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Introduction Maple Syrup Urine Disease (MSUD) is a rare metabolic disorder requiring lifelong restriction of branched-chain amino acids (BCAAs), and targeted supplementation with valine and isoleucine to maintain metabolic stability. Methods A prospective, open-label, observational study was conducted over 56 days in 5 paediatric patients mean age 8.8 years (range 3–14) with classical MSUD. In Phase 1 (Days 0–28), participants received the ready to use (RTU) liquid valine formulation, while continuing their usual powdered isoleucine supplement. In Phase 2 (Days 29–56), participants returned to powdered valine and changed to the ready to use RTU liquid isoleucine supplement. Weekly plasma BCAAs were monitored. Acceptability, gastrointestinal tolerance, adherence, and dietary intake were assessed through questionnaires and food diaries. Results RTU liquid valine and isoleucine supplements were well tolerated and accepted by all participants. Plasma leucine decreased when taking both liquid valine (mean leucine 253 µmol/L) and isoleucine (mean leucine 219 µmol/L) compared to baseline (mean leucine 356 µmol/L). Required doses of valine and isoleucine decreased by 30% and 18%, respectively, suggesting improved adherence or enhanced efficacy. Palatability and ease of use were rated more favourably for the RTU products, with no adverse effects or adherence issues reported. Dietary intake remained stable throughout the study. Discussion These preliminary findings suggest that RTU valine and isoleucine formulations may offer potential advantages in MSUD management, simplifying administration, and enhancing user satisfaction. While limited by sample size and short-term evaluation, their practicality and patient-centered design warrant further investigation in larger, more diverse populations to establish long-term efficacy and broader applicability.

Background Effective management of phenylketonuria (PKU) requires consistent blood phenylalanine (Phe) control. However, patients, particularly those with classical PKU, often experience diurnal fluctuations, particularly with early morning Phe levels after an overnight fast. These fluctuations have been linked to neurocognitive and psychological impairments. This 4-week, randomized, controlled crossover study evaluated the efficacy of a prolonged-release amino acid (PR-AA) compared to a conventional free amino acid-based protein substitute (AA) in reducing early morning blood Phe levels in patients with classical PKU. Methods Participants on a low-Phe diet supplemented with protein substitutes were randomly assigned to one of two treatment arms: Arm A, participants received the PR-AA as a single evening dose for 7 days, followed by a 2-week washout period, then crossed over to receive their usual AA protein substitute for all daily doses for another 7 days. Arm B, the order was reversed. All other daily protein substitute doses remained unchanged, using the patients’ usual Phe-free L-AA protein substitute throughout the study. Blood Phe and tyrosine (Tyr) levels, Phe/Tyr ratio, branched-chain amino acids (BCAAs), urinary nitrogen and creatinine excretion, tolerability, and patient acceptability were assessed. Results From 16 eligible patients, 13 children with classical PKU ( n= 8 females, 62%) with a mean age of 11.8 ± 3.2 years completed the study. Administration of the PR-AA significantly reduced early morning Phe levels compared to AA (mean difference from baseline to the end of treatment with PR-AA: 63.6 ± 28.93 µmol/L; −17.8%; p =  0.0484; with AA: 95.5 ± 28.9 µmol/L; +27.6%; p =  0.0063). Subgroup analyses indicated greater benefit in patients < 12 years and in those with higher baseline Phe level (>360 μmol/L). PR-AA also significantly increased blood Tyr levels, and improved the Phe/Tyr ratio. No significant differences were observed for other parameters. PR-AA was well tolerated, with high adherence. Conclusions PR-AA demonstrated improved metabolic control, particularly in reducing early morning Phe levels. PR-AA may be a useful alternative protein substitute for patients with classical PKU, particularly those with poor metabolic control. Further long-term studies are warranted to assess sustained efficacy, adherence, and neurocognitive outcomes.

Differences in levels of academic achievement according to socio‐economic status (SES), and parental education in particular, have been a persistent feature of Australian education systems. Young people with highly educated parents are more likely than their peers with low‐educated parents to attain high levels of achievement at school. Students with low levels of achievement are less likely than their high achieving peers to complete Year 12 and are more likely to experience negative post‐school outcomes. The SES of the neighbourhood, and in particular, the school attended, has also been found to have an effect on levels of both academic achievement and attainment. For this paper, we conduct analyses of National Assessment Program – Literacy and Numeracy test scores for four cohorts of secondary school students attending government schools in the Australian Capital Territory to examine the associations between parental education, school attended and levels of educational achievement. Our findings show that students with university‐educated parents achieve at much higher levels than their peers with low‐educated parents and that attending a school with a higher proportion of students from educationally disadvantaged families has a negative effect on educational achievement.

