Low-Protein Diets Composed of Protein Recovered from Food Processing Supported Growth, but Induced Mild Hepatic Steatosis Compared with a No-Protein Diet in Young Female Rats.

BACKGROUND: Living in low-income countries often restricts the consumption of adequate protein and animal protein. OBJECTIVES: This study aimed to investigate the effects of feeding low-protein diets on growth and liver health using proteins recovered from animal processing. METHODS: Female Sprague-Dawley rats (aged 28 d) were randomly assigned (n = 8 rats/group) to be fed standard purified diets with 0% or 10% kcal protein that was comprised of either carp, whey, or casein. RESULTS: Rats that were fed low-protein diets showed higher growth but developed mild hepatic steatosis compared to rats that were fed a no-protein diet, regardless of the protein source. Real-time quantitative polymerase chain reactions targeting the expression of genes involved in liver lipid homeostasis were not significantly different among groups. Global RNA-sequencing technology identified 9 differentially expressed genes linked to folate-mediated 1-carbon metabolism, endoplasmic reticulum (ER) stress, and metabolic diseases. Canonical pathway analysis revealed that mechanisms differed depending on the protein source. ER stress and dysregulated energy metabolism were implicated in hepatic steatosis in carp- and whey-fed rats. In contrast, impaired liver one-carbon methylations, lipoprotein assembly, and lipid export were implicated in casein-fed rats. CONCLUSIONS: Carp sarcoplasmic protein showed comparable results to commercially available casein and whey protein. A better understanding of the molecular mechanisms in hepatic steatosis development can assist formulation of proteins recovered from food processing into a sustainable source of high-quality protein.

RNA-sequencing revealed apple pomace ameliorates expression of genes in the hypothalamus associated with neurodegeneration in female rats fed a Western diet during adolescence to adulthood.

OBJECTIVES: Apple pomace, a waste byproduct of apple processing, is rich in nutrients (e.g. polyphenols and soluble fiber) with the potential to be neuroprotective. The aim of this study was to employ RNA-sequencing (RNASeq) technology to investigate diet-gene interactions in the hypothalamus of rats after feeding a Western diet calorically substituted with apple pomace. METHODS: Adolescent (age 21-29 days) female Sprague-Dawley rats were randomly assigned (n = 8 rats/group) to consume either a purified standard diet, Western (WE) diet, or Western diet calorically substituted with 10% apple pomace (WE/AP) for 8 weeks. RNA-seq was performed (n = 5 rats/group) to determine global differentially expressed genes in the hypothalamus. RESULTS: RNA-seq results comparing rats fed WE to WE/AP revealed 15 differentially expressed genes in the hypothalamus. Caloric substitution of WE diet with 10% apple pomace downregulated (q < 0.06) five genes implicated in brain aging and neurodegenerative disorders: synuclein alpha, phospholipase D family member 5, NADH dehydrogenase Fe-S protein 6, choline O-acetyltransferase, and frizzled class receptor 6. DISCUSSION: Altered gene expression of these five genes suggests that apple pomace ameliorated synthesis of the neurotransmitter, acetylcholine, in rats fed a WE diet. Apple pomace, a rich source of antioxidant polyphenols and soluble fiber, has been shown to reverse nonalcoholic fatty liver disease (NAFLD). Diet-induced NAFLD decreases hepatic de novo synthesis of choline, a precursor to acetylcholine. Based on preclinical evidence, apple pomace has the potential to be a sustainable functional food for maintaining brain function and for reducing the risk of neurodegeneration.

Thymopoiesis following HSCT; a retrospective review comparing interventions for aGVHD in a pediatric cohort.

