant/mortality was 4.13 (95% CI 3.48 - 4.90) and the weighted HR was 1.49 (95% CI 1.19 - 1.86). Survival curves stratified by quartile of cumulative variability demonstrated an increased hazard of lung transplant/mortality as the proportion of cumulative ppFEV1 variability increased. CONCLUSIONS: We found a strong association between ppFEV1 variability and lung transplant or mortality in a cohort of people with CF in the US.

Potency-Enhanced Peptidomimetic VHL Ligands with Improved Oral Bioavailability.

The von Hippel-Lindau (VHL) protein plays a pivotal role in regulating the hypoxic stress response and has been extensively studied and utilized in the targeted protein degradation field, particularly in the context of bivalent degraders. In this study, we present a comprehensive peptidomimetic structure-activity relationship (SAR) approach, combined with cellular NanoBRET target engagement assays to enhance the existing VHL ligands. Through systematic modifications of the molecule, we identified the 1,2,3-triazole group as an optimal substitute of the left-hand side amide bond that yields 10-fold higher binding activity. Moreover, incorporating conformationally constrained alterations on the methylthiazole benzylamine moiety led to the development of highly potent VHL ligands with picomolar binding affinity and significantly improved oral bioavailability. We anticipate that our optimized VHL ligand, GNE7599, will serve as a valuable tool compound for investigating the VHL pathway and advancing the field of targeted protein degradation.

Active workstations: A literature review on workplace sitting.

The purpose of this paper is to further understand current literature on prolonged sitting, sitting posture and active sitting solutions. This paper is divided into three sections: The first section (Part I) is a comprehensive overview of the literature on how a static prolonged seated posture can affect: spinal health, trunk posture, contact pressure/discomfort development and vascular issues. The second section (Part II) reviews and qualitatively compares the four working postures recognized in ANSI/HFES 100-2007: reclined sitting, upright sitting, declined sitting and standing. The final section (Part III) is a summary of research on active chairs that revolves around the two types of movement patterns: 1- sustaining continual movement over a range of postures, occasionally reaching neutral lordosis, and 2- maintaining high frequency and duration of daily light contractile activity in the legs (or lower limbs).

The transcription factor ZNF469 regulates collagen production in liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) - characterized by excess accumulation of fat in the liver - now affects one third of the world's population. As NAFLD progresses, extracellular matrix components including collagen accumulate in the liver causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply-characterized cohort of patients spanning the full histopathologic spectrum of NAFLD. CRISPR-based genetic knockout of the top 100 TFs identified ZNF469 as a regulator of collagen expression in primary human hepatic stellate cells (HSCs). Gain- and loss-of-function studies established that ZNF469 regulates collagen genes and genes involved in matrix homeostasis through direct binding to gene bodies and regulatory elements. By integrating multiomic large-scale profiling of human biopsies with extensive experimental validation we demonstrate that ZNF469 is a transcriptional regulator of collagen in HSCs. Overall, these data nominate ZNF469 as a previously unrecognized determinant of NAFLD-associated liver fibrosis.

Framework to Quantify Uncertainty in Microplastic Concentrations in Wastewaters and Sludges Incorporating Analytical Recovery Information into Data Analysis.

Wastewater treatment plants (WWTPs) serve a pivotal role in transferring microplastics (MPs) from wastewater to sludge streams, thereby exerting a significant influence on their release into the environment and establishing wastewater and biosolids as vectors for MP transport and delivery. Hence, an accurate understanding of the fate and transport of MPs in WWTPs is vital. Enumeration is commonly used to estimate concentrations of MPs in performance evaluations of treatment processes, and risk assessment also typically involves MP enumeration. However, achieving high accuracy in concentration estimates is challenging due to inherent uncertainty in the analytical workflow to collect and process samples and count MPs. Here, sources of random error in MP enumeration in wastewater and other matrices were investigated using a modeling approach that addresses the sources of error associated with each step of the analysis. In particular, losses are reflected in data analysis rather than merely being measured as a validation step for MP extraction methods. A model for addressing uncertainty in the enumeration of microorganisms in water was adapted to include key assumptions relevant to the enumeration of MPs in wastewater. Critically, analytical recovery, the capacity to successfully enumerate particles considering losses and counting error, may be variable among MPs due to differences in size, shape, and type (differential analytical recovery) in addition to random variability between samples (nonconstant analytical recovery). Accordingly, differential analytical recovery among the categories of MPs was added to the existing model. This model was illustratively applied to estimate MP concentrations from simulated data and quantify uncertainty in the resulting estimates. Increasing the number of replicates, counting categories of MPs separately, and accounting for both differential and nonconstant analytical recovery improved the accuracy of MP enumeration. This work contributes to developing guidelines for analytical procedures quantifying MPs in diverse types of samples and provides a framework for enhanced interpretation of enumeration data, thereby facilitating the collection of more accurate and reliable MP data in environmental studies.

