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Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate of just 13 %. Conventional therapies fail due to acquired chemoresistance. We previously identified MutY-Homolog (MYH), a protein that repairs oxidative DNA damage, as a therapeutic target that induces apoptosis in PDAC cells. However, we did not understand the mechanism driving these anti-PDAC effects, nor did we have a means to therapeutically inhibit MYH. In this study, we demonstrated that MYH inhibition induces DNA damage and checkpoint activation in PDAC cells. Using a clinically-relevant PDAC mouse model, we showed that therapeutic MYH-siRNA delivery using Star 3 nanoparticles increased intratumoural PDAC cell death, but did not inhibit tumour growth. Finally, we showed that MYH knockdown in PDAC cells sensitised them to the anti-proliferative and anti-clonogenic effects of oxaliplatin and olaparib. Our findings identify a potential novel therapeutic approach for PDAC that induces a therapeutically exploitable DNA repair vulnerability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Polycyclic Aromatic Hydrocarbons (PAHs) and Polychlorinated Biphenyls (PCBs) are recalcitrant organic pollutants often detected in stormwater. Various stormwater control measures (SCMs) can remove PAHs and PCBs by filtration, adsorption, and biodegradation. However, dissolved PAHs and PCBs remain present in the treated outflow of SCMs. To provide further treatment, two types of biochar (biochar A and biochar B), a granular activated carbon (GAC), and a regenerated GAC (RAC) were tested in a column study with synthetic stormwater containing PAHs and PCBs in low concentrations. Results showed that PAH concentrations were reduced by 98.2-99.8% (range: 62% of the PCBs accumulated at the first third of the column due to adsorption onto the black carbon material thus providing information for management. The difference in treatment performances of different PAHs and PCBs may be caused by the molecular structure of the contaminants. Lifetime calculations indicated that biochar had lifetimes >36-51 years, while GAC and RAC showed lifetimes longer than 147 and 206 years, respectively, based on predicted precipitation for scaled up designs. The results showed that biochar and activated carbons can be efficient adsorbents for stormwater polishing treatment. With consideration of efficiency, sustainability and cost, RAC is recommended for polishing treatment of dissolved PAHs and PCBs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Limited normative reference data are available for validated outcomes of flexible endoscopic evaluation of swallowing (FEES). We aimed to examine healthy swallowing via FEES in community-dwelling healthy adults to derive a preliminary reference dataset of normative validated FEES outcomes to guide clinical interpretation and diagnostic decision-making., Methods: Adults with no history of dysphagia-related disease underwent simultaneous videofluoroscopy and FEES imaging using a standardized 11-item bolus protocol. Trained raters performed duplicate, independent, blinded ratings of the New Zealand Secretion Scale (NZSS), Penetration-Aspiration Scale (PAS), and Dynamic Imaging Grade of Swallowing Toxicity-FEES (DIGEST-FEES) validated scales. Descriptive statistics were performed at the bolus (PAS) and participant level (NZSS, DIGEST-FEES)., Results: 361 swallows from 33 community-dwelling adults (36.6 ± 14.7 years old) were analyzed. In rank order, distribution profiles were: (1) NZSS: 95% normal (NZSS = 0), 5% abnormal (NZSS = 4); (2) Worst PAS: 73% safe (PAS 1-2, n = 24), 21% penetration above the true vocal folds (PAS 3, n = 7), 6% deep penetration to the true vocal folds (PAS = 5, n = 2); (3) DIGEST-FEES Safety Grades: 91% Grade 0 (normal, n = 30), 9% Grade 1 (mild impairment, n = 3); (4) DIGEST-FEES Efficiency Grades: 73% Grade 0 (normal, n = 24), 24% Grade 1 (mild impairment, n = 8), 3% Grade 2 (moderate impairment, n = 1)., Conclusion: This preliminary healthy FEES dataset highlights variation in swallowing safety and efficiency and suggests careful interpretation of FEES outcomes to avoid over-pathologizing impairment. Future studies are warranted to obtain additional normative data in diverse populations to further understand normal variation in FEES outcomes to guide clinically meaningful diagnostic cut-points., Level of Evidence: 3 Laryngoscope, 135:1034-1038, 2025., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

