SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis.

The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. Genetic evidence indicates the important roles of SPY in diverse developmental and physiological processes. However, the upstream signal controlling SPY activity and the downstream substrate proteins O-fucosylated by SPY remain largely unknown. Here, we demonstrated that SPY mediates sugar-dependent growth in Arabidopsis (Arabidopsis thaliana). We further identified hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry. All the O-fucosylation events quantified in our proteomic analyses were undetectable or dramatically decreased in the spy mutants, and thus likely catalyzed by SPY. The O-fucosylome includes mostly nuclear and cytosolic proteins. Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. The O-fucosylome also includes many proteins modified by O-linked N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development.

Neurodevelopmental and other phenotypes recurrently associated with heterozygous BAZ2B loss-of-function variants.

The bromodomain adjacent to zinc finger 2B (BAZ2B) gene encodes a chromatin remodeling protein that has been shown to perform a variety of regulatory functions. It has been proposed that loss of BAZ2B function is associated with neurodevelopmental phenotypes, and some recurrent structural birth defects and dysmorphic features have been documented among individuals carrying heterozygous loss-of-function BAZ2B variants. However, additional evidence is needed to confirm that these phenotypes are attributable to BAZ2B deficiency. Here, we report 10 unrelated individuals with heterozygous deletions, stop-gain, frameshift, missense, splice junction, indel, and start-loss variants affecting BAZ2B. These included a paternal intragenic deletion and a maternal frameshift variant that were inherited from mildly affected or asymptomatic parents. The analysis of molecular and clinical data from this cohort, and that of individuals previously reported, suggests that BAZ2B haploinsufficiency causes an autosomal dominant neurodevelopmental syndrome that is incompletely penetrant. The phenotypes most commonly seen in association with loss of BAZ2B function include developmental delay, intellectual disability, autism spectrum disorder, speech delay-with some affected individuals being non-verbal-behavioral abnormalities, seizures, vision-related issues, congenital heart defects, poor fetal growth, and an indistinct pattern of dysmorphic features in which epicanthal folds and small ears are particularly common.

Artificial Intelligence Driven Prehospital ECG Interpretation for the Reduction of False Positive Emergent Cardiac Catheterization Lab Activations: A Retrospective Cohort Study.

OBJECTIVES: Data suggest patients suffering acute coronary occlusion myocardial infarction (OMI) benefit from prompt primary percutaneous intervention (PPCI). Many emergency medical services (EMS) activate catheterization labs to reduce time to PPCI, but suffer a high burden of inappropriate activations. Artificial intelligence (AI) algorithms show promise to improve electrocardiogram (ECG) interpretation. The primary objective was to evaluate the potential of AI to reduce false positive activations without missing OMI. METHODS: Electrocardiograms were categorized by (1) STEMI criteria, (2) ECG integrated device software and (3) a proprietary AI algorithm (Queen of Hearts (QOH), Powerful Medical). If multiple ECGs were obtained and any one tracing was positive for a given method, that diagnostic method was considered positive. The primary outcome was OMI defined as an angiographic culprit lesion with either TIMI 0-2 flow; or TIMI 3 flow with either peak high sensitivity troponin-I > 5000 ng/L or new wall motion abnormality. The primary analysis was per-patient proportion of false positives. RESULTS: A total of 140 patients were screened and 117 met criteria. Of these, 48 met the primary outcome criteria of OMI. There were 80 positives by STEMI criteria, 88 by device algorithm, and 77 by AI software. All approaches reduced false positives, 27% for STEMI, 22% for device software, and 34% for AI (p < 0.01 for all). The reduction in false positives did not significantly differ between STEMI criteria and AI software (p = 0.19) but STEMI criteria missed 6 (5%) OMIs, while AI missed none (p = 0.01). CONCLUSIONS: In this single-center retrospective study, an AI-driven algorithm reduced false positive diagnoses of OMI compared to EMS clinician gestalt. Compared to AI (which missed no OMI), STEMI criteria also reduced false positives but missed 6 true OMI. External validation of these findings in prospective cohorts is indicated.

Using latent variable modelling to identify etiological heterogeneity in preterm delivery.