Ending "domestic helicopter research".

"Helicopter research" refers to a practice where researchers from wealthier countries conduct studies in lower-income countries with little involvement of local researchers or community members. This practice also occurs domestically. In this Commentary, we outline strategies to curb domestic helicopter research and to foster equity-centered collaborations.

Dronedarone for the Treatment of Atrial Arrhythmias in Adults With Congenital Heart Disease.

BACKGROUND: Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart disease, but data are limited about its use in adults with congenital heart disease of moderate to great complexity. METHODS: A single-center, retrospective chart review of 21 adults with congenital heart disease of moderate to great complexity who were treated with dronedarone for atrial tachyarrhythmias was performed. RESULTS: The median (IQR) age at dronedarone initiation was 35 (27.5-39) years. Eleven patients (52%) were male. Ten patients (48%) had New York Heart Association class I disease, 10 (48%) had class II disease, and 1 (5%) had class III disease. Ejection fraction at initiation was greater than 55% in 11 patients (52%), 35% to 55% in 9 patients (43%), and less than 35% in 1 patient (5%). Prior treatments included ß-blockers (71%), sotalol (38%), amiodarone (24%), digoxin (24%), and catheter ablation (38%). Rhythm control was complete in 5 patients (24%), partial in 6 (29%), and inadequate in 10 (48%). Two patients (10%) experienced adverse events, including nausea in 1 (5%) and cardiac arrest in 1 (5%), which occurred 48 months after initiation of treatment. There were no deaths during the follow-up period. The median (IQR) follow-up time for patients with complete or partial rhythm control was 20 (1-54) months. CONCLUSION: Dronedarone can be effective for adult patients with congenital heart disease and atrial arrhythmias for whom more established therapies have failed, and with close monitoring it can be safely tolerated.

A histological and diceCT-derived 3D reconstruction of the avian visual thalamofugal pathway.

Amniotes feature two principal visual processing systems: the tectofugal and thalamofugal pathways. In most mammals, the thalamofugal pathway predominates, routing retinal afferents through the dorsolateral geniculate complex to the visual cortex. In most birds, the thalamofugal pathway often plays the lesser role with retinal afferents projecting to the principal optic thalami, a complex of several nuclei that resides in the dorsal thalamus. This thalamic complex sends projections to a forebrain structure called the Wulst, the terminus of the thalamofugal visual system. The thalamofugal pathway in birds serves many functions such as pattern discrimination, spatial memory, and navigation/migration. A comprehensive analysis of avian species has unveiled diverse subdivisions within the thalamic and forebrain structures, contingent on species, age, and techniques utilized. In this study, we documented the thalamofugal system in three dimensions by integrating histological and contrast-enhanced computed tomography imaging of the avian brain. Sections of two-week-old chick brains were cut in either coronal, sagittal, or horizontal planes and stained with Nissl and either Gallyas silver or Luxol Fast Blue. The thalamic principal optic complex and pallial Wulst were subdivided on the basis of cell and fiber density. Additionally, we utilized the technique of diffusible iodine-based contrast-enhanced computed tomography (diceCT) on a 5-week-old chick brain, and right eyeball. By merging diceCT data, stained histological sections, and information from the existing literature, a comprehensive three-dimensional model of the avian thalamofugal pathway was constructed. The use of a 3D model provides a clearer understanding of the structural and spatial organization of the thalamofugal system. The ability to integrate histochemical sections with diceCT 3D modeling is critical to better understanding the anatomical and physiologic organization of complex pathways such as the thalamofugal visual system.