In this article, we present a case study that illustrates the nurse's obligation in applying clinical judgment in determining the applicability and appropriateness of carrying out a standing order, and how nurses can navigate institutional policies that reinforce a gender binary and heteronormative ideals of womanhood while depriving the client of their autonomy. The case study also reveals some of the challenges transgender, nonbinary, and other gender expansive people may experience when health care institutions have standing orders that are not inclusive of all gender identities., Competing Interests: Disclosure Dr E.C. Cicero was supported by grants from the Alzheimer's Association (23AARGD-NTF-1028973), The National Institute on Alcohol Abuse and Alcoholism (R01AA030275), and the National Institute on Aging (K23AG084851). Dr J.D. Bosse was partially supported by a career development grant funded by the National Center for Complementary and Integrative Health (K01AT012495). The statements in this article are solely the responsibility of the author and do not necessarily represent the views of the Alzheimer’s Association or the National Institutes of Health., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Swallow and cough dysfunction are possible surgical complications of lung transplantation (LT). We examined voluntary cough strength, sensorimotor reflexive cough integrity, and swallow-related respiratory rate (RR) across swallowing safety and aspiration response groups in recovering LT recipients., Methods: Forty-five LT recipients underwent flexible endoscopic evaluation of swallowing indexed by the validated Penetration Aspiration Scale. RR before and after a 3-ounce water drinking task was measured. Voluntary and reflexive cough screening were performed to index motor and sensory outcomes. T-tests, one-way ANOVAs, and chi-square (odds ratios) were used., Results: 60% of patients exhibited laryngeal penetration (n = 27) and 40% demonstrated tracheal aspiration (n = 18); 72% (n = 13) demonstrated silent aspiration. Baseline RR was higher in aspirators versus non-aspirators (26.5 vs. 22.6, p = 0.04) and in silent aspirators compared to non-silent aspirators (27.9 vs. 20.7, p = 0.01). RR change post-swallowing did not differ between aspiration response groups; however, it was significantly higher in aspirators compared to non-aspirators (3 vs. -2, p = 0.02). Compared to non-silent aspirators, silent aspirators demonstrated reduced voluntary cough peak expiratory flow (PEF; 166 vs. 324 L/min, p = 0.01). PEF, motor and urge to cough reflex cough ratings did not differ between aspirators and non-aspirators. Silent aspirators demonstrated a 7.5 times higher odds of failing reflex cough screening compared to non-silent aspirators (p = 0.07)., Conclusions: During the acute recovery period, all LT participants demonstrated some degree of unsafe swallowing and reduced voluntary cough strength. Silent aspirators exhibited elevated RR, reduced voluntary cough physiologic capacity to defend the airway, and a clinically distinguishable blunted motor response to reflex cough screening., (© 2022 John Wiley & Sons Ltd.)