AIMS: To identify a subgroup of mothers at high risk of preterm delivery, defined by empirical classes of multimorbidity and recurrence across three consecutive births. METHODS: The data were extracted from the perinatal data collection (PDC) of all inpatient live births (n = 435 912) occurring in the Australian state of Queensland between January 2009 and December 2015. Within this data, a total of 7714 primiparous mothers delivered three consecutive singleton live births (total births = 23 142), and comprise the sample for all analyses. RESULTS: The LCA indicated a four-class solution fit the data best at each time point, including (i) a 'normative' or healthy class with little morbidity (including >80% of the sample at each birth); (ii) a preterm, high morbidity class (<2% of the sample); (ii) a delivery morbidity class (4-8% of the sample); and (iii) preterm, low morbidity class (5-6% of the sample). Each group exhibited unique and consistent associations with maternal and pregnancy-related factors across births. After accounting for these factors, the high morbidity class and preterm, low morbidity class strongly predicted these same classes across consecutive births, and from birth 1 to birth 3 (second-order transition). CONCLUSIONS: A small but highly morbid class of neonatal deliveries emerged, exhibiting strong continuity across consecutive births (odds ratios >10), independent of a range of maternal and pregnancy-related factors. This group of women, if subject to further investigation, could provide valuable insight into the aetiology of prematurity and associated morbidity, perhaps providing information to improve birth outcomes among all women.

Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry.

Defining protein-protein interactions (PPIs) in their native environment is crucial to understanding protein structure and function. Cross-linking-mass spectrometry (XL-MS) has proven effective in capturing PPIs in living cells; however, the proteome coverage remains limited. Here, we have developed a robust in vivo XL-MS platform to facilitate in-depth PPI mapping by integrating a multifunctional MS-cleavable cross-linker with sample preparation strategies and high-resolution MS. The advancement of click chemistry-based enrichment significantly enhanced the detection of cross-linked peptides for proteome-wide analyses. This platform enabled the identification of 13,904 unique lysine-lysine linkages from in vivo cross-linked HEK 293 cells, permitting construction of the largest in vivo PPI network to date, comprising 6,439 interactions among 2,484 proteins. These results allowed us to generate a highly detailed yet panoramic portrait of human interactomes associated with diverse cellular pathways. The strategy presented here signifies a technological advancement for in vivo PPI mapping at the systems level and can be generalized for charting protein interaction landscapes in any organisms.

Congenital diaphragmatic hernia in siblings with PIGA-related congenital disorder of glycosylation.

There are over 150 proteins involved in glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis, a class within the larger category of congenital disorders of glycosylation (CDG). Pathogenic variants identified in phosphatidylinositol glycan class A protein (PIGA) are associated with X-linked PIGA-CDG, a GPI-anchor defect. The disease has primarily been characterized by hypotonia, epilepsy, and global developmental delay; however, only 89 known cases are reported, so the phenotypic spectrum has likely not yet been fully delineated. Congenital diaphragmatic hernia (CDH) has been reported in patients with various GPI-anchor related defects but has only been described in one prior individual with PIGA-CDG. Here, we describe the second and third reported cases of CDH in two brothers with PIGA-CDG caused by a pathogenic missense variant in PIGA: c.355C > T, p.R119W. Chromosomal microarray and whole exome sequencing did not reveal another plausible explanation for the CDH. We relate our patients' clinical features to the single previously reported individual with CDH and PIGA-CDG. We then compare this case series with the subset of individuals with CDH and other GPI-anchor defects. These findings suggest that CDH should be considered in the phenotypic disease spectrum of PIGA-CDG.

Differences in temperature responses among phenological processes in diverse Ethiopian sorghum germplasm can affect their specific adaptation to environmental conditions.

BACKGROUND AND AIMS: Main shoot total leaf number (TLN) is a key determinant of plant leaf area and crop adaptation. Environmental factors other than photoperiod can affect TLN in sorghum, implying that leaf appearance rate (LAR) and development rate can differ in response to temperature. The objectives of this study were to determine (1) if temperature effects on TLN can be explained as a consequence of differences in temperature responses across phenological processes and (2) if genotypic differences in these responses can be linked to agroecological adaptation. METHODS: Nineteen sorghum genotypes were sown on 12 dates at two locations in Ethiopia with contrasting altitude, creating temperature differences independent of photoperiod. TLN and temperature were recorded in all experiments and LAR for six sowing dates. KEY RESULTS: Eleven of the genotypes showed a temperature effect on TLN, which was associated with a significantly higher base temperature (Tbase) for LAR than for pre-anthesis development rate (DR). In contrast, genotypes with no effect of temperature on TLN had similar Tbase for LAR and DR. Across genotypes, Tbase for LAR and DR were highly correlated, but genotypes with low Tbase had the greatest difference in Tbase between the two processes. Genotypic differences were associated with racial grouping. CONCLUSIONS: Genotypic and racial differences in responses of phenological processes to temperature, in particular in Tbase, can affect specific adaptation to agroecological zones, as these differences can affect TLN in response to temperature and hence canopy size and the duration of the pre-anthesis period. These can both affect the amount of water used and radiation intercepted pre-anthesis. A multi-disciplinary approach is required to identify genotype × environment × management combinations that can best capture the ensuing specific adaptation.

