Lessons learned from 5 years of pegvaliase in US clinics: A case series.

Objective: To provide insights and strategies for pegvaliase management in challenging cases with phenylketonuria (PKU) based on the first 5 years of experience with pegvaliase in real-world clinical practice.

Methods: Twelve PKU experts gathered during a one-day, in-person meeting to discuss clinical cases illustrating important lessons from their experiences treating patients with pegvaliase in real-world clinical practice. Challenges with pegvaliase experienced prior to and during treatment and corresponding strategies to overcome them were discussed.

Bioavailability of mango (poly)phenols: An evaluation of the impact of the colon, and phenylalanine and tyrosine on the production of phenolic catabolites.

A mango pulp purée was ingested by ileostomists, whose colon had been removed surgically, and subjects with a full gastrointestinal (GI) tract, after which ileal fluid, urine and feces were collected over a 24 h period and analysed by UHPLC-HR-MS. The main (poly)phenols in the purée were gallotannins (356 μmol) and two hydroxy-methoxy-cinnamoyl glucose esters (43 μmol) together with the aromatic amino acids phenylalanine (22 μmol) and tyrosine (209 μmol). Analysis of ileal fluid revealed almost all the ingested gallotannins appeared to have broken down in the upper GI tract with the released benzoic acids being rapidly absorbed into the circulatory system prior to urinary excretion mainly as phase-2 metabolites.

Eating disorders and COVID-19 - different or just more?

Background: COVID-19 saw an increase in child mental health presentations internationally. Clinicians analogised the exponential increase in anorexia nervosa to a 'tsunami' or 'outbreak', raising parallel concerns regarding medical and psychological risks (Marsh in The Guardian, 2021; Leask in NZ Herald, 2021; Monteleone et al. in Eat Weight Disord 26(8):2443-2452, 2021) .

Exploring and disentangling the production of potentially bioactive phenolic catabolites from dietary (poly)phenols, phenylalanine, tyrosine and catecholamines.

Following ingestion of fruits, vegetables and derived products, (poly)phenols that are not absorbed in the upper gastrointestinal tract pass to the colon, where they undergo microbiota-mediated ring fission resulting in the production of a diversity of low molecular weight phenolic catabolites, which appear in the circulatory system and are excreted in urine along with their phase II metabolites. There is increasing interest in these catabolites because of their potential bioactivity and their use as biomarkers of (poly)phenol intake. Investigating the fate of dietary (poly)phenolics in the colon has become confounded as a result of the recent realisation that many of the phenolics appearing in biofluids can also be derived from the aromatic amino acids, l-phenylalanine and l-tyrosine, and to a lesser extent catecholamines, in reactions that can be catalysed by both colonic microbiota and endogenous mammalian enzymes.

Development of Novel Membrane Disrupting Lipoguanidine Compounds Sensitizing Gram-Negative Bacteria to Antibiotics.

A new class of amphiphilic molecules, the lipoguanidines, designed as hybrids of guanidine and fatty acid compounds, has been synthesized and developed. The new molecules present both a guanidine polar head and a lipophilic tail that allow them to disrupt bacterial membranes and to sensitize Gram-negative bacteria to the action of the narrow-spectrum antibiotics rifampicin and novobiocin. The lipoguanidine sensitizes , , , and to rifampicin, thereby reducing the antibiotic minimum inhibitory concentrations (MIC) up to 256-fold.

A critical examination of human data for the biological activity of quercetin and its phase-2 conjugates.

This critical review examines evidence for beneficial effects of quercetin phase-2 conjugates from clinical intervention studies, volunteer feeding trials, and in vitro work. Plasma concentrations of quercetin-3--glucuronide (Q3G) and 3'-methylquercetin-3-glucuronide (3'MQ3G) after supplementation may produce beneficial effects in macrophages and endothelial cells, respectively, especially if endogenous deglucuronidation occurs, and lower blood uric acid concentration via quercetin-3'--sulfate (Q3'S). Unsupplemented diets produce much lower concentrations (<50 nmol/l) rarely investigated in vitro.