Background: There is limited evidence regarding the optimal time to commence parenteral nutrition (PN) in term and late preterm infants., Design: Single-centre, non-blinded, exploratory randomised controlled trial., Setting: A level-3 neonatal unit in a stand-alone paediatric hospital., Patients: Infants born ≥34 weeks of gestation and ≤28 days, who needed PN. Eligible infants were randomised on day 1 or day 2 of admission., Interventions: Early (day 1 or day 2 of admission, N=30) or late (day 6 of admission, N=30) PN., Main Outcome Measures: Plasma phenylalanine and F 2 -isoprostane levels on day 4 and day 8 of admission. Secondary outcomes were amino-acid and fatty-acid profiles on day 4 and day 8, and clinical outcomes., Results: The postnatal age at randomisation was similar between the groups (2.3 (SD 0.8) vs 2.3 (0.7) days, p=0.90). On day 4, phenylalanine levels in early-PN infants were higher than in late-PN (mean (SD) 62.9 (26.7) vs 45.5 (15.3) µmol/L; baseline-adjusted percentage difference 25.8% (95% CI 11.6% to 39.9%), p<0.001). There was no significant difference in phenylalanine levels between the two groups on day 8. There was no significant difference between the groups for F 2 -isoprostane levels on day 4 (early-PN mean (SD) 389 (176) vs late-PN 419 (291) pg/mL; baseline-adjusted percentage difference: -4.4% (95% CI -21.5% to 12.8%) p=0.62) and day 8 (mean (SD) 305 (125) vs 354 (113) pg/mL; adjusted mean percentage difference -16.1 (95% CI -34.1 to 1.9) p=0.09).Postnatal growth restriction for weight was less severe in the early-PN group (change in weight z-score from baseline to discharge: -0.6 (0.6) vs -1.0 (0.6); p=0.02). The incidence of hyperglycaemia was greater in the early-PN group (20/30 (66.7%) vs 11/30 (36.7%), p=0.02)., Conclusions: The timing of the commencement of PN did not seem to affect the degree of oxidative stress in critically ill term and late preterm infants. The effect of transiently high plasma phenylalanine with early PN on clinical outcomes requires further investigation., Trial Registration Number: ACTRN12620000324910., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bioretention is an increasingly common stormwater control measure (SCM) for mitigation of stormwater quantity and quality. Studies from lab to field scale have shown successful removal of total metals from stormwater, especially Cu and Zn which are ubiquitous in the urban environment yet detrimental to aquatic ecosystems. While bioretention effectively removes particulate matter and particulate bound (PB) contaminants, removal performance of dissolved metals has been neglected in field studies. After approximately two decades of these systems being implemented, with a typical design-life of 20 years, performance of mature systems is unknown. This study examined the performance of a 16- to 18-year-old bioretention cell by characterizing Cu and Zn partitioning and removal. Flow-weighted composite samples of stormwater and bioretention effluent were collected and analyzed for total and dissolved metals. Size-fractioned road-deposited sediments (RDS) were collected and analyzed for metals and particle size distribution. The comparison of RDS and PB metals showed that PB-Zn was enriched in stormwater, indicating higher mobility of PB-Zn compared to PB-Cu. The mature bioretention system effectively removed particulates and PB-metals with average load reductions of 82% and 83%, respectively. While concentrations for dissolved metals were low (<40 μg/L), no significant difference between influent and effluent was observed. Effluent concentrations of total and dissolved Cu, total organic carbon, and particulates were not significantly different from those measured over 10 years ago at the site, while total Zn effluent concentration slightly increased. MINTEQ speciation modeling showed that Cu was approximately 100% bound with dissolved organic matter (DOM) in all bioretention effluent. While Zn was also mostly bound with DOM in effluent, some events showed free ionic Zn reaching concentrations in the same order of magnitude. Media amendments, maintenance, and monitoring of SCMs should be considered where further removal of dissolved metals is necessary for the protection of aquatic environments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Birthe V. Kjellerup reports financial support was provided by Strategic Environmental Research and Development Program. Kristen Croft reports financial support was provided by National Science Foundation (Amy Sapkota, PI)., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Phenyl-γ-valerolactones (PVLs) have been identified as biomarkers of dietary flavan-3-ol exposure, although their utility requires further characterization., Objectives: We investigated the performance of a range of PVLs as biomarkers indicative of flavan-3-ol intake., Methods: We report the results of 2 companion studies: a 5-way randomized crossover trial (RCT) and an observational cross-sectional study. In the RCT (World Health Organization, Universal Trial Number: U1111-1236-7988), 16 healthy participants consumed flavan-3-ol-rich interventions (of apple, cocoa, black tea, green tea, or water [control]) for 1 d each. First morning void samples and 24-h urine samples were collected with diet standardized throughout. For each participant, 1 intervention period was extended (to 2 d) to monitor PVL kinetics after repeat exposure. In the cross-sectional study, 86 healthy participants collected 24-h urine samples, and concurrent weighed food diaries from which flavan-3-ol consumption was estimated using Phenol-Explorer. A panel of 10 urinary PVLs was quantified using liquid chromatography tandem mass spectrometry., Results: In both studies, 2 urinary PVLs [5-(3'-hydroxyphenyl)-γ-valerolactone-4'-sulfate and putatively identified 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-glucuronide] were the principal compounds excreted (>75%). In the RCT, the sum of these PVLs was significantly higher than the water (control) after each intervention; individually, there was a shift from sulfation toward glucuronidation as the total excretion of PVLs increased across the different interventions. In the extended RCT intervention period, no accumulation of these PVLs was observed after consecutive days of treatment, and after withdrawal of treatment on the third day, there was a return toward negligible PVL excretion. All results were consistent, whether compounds were measured in 24-h urine or first morning void samples. In the observational study, the sum of the principal PVLs correlated dose dependently (R s = 0.37; P = 0.0004) with dietary flavan-3-ol intake, with similar associations for each individually., Conclusions: Urinary 5-(3'-hydroxyphenyl)-γ-valerolactone-4'-sulfate and putatively identified 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-glucuronide are recommended biomarkers for dietary flavan-3-ol exposure., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Poor oral health is associated with adverse outcomes in critical care settings. Although provision of oral care is a fundamental aspect of nursing practice, both formal training and practice among nursing staff remain unclear., Method: Cardiothoracic intensive care unit nurses were recruited to complete a 16-item survey regarding training, confidence, methods, prioritization, and barriers to provision of oral care., Results: A total of 108 nurses participated (70% response rate). Formal training in oral care was reported by 38%, most frequently reported as less than 1 hour (53%) in duration. Of the respondents, 70% reported confidence in providing oral care. Nine methods and 16 products were identified, with variability in the frequency of provision. Prioritization of oral care was rated most frequently as moderate (53%), with 28% reporting barriers., Conclusion: Despite limited formal training, surveyed nurses reported confidence in providing oral care. Methods, frequency, and prioritization were variable. Both development of formal curricula and evaluation of adherence to standardized protocols for oral care are warranted. [ J Contin Educ Nurs. 2023;54(7):313-321.] .

