Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia

Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide–induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease

Non-Equilibrium Statistical Physics of Currents in Queuing Networks

We consider a stable open queuing network as a steady non-equilibrium system of interacting particles. The network is completely specified by its underlying graphical structure, type of interaction at each node, and the Markovian transition rates between nodes. For such systems, we ask the question ``What is the most likely way for large currents to accumulate over time in a network ?'', where time is large compared to the system correlation time scale. We identify two interesting regimes. In the first regime, in which the accumulation of currents over time exceeds the expected value by a small to moderate amount (moderate large deviation), we find that the large-deviation distribution of currents is universal (independent of the interaction details), and there is no long-time and averaged over time accumulation of particles (condensation) at any nodes. In the second regime, in which the accumulation of currents over time exceeds the expected value by a large amount (severe large deviation), we find that the large-deviation current distribution is sensitive to interaction details, and there is a long-time accumulation of particles (condensation) at some nodes. The transition between the two regimes can be described as a dynamical second order phase transition. We illustrate these ideas using the simple, yet non-trivial, example of a single node with feedback.Comment: 26 pages, 5 figure

Gram Negative Wound Infection in Hospitalised Adult Burn Patients-Systematic Review and Metanalysis-

BACKGROUND: Gram negative infection is a major determinant of morbidity and survival. Traditional teaching suggests that burn wound infections in different centres are caused by differing sets of causative organisms. This study established whether Gram-negative burn wound isolates associated to clinical wound infection differ between burn centres. METHODS: Studies investigating adult hospitalised patients (2000-2010) were critically appraised and qualified to a levels of evidence hierarchy. The contribution of bacterial pathogen type, and burn centre to the variance in standardised incidence of Gram-negative burn wound infection was analysed using two-way analysis of variance. PRIMARY FINDINGS: Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanni, Enterobacter spp., Proteus spp. and Escherichia coli emerged as the commonest Gram-negative burn wound pathogens. Individual pathogens' incidence did not differ significantly between burn centres (F (4, 20) = 1.1, p = 0.3797; r2 = 9.84). INTERPRETATION: Gram-negative infections predominate in burn surgery. This study is the first to establish that burn wound infections do not differ significantly between burn centres. It is the first study to report the pathogens responsible for the majority of Gram-negative infections in these patients. Whilst burn wound infection is not exclusive to these bacteria, it is hoped that reporting the presence of this group of common Gram-negative "target organisms" facilitate clinical practice and target research towards a defined clinical demand.peer-reviewe

Cultural safety involves new professional roles: A rapid review of interventions in Australia, the United States, Canada and New Zealand

Abstract Cultural safety is a decolonizing and transformative approach to health care aimed at achieving health care that recognizes, respects and nurtures the needs, rights and identities of Indigenous peoples. Such a transformation requires new or radically reimagined professional roles. Based on a rapid review design, this synthesis aimed to identify fundamental characteristics of cultural safety interventions that involved the creation or transformation of professional roles. The 23 included studies presented three main categories of professional roles for cultural safety. These roles were focused on (a) supporting health care system navigation, (b) providing a new or improved service offering, and (c) building organizational capacity to provide culturally safe health care. Our results demonstrate that cultural safety can be implemented by key actors playing different roles at different levels of the health care organization. These roles should be viewed as complementary to one another and be defined and implemented in partnership with Indigenous partners. © The Author(s) 2023

Dealing with Uncertainties in MCDA

This chapter presents various approaches to incorporating formalmodelling of risks and uncertainties into multi-criteria decision analysis,in a theoretically valid but also operationally meaningful manner. Weconsider both internal uncertainties (in the formulation and modellingof the decision problem), and external uncertainties arising fromexogenous factors, but with greater attention paid to the latter. Aftera broad discussion on the meaning of uncertainty, we first reviewapproaches to sensitivity analysis, which is particularly, although notexclusively, relevant to internal uncertainties. We discuss the role,but also some limitations, of representing uncertainties in formalprobabilistic structures, linked also to concepts of expected (multiattribute) utility theory. Such probability/utility approaches may be usedin explicitly identifying a most preferred solution, or simply to eliminatecertain courses of action when stochastically dominated (in varioussenses) by others. In some contexts it may be useful to view minimizationof various risk measures as additional criteria in more standard MCDAmodels, and we comment on advantages and disadvantages of suchapproaches. Finally we discuss the integration of MCDA with scenarioplanning, in order to deal with deeper uncertainties (not easily if at allrepresentable by probability models), particularly in a strategic planningcontext. The emphasis throughout is on the practice of MCDA rather thanon esoteric theoretical results.<br/