Acute graft-versus-host disease (aGVHD) complicates allogeneic hematopoietic stem cell transplantation (HSCT), and is treated with topical and/or systemic corticosteroids. Systemic corticosteroids and aGVHD damage thymic tissue. We compared thymopoietic effect of topical steroid therapy, corticosteroids and extracorporeal photopheresis (ECP) in 102 pediatric allogeneic HSCT patients. We categorized patients into 4 groups: - no aGVHD, aGVHD treated with topical or systemic steroid, or ECP. Naïve CD4+CD45RA+CD27+ T-lymphocyte values at 3, 6, 9, 12months post-HSCT were recorded: for ECP patients, values were recorded at 3, 6, 9, 12months during ECP. Differences were compared using the Kruskal-Wallis test. 41 patients had no aGVHD, 23 had aGVHD treated topically or systemically (25), 13 received ECP. Rate of thymopoiesis was significantly different between all groups at all time-points post-transplant (p=0.002, p<0.001, p<0.001, p=0.001 respectively). Even mild aGVHD impairs thymopoiesis. Worst recovery was in ECP patients. Earlier institution of ECP may speed thymic recovery.

Implications of Observed and Simulated Soil Carbon Sequestration for Management Options in Corn-based Rotations.

Managing cropping systems to sequester soil organic C (SOC) improves soil health and resilience to changing climate. Perennial crops, no-till planting, manure, and cover crops can add SOC; however, their impacts have not been well documented in the northeastern United States. Our objectives were (i) to monitor SOC from a bioenergy cropping study in Pennsylvania that included a corn ( L.)-soybean [ (L.) Merr.]-alfalfa ( L.) rotation, switchgrass ( L.), and reed canarygrass ( L.); (ii) to use the CQESTR model to predict SOC sequestration in the bioenergy crops (with and without projected climate change); and (iii) to use CQESTR to simulate influence of tillage, manure, cover cropping, and corn stover removal in typical dairy forage (silage corn-alfalfa) or grain corn-soybean rotations. Over 8 yr, measured SOC increased 0.4, 1.1, and 0.8 Mg C ha yr in the bioenergy rotation, reed canarygrass, and switchgrass, respectively. Simulated and measured data were significantly correlated ( < 0.001) at all depths. Predicted sequestration (8-14 Mg C ha over 40 yr) in dairy forage rotations was much larger than with corn-soybean rotations (-4.0-0.6 Mg C ha over 40 yr), due to multiple years of perennial alfalfa. No-till increased sequestration in the simulated dairy forage rotation and prevented a net loss of C in corn-soybean rotations. Simulations indicated limited impact of cover crops and manure on long-term SOC sequestration. The low solids content of liquid dairy manure is the likely reason for the less-than-expected impact of manure. Overall, simulations suggest that inclusion of alfalfa provides the greatest potential for SOC sequestration with a typical Pennsylvania crop rotation.

Differential effects of altered patterns of movement and strain on joint cell behaviour and skeletal morphogenesis.

OBJECTIVE: There is increasing evidence that joint shape is a potent predictor of osteoarthritis (OA) risk; yet the cellular events underpinning joint morphogenesis remain unclear. We sought to develop a genetically tractable animal model to study the events controlling joint morphogenesis. DESIGN: Zebrafish larvae were subjected to periods of flaccid paralysis, rigid paralysis or hyperactivity. Immunohistochemistry and transgenic reporters were used to monitor changes to muscle and cartilage. Finite Element Models were generated to investigate the mechanical conditions of rigid paralysis. Principal component analysis was used to test variations in skeletal morphology and metrics for shape, orientation and size were applied to describe cell behaviour. RESULTS: We show that flaccid and rigid paralysis and hypermobility affect cartilage element and joint shape. We describe differences between flaccid and rigid paralysis in regions showing high principal strain upon muscle contraction. We identify that altered shape and high strain occur in regions of cell differentiation and we show statistically significant changes to cell maturity occur in these regions in paralysed and hypermobile zebrafish. CONCLUSION: While flaccid and rigid paralysis and hypermobility affect skeletal morphogenesis they do so in subtly different ways. We show that some cartilage regions are unaffected in conditions such as rigid paralysis where static force is applied, whereas joint morphogenesis is perturbed by both flaccid and rigid paralysis; suggesting that joints require dynamic movement for accurate morphogenesis. A better understanding of how biomechanics impacts skeletal cell behaviour will improve our understanding of how foetal mechanics shape the developing joint.

The long-term psychosocial impact of cancer: the views of young adult survivors of childhood cancer.