Tobacco Harm Reduction with Vaporised Nicotine (THRiVe): A Feasibility Trial of Nicotine Vaping Products for Smoking Cessation Among People Living with HIV.

People living with HIV (PLHIV) have high rates of tobacco smoking. Nicotine vaping products (NVPs) may promote tobacco smoking cessation and/or harm reduction. This study aimed to trial the feasibility of NVPs for promoting tobacco smoking cessation among PLHIV. The Tobacco Harm Reduction with Vaporised Nicotine (THRiVe) study was a mixed-methods trial among 29 PLHIV who used tobacco daily. Participants trialled a 12-week intervention of NVPs. This study reports descriptive analyses of quantitative data on tobacco abstinence and associated adverse events. Short-term abstinence (7-day point prevalence; i.e., no tobacco use for 7 days) was achieved by 35% of participants at Week 12 and 31% reported short-term abstinence at Week 24. Sustained medium-term abstinence (8 weeks' abstinence) was achieved by 15% of participants at Week 12 and 31% at Week 24. Most adverse events were mild. NVPs may represent a feasible and potentially effective short-to-medium term tobacco smoking cessation aid and/or harm reduction strategy among PLHIV.

Essential emergency and critical care as a health system response to critical illness and the COVID19 pandemic: what does it cost?

Essential Emergency and Critical Care (EECC) is a novel approach to the care of critically ill patients, focusing on first-tier, effective, low-cost, life-saving care and designed to be feasible even in low-resourced and low-staffed settings. This is distinct from advanced critical care, usually conducted in ICUs with specialised staff, facilities and technologies. This paper estimates the incremental cost of EECC and advanced critical care for the planning of care for critically ill patients in Tanzania and Kenya.The incremental costing took a health systems perspective. A normative approach based on the ingredients defined through the recently published global consensus on EECC was used. The setting was a district hospital in which the patient is provided with the definitive care typically provided at that level for their condition. Quantification of resource use was based on COVID-19 as a tracer condition using clinical expertise. Local prices were used where available, and all costs were converted to USD2020.The costs per patient day of EECC is estimated to be 1 USD, 11 USD and 33 USD in Tanzania and 2 USD, 14 USD and 37 USD in Kenya, for moderate, severe and critical COVID-19 patients respectively. The cost per patient day of advanced critical care is estimated to be 13 USD and 294 USD in Tanzania and USD 17 USD and 345 USD in Kenya for severe and critical COVID-19 patients, respectively.EECC is a novel approach for providing the essential care to all critically ill patients. The low costs and lower tech approach inherent in delivering EECC mean that EECC could be provided to many and suggests that prioritizing EECC over ACC may be a rational approach when resources are limited.

Elucidating local diffusion dynamics in nickel-rich layered oxide cathodes.

Elucidating Li-ion transport properties is essential for designing suitable methodologies to optimise electrochemical performance in Ni-rich cathodes for high energy density Li-ion batteries. Here, we report the local-scale Li-diffusion characteristics of a series of nickel-rich layered oxide cathodes, prepared via microwave methods, using muon spin relaxation methods. Our results detail the effects of cation dopants, selected for structure stability, on transport properties in candidate nickel-rich chemistries. We find that the local diffusion properties improve with increasing nickel content. Our results demonstrate that these observations are dependant on substitutional effects.

SHOT UK Collaborative Reviewing and Reforming IT Processes in Transfusion (SCRIPT) survey: Laboratory information management systems: Are we ready for digital transformation?