Background In phenylketonuria (PKU), attending multidisciplinary clinic reviews is an important aspect of life-long care. Since the COVID-19 pandemic, video and telephone clinics are used as alternative methods for people with PKU to have contact with their care team. There is limited research concerning patient preference, experience and perceptions of alternative types of clinic review. Individuals from the UK with PKU and their caregivers were invited to complete an online questionnaire, hosted on the National Society for PKU (NSPKU) website and social media platform. Results Data was available from 203 respondents. Forty one per cent of respondents ( n  = 49/119) preferred in-person clinics; 41% ( n  = 49) a hybrid of in-person, video and telephone clinics; 9% ( n  = 11) video clinics only, 6% ( n  = 7) telephone only and 3% ( n =  3) were unsure. The main respondent obstacles to in-person clinics were costs, travel and time, but this was balanced by the benefits of a physical examination and better patient engagement/motivation. Twenty one per cent ( n  = 36/169) of respondents were uncomfortable with the number of healthcare professionals (HCPs) in a clinic room. Patients were less likely to consult with a doctor on video (64%, n  = 91/143) or phone (50%, n =  59/119) reviews compared to in-person (80%, n  = 146/183). Issues with video and telephone reviews included the shorter time length of review, distractions, technical issues and poor patient engagement. Conclusions Online video and telephone clinic platforms were effective in overcoming the challenging circumstances in management, monitoring and treatment of patients with PKU during the COVID-19 pandemic. However, in-person clinics remain the preferred respondent option. It is important that HCPs are flexible, enabling people with PKU a choice of clinic options according to their individual clinical need and circumstances.

Background Phenylalanine-free infant formula is an essential source of safe protein in a phenylalanine restricted diet, but its efficacy is rarely studied. We report a multicentre, open, longitudinal, prospective intervention study on a phenylalanine-free infant formula (PKU Start: Vitaflo International Ltd.). Results This was a 2-part study: part I (28 days short term evaluation) and part II (12 months extension). Data was collected on infant blood phenylalanine concentrations, dietary intake, growth, and gastrointestinal tolerance. Ten infants ( n  = 8 males, 80%), with a median age of 14 weeks (range 4–36 weeks) were recruited from 3 treatment centres in the UK. Nine of ten infants completed the 28-day follow-up (one caregiver preferred the usual phenylalanine-free formula and discontinued the study formula after day 14) and 7/9 participated in study part II. The phenylalanine-free infant formula contributed a median of 57% (IQR 50–62%) energy and 53% (IQR 33–66%) of total protein intake from baseline to the end of the part II extension study. During the 12-month follow-up, infants maintained normal growth and satisfactory blood phenylalanine control. Any early gastrointestinal symptoms (constipation, colic, vomiting and poor feeding) improved with time. Conclusion The study formula was well tolerated, helped maintain good metabolic control, and normal growth in infants with PKU. The long-term efficacy of phenylalanine-free infant formula should continue to be observed and monitored.

Background In children with phenylketonuria (PKU), transitioning protein substitutes at the appropriate developmental age is essential to help with their long-term acceptance and ease of administration. We assessed the parental experiences in transitioning from a second stage to third stage liquid or powdered protein substitute in patients with PKU. Results Sixteen interviews (23 open-ended questions) were carried out with parents/caregivers of children with PKU (8 females, 50%) with a median age of 8 years (range 5–11 years), continuously treated with diet, and on a third stage protein substitute. Parents/caregivers identified common facilitators and barriers during the third stage protein substitute transition process. The main facilitators were: child and parent motivation, parent knowledge of the transition process, a role model with PKU, low volume and easy preparation of the third stage protein substitute (liquid/powder), anticipation of increasing child independence, lower parent workload, attractive packaging, better taste and smell, school and teacher support, dietetic plans and guidance, PKU social events, child educational materials and written resources. The main barriers were child aversion to new protein substitutes, poor child behaviour, child aged > 5 years, parental fear of change, the necessity for  parental time and persistence, loss of parental control, high product volume, different taste, smell, and texture of new protein substitutes, and peer bullying. Conclusion A stepwise, supportive approach is necessary when transitioning from second to third stage protein substitutes in PKU. Future studies are needed to develop guidance to assist parents/caregivers, health professionals, and teachers during the transition process.