American Society for Metabolic and Bariatric Surgery 2022 estimate of metabolic and bariatric procedures performed in the United States.

BACKGROUND: Metabolic and bariatric surgery (MBS), despite being the most effective durable treatment for obesity, remains underused as approximately 1% of all qualified patients undergo surgery. The American Society for Metabolic and Bariatric Surgery established a Numbers Taskforce to specify the annual rate of obesity treatment interventions utilization and to determine if patients in need are receiving appropriate treatment. OBJECTIVE: To provide the best estimated number of metabolic and bariatric procedures being performed in the United States in 2022. SETTING: United States. METHODS: We reviewed data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program and National Surgical Quality Improvement Program. In addition, data from industry and state databases were used to estimate activity at non-accredited centers. Data from 2022 were compared mainly with data from the previous 2 years. RESULTS: Compared with 2021, the total number of MBS performed in 2022 increased from approximately 262,893 to 280,000. The sleeve gastrectomy (SG) continues to be the most commonly performed procedure. The gastric bypass procedure trend remained relatively stable. The percentage of revision procedures and biliopancreatic diversion with duodenal switch procedures increased slightly. Intragastric balloon placement increased from the previous year. Endoscopic sleeve gastroplasty increased in numbers. CONCLUSIONS: There was a 6.5% increase in MBS volume from 2021 to 2022 and a 41% increase from 2020, which demonstrates a recovery from the COVID-19 pandemic. SG continues to be the most dominant MBS procedure.

Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop.

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.

The impact of switching to race-neutral reference equations on FEV1 percent predicted among people with cystic fibrosis.

RATIONALE: The American Thoracic Society recommended switching to race-neutral spirometry reference equations, as race is a social construct and to avoid normalizing disparities in lung function due to structural racism. Understanding the impact of the race-neutral equations on percent predicted forced expiratory volume in one second (ppFEV1) in people with cystic fibrosis (PwCF) will help prepare patients and providers to interpret pulmonary function test results. OBJECTIVE(S): To quantify the impact of switching from Global Lung Initiative (GLI) 2012 race-specific to GLI 2022 Global race-neutral reference equations on the distribution of ppFEV1 among PwCF of different races. METHODS: Cross-sectional analysis of FEV1 among PwCF ages ≥6 years in the 2021 U.S. Cystic Fibrosis Foundation Patient Registry. We describe the absolute difference in ppFEV1 between the two reference equations by reported race and the effect of age and height on this difference. RESULTS: With the switch to GLI Global, ppFEV1 will increase for White (median increase 4.7, (IQR: 3.1; 6.4)) and Asian (2.6 (IQR: 1.6; 3.7)) individuals and decrease for Black individuals (-7.7, (IQR: -10.9; -5.2)). Other race categories will see minimal changes in median ppFEV1. Individuals with higher baseline ppFEV1 and younger age will see a greater change in ppFEV1 (i.e., a greater improvement among White and Asian individuals and a greater decline among Black individuals). CONCLUSIONS: Switching from GLI 2012 race-specific reference equations to GLI 2022 Global race-neutral equations will result in larger reductions in ppFEV1 among Black individuals with CF than increases among White and Asian people with CF.

Sex- and operation-dependent effects on 5-year weight loss results of bariatric surgery.