It is rare for studies to approach psychosocial outcomes of childhood cancer in a holistic and explanatory way. Doing so would enable a greater understanding of why and in what way a young person's life may be affected by cancer. This qualitative study aimed to explore the views of childhood cancer survivors (CCS) regarding how they perceive their illness to have influenced them and their subsequent lives. Twelve CCS with a median age of 23 years old took part in either a focus group or a telephone interview. Data were analysed using thematic analysis. The main themes were altered life perspectives, perceptions of self and lasting effects on relationships. Through these themes, the survivors gave insight into how their experience had influenced their views and how this had impacted on different areas of their lives. Although positive aspects were discussed, enduring issues were reported by some. Findings suggest that despite high levels of achievement, some survivors may still benefit from further information and support especially in relation to relationships and fertility. This study will inform the development of a questionnaire aiming to collect important information on the many factors which may influence long-term psychosocial outcomes in CCS.

Diet switch pre-vaccination improves immune response and metabolic status in formerly obese mice.

Metabolic disease is epidemiologically linked to severe complications upon influenza virus infection, thus vaccination is a priority in this high-risk population. Yet, vaccine responses are less effective in these same hosts. Here we examined how the timing of diet switching from a high-fat diet to a control diet affected influenza vaccine efficacy in diet-induced obese mice. Our results demonstrate that the systemic meta-inflammation generated by high-fat diet exposure limited T cell maturation to the memory compartment at the time of vaccination, impacting the recall of effector memory T cells upon viral challenge. This was not improved with a diet switch post-vaccination. However, the metabolic dysfunction of T cells was reversed if weight loss occurred 4 weeks before vaccination, restoring a functional recall response. This corresponded with changes in the systemic obesity-related biomarkers leptin and adiponectin, highlighting the systemic and specific effects of diet on influenza vaccine immunogenicity.

New tools for studying osteoarthritis genetics in zebrafish.

OBJECTIVE: Increasing evidence points to a strong genetic component to osteoarthritis (OA) and that certain changes that occur in osteoarthritic cartilage recapitulate the developmental process of endochondral ossification. As zebrafish are a well validated model for genetic studies and developmental biology, our objective was to establish the spatiotemporal expression pattern of a number of OA susceptibility genes in the larval zebrafish providing a platform for functional studies into the role of these genes in OA. DESIGN: We identified the zebrafish homologues for Mcf2l, Gdf5, PthrP/Pthlh, Col9a2, and Col10a1 from the Ensembl genome browser. Labelled probes were generated for these genes and in situ hybridisations were performed on wild type zebrafish larvae. In addition, we generated transgenic reporter lines by modification of bacterial artificial chromosomes (BACs) containing full length promoters for col2a1 and col10a1. RESULTS: For the first time, we show the spatiotemporal expression pattern of Mcf2l. Furthermore, we show that all six putative OA genes are dynamically expressed during zebrafish larval development, and that all are expressed in the developing skeletal system. Furthermore, we demonstrate that the transgenic reporters we have generated for col2a1 and col10a1 can be used to visualise chondrocyte hypertrophy in vivo. CONCLUSION: In this study we describe the expression pattern of six OA susceptibility genes in zebrafish larvae and the generation of two new transgenic lines marking chondrocytes at different stages of maturation. Moreover, the tools used demonstrate the utility of the zebrafish model for functional studies on genes identified as playing a role in OA.

Developing a national 'low risk' febrile neutropenia framework for use in children and young people's cancer care.

PURPOSE: A Delphi study was undertaken to develop a framework guidance that would rationalise and standardise the care of children with febrile neutropenia (FNP) across the UK. METHODS: A mailed Delphi survey was undertaken with health professionals working in children's cancer units. The survey employed two rounds of feedback on 22 practice statements drawn from a systematic review of clinical evidence. Consensus was assumed for any statement where 80+ % of respondents indicated that they "agreed" or "strongly agreed". RESULTS: Consensus was reached on 21 of the 22 practice statements in round 1 that were categorised into six areas: definition of fever and neutropenia, initial management and choice of antibiotic, defining low-risk patients, strategy in low-risk patients and alternative approaches. Consensus could not be reached on whether patients needed to be afebrile to be suitable for discharge and the required length of outpatient antibiotic treatment. CONCLUSIONS: A Delphi survey allowed the successful development of a national framework for identification and management of children with FNP. The use of an existing well-functioning professional network was key in this project's success.