Introduction In both clinical neurodegenerative diseases and normal ageing, the brain is an organ that is particularly susceptible to oxidative injury from free radicals and reactive oxygen species (ROS). These [...], The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group. Key words antioxidant; aged; cognition; oxidative stress; Pycnogenol

A diet rich in polyphenolic compounds has recognized health benefits, and as such is routinely monitored as part of dietary intervention studies. A method for the simultaneous determination of 36 phenolic compounds, including phenolic acids and flavonoids, using liquid chromatography and tandem mass spectrometry is described here. The target analytes were quantified based on their specific mass spectral fragments using a selected reaction monitoring approach. A C18 column with embedded aromatic functionality ensured separation of all phenolic compounds studied which included several pairs of isomers. Sample preparation involved the use of β-glucuronidase to release the phenolic compounds from their conjugated forms. The intra-day and inter-day precision and accuracy was less than 7% for all phenolic compounds studied. Recoveries, where plasma was spiked with three different concentrations of the analytes, ranged from 95-115%. The limits of detection and quantification were 0.23-3.89 and 1.15-7.79 nM, respectively. The method was successfully applied to real samples and the range reported for each phenolic compound, with the exception of hydroferulic acid, nordihydroguaiaretic acid, methylgallate, and m-coumaric acid, was at least an order of magnitude higher than the limit of quantification for the method., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The extent of abdominal aortic calcification (AAC) is a major predictor of vascular disease events. We have previously found regular apple intake, a major source of dietary flavonoids, associates with lower AAC. Whether total dietary flavonoid intake impacts AAC remains unknown. Here, we extend our observations to habitual intakes of total flavonoids, flavonoid subclasses, and specific flavonoid-containing foods, with the odds of extensive AAC., Methods: We conducted cross-sectional analyses on 881 females (median [interquartile range] age, 80 [78-82] years; body mass index, 27 [24-30] kg/m 2 ) from the PLSAW (Perth Longitudinal Study of Ageing Women). Flavonoid intake was calculated from food-frequency questionnaires. Calcifications of the abdominal aorta were assessed on lateral lumbar spine images and categorized as less extensive or extensive. Logistic regression was used to investigate associations., Results: After adjusting for demographic, lifestyle and dietary confounders, participants with higher (Q4), compared with lower (Q1) intakes, of total flavonoids, flavan-3-ols, and flavonols had 36% (odds ratio [95% CI], 0.64 [0.43-0.95]), 39% (0.61 [0.40-0.93]) and 38% (0.62 [0.42-0.92]) lower odds of extensive AAC, respectively. In food-based analyses, higher black tea intake, the main source of total flavonoids (75.9%), associated with significantly lower odds of extensive AAC (2-6 cups/d had 16%-42% lower odds compared with 0 daily intake). In a subset of nonconsumers of black tea, the association of total flavonoid intake with AAC remained (Q4 versus Q1 odds ratio [95% CI], 0.11 [0.02-0.54])., Conclusions: In older women, greater habitual dietary flavonoid intake associates with less extensive AAC.

Dietary nitrate, found predominantly in green leafy vegetables and other vegetables such as radish, celery, and beetroot, has been shown to beneficially modulate inflammatory processes and immune cell function in animals and healthy individuals. The impact of increased nitrate intake on soluble inflammatory mediators in individuals with hypertension is unclear. We assessed whether the daily consumption of dietary nitrate via beetroot juice for 1-week lowered levels of circulating inflammatory markers in men and women with treated hypertension. Twenty-seven male and female participants were recruited to a randomized, placebo-controlled, double-blind crossover trial. The effects of 1-week intake of nitrate-rich beetroot juice versus 1-week intake of nitrate-depleted beetroot juice (placebo) were investigated. Plasma concentrations of circulating soluble adhesion molecules (ICAM-1, VCAM-1, CD62E, CD62P), inflammatory cytokines (IL-1β, IL-6, IL-10, IL-12p70, TNF-α) and chemokines (IL-8, MCP-1) were measured by multiplex flow cytometric bead array in samples collected on day 7 of each intervention period. Other outcomes included alterations in nitrate metabolism assessed by measuring nitrate and nitrite concentrations in plasma, saliva, and urine. One week of beetroot juice did not alter levels of the soluble adhesion markers or cytokines assessed. A 7-fold increase in salivary nitrite, an 8-fold increase in salivary nitrate, a 3-fold increase in plasma nitrate and nitrite, and a 4-fold increase in urinary nitrate and nitrite compared to the placebo was observed ( p < 0.001 for all comparisons). Increasing dietary nitrate consumption over 7 days is not effective in reducing soluble inflammatory mediators in individuals with treated hypertension. This trial was registered at anzctr.org.au as ACTRN 12613000116729.

Objective: The objective of this retrospective study was to find out (i) the prevalence of deep carious lesions, both untreated and previously treated, among 14- and 15-year olds and (ii) how deep carious lesions were managed in a Finnish public health care setting., Materials and Methods: A random sample of 278 patients was taken from 3990 patients at the oral health care of the City of Helsinki. Radiographic subsample consisted of patients with bitewing and periapical radiographs (n = 128, 46% of the total sample). Deep carious lesions (extending to at least the inner half of dentine), deep restorations, direct pulp cappings, root canal treatments, and extractions in permanent premolars and molars were recorded from the radiographs. Patients with untreated deep carious lesions were followed up for 24 months., Results: In the total sample 12% had at least one untreated deep carious lesion, 10% at least one deep restoration, and 19% at least one untreated or previously treated deep carious lesion. The follow-up cohort included 48 deep carious lesions in 26 patients. Complete excavation was the most frequently chosen method (81% for lesions reaching the inner half of dentine and 56% the inner third or deeper), followed by stepwise excavation (19% and 37%, respectively)., Conclusions: One-fifth of 14-15-year-olds had at least one untreated or previously treated deep carious lesion. The choice for the carious tissue removal did not follow the current recommendations for less invasive methods., Clinical Relevance: Continuing education is needed to improve the diagnostics and management of deep carious lesions., (© 2022. The Author(s).)