OBJECTIVES: To understand the use, functionality and interoperability of laboratory information management systems (LIMS) in UK transfusion laboratories. BACKGROUND: LIMS are widely used to support safe transfusion practice. LIMS have the potential to reduce the risk of laboratory error using algorithms, flags and alerts that support compliance with best practice guidelines and regulatory standards. Reporting to Serious Hazards of Transfusion (SHOT), the United Kingdom (UK) haemovigilance scheme, has identified cases where the LIMS could have prevented errors but did not. Shared care of patients across different organisations and the development of pathology networks has raised challenges relating to interoperability of IT systems both within, and between, organisations. METHODS AND MATERIALS: A survey was distributed to all SHOT-reporting organisations to understand the current state of LIMS in the UK, prevalence of expertise in transfusion IT, and barriers to progress. Survey questions covered LIMS interoperability with other IT systems used in the healthcare setting. RESULTS: A variety of LIMS and version numbers are in use in transfusion laboratories, LIMS are not always updated due to resource constraints. Respondents identified interoperability and improved functionality as the main requirements for transfusion safety. CONCLUSION: A nationally agreed set of minimum standards for transfusion LIMS is required for safe practice. Adequate resources, training and expertise should be provided to support the effective use and timely updates of LIMS. A single LIMS solution should be in place for transfusion laboratories working within a network and interoperability with other systems should be explored to further improve practice.

Lysosomal Storage and Albinism Due to Effects of a De Novo CLCN7 Variant on Lysosomal Acidification.

Optimal lysosome function requires maintenance of an acidic pH maintained by proton pumps in combination with a counterion transporter such as the Cl-/H+ exchanger, CLCN7 (ClC-7), encoded by CLCN7. The role of ClC-7 in maintaining lysosomal pH has been controversial. In this paper, we performed clinical and genetic evaluations of two children of different ethnicities. Both children had delayed myelination and development, organomegaly, and hypopigmentation, but neither had osteopetrosis. Whole-exome and -genome sequencing revealed a de novo c.2144A>G variant in CLCN7 in both affected children. This p.Tyr715Cys variant, located in the C-terminal domain of ClC-7, resulted in increased outward currents when it was heterologously expressed in Xenopus oocytes. Fibroblasts from probands displayed a lysosomal pH approximately 0.2 units lower than that of control cells, and treatment with chloroquine normalized the pH. Primary fibroblasts from both probands also exhibited markedly enlarged intracellular vacuoles; this finding was recapitulated by the overexpression of human p.Tyr715Cys CLCN7 in control fibroblasts, reflecting the dominant, gain-of-function nature of the variant. A mouse harboring the knock-in Clcn7 variant exhibited hypopigmentation, hepatomegaly resulting from abnormal storage, and enlarged vacuoles in cultured fibroblasts. Our results show that p.Tyr715Cys is a gain-of-function CLCN7 variant associated with developmental delay, organomegaly, and hypopigmentation resulting from lysosomal hyperacidity, abnormal storage, and enlarged intracellular vacuoles. Our data supports the hypothesis that the ClC-7 antiporter plays a critical role in maintaining lysosomal pH.

Lower citrate synthase activity, mitochondrial complex expression, and fewer oxidative myofibers characterize skeletal muscle from growth-restricted fetal sheep.

Skeletal muscle from the late gestation sheep fetus with intrauterine growth restriction (IUGR) has evidence of reduced oxidative metabolism. Using a sheep model of placental insufficiency and IUGR, we tested the hypothesis that by late gestation, IUGR fetal skeletal muscle has reduced capacity for oxidative phosphorylation because of intrinsic deficits in mitochondrial respiration. We measured mitochondrial respiration in permeabilized muscle fibers from biceps femoris (BF) and soleus (SOL) from control and IUGR fetal sheep. Using muscles including BF, SOL, tibialis anterior (TA), and flexor digitorum superficialis (FDS), we measured citrate synthase (CS) activity, mitochondrial complex subunit abundance, fiber type distribution, and gene expression of regulators of mitochondrial biosynthesis. Ex vivo mitochondrial respiration was similar in control and IUGR muscle. However, CS activity was lower in IUGR BF and TA, indicating lower mitochondrial content, and protein expression of individual mitochondrial complex subunits was lower in IUGR TA and BF in a muscle-specific pattern. IUGR TA, BF, and FDS also had lower expression of type I oxidative fibers. Fiber-type shifts that support glycolytic instead of oxidative metabolism may be advantageous for the IUGR fetus in a hypoxic and nutrient-deficient environment, whereas these adaptions may be maladaptive in postnatal life.

Which interventions improve HPV vaccination uptake and intention in children, adolescents and young adults? An umbrella review.