Investigating the origins of nanostructural variations in differential ethnic hair types using X-ray scattering techniques.

OBJECTIVE: Human hair is a major determinant of visual ethnic differentiation. Although hair types are celebrated as part of our ethnic diversity, the approach to hair care has made the assumption that hair types are structurally and chemically similar. Although this is clearly not the case at the macroscopic level, the intervention of many hair treatments is at the nanoscopic and molecular levels. The purpose of the work presented here is to identify the main nanoscopic and molecular hierarchical differences across five different ethnic hair types from hair fibres taken exclusively from the scalp. These are Afro (subdivided into elastic 'rubber' and softer non-elastic 'soft'), Chinese, European and Mullato (mixed race). METHODS: Small angle X-Ray scattering (SAXS) is a technique capable of resolving nanostructural variations in complex materials. Individual hair fibres from different ethnic hair types were used to investigate structural features found in common and also specific to each type. Simultaneous wide angle X-Ray scattering (WAXS) was used to analyse the submolecular level structure of the fibrous keratin present. The data sets from both techniques were analysed with principal component analysis (PCA) to identify underlying variables. RESULTS: Principal component analysis of both SAXS and WAXS data was shown to discriminate the scattering signal between different hair types. The X-ray scattering results show a common underlying keratin intermediate filament (KIF) structure. However, distinct differences were observed in the preferential orientation and intensity signal from the lipid component of the hair. In addition, differences were observed in the intensity distribution of the very low-angle sample-dependent diffuse scatter surrounding the 'beamstop.' CONCLUSION: The results indicate that the fibrous keratin scaffold remains consistent between ethnic hair types. The hierarchies made by these may be modulated by variation in the content of keratin-associated proteins (KAPs) and lipids that alter the interfacial structures and lead to macroscopic differences in hair morphology.

Opportunities and challenges of tackling Scope 3 "Indirect" emissions from residential hot water.

The water sector could play a major role towards a Net Zero greenhouse gas (GHG) future if Scope 3 emissions were embraced and operationalised. Significant opportunities and challenges exist in tackling Scope 3 emissions including those associated with customer hot water use. Present GHG emission reduction practices predominantly focus on Scope 1 "within utility" and Scope 2 "purchased energy" emissions. In the urban water cycle, Scope 3 "indirect" emissions dominate, and water use is only one example of Scope 3 emissions. Over 90% of all water cycle GHG emissions can be attributed to water use in residential, industrial and commercial premises, collectively some 7% of global GHG emissions. One possibility is for water utilities to actively support efficient hot water use such as new ultra-low flow shower heads. Scope 3 opportunities also offer a range of cost-effective emissions-reduction opportunities, particularly when the wider perspective of "community value" is considered and not just a "business financial perspective". Hot water efficiency is additionally essential to Net Zero carbon futures, even with decarbonised grids, because most major Net Zero roadmaps require energy efficiency gains. Scientific and management advance needed includes: accounting methodologies, clear roles, collaboration, new business models, and clear definitions. The water sector has the opportunity to play a significant role in achieving Net Zero cities. The decision how much is yet to be made.

Joint consensus statement on the vaccination of adult and paediatric haematopoietic stem cell transplant recipients: Prepared on behalf of the British society of blood and marrow transplantation and cellular therapy (BSBMTCT), the Children's cancer and Leukaemia Group (CCLG), and British Infection Association (BIA).

Haematopoietic stem cell transplant (HSCT) recipients have deficiencies in their adaptive immunity against vaccine preventable diseases. National and International guidance recommends that HSCT recipients are considered 'never vaccinated' and offered a comprehensive course of revaccination. This position statement aims to draw upon the current evidence base and existing guidelines, and align this with national vaccine availability and licensing considerations in order to recommend a pragmatic and standardised re-vaccination schedule for adult and paediatric HSCT recipients in the UK.

The interplay of Western diet and binge drinking on the onset, progression, and outlook of liver disease.