Stormwater from complex land uses is an important contributor of contaminants of concern (COCs) such as polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), Copper, and Zinc to receiving water bodies. A large portion of these COCs bind to particulate matter in stormwater, which can be removed through filtration by traditional media. However, the remaining dissolved COCs can be significant and require special attention such as engineered treatment measures and media. Biochar is a porous sorbent produced from a variety of organic materials. In the last decade biochar has been gaining attention as a stormwater treatment medium due to low cost compared to activated carbon. However, biochar is not a uniform product and selection of an appropriate biochar for the removal of specific contaminants can be a complex process. Biochars are synthesized from various feedstocks and using different manufacturing approaches, including pyrolysis temperature, impact the biochar properties thus affecting ability to remove stormwater contaminants. The local availability of specific biochar products is another important consideration. An evaluation of proposed stormwater control measure (SCM) media needs to consider the dynamic conditions associated with stormwater and its management, but the passive requirements of the SCM. The media should be able to mitigate flood risks, remove targeted COCs under high flow SCM conditions, and address practical considerations like cost, sourcing, and construction and maintenance. This paper outlines a process for selecting promising candidates for SCM media and evaluating their performance through laboratory tests and field deployment with special attention to unique stormwater considerations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Wastewater surveillance, also known as wastewater-based epidemiology (WBE), has been successfully used to detect SARS-CoV-2 and other viruses in sewage in many locations in the United States and globally. This includes implementation of the surveillance on college and university campuses. A two-phase study was conducted during the 2020-2021 academic year to test the feasibility of a WBE system on campus and to supplement the clinical COVID-19 testing performed for the student, staff, and faculty body. The primary objective during the Fall 2020 semester was to monitor a large portion of the on-campus population and to obtain an understanding of the spreading of the SARS-CoV-2 virus. The Spring 2021 objective was focused on selected residence halls and groups of residents on campus, as this was more efficient and relevant for an effective follow-up response. Logistical problems and planning oversights initially occurred but were corrected with improved communication and experience. Many lessons were learned, including effective mapping, site planning, communication, personnel organization, and equipment management, and obtained along the way, thereby paving an opportune guide for future planning efforts. PRACTITIONER POINTS: WBE was successful in the detection of many SARS-CoV-2 variants incl. Alpha, Beta, Gamma, Delta, Lambda, Mu, and Omicron. Careful planning and contingencies were essential for a successful implementation of a SARS-CoV-2 monitoring program. A surveillance program may be important for detection and monitoring of other public health relevant targets in wastewater incl. bacteria, viruses, fungi and viruses. Diverse lessons were learned incl. effective mapping, site planning, communication, personnel organization, and equipment management, thereby providing a guide for future planning efforts., (© 2022 The Authors. Water Environment Research published by Wiley Periodicals LLC on behalf of Water Environment Federation.)

Background: Despite the wide use of parenteral nutrition (PN) in neonatal intensive care units (NICU), there is limited evidence regarding the optimal time to commence PN in term and late preterm infants. The recommendations from the recently published ESPGHAN/ESPEN/ESPR/CPEN and NICE guidelines are substantially different in this area, and surveys have reported variations in clinical practice. The aim of this randomised controlled trial (RCT) is to evaluate the benefits and risks of early versus late PN in term and late preterm infants., Methods/design: This study is a single-centre, non-blinded RCT in the NICU of Perth Children's Hospital, Western Australia.A total of 60 infants born ≥34 weeks of gestation who have a high likelihood of intolerance to enteral nutrition (EN) for at least 3-5 days will be randomised to early (day 1 or day 2 of admission) or late commencement (day 6 of admission) of PN after informed parental consent. In both groups, EN will be commenced as early as clinically feasible. Primary outcomes are plasma phenylalanine and plasma F 2 -isoprostane levels on Day 4 and Day 8 of admission. Secondary outcomes are total and individual plasma amino acid profiles, plasma and red blood cell fatty acid profiles, in-hospital all-cause mortality, hospital-acquired infections, length of hospital/NICU stay, z scores and changes in z scores at discharge for weight, height and head circumference, time to full EN, duration of respiratory (mechanical, non-invasive) support, duration of inotropic support, the incidence of hyper and hypoglycaemia, incidence of metabolic acidosis, liver function, blood urea nitrogen, and C-reactive protein (CRP)., Discussion: This RCT will examine the effects of early versus late PN in term and late preterm infants by comparing key biochemical and clinical outcomes and has the potential to identify underlying pathways for beneficial or harmful effects related to the timing of commencement of PN in such infants., Trial Registration: ANZCTR; ACTRN12620000324910 (3rd March 2020)., (© 2022. The Author(s).)