Potential impacts of proposed lithium extraction on biodiversity and conservation in the contiguous United States.

To address climate change, the United States is offering consumers incentives to purchase electric vehicles containing domestically derived lithium batteries. New extraction facilities required to supply this lithium may have environmental impacts, including impacts on biodiversity. To reveal potential impacts, we mapped 72 proposed lithium extraction sites across the contiguous United States and overlaid these with data for species occurrences, conservation value, habitat, and land management designations.

Exploring the preparedness of newly qualified general practitioners for independent practice in Ireland.

Background: Newly qualified general practitioners' (NQGPs) experiences of transition to independent practice are varied. Most Irish GP graduates see themselves as either assistant GPs, salaried GPs or locum GPs one year post-qualification, yet anticipate partnership ten years post-qualification. Research into GP trainees' transition to independent practice is scarce, yet perceived lack of preparedness can be associated with emotional exhaustion and burnout.

Assessment of human inter-individual variability of phloretin metabolites in urine after apple consumption. AppleCOR study.

: This study aimed to assess the inter-individual variation in phloretin absorption and metabolism and to seek possible phloretin metabotypes following apple snack consumption. : The excreted phloretin metabolites in 24 h urine samples were determined by UPLC-MS/MS in 62 volunteers after acute and sustained (6 weeks) interventions in a randomized and parallel study with a daily supplementation of 80 g of a low-phloretin (39.5 μmol) or a high-phloretin (103 μmol) freeze-dried apple snacks.

Machine learning augmentation reduces prediction error in collective forecasting: development and validation across prediction markets with application to COVID events.

Background: The recent COVID-19 pandemic highlighted the challenges for traditional forecasting. Prediction markets are a promising way to generate collective forecasts and could potentially be enhanced if high-quality crowdsourced inputs were identified and preferentially weighted for likely accuracy in real-time with machine learning.

Methods: We aim to leverage human prediction markets with real-time machine weighting of likely higher accuracy trades to improve performance.

Patient Experience of Lichen Planus: A Qualitative Exploration of Signs, Symptoms, and Health-Related Quality of Life Impacts.

Introduction: Lichen planus (LP) is an inflammatory skin disorder that can present in various forms across the body, including lesions on the skin (cutaneous LP [CLP]), scalp (lichen planopilaris [LPP]), and mucosal regions (mucosal LP [MLP]). Qualitative exploration of the patient experience of LP, notably symptoms and impacts on health-related quality of life (HRQoL), is limited. A scarcity of research was also identified relating to emotional wellbeing impacts of CLP patients.

A Systematic Review and Comprehensive Evaluation of Human Intervention Studies to Unravel the Bioavailability of Hydroxycinnamic Acids.

Hydroxycinnamic acids (HCAs) are the main phenolic acids in the western diet. Harmonizing the available information on the absorption, distribution, metabolism, and excretion (ADME) of HCAs is fundamental to unraveling the compounds responsible for their health effects. This work systematically assessed pharmacokinetics, including urinary recovery, and bioavailability of HCAs and their metabolites, based on literature reports.

Excretion by subjects on a low (poly)phenol diet of phenolic gut microbiota catabolites sequestered in tissues or associated with catecholamines and surplus amino acids.

Phenolic catabolites excreted by fasting subjects with a functioning colon and ileostomists on a low (poly)phenol diet have been investigated. Urine was collected over a 12 h fasting period after adherence to a low (poly)phenol diet for 36 h. UHPLC-HR-MS quantified 77 phenolics.

Improved cookstoves to reduce household air pollution exposure in sub-Saharan Africa: A scoping review of intervention studies.

Household air pollution (HAP), primarily from biomass fuels used for cooking, is associated with adverse health outcomes and premature mortality. It affects almost half of the world's population, especially in low-income and low-resourced communities. However, many of the 'improved' biomass cookstoves (ICS) aimed at reducing HAP lack empirical evidence of pollutant reduction and reliability in the field.

HSE National Clinical Programme for Eating Disorders in Ireland: COVID-19 pandemic and eating disorder care in a new national eating disorder service.