BACKGROUND: Weight loss response after bariatric surgery is highly variable, and several demographic factors are associated with differential responses to surgery. Preclinical studies demonstrate numerous sex-specific responses to bariatric surgery, but whether these responses are also operation dependent is unknown. OBJECTIVE: To examine sex-specific weight loss outcomes up to 5 years after laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). SETTING: Single center, university, United States. METHODS: Retrospective, observational cohort study including RYGB (n = 5057) and vertical SG (n = 2041) patients from a single, academic health center. Percentage total weight loss (TWL) over time was examined with generalized linear mixed models to determine the main and interaction effects of surgery type on weight loss by sex. RESULTS: TWL demonstrated a strong sex-by-procedure interaction, with women having a significant advantage with RYGB compared with SG (adjusted difference at 5 yr: 8.0% [95% CI: 7.5-8.5]; P < .001). Men also experienced greater TWL over time with RYGB or SG, but the difference was less and clinically insignificant (adjusted difference at 5 yr: 2.9% [2.0-3.8]; P < .001; P interaction between sex and procedure type = .0001). Overall, women had greater TWL than men, and RYGB patients had greater TWL than SG patients (adjusted difference at 5 yr: 3.1% [2.4-3.2] and 6.9% [6.5-7.3], respectively; both P < .0001). Patients with diabetes lost less weight compared with those without (adjusted difference at 5 yr: 3.0% [2.7-3.2]; P < .0001). CONCLUSIONS: Weight loss after bariatric surgery is sex- and procedure-dependent. There is an association suggesting a clinically insignificant difference in weight loss between RYGB and SG among male patients at both the 2- and 5-year postsurgery time points.

A comprehensive floc model for simulating simultaneous nitrification, denitrification, and phosphorus removal.

A comprehensive floc model for simultaneous nitrification, denitrification, and phosphorus removal (SNDPR) was designed, incorporating polyphosphate-accumulating organisms (PAOs), glycogen-accumulating organisms (GAOs), intrinsic half-saturation coefficients, and explicit external mass transfer terms. The calibrated model was able to effectively describe experimental data over a range of operating conditions. The estimated intrinsic half-saturation coefficients of oxygen values for ammonia-oxidizing bacteria, nitrite-oxidizing bacteria, ordinary heterotrophic organisms (OHOs), PAOs, and GAOs were set at 0.08, 0.18, 0.03, 0.07, and 0.1 mg/L, respectively. Simulation suggested that low dissolved oxygen (DO) environments favor K-strategist nitrifying bacteria and PAOs. In SNDPR, virtually all influent and fermentation-generated volatile fatty acids were assimilated as polyhydroxyalkanoates by PAOs in the anaerobic phase. In the aerobic phase, PAOs absorbed 997 % and 171 % of the benchmark influent total phosphorus mass loading through aerobic growth and denitrification via nitrite. These high percentages were because they were calculated relative to the influent total phosphorus, rather than total phosphorus at the end of the anaerobic period. When considering simultaneous nitrification and denitrification, about 23.1 % of influent total Kjeldahl nitrogen was eliminated through denitrification by PAOs and OHOs via nitrite, which reduced the need for both oxygen and carbon in nitrogen removal. Moreover, the microbial and DO profiles within the floc indicated a distinct stratification, with decreasing DO and OHOs, and increasing PAOs towards the inner layer. This study demonstrates a successful floc model that can be used to investigate and design SNDPR for scientific and practical purposes.

Intragraft memory-like CD127hiCD4+Foxp3+ Tregs maintain transplant tolerance.

CD4+Foxp3+ regulatory T cells (Tregs) play an essential role in suppressing transplant rejection, but their role within the graft and heterogeneity in tolerance are poorly understood. Here, we compared phenotypic and transcriptomic characteristics of Treg populations within lymphoid organs and grafts in an islet xenotransplant model of tolerance. We showed Tregs were essential for tolerance induction and maintenance. Tregs demonstrated heterogeneity within the graft and lymphoid organs of tolerant mice. A subpopulation of CD127hi Tregs with memory features were found in lymphoid organs, presented in high proportions within long-surviving islet grafts, and had a transcriptomic and phenotypic profile similar to tissue Tregs. Importantly, these memory-like CD127hi Tregs were better able to prevent rejection by effector T cells, after adoptive transfer into secondary Rag-/- hosts, than naive Tregs or unselected Tregs from tolerant mice. Administration of IL-7 to the CD127hi Treg subset was associated with a strong activation of phosphorylation of STAT5. We proposed that memory-like CD127hi Tregs developed within the draining lymph node and underwent further genetic reprogramming within the graft toward a phenotype that had shared characteristics with other tissue or tumor Tregs. These findings suggested that engineering Tregs with these characteristics either in vivo or for adoptive transfer could enhance transplant tolerance.