Background: We aimed to determine dysphagia profiles before and after lung transplantation (prevalence, incidence) and to examine predictors and health-related outcomes of aspiration in individuals undergoing lung transplantation., Methods: A retrospective single-center study of consecutive adults undergoing lung transplantation and completing a postoperative videofluoroscopic swallowing study between 2017 and 2020 was conducted. The validated penetration aspiration scale indexed swallowing safety and clinical outcomes were extracted from electronic medical records. T-tests, chi square with odds ratios, and multivariable logistic regression were conducted., Results: Two hundred five participants were identified who underwent lung transplantation and a postoperative swallowing exam. Of those who underwent both a pre- and postoperative swallowing exam (n = 170), preoperatively 83% demonstrated safe swallowing and 17% unsafe swallowing. Following lung transplantation, 16% demonstrated safe swallowing and 84% demonstrated unsafe swallowing (39% penetration, 45% aspiration). Independent predictors of postoperative aspiration were venous-venous extracorporeal membrane oxygenation (odds ratio [OR]: 6.7, confidence interval [CI]: 2.0-81.5) and reintubation (OR: 4.5, CI: 1.0-60.3), p < .05. Compared to non-aspirators, aspirators demonstrated higher odds of being discharged to a dependent care setting (OR: 2.3, CI: 1.2-4.5), p < .05. Aspirators spent significantly longer NPO (median = 138.0 hours, 25th percentile, 75th percentile = 75.7, 348.3) compared to non-aspirators (median = 85.0 hours, 25th percentile, 75th percentile = 48.0, 131.6, p < .001)., Conclusions: Pre-existing dysphagia was low in this cohort of patients undergoing lung transplantation, however increased approximately 5-fold following lung transplantation and was associated with increased morbidity., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

High COVID-19 mortality among Black communities heightened the pandemic's devastation. In the state of Louisiana, the racial disparity associated with COVID-19 mortality was significant; Black Americans accounted for 50% of known COVID-19-related deaths while representing only 32% of the state's population. In this paper, we argue that structural racism resulted in a synergistic framework of cumulatively negative determinants of health that ultimately affected COVID-19 deaths in Louisiana Black communities. We identify the spatial distribution of social, environmental, and economic stressors across Louisiana parishes using hot spot analysis to develop aggregate stressors. Further, we examine the correlation between stressors, cumulative health risks, COVID-19 mortality, and the size of Black populations throughout Louisiana. We hypothesized that parishes with larger Black populations (percentages) would have larger stressor values and higher cumulative health risks as well as increased COVID-19 mortality rates. Our results suggest two categories of parishes. The first group has moderate levels of aggregate stress, high population densities, predominately Black populations, and high COVID-19 mortality. The second group of parishes has high aggregate stress, lower population densities, predominantly Black populations, and initially low COVID-19 mortality that increased over time. Our results suggest that structural racism and inequities led to severe disparities in initial COVID-19 effects among highly populated Black Louisiana communities and that as the virus moved into less densely populated Black communities, similar trends emerged.

The increasing proportion of older citizens in our society reflects a need to better understand age-related biological underpinnings of mood, as depression in older age may be under-diagnosed. Pre-clinical and human studies evidence a relationship between oxidative stress (OS) biomarkers in depression symptoms, and an influence of biological factors such as Body Mass Index (BMI), but focus has been clinical or younger samples, and less is known about patterns in healthy older adults. We investigated these associations with data derived from the Australian Research Council Longevity Study (ARCLI; ANZCTR12611000487910), in 568 healthy adults aged 60-75 years using F 2 -Isoprostanes plasma levels, and controlling for demographic factors, in assessing mood via the Beck Depression Inventory-II, Chalder Fatigue Scale, and General Health Questionnaire 12. Elevated F 2 -Isoprostanes contributed to depressed mood on the BDI-II and reduced general health on the GHQ-12. BMI was positively associated with Chalder Fatigue scores, yet better ratings on the GHQ-12. Females had significantly higher F 2 -Isoprostanes than males. The results suggest that in otherwise healthy older adults, mood and mental health are reduced with increases in oxidative stress markers, exhibiting similar patterns observed in clinical groups. Sex as a factor should be considered when assessing OS levels in systemic pathologies. BMI as a modifiable risk factor for maintenance of mental health, and OS modification through nutrient supplementation, are discussed. The findings contribute to understanding oxidative stress marker patterns in healthy older adults and their potential role in mood symptoms and mental health.