BACKGROUND: Human papillomavirus (HPV) vaccination offers protection against the virus responsible for cervical, oropharyngeal, anal, vulval and penile cancers. However, there is considerable variation across, and even within, countries as to how HPV vaccination is offered and accepted. This review aimed to identify what interventions exist to promote uptake and how effective they are. METHODS: We conducted an umbrella review using the JBI (Joanna Briggs Institute) methodology to evaluate routine or catch-up interventions to increase HPV vaccination uptake and/or intention for children aged 9 years and older, adolescents and young adults up to 26. Comprehensive searches for English language quantitative systematic reviews, published between January 2011 and July 2021, were conducted across five databases. After reviewing titles and abstract, relevant papers were independently assessed in detail. MAIN RESULTS: From 1046 records identified, 10 articles were included in the review. They reported on 95 randomised controlled trials, 28 quasi-experimental studies, 14 cohort studies, 6 non-randomised pretest/post-test studies with control groups, 5 single-group pretest/post-test studies, 1 single-group post-test study and 1 randomised longitudinal study. Some interventions promoted change at the individual, community or organisational level, while others used a multicomponent approach. Face-to-face presentations, printed information and supplementing both strategies with additional components appear effective at increasing vaccination intention, while reminders and multicomponent strategies, especially ones that include some intervention aimed at provider level, appear effective at increasing vaccination uptake. Interventions that did not lead to an improvement in HPV vaccination intention or uptake varied in design and impacts were inconsistent across children/adolescents, young adults or parents. CONCLUSION: The evidence suggests that there is no single solution to increasing vaccination uptake and that different approaches may be better suited to certain populations. However, generalisations are limited by poor reporting and a paucity of studies beyond the USA. Further high-quality studies, therefore, are needed to understand how best to increase HPV vaccination uptake in different target populations.

Methionine synthase deficiency: Variable clinical presentation and benefit of early diagnosis and treatment.

Methionine synthase deficiency (cblG complementation group) is a rare inborn error of metabolism affecting the homocysteine re-methylation pathway. It leads to a biochemical phenotype of hyperhomocysteinemia and hypomethioninemia. The clinical presentation of cblG is variable, ranging from seizures, encephalopathy, macrocytic anemia, hypotonia, and feeding difficulties in the neonatal period to onset of psychiatric symptoms or acute neurologic changes in adolescence or adulthood. Given the variable and nonspecific symptoms seen in cblG, the diagnosis of affected patients is often delayed. Medical management of cblG includes the use of hydroxocobalamin, betaine, folinic acid, and in some cases methionine supplementation. Treatment has been shown to lead to improvement in the biochemical profile of affected patients, with lowering of total homocysteine levels and increasing methionine levels. However, the published literature contains differing conclusions on whether treatment is effective in changing the natural history of the disease. Herein, we present five patients with cblG who have shown substantial clinical benefit from treatment with objective improvement in their neurologic outcomes. We demonstrate more favorable outcomes in our patients who were treated early in life, especially those who were treated before neurologic symptoms manifested. Given improved outcomes from treatment of presymptomatic patients, cblG warrants inclusion in newborn screening.

Differences in advanced glycation endproducts (AGEs) in plasma from birds and mammals of different body sizes and ages.

Birds and mammals provide a physiological paradox: similar-sized mammals live shorter lives than birds; yet, birds have higher blood glucose concentrations than mammals, and higher basal metabolic rates. We have previously shown that oxidative stress patterns between mammals and birds differ, so that birds, generally, have lower blood antioxidant capacity, and lower lipid peroxidation concentration. There is a close association between oxidative stress and the production of carbohydrate-based damaged biomolecules, Advanced Glycation End-products (AGEs). In mammals, AGEs can bind to their receptor (RAGE), which can lead to increases in reactive oxygen species (ROS) production, and can decrease antioxidant capacity. Here, we used plasma from birds and mammals to address whether blood plasma AGE-BSA concentration is associated with body mass and age in these two groups. We found a statistically significantly higher average concentrations of AGE-BSA in birds compared with mammals, and we found a significantly positive correlation between AGE-BSA and age in mammals, though, this correlation disappeared after phylogenetic correction. We propose that the higher AGE concentration in birds is mainly attributable to greater AGE-production due to elevated basal glucose concentrations and decreased AGE-clearance given differences in glomerular filtration rates in birds compared with mammals. Additionally, due to the potential lack of an AGE receptor in birds, AGE accumulation may not be closely linked to oxidative stress and therefore pose a lesser physiological challenge in birds compared to mammals.