Trace element fingerprinting of cockle (Cerastoderma edule) shells can reveal harvesting location in adjacent areas

Determining seafood geographic origin is critical for controlling its quality and safeguarding the interest of consumers. Here, we use trace element fingerprinting (TEF) of bivalve shells to discriminate the geographic origin of specimens. Barium (Ba), manganese (Mn), magnesium (Mg), strontium (Sr) and lead (Pb) were quantified in cockle shells (Cerastoderma edule) captured with two fishing methods (by hand and by hand-raking) and from five adjacent fishing locations within an estuarine system (Ria de Aveiro, Portugal). Results suggest no differences in TEF of cockle shells captured by hand or by hand-raking, thus confirming that metal rakes do not act as a potential source of metal contamination that could somehow bias TEF results. In contrast, significant differences were recorded among locations for all trace elements analysed. A Canonical Analysis of Principal Coordinates (CAP) revealed that 92% of the samples could be successfully classified according to their fishing location using TEF. We show that TEF can be an accurate, fast and reliable method to determine the geographic origin of bivalves, even among locations separated less than 1 km apart within the same estuarine system. Nonetheless, follow up studies are needed to determine if TEF can reliably discriminate between bivalves originating from different ecosystems

CHARACTERISTICS OF THE MINERAL CONSTITUENTS OF SOME ALBIC AND SPODIC HORIZONS AS RELATED TO THEIR CHARGE PROPERTIES

Some physical, chemical and mineralogical properties of five albic and six spodic horizons were studied in an attempt to relate their composition to their charge properties. The samples investigated contained less than 3% clay and had specific surface areas less than 30 m2/g. pH values measured in M NaF were lower than 9.5 for the A2 horizons but higher than 10.5 for all the Bir horizons studied. Mineralogy of the clay fraction was studied by using X-ray diffraction, infrared spectroscopy, and thermogravimetric analysis along with selective chemical dissolution analyses. Chloritized vermiculite was the dominant phyllosilicate in the Bir samples, while montmorillonite dominated in the clay fraction of most of the A2 samples. Amorphous constituents, as determined by acid ammonium oxalate and 0.5 N NaOH extractions, represented up to 40% of the clay-sized fraction of some of the samples. Primary minerals such as quartz, feldspars and to a lesser extent hornblende and magnetite were the major constituents of the coarser fractions. The change in chemical and mineralogical compositions of the A2 and Bir horizons sharply reflected the variation that existed in their overall electrochemical behavior as shown by the potentiometric titration curves. A2 horizons usually behaved like a constant surface charge system, while the Bir samples reacted like a constant surface potential system with PZC values varying between pH 4.1 and 4.9. </jats:p

CARACTERISTIQUES MINERALOGIQUES ET CHIMIQUES DE QUELQUES SOLS SABLEUX DU QUEBEC EN REGARD DE LEUR EVOLUTION PEDOLOGIQUE

A, B and C horizons of 13 sandy soil series were sampled in the lowlands of southern Quebec. From the amounts of pyrophosphate-extractable Fe and Al and clay contents, nine of these profiles were classified as Podzolic soils while the others were Brunisols. Formation of montmorillonite and dissolution of chlorite in Ae horizons indicate intense weathering of the minerals at this level. In the B horizons, vermiculite that was present in the parent material or resulted from the alteration of illite was often chloritized. Values of pH measured in 1 M NaF were generally higher than 10.2 for the B horizons. The amounts of phosphorus retained by the samples varied in the following ranges: 23–397 μg P/g of soil for A horizons, 301–1578 μg P/g of soil for B horizons and 71–296 μg P/g of soil for C horizons. Cation exchange capacity of the soils was lower than 10 meq/100 g of soil, except in those horizons that contained high amounts of organic matter and where values up to 27.6 meq/100 g were measured. Using regression equations, values were obtained for the CEC of the organic matter and the clay fraction of these sandy soils. </jats:p