Non-alcoholic fatty liver disease and alcoholic liver disease, the two most prevalent liver diseases worldwide, share a common pathology but have largely been considered disparate diseases. Liver diseases are widely underestimated, but their prevalence is increasing worldwide. The Western diet (high-fat, high-sugar) and binge drinking (rapid consumption of alcohol in a short period of time) are two highly prevalent features of standard life in the United States, and both are linked to the development and progression of liver disease. Yet, few studies have been conducted to elucidate their potential interactions. Data shows binge drinking is on the rise in several age groups, and poor dietary trends continue to be prevalent. This review serves to summarize the sparse findings on the hepatic consequences of the combination of binge drinking and consuming a Western diet, while also drawing conclusions on potential future impacts. The data suggest the potential for a looming liver disease epidemic, indicating that more research on its progression as well as its prevention is needed on this critical topic.

The chance of transition: strategies for multidisciplinary collaboration.

Many long-term childhood cancer survivors suffer from treatment-related late effects, which may occur in any organ and include a wide spectrum of conditions. Long-term follow-up (LTFU) is recommended to facilitate early diagnosis and to ensure better health outcomes. Due to the heterogeneity of these sequelae, different specialists work together in the diagnosis and treatment of these conditions. Experts from both pediatric and internal medicine are involved in age-appropriate care by providing a transition process. Hence, LTFU of childhood cancer survivors is a prototypic example of multidisciplinary care for patients with complex needs treated in a specialized setting. International collaborations of healthcare professionals and scientists involved in LTFU of childhood cancer survivors, such as the International Guideline Harmonization Group, compile surveillance recommendations that can be clinically adopted all over the world. These global networks of clinicians and researchers make a joint effort to address gaps in knowledge, increase visibility and awareness of cancer survivorship and provide an excellent example of how progress in clinical care and scientific research may be achieved by international and multidisciplinary collaboration.

Cannabis use and non-clinical dimensions of psychosis in university students presenting to primary care.

OBJECTIVE: To explore the relationship between cannabis use and self-reported dimensions of psychosis in a population of university students presenting for any reason to primary care. METHOD: One thousand and forty-nine students attending the Student Health Unit, National University of Ireland, Galway, completed self-report questionnaires on alcohol and substance misuse, non-clinical dimensions of psychosis [Community Assessment of Psychic Experiences (CAPE)], anxiety and depression [Hospital Anxiety and Depression Scale (HADS)]. Association of cannabis use with psychiatric symptoms was explored whilst controlling for confounds. RESULTS: More frequent cannabis use was independently associated with greater intensity of positive, negative and depressive psychotic symptoms. The earlier the age of onset of cannabis use, the more positive psychotic symptoms were reported. CONCLUSION: These findings support the hypotheses that cannabis use increases the risk of developing psychotic symptoms and that this risk is further increased in those individuals who use cannabis more heavily and commence it at a younger age.

Developing and comparing methods for measuring the content of care in mental health services.

BACKGROUND: Measurement of what happens in mental health services is needed to describe services, identify variation in care provision and understand service outcomes. However, there is no consensus about appropriate methods or measures for content of care. Previous research has primarily used a single information source and prioritised staff over patient perspectives on content of care. This study aims to enhance understanding of how to measure content of care by developing and evaluating four instruments, each using a different measurement method. METHODS: Development is described by four instruments-CaSPAR, CaRICE, CCCQ-S and CCCQ-P-which use researcher observation, staff-report and patient-report to measure the intensity and nature of care at services. Inter-rater reliability of CaRICE and CCCQ-S was investigated. Concordance between staff and patient perspectives was explored through assessing inter-rater agreement of CCCQ-S and CCCQ-P questionnaires. The convergence of data from the measures collected in an inpatient multi-site study was investigated. RESULTS: CaRICE demonstrated good inter-rater reliability (κ = 0.71). CCCQ-S inter-rater reliability was poor. Concordance between staff and patient reports was low: there was a trend for patients to report less care received than staff reported had been provided. Results from CaSPAR, CaRICE and CCCQ-P exhibited divergence, indicating possible differences in patient, staff and researcher perspectives. DISCUSSION: Information about content of care should be sought as close as possible to the point of delivery. There may be differing, valid perspectives about care provided by services. Further development of methods to measure content of care is required. Meanwhile, a multi-methods approach should be adopted, which allows inclusion of different perspectives (specifically including the patient's perspective) and triangulation of results from different measurement methods. CaSPAR, CaRICE and CCCQ-P can provide multi-perspective content of care measurement in inpatient services.