Increases in urbanization have led to increased stormwater runoff and mobilization of pollutants from urban watersheds. Discharge of these pollutants often leads to contamination of receiving water bodies. Chemical characterization of urban stormwater is necessary to gain deeper insights into the ecological impacts of urban runoff and to evaluate parameters that influence possible treatment technologies. This study assessed stormwater event mean concentrations and particle size fractions from field studies reported in national/international stormwater quality databases (The National Stormwater Quality and The Best Management Practices databases) and peer-reviewed literature. This characterization of urban stormwater includes statistical evaluation of probability distribution, consideration of dissolved and particulate-bound pollutants and focuses on partitioning and speciation behavior. Solids, nutrients, metals, organic pollutants, and bacterial pathogen indicators were evaluated. A significant fraction of stormwater phosphorus, metals and organic pollutants are particle-bound. Results from the speciation of metals demonstrated that metals are predominantly present as either inner-sphere or electrostatic complexes with dissolved organic matter. This study provides a comprehensive overview of the myriad pollutants found in urban stormwater and provides a starting point for addressing ubiquitous and emerging contaminants. Finally, research needs for further detailed stormwater characterization were identified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background. Nitric oxide (NO) is an important vascular signaling molecule that plays a role in vascular homeostasis. A reduction in NO bioavailability is thought to contribute to endothelial dysfunction, an early risk factor for both cardiovascular disease and type 2 diabetes. Dietary nitrate, through the nitrate-nitrite-NO pathway, may provide an alternate source of NO when the endogenous eNOS system is compromised. In addition to a role in the vascular system, NO may also play a role in the metabolic syndrome including obesity and glucose tolerance. Aim. To investigate the effect of long-term dietary nitrate supplementation on development of the metabolic syndrome in mice fed a high-fat diet. Methods. Following 1 week of acclimatisation, male (6–8 weeks) C57BL6 mice were randomly assigned to the following groups (10/group) for 12 weeks: (i) normal chow + NaCl (1 mmol/kg/day), (ii) normal chow + NaNO3 (1 mmol/kg/day), (iii) high-fat diet + NaCl (1 mmol/kg/day), and (iv) high-fat diet + NaNO3 (1 mmol/kg/day). Body weight and food consumption were monitored weekly. A subset of mice (5/group) underwent running wheel assessment. At the end of the treatment period, all mice underwent fasting glucose tolerance testing. Caecum contents, serum, and tissues (liver, skeletal muscle, white and brown adipose, and kidney) were collected, frozen, and stored at −80°C until analysis. Results. Consumption of the high-fat diet resulted in significantly greater weight gain that was not affected by dietary nitrate. Mice on the high-fat diet also had impaired glucose tolerance that was not affected by dietary nitrate. There was no difference in adipose tissue expression of thermogenic proteins or energy expenditure as assessed by the running wheel activity. Mice on the high-fat diet and those receiving dietary nitrate had reduced caecum concentrations of both butyrate and propionate. Conclusions. Dietary nitrate does not prevent development of the metabolic syndrome in mice fed a high-fat diet. This may be due, in part due, to reductions in the concentration of important short-chain fatty acids. [ABSTRACT FROM AUTHOR]

Background Biomechanical effects of anterior knee pain are difficult to distinguish from effects of other factors also related to knee injury (e.g., joint effusion). The purpose of this study was to evaluate independent effects of anterior knee pain on landing and jumping biomechanics. Methods Thirteen healthy participants performed a land and jump movement task, under three experimental conditions (pre-pain, pain, and post-pain), during one data collection session. One 1-ml injection of hypertonic saline into the infrapatellar fat pad was used to induce experimental anterior knee pain during the pain condition. Participant-perceived anterior knee pain was measured every 2 min throughout data collection. Landing and jumping biomechanics were measured and compared between the experimental conditions using a functional statistical approach. Findings The aforementioned injection increased mean participant-perceived anterior knee pain, from zero during the pre-pain condition to 2.6 ± 0.71 cm during the pain condition. Vertical ground reaction force, knee flexion angle, and internal knee extension moment decreased by approximately 0.100 body weights, 3°, and 0.010 Nm/body weight × body height, respectively, between the pre-pain and pain conditions. Conversely, hip flexion angle and internal hip extension moment increased by approximately 3° and 0.006 Nm/body weight × body height, respectively, between the pre-pain and pain conditions. Several biomechanical changes persisted after anterior knee pain abatement (the post-pain condition). Interpretation Anterior knee pain alters landing and jumping biomechanics, independent of other injury-related factors. These altered biomechanics likely change knee joint loading patterns and might increase risk for chronic knee joint injury and/or pathology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background/study context : F 2 -Isoprostanes are putative markers of oxidative stress, one of the processes associated with biological senescence. Evidence exists for elevated F 2 -Isoprostanes in chronic conditions including psychiatric disorders. Few studies have examined the relationship between oxidative stress and mood in older healthy samples, to establish the influence on mental health. Given current aging demographics in many nations, management of brain and mental health is crucial for longevity, chronic disease management, and quality of life. Method : We investigated the relationship between F 2 -Isoprostanes, a marker for oxidative stress, and anxiety and mood in 262 healthy adults aged 60-75 years, using baseline data from the Australian Research Council Longevity Intervention (ARCLI; ANZCTR12611000487910), a 12-month nutraceutical intervention study. Results : Higher F2 levels significantly predicted increased Depression-dejection and Anger-hostility subscale scores from the Profile of Mood States (POMS). Fatigue-inertia subscale was predicted by increased Body Mass Index. Spielberger State-Trait Inventory (STAI) scores were significantly higher in females. Conclusion : While the primary outcome data did not find a definitive relationship between F2 and total mood or general anxiety levels, the sub-scale data adds weight toward growing literature that biological processes such as oxidative stress are in part related to mood. This is a modifiable risk factor contributing to physical and mental wellbeing that are crucial to healthy aging.

