The effect of insulin and amino acids on muscle and whole body protein turnover in patients with type 1 diabetes

Deficiency of insulin results in a net loss of lean body mass and wasting of muscle. The defect of protein turnover underlying the loss of skeletal muscle could be a reduction in the rate of protein synthesis, an increase in the rate of protein breakdown or a combination of both. In the present work the abnormalities of protein metabolism occurring during insulin deficiency have been investigated in patients with type 1 diabetes, and the acute effects of insulin replacement, during different conditions of nutrient supply, have been investigated both in patients with type 1 diabetes and in healthy subjectsIncorporation of L-(l-23C)leucine into biopsied skeletal muscle, arteriovenous leg exchange of L-(12N)phenylalanine and of L-(l-23C)leucine, and net release of 3-methylhistidine from leg tissues were used to assess muscle mixed protein synthesis, muscle mixed protein turnover and myofibrillar protein breakdown, respectively. Whole-body protein turnover was assessed by tracer dilution using L-(l-23C)leucine and L-(15N)phenylalanine.Infusion of insulin reduced skeletal muscle mixed protein breakdown, both when plasma amino acids were allowed to fall and when their concentrations were elevated by exogenous amino acid infusion. In the diabetic patients muscle protein synthesis was not increased by insulin infusion alone; infusion of insulin combined with amino acids apparently increased synthesis as assessed by phenylalanine exchange but not when assessed by either leucine exchange or incorporation into muscle. In the healthy subjects there was a faster rate of muscle protein synthesis, assessed by phenylalanine exchange, during combined insulin with amino acid infusion in comparison with the diabetic patients. In healthy subjects infusion of mixed amino acids alone exerted an anabolic effect on muscle protein synthesis with little, if any, alteration in the extent of either mixed or myofibrillar muscle protein breakdown. In comparisons with postabsorptive healthy subjects, abnormalities of muscle protein synthesis and breakdown and of amino acid oxidation in were not identified in type 1 diabetic patients during insulin withdrawal.n the diabetic patients infusion of insulin alone reduced whole-body protein breakdown but also reduced protein synthesis to an equivalent extent; there was no net benefit on protein balance. However, infusion of insulin combined with amino acids reduced protein breakdown and improved net balance with no change in synthesis. In contrast, in the healthy subjects the same doses of insulin combined with amino acids stimulated protein synthesis in addition to reducing protein breakdown. The effects of amino acids alone in healthy subjects was both to stimulate whole-body protein synthesis and to reduce protein breakdown.These investigations suggest that insulin exerts an anabolic action by reducing protein breakdown; insulin is only able to increase protein synthesis during conditions of increased amino acid availability. Muscle protein synthesis was resistant to stimulation by insulin in type 1 diabetic patients

The RETREAT score provides valid predictions regarding hepatocellular carcinoma recurrence after liver transplantation

Prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) with knowledge of explant data is important for guiding post-LT surveillance and treatment. The RETREAT score was recently introduced for this purpose, but has not been validated outside the USA. In a retrospective single-center study of 169 consecutive patients undergoing LT in Gothenburg, through 2000-2017 (mean age 57 years, 80% men), there were 34 HCC recurrences during a median 4.6-year follow-up. The 5-year cumulative incidence of HCC recurrence was 0% with RETREAT scores of 0-1 (18%), 11-22% with scores of 2-4 (58%), and 65% with scores of 5-8 (24%). The C-statistic, as a measure of discrimination for prediction of HCC recurrence was 0.762, 0.664, 0.616, and 0.717, for the RETREAT score, Milan criteria, UCSF criteria, and post-MORAL criteria. The RETREAT score had no significant impact on patient survival after HCC recurrence (HR 1.00, P = 0.97). In conclusion, the RETREAT score provided valid predictions of post-LT HCC recurrence in a European setting, with the ability to discriminate between high, intermediate, and low risk for HCC recurrence in a clinically important way. Prognosis after recurrence did not differ according to the RETREAT score in our study.Peer reviewe

Battery Separator Characterization and Evaluation Procedures for NASA's Advanced Lithium-Ion Batteries

To address the future performance and safety requirements for the electrical energy storage technologies that will enhance and enable future NASA manned aerospace missions, advanced rechargeable, lithium-ion battery technology development is being pursued within the scope of the NASA Exploration Technology Development Program s (ETDP's) Energy Storage Project. A critical cell-level component of a lithium-ion battery which significantly impacts both overall electrochemical performance and safety is the porous separator that is sandwiched between the two active cell electrodes. To support the selection of the optimal cell separator material(s) for the advanced battery technology and chemistries under development, laboratory characterization and screening procedures were established to assess and compare separator material-level attributes and associated separator performance characteristics