Background: The COVID-19 pandemic experience was different in each country (e.g., prevalence, societal restrictions).

Qualitative concept elicitation and cognitive debriefing interviews of symptoms, impacts and selected customized PROMIS Short Forms: a study in patients with axial spondyloarthritis.

Background: Sleep disturbance, pain, and fatigue are key symptoms/impacts of axial spondyloarthritis (axSpA). Three customized Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms (Sleep Disturbance, Pain Interference, and Fatigue) have been proposed for use in axSpA to assess these key disease concepts. This study was designed to further understand the patient experience of axSpA and evaluate the content validity of the three customized PROMIS Short Forms to support their use in axSpA clinical trials.

Synergy between Winter Flounder antimicrobial peptides.

Some antimicrobial peptides (AMPs) have potent bactericidal activity and are being considered as potential alternatives to classical antibiotics. In response to an infection, such AMPs are often produced in animals alongside other peptides with low or no perceivable antimicrobial activity, whose role is unclear. Here we show that six AMPs from the Winter Flounder (WF) act in synergy against a range of bacterial pathogens and provide mechanistic insights into how this increases the cooperativity of the dose-dependent bactericidal activity and potency that enable therapy.

Insights into the Spectrum of Activity and Mechanism of Action of MGB-BP-3.

MGB-BP-3 is a potential first-in-class antibiotic, a Strathclyde Minor Groove Binder (S-MGB), that has successfully completed Phase IIa clinical trials for the treatment of associated disease. Its precise mechanism of action and the origin of limited activity against Gram-negative pathogens are relatively unknown. Herein, treatment with MGB-BP-3 alone significantly inhibited the bacterial growth of the Gram-positive, but not Gram-negative, bacteria as expected.

Metabolism of phenolics in coffee and plant-based foods by canonical pathways: an assessment of the role of fatty acid β-oxidation to generate biologically-active and -inactive intermediates.

ω-Phenyl-alkenoic acids are abundant in coffee, fruits, and vegetables. Along with ω-phenyl-alkanoic acids, they are produced from numerous dietary (poly)phenols and aromatic amino acids in vivo. This review addresses how phenyl-ring substitution and flux modulates their gut microbiota and endogenous β-oxidation.

Human colonic catabolism of dietary flavan-3-ol bioactives.

Understanding the fate of ingested polyphenols is crucial in elucidating the molecular mechanisms underlying the beneficial effects of a fruit and vegetable-based diet. This review focuses on the colon microbiota-mediated transformation of the flavan-3-ols and the structurally related procyanidins found in dietary plant foods and beverages, plus the flavan-3-ol-derived theaflavins of black tea, and the post-absorption phase II metabolism of the gut microbiota catabolites. Despite significant advances in the last decade major analytical challenges remain.

Bactericidal Effect of Ultrasound-Responsive Microbubbles and Sub-inhibitory Gentamicin against Pseudomonas aeruginosa Biofilms on Substrates With Differing Acoustic Impedance.

The aim of this research was to explore the interaction between ultrasound-activated microbubbles (MBs) and Pseudomonas aeruginosa biofilms, specifically the effects of MB concentration, ultrasound exposure and substrate properties on bactericidal efficacy. Biofilms were grown using a Centre for Disease Control (CDC) bioreactor on polypropylene or stainless-steel coupons as acoustic analogues for soft and hard tissue, respectively. Biofilms were treated with different concentrations of phospholipid-shelled MBs (10-10 MB/mL), a sub-inhibitory concentration of gentamicin (4 µg/mL) and 1-MHz ultrasound with a continuous or pulsed (100-kHz pulse repetition frequency, 25% duty cycle, 0.

National Clinical Programme for Eating Disorders: a pragmatic review of a new national eating disorder service in Ireland.

Objective: The Health Service Executive National Clinical Programme for Eating Disorders (NCPED) launched a Model of Care for Eating Disorder Services in Ireland in 2018. Currently, one adult and two child and adolescent eating disorder services are operational out of a total of sixteen recommended. The three objectives of this paper are to describe the early (1) referral pattern, (2) level of service activity and (3) the level of service user satisfaction.