Clinical outcomes and health-related quality of life (HRQOL) following haemopoietic stem cell transplantation (HSCT) for paediatric leukaemia.

BACKGROUND: Haemopoietic stem cell transplantation (HSCT) is a life-saving but intensive procedure associated with potentially severe adverse late effects. We aimed to determine morbidity and health-related quality of life (HRQOL) in a sample of survivors aged 8-18 years at least 1 year post HSCT for paediatric acute leukaemia, compared with a non-transplanted group of survivors matched for age, gender, initial disease and time since treatment. METHODS: Families (N = 54; HSCT n= 29) recruited from four UK centres completed measures of child behaviour and school attendance, HRQOL and finances. Mothers completed measures of their own well-being. Clinical outcome data were extracted from medical records. RESULTS: Children in the HSCT group had significantly more late effects and had received more tests for vision, bone, dental and skin health, and thyroid, lung, and gonadal function than the non-transplanted group. HRQOL scores for the HSCT group were significantly lower in all domains compared with the non-transplanted group and population norms, but were not significantly related to clinical indices. Mothers in the HSCT group had significantly poorer mental well-being than population norms. CONCLUSION: Significant morbidity and compromised HRQOL was found in survivors of HSCT. The burden of caring for a child after HSCT has a continuing toll on mothers' well-being.The importance of counselling families about possible long-term consequences is emphasized.

Health-related quality of life and financial impact of caring for a child with Thalassaemia Major in the UK.

BACKGROUND: Thalassaemia Major (TM) is a serious condition characterized by life-long dependence on blood transfusions and chelation therapy. Our aim was to determine health-related quality of life (HRQOL) in children with TM living in the UK, and the impact of caring for a child receiving National Health Service treatment on family finances. METHODS: This was a cross-sectional assessment of HRQOL in children (n= 22) with TM aged 8-18 years. Children were recruited from three UK Paediatric Haematology and Bone Marrow Transplant centres. Mothers completed measures of their child's HRQOL [PedsQL 4.0 (Measurement Model for the Pediatric Quality of Life Inventory, James W. Varni PhD, PedMetrics, Quantifying the Qualitative SM, Copyright 1998-2009)] and behaviour (Strengths and Difficulties questionnaire), and the impact of caring for the child on family finances. RESULTS: Child behaviour was within the normal range but child HRQOL was significantly lower than population norms. Family financial concerns associated with TM were associated with poorer child HRQOL (P= 0.020). CONCLUSIONS: Thalassaemia Major poses a considerable challenge to child HRQOL, well documented in areas of the world where TM is prevalent. Despite the availability of National Health Service care and financial benefits our study suggests a similar burden in the UK.

Alternatives to standard acute in-patient care in England: short-term clinical outcomes and cost-effectiveness.

BACKGROUND: Outcomes following admission to residential alternatives to standard in-patient mental health services are underresearched. AIMS: To explore short-term outcomes and costs of admission to alternative and standard services. METHOD: Health of the Nation Outcome Scales (HoNOS), Threshold Assessment Grid (TAG), Global Assessment of Functioning (GAF) and admission cost data were collected for six alternative services and six standard services. RESULTS: All outcomes improved during admission for both types of service (n = 433). Adjusted improvement was greater for standard services in scores on HoNOS (difference 1.99, 95% CI 1.12-2.86), TAG (difference 1.40, 95% CI 0.39-2.51) and GAF functioning (difference 4.15, 95% CI 1.08-7.22) but not GAF symptoms. Admissions to alternatives were 20.6 days shorter, and hence cheaper (UK pound3832 v. pound9850). Standard services cost an additional pound2939 per unit HoNOS improvement. CONCLUSIONS: The absence of clear-cut advantage for either type of service highlights the importance of the subjective experience and longer-term costs.