Gastroblastoma with a novel EWSR1-CTBP1 fusion presenting in adolescence.

Gastroblastomas are rare tumors with a biphasic epithelioid/spindle cell morphology that typically present in early adulthood and have recurrent MALAT1-GLI1 fusions. We describe an adolescent patient with Wiskott-Aldrich syndrome who presented with a large submucosal gastric tumor with biphasic morphology. Despite histologic features consistent with gastroblastoma, a MALAT1-GLI1 fusion was not found in this patient's tumor; instead, comprehensive molecular profiling identified a novel EWSR1-CTBP1 fusion and no other significant genetic alterations. The tumor also overexpressed NOTCH and FGFR by RNA profiling. The novel fusion and expression profile suggest a role for epithelial-mesenchymal transition in this tumor, with potential implications for the pathogenesis of biphasic gastric tumors such as gastroblastoma.

Lung metabolomics after ischemic acute kidney injury reveals increased oxidative stress, altered energy production, and ATP depletion.

Acute kidney injury (AKI) is a complex disease associated with increased mortality that may be due to deleterious distant organ effects. AKI associated with respiratory complications, in particular, has a poor outcome. In murine models, AKI is characterized by increased circulating cytokines, lung chemokine upregulation, and neutrophilic infiltration, similar to other causes of indirect acute lung injury (ALI; e.g., sepsis). Many causes of lung inflammation are associated with a lung metabolic profile characterized by increased oxidative stress, a shift toward the use of other forms of energy production, and/or a depleted energy state. To our knowledge, there are no studies that have evaluated pulmonary energy production and metabolism after AKI. We hypothesized that based on the parallels between inflammatory acute lung injury and AKI-mediated lung injury, a similar metabolic profile would be observed. Lung metabolomics and ATP levels were assessed 4 h, 24 h, and 7 days after ischemic AKI in mice. Numerous novel findings regarding the effect of AKI on the lung were observed including 1) increased oxidative stress, 2) a shift toward alternate methods of energy production, and 3) depleted levels of ATP. The findings in this report bring to light novel characteristics of AKI-mediated lung injury and provide new leads into the mechanisms by which AKI in patients predisposes to pulmonary complications.

REVIEW: Practical strategies to maintain anabolism by intravenous nutritional management in children with inborn metabolic diseases.

One of the most vital elements of management for patients with inborn errors of intermediary metabolism is the promotion of anabolism, the state in which the body builds new components, and avoidance of catabolism, the state in which the body breaks down its own stores for energy. Anabolism is maintained through the provision of a sufficient supply of substrates for energy, as well as critical building blocks of essential amino acids, essential fatty acids, and vitamins for synthetic function and growth. Patients with metabolic diseases are at risk for decompensation during prolonged fasting, which often occurs during illnesses in which enteral intake is compromised. During these times, intravenous nutrition must be supplied to fully meet the specific nutritional needs of the patient. We detail our approach to intravenous management for metabolic patients and its underlying rationale. This generally entails a combination of intravenous glucose and lipid as well as early introduction of protein and essential vitamins. We exemplify the utility of our approach in case studies, as well as scenarios and specific disorders which require a more careful administration of nutritional substrates or a modification of macronutrient ratios.

Magnetic Field Induced Quantum Spin Liquid in the Two Coupled Trillium Lattices of K_{2}Ni_{2}(SO_{4})_{3}.

Quantum spin liquids are exotic states of matter that form when strongly frustrated magnetic interactions induce a highly entangled quantum paramagnet far below the energy scale of the magnetic interactions. Three-dimensional cases are especially challenging due to the significant reduction of the influence of quantum fluctuations. Here, we report the magnetic characterization of K_{2}Ni_{2}(SO_{4})_{3} forming a three-dimensional network of Ni^{2+} spins. Using density functional theory calculations, we show that this network consists of two interconnected spin-1 trillium lattices. In the absence of a magnetic field, magnetization, specific heat, neutron scattering, and muon spin relaxation experiments demonstrate a highly correlated and dynamic state, coexisting with a peculiar, very small static component exhibiting a strongly renormalized moment. A magnetic field B≳4 T diminishes the ordered component and drives the system into a pure quantum spin liquid state. This shows that a system of interconnected S=1 trillium lattices exhibits a significantly elevated level of geometrical frustration.