Protein is the most satiating macronutrient, increasing secretion of gastrointestinal hormones and diet induced thermogenesis. In phenylketonuria (PKU), natural protein is restricted with approximately 80% of intake supplied by a synthetic protein source, which may alter satiety response. Casein glycomacropeptide (CGMP-AA), a carbohydrate containing peptide and alternative protein substitute to amino acids (AA), may enhance satiety mediated by its bioactive properties. Aim: In a three-year longitudinal; prospective study, the effect of AA and two different amounts of CGMP-AA (CGMP-AA only (CGMP100) and a combination of CGMP-AA and AA (CGMP50) on satiety, weight and body mass index (BMI) were compared. Methods: 48 children with PKU completed the study. Median ages of children were: CGMP100; (n = 13), 9.2 years; CGMP50; (n = 16), 7.3 years; and AA (n = 19), 11.1 years. Semi-quantitative dietary assessments and anthropometry (weight, height and BMI) were measured every three months. Results: The macronutrient contribution to total energy intake from protein, carbohydrate and fat was similar across the groups. Adjusting for age and gender, no differences in energy intake, weight, BMI, incidence of overweight or obesity was apparent between the groups. Conclusion: In this three-year longitudinal study, there was no indication to support a relationship between CGMP and satiety, as evidenced by decreased energy intake, thereby preventing overweight or obesity. Satiety is a complex multi-system process that is not fully understood.

In June 2020 the Minister for Education, Dan Tehan announced the Job-ready Graduate Package which aimed to provide the price signals the Coalition Government believes are necessary to generate the skills required in the Australian labour market in the post-COVID-19 world. This paper uses existing evidence to argue that the proposed Job-ready Graduate Package is likely to miss its mark, crucially with respect to having a medium-term impact on student choice. The paper draws on evidence of employment patterns of new graduates and established graduates in the Australian labour market to assess the economic argument that certain degree disciplines are more 'job ready' than others; the rationale behind 'picking winners' and the economic case for the proposed funding structure. The evidence from previous changes in the HECS/HELP rates, which were not as large as the proposed ones, suggests that they are unlikely to have a significant effect on student choices. This is not surprising given the wide range of factors that influence choice of discipline including student preferences, educational background, the employment and income of existing graduates, socio-economic background, career guidance and school experience, occupational expectations, psychological attributes and university entrance scores. The idea of 'picking winners' among disciplines for study to generate 'job-ready' graduates faces many difficulties in the uncertain post-COVID-19 world against a background of long-term changes in the economic structure of the economy. Working lives can last for over 40 years and people can move between occupations, adapting skills and retraining over time. Individuals are best placed to make these choices for themselves rather than relying on government direction. [Author abstract]

The nucleoid-associated protein FIS is a global regulator of gene expression and chromosome structure in Escherichia coli and Salmonella enterica. Despite the importance of FIS for infection and intracellular invasion, very little is known about the regulation of S. enterica fis expression. Under standard laboratory growth conditions, fis is highly expressed during rapid growth but is then silenced as growth slows. However, if cells are cultured in non-aerated conditions, fis expression is sustained during stationary phase. This led us to test whether the redox-sensing transcription factors ArcA and FNR regulate S. enterica fis. Deletion of FNR had no detectable effect, whereas deletion of ArcA had the unexpected effect of further elevating fis expression in stationary phase. ArcA required RpoS for induction of fis expression, suggesting that ArcA indirectly affects fis expression. Other putative regulators were found to play diverse roles: FIS acted directly as an auto-repressor (as expected), whereas CRP had little direct effect on fis expression. Deleting regions of the fis promoter led to the discovery of a novel anaerobically-induced transcription start site (Pfis-2) upstream of the primary transcription start site (Pfis-1). Promoter truncation also revealed that the shortest functional fis promoter was incapable of sustained expression. Moreover, fis expression was observed to correlate directly with DNA supercoiling in non-aerated conditions. Thus, the full-length S. enterica fis promoter region may act as a topological switch that is sensitive to stress-induced duplex destabilisation and up-regulates expression in non-aerated conditions.