Background Chronic hepatitis C (CHC) is a viral liver disease characterised by oxidative stress and inflammation leading to fibrosis, liver injury, cirrhosis and increased risk of liver cancer and reduced quality of life (QOL). Antioxidant phytonutrients have potential to limit inflammation and reduce co-morbidities associated with CHC. This randomised, placebo-controlled trial investigated the effects of two naturopathic treatments consisting of antioxidant nutrients and herbal medicines against placebo on liver function and QOL in people with CHC. Methods A randomised, double-blind, placebo-controlled clinical trial was conducted in three Australian teaching hospitals in New South Wales. One hundred and eighteen participants with compensated CHC-related disease were recruited through liver outpatient clinics and randomised to one of three groups: silymarin; silymarin with 13 other antioxidants (SOX); or placebo. Study duration was 48 weeks: 24 weeks on active treatment or placebo, and 24 weeks follow-up post treatment. Outcome measures included alanine aminotransferase (ALT), F2-isoprostanes (oxidative stress), HCV RNA (viral load), FibroTest (liver damage), and QOL. Results The use of silymarin with antioxidants (SOX) achieved a higher rate of ALT normalisation (primary outcome) than placebo (P=0.02) or silymarin alone (P=0.003) at week 24. In addition, there was significant improvement in the Hepatitis Quality of Life Questionnaire (HQLQ) Mental Component Summary (MCS) in the SOX group (P=0.002). There were no significant changes in F2-isoprostanes, HCV RNA or FibroTest. Conclusions This study has shown that the use of a complex naturopathic herbal and nutritional treatment can normalise ALT and improve QOL in participants with compensated CHC-related disease. [ABSTRACT FROM AUTHOR]

Accentuated blood pressure (BP) fluctuation and low cerebral blood flow (CBF) response to CO 2 increase the risk of transient ischemic attack (TIA) recurrence and stroke in TIA patients. Improving cardio- and cerebrovascular function may reduce stroke risk. We found dietary nitrate lowered dynamic blood pressure variability (BPV) in rats and improved cerebrovascular CO 2 reactivity in healthy individuals. In 30 TIA patients, we examined the effects of a 7-day supplementation of dietary nitrate (0.1 mmol·kg -1 ·day -1 ) on cerebrovascular function using a randomized, single-blinded, placebo-controlled study design. We hypothesized that 7-day dietary nitrate supplementation would decrease variabilities in BP and CBF and improve CBF-CO 2 slope and cerebral autoregulation (CA). We assessed beat-to-beat middle cerebral artery blood velocity (MCAv; index of CBF) and BP at rest and during CO 2 breathing. Transfer function analysis was performed on beat-to-beat MCAv and BP to determine CA parameters (gain, phase, and coherence). Irrespective of treatment, high- and low-frequency BP-MCAv gain and MCAv-CO 2 slope increased 7 days following TIA onset, while low-frequency BPV decreased ( P < 0.05 vs. baseline). At follow-up, dietary nitrate elevated plasma nitrate concentration by ~547% ( P < 0.001) and moderately lowered BPV ( d  = 0.6, P = 0.011), MCAv variability ( d  = 0.7, P = 0.018), and BP-MCAv coherence ( d  = 0.7, P = 0.008) in the very-low-frequency range (0.02-0.07 Hz), while MCAv-CO 2 slope and arterial stiffness were unaffected ( P > 0.05). Concurrent with standard treatment, dietary nitrate supplementation reduces BP and CBF fluctuation and improves cerebral autoregulation in TIA patients, without affecting cerebrovascular CO 2 reactivity. NEW & NOTEWORTHY We found dietary nitrate supplementation reduced blood pressure and brain blood flow fluctuations and improved the relationship between blood pressure and brain blood flow in transient ischemic attack patients. Meanwhile, dietary nitrate had no effects on the brain blood vessels' response to CO 2 . We attribute the improved brain blood flow stability to the improved myogenic control of blood pressure with dietary nitrate. Our findings indicate that dietary nitrate could be an effective strategy for stabilizing blood pressure and brain blood flow following transient ischemic attack.