Renal function after liver transplantation : Real-world experience with basiliximab induction and delayed reduced-dose tacrolimus

Background: Routine use of delayed reduced-dose calcineurin-inhibitor treatment with induction immunosuppression in liver transplantation to minimize post-operative kidney injury is still scarce. im: To evaluate real-world experience of basiliximab induction with delayed reduced-dose tacrolimus. Methods: In a retrospective cohort study, kidney function was evaluated pre-and postoperatively by mea-sured glomerular filtration rate (mGFR). Adult patients undergoing liver transplantation between 20 0 0 and 2017 were divided into a conventional treatment group (immediate-introduction of tacrolimus, tar-get trough levels 10-15 ng/mL, and corticosteroids, n = 203) and a revised treatment group (basiliximab induction, reduced-dose tacrolimus, target through levels 5-8 ng/mL, delayed until day three, and my-cophenolate mofetil 20 0 0 mg/day, n = 343). Results: Mean mGFR was similar between groups at wait-listing (85.3 vs 84.1 ml/min/1.73m2, p = 0.60), but higher in the revised treatment group at 3 (56.8 vs 63.4 ml/min/1.73m2, p = 0.004) and 12 months post-transplant (60.9 vs 69.7 ml/min/1.73m2, p < 0.001); this difference remained after correcting for mul-tiple confounders and was independent of pre-transplant mGFR. In the revised treatment group, biopsy proven acute rejection rate was lower (38% vs. 21%, p < 0.001), and graft-survival better ( p = 0.01). Conclusion: Basiliximab induction with delayed reduced-dose tacrolimus is associated with less kidney injury when compared to standard-dose tacrolimus, without increased risk of rejection, graft loss or death. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.Peer reviewe

Temperature response functions (G-functions) for single pile heat exchangers

Foundation piles used as heat exchangers as part of a ground energy system have the potential to reduce energy use and carbon dioxide emissions from new buildings. However, current design approaches for pile heat exchangers are based on methods developed for boreholes which have a different geometry, with a much larger aspect (length to diameter) ratio. Current methods also neglect the transient behaviour of the pile concrete, instead assuming a steady state resistance for design purposes. As piles have a much larger volume of concrete than boreholes, this neglects the significant potential for heat storage within the pile. To overcome these shortcomings this paper presents new pile temperature response functions (G-functions) which are designed to reflect typical geometries of pile heat exchangers and include the transient response of the pile concrete. Owing to the larger number of pile sizes and pipe configurations which are possible with pile heat exchangers it is not feasible to developed a single unified G-function and instead upper and lower bound solutions are provided for different aspects ratios

Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival

Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five–year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience

Variation in hospital admission from the emergency department for children with cancer: A Pediatric Health Information System study

Background Children with cancer experience a wide range of conditions that require urgent evaluation in the emergency department (ED), yet variation in admission rates is poorly documented. Procedure We performed a retrospective cohort study using the Pediatric Health Information System of ED encounters by children with cancer between July 2012 and June 2015. We compared demographics for admitted versus discharged using univariate statistics, and calculated admission rates by hospital, diagnosis, day of the week, and weekend versus weekday. We assessed the degree of interhospital admission rates using the index of dispersion (ID). Results Children with cancer had 60 054 ED encounters at 37 hospitals. Overall, 62.5% were admitted (range 43.2%-92.1%, ID 2.6) indicating overdispersed admission rates with high variability. Children with cancer that visited the ED for a primary diagnosis of fever experienced the largest amount of variability in admission with rates ranging from 10.4% to 74.1% (ID 8.1). Less variability existed among hospital admission rates for both neutropenia (range 60%–100%, ID 1.0) and febrile neutropenia (FN) (range 66.7%-100%, ID 0.83). Admission rates by day of the week did not demonstrate significant variability for any of the scenarios examined (overall P = 0.91). There were no differences by weekend versus weekday either (overall P = 0.52). Conclusion The percentage of children with cancer admitted through the ED varies widely by institution and diagnosis. Standardization of best practices for children with cancer admitted through the ED should be an area of continued improvement

Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma is Associated with Improved Survival

Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between 1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five-year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience