Correlations between H2 Permeation and Physical/Mechanical Properties in Ethylene Propylene Diene Monomer Polymers Blended with Carbon Black and Silica Fillers.

H2 permeation in peroxide-crosslinked EPDM blended with carbon black (CB) and silica fillers was studied at pressures ranging from 1.2 MPa to 90 MPa via the volumetric analysis technique. H2 uptake in the CB-filled EPDM revealed dual-sorption behaviors via Henry's law and the Langmuir model, which were attributed to H2 absorption by the polymer chains and H2 adsorption at the filler interfaces, respectively. Additionally, single-sorption mechanisms were observed for neat EPDM and silica-blended EPDM according to Henry's law, indicating H2 absorption by the polymer chain. The linear decreases in the diffusivity with filler content for the silica-blended EPDMs were attributed to increases in the diffusion paths caused by the filler. Exponential decreases in the diffusivity with increasing filler content and in the permeation with the physical/mechanical properties for CB-filled EPDMs were caused by decreases in the fractional free volume due to increased densities for the EPDM composites. Moreover, good filler-dependent correlations between permeability and density, hardness, and tensile strength were demonstrated for EPDMs used as sealing materials for O-rings. From the resulting equation, we predicted the permeation value without further measurements. Thus, we can select EPDM candidates satisfying the permeation guidelines used in hydrogen infrastructure for the future hydrogen economy.

Where Do We Go From Here? A Framework for Using Susceptible-Infectious-Recovered Models for Policy Making in Emerging Infectious Diseases.

OBJECTIVES: Throughout the coronavirus disease 2019 pandemic, susceptible-infectious-recovered (SIR) modeling has been the preeminent modeling method to inform policy making worldwide. Nevertheless, the usefulness of such models has been subject to controversy. An evolution in the epidemiological modeling field is urgently needed, beginning with an agreed-upon set of modeling standards for policy recommendations. The objective of this article is to propose a set of modeling standards to support policy decision making. METHODS: We identify and describe 5 broad standards: transparency, heterogeneity, calibration and validation, cost-benefit analysis, and model obsolescence and recalibration. We give methodological recommendations and provide examples in the literature that employ these standards well. We also develop and demonstrate a modeling practices checklist using existing coronavirus disease 2019 literature that can be employed by readers, authors, and reviewers to evaluate and compare policy modeling literature along our formulated standards. RESULTS: We graded 16 articles using our checklist. On average, the articles met 6.81 of our 19 categories (36.7%). No articles contained any cost-benefit analyses and few were adequately transparent. CONCLUSIONS: There is significant room for improvement in modeling pandemic policy. Issues often arise from a lack of transparency, poor modeling assumptions, lack of a system-wide perspective in modeling, and lack of flexibility in the academic system to rapidly iterate modeling as new information becomes available. In anticipation of future challenges, we encourage the modeling community at large to contribute toward the refinement and consensus of a shared set of standards for infectious disease policy modeling.

Immunopathological manifestations in Kabuki syndrome: a registry study of 177 individuals.

PURPOSE: Kabuki syndrome (KS) (OMIM 147920 and 300867) is a rare genetic disorder characterized by specific facial features, intellectual disability, and various malformations. Immunopathological manifestations seem prevalent and increase the morbimortality. To assess the frequency and severity of the manifestations, we measured the prevalence of immunopathological manifestations as well as genotype-phenotype correlations in KS individuals from a registry. METHODS: Data were for 177 KS individuals with KDM6A or KMT2D pathogenic variants. Questionnaires to clinicians were used to assess the presence of immunodeficiency and autoimmune diseases both on a clinical and biological basis. RESULTS: Overall, 44.1% (78/177) and 58.2% (46/79) of KS individuals exhibited infection susceptibility and hypogammaglobulinemia, respectively; 13.6% (24/177) had autoimmune disease (AID; 25.6% [11/43] in adults), 5.6% (10/177) with ≥2 AID manifestations. The most frequent AID manifestations were immune thrombocytopenic purpura (7.3% [13/177]) and autoimmune hemolytic anemia (4.0% [7/177]). Among nonhematological manifestations, vitiligo was frequent. Immune thrombocytopenic purpura was frequent with missense versus other types of variants (p = 0.027). CONCLUSION: The high prevalence of immunopathological manifestations in KS demonstrates the importance of systematic screening and efficient preventive management of these treatable and sometimes life-threatening conditions.

Inflammatory and oxidative stress biomarkers in alkaptonuria: data from the DevelopAKUre project.

OBJECTIVE: The aim of this work was to assess baseline serum levels of established biomarkers related to inflammation and oxidative stress in samples from alkaptonuric subjects enrolled in SONIA1 (n = 40) and SONIA2 (n = 138) clinical trials (DevelopAKUre project). METHODS: Baseline serum levels of Serum Amyloid A (SAA), IL-6, IL-1ß, TNFα, CRP, cathepsin D (CATD), IL-1ra, and MMP-3 were determined through commercial ELISA assays. Chitotriosidase activity was assessed through a fluorimetric method. Advanced Oxidation Protein Products (AOPP) were determined by spectrophotometry. Thiols, S-thiolated proteins and Protein Thiolation Index (PTI) were determined by spectrophotometry and HPLC. Patients' quality of life was assessed through validated questionnaires. RESULTS: We found that SAA serum levels were significantly increased compared to reference threshold in 57.5% and 86% of SONIA1 and SONIA2 samples, respectively. Similarly, chitotriosidase activity was above the reference threshold in half of SONIA2 samples, whereas CRP levels were increased only in a minority of samples. CATD, IL-1ß, IL-6, TNFα, MMP-3, AOPP, thiols, S-thiolated protein and PTI showed no statistically significant differences from control population. We provided evidence that alkaptonuric patients presenting with significantly higher SAA, chitotriosidase activity and PTI reported more often a decreased quality of life. This suggests that worsening of symptoms in alkaptonuria (AKU) is paralleled by increased inflammation and oxidative stress, which might play a role in disease progression. CONCLUSIONS: Monitoring of SAA may be suggested in AKU to evaluate inflammation. Though further evidence is needed, SAA, chitotriosidase activity and PTI might be proposed as disease activity markers in AKU.

Molecular, clinical and neuropsychological study in 31 patients with Kabuki syndrome and KMT2D mutations.

Kabuki syndrome (KS-OMIM 147920) is a rare developmental disease characterized by the association of multiple congenital anomalies and intellectual disability. This study aimed to investigate intellectual performance in children with KS and link the performance to several clinical features and molecular data. We recruited 31 children with KMT2D mutations who were 6 to 16 years old. They all completed the Weschler Intelligence Scale for Children, fourth edition. We calculated all indexes: the Full Scale Intellectual Quotient (FSIQ), Verbal Comprehension Index (VCI), Perceptive Reasoning Index (PRI), Processing Speed Index (PSI), and Working Memory Index (WMI). In addition, molecular data and several clinical symptoms were studied. FSIQ and VCI scores were 10 points lower for patients with a truncating mutation than other types of mutations. In addition, scores for FSIQ, VCI and PRI were lower for children with visual impairment than normal vision. We also identified a discrepancy in indexes characterized by high WMI and VCI and low PRI and PSI. We emphasize the importance of early identification and intensive care of visual disorders in patients with KS and recommend individual assessment of intellectual profile.

Impact of preoperative calculation of nephron volume loss on future of partial nephrectomy techniques; planning a strategic roadmap for improving functional preservation and securing oncological safety.

OBJECTIVES: To assess the correlation of the resected and ischaemic volume (RAIV), which is a preoperatively calculated volume of nephron loss, with the amount of postoperative renal function (PRF) decline after minimally invasive partial nephrectomy (PN) in a multi-institutional dataset. PATIENTS AND METHODS: We identified 348 patients from March 2005 to December 2013 at six institutions. Data on all cases of laparoscopic (n = 85) and robot-assisted PN (n = 263) performed were retrospectively gathered. Univariable and multivariable linear regression analyses were used to identify the associations between various time points of PRF and the RAIV, as a continuous variable. RESULTS: The mean (sd) RAIV was 24.2 (29.2) cm3 . The mean preoperative estimated glomerular filtration rate (eGFR) and the eGFRs at postoperative day 1, 6 and 36 months after PN were 91.0 and 76.8, 80.2 and 87.7 mL/min/1.73 m2 , respectively. In multivariable linear regression analysis, the amount of decline in PRF at follow-up was significantly correlated with the RAIV (ß 0.261, 0.165, 0.260 at postoperative day 1, 6 and 36 months after PN, respectively). This study has the limitation of its retrospective nature. CONCLUSION: Preoperatively calculated RAIV significantly correlates with the amount of decline in PRF during long-term follow-up. The RAIV could lead our research to the level of prediction of the amount of PRF decline after PN and thus would be appropriate for assessing the technical advantages of emerging techniques.

Micro mercury trapped ion clock prototypes with 10[Formula: see text] frequency stability in 1-liter packages.

Modern communication and navigation systems are increasingly relying on atomic clocks. As timing precision requirements increase, demands for lower SWaP (size, weight, and power) clocks rise. However, it has been challenging to break through the general trade-off trend between the clock stability performance and SWaP. Here we demonstrate micro mercury trapped ion clock (M2TIC) prototypes integrated with novel micro-fabricated technologies to simultaneously achieve high performance and low SWaP. The M2TIC prototypes could reach the [Formula: see text]-stability level in 1 day with a SWaP of 1.1 L, 1.2 kg, and under 6 W of power. This stability level is comparable to the widely used rack-mount Microchip 5071A cesium frequency standard. These standalone prototypes survived regular commercial shipping across the North American continent to a government laboratory, where their performance was independently tested. The M2TIC sets a new reference point for SWaP and performance and opens opportunities for high-performance clocks in terrestrial and space applications.

Creating a human brain proteome atlas--13th HUPO BPP Workshop March 30-31, 2010, Ochang, Korea.

The HUPO Brain Proteome Project (HUPO BPP) held its 13th workshop in Ochang from March 30th to 31st, 2010 prior to the Korean HUPO 10th Annual International Proteomics Conference. The principal aim of this project is to obtain a better understanding of neurodiseases and aging with the ultimate objective of discovering prognostic and diagnostic biomarkers, in addition to the development of novel diagnostic techniques and new medications. The attendees came together to discuss progress in the clinical neuroproteomics of human and to define the needs and guidelines required for more advanced proteomics approaches.

Creating a human brain proteome atlas--14th HUPO BPP workshop September 20-21, 2010, Sydney, Australia.

The HUPO Brain Proteome Project (HUPO BPP) held its 14th workshop during the HUPO 9th Annual World Congress in Sydney, Australia. The principal aim of this project is to discover prognostic and diagnostic biomarkers associated with neurodegenerative diseases and brain aging, with the ultimate objective of obtaining a better understanding of these conditions and creating roads for the development of novel diagnostic techniques and effective treatments. The attendees came together to discuss progress in the human clinical neuroproteomics and to define the needs and guidelines required for more advanced proteomics approaches.

Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine:arginine.

Postprandial hyperglycemia induces vascular endothelial dysfunction (VED) and increases future cardiovascular disease risk. We hypothesized that postprandial hyperglycemia would decrease vascular function in healthy men by inducing oxidative stress and proinflammatory responses and increasing asymmetric dimethylarginine:arginine (ADMA:arginine), a biomarker that is predictive of reduced NO biosynthesis. In a randomized, cross-over design, healthy men (n = 16; 21.6 ± 0.8 y) ingested glucose or fructose (75 g) after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose and insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine, and ADMA were measured at regular intervals during the 3-h postprandial period. Baseline FMD did not differ between trials (P > 0.05). Postprandial FMD was reduced following the ingestion of glucose only. Postprandial MDA concentrations increased to a greater extent following the ingestion of glucose compared to fructose. Plasma arginine decreased and the ratio of ADMA:arginine increased to a greater extent following the ingestion of glucose. Inflammatory cytokines and cellular adhesion molecules were unaffected by the ingestion of either sugar. Postprandial AUC(0-3 h) for FMD and MDA were inversely related (r = -0.80; P < 0.05), suggesting that hyperglycemia-induced lipid peroxidation suppresses postprandial vascular function. Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation. Postprandial alterations in arginine and ADMA:arginine also suggest that acute hyperglycemia may induce VED by decreasing NO bioavailability through an oxidative stress-dependent mechanism. Additional work is warranted to define whether inhibiting lipid peroxidation and restoring arginine metabolism would mitigate hyperglycemia-mediated decreases in vascular function.

Left paratracheal pressure versus cricoid pressure for successful laryngeal mask airway insertion in adult patients: a randomized, non-inferiority trial.

BACKGROUND: Cricoid pressure (CP) is used to prevent pulmonary aspiration of regurgitated gastric contents and gastric insufflation during positive-pressure ventilation. However, CP impedes the successful insertion of laryngeal mask airway (LMA). Left paratracheal pressure (LPP), a maneuver of applying backward digital force at the lower left paratracheal level, was recently introduced as an alternative to CP. We assessed whether LPP is non-inferior to CP in successful LMA insertion on the first attempt in adult patients undergoing general anesthesia. METHODS: In this non-inferiority randomized controlled trial, 108 patients undergoing general anesthesia were randomly allocated to receive either LPP or CP during LMA insertion. The primary outcome was the success rate of LMA insertion on the first attempt. The margin of non-inferiority was defined as 15%. RESULTS: The success rate of LMA insertion on the first attempt was 68.5% (37/54) in the LPP group and 51.9% (28/54) in the CP group (P=0.077) with between-group difference of 16.7% (two-sided 95% CI, -1.9% to 35.2%). Time for successful device insertion was comparable in the two groups (P=0.355), whereas LMA insertion was easier in the LPP group than in the CP group (P=0.001). There was no significant difference between the two groups for change in antral cross-sectional area measured before and after mask ventilation (P=0.081). No serious complication was evident in any group. CONCLUSIONS: This randomized clinical trial demonstrated the non-inferiority of LPP over CP in the success rate of LMA insertion on the first attempt in adult patients undergoing general anesthesia.

Epilepsy with dual pathology: surgical treatment of cortical dysplasia accompanied by hippocampal sclerosis.

PURPOSE: The presence of two or more epileptogenic pathologies in patients with epilepsy is often observed, and the coexistence of focal cortical dysplasia (FCD) with hippocampal sclerosis (HS) is one of the most frequent clinical presentations. Although surgical resection has been an important treatment for patients with refractory epilepsy associated with FCD, there are few studies on the surgical treatment of FCD accompanied by HS, and treatment by resection of both neocortical dysplastic tissue and hippocampus is still controversial. METHODS: We retrospectively recruited epilepsy patients who had undergone surgical treatment for refractory epilepsy with the pathologic diagnosis of FCD and the radiologic evidence of HS. We evaluated the prognostic roles of clinical factors, various diagnostic modalities, surgical procedures, and the severity of pathology. RESULTS: A total of 40 patients were included, and only 35.0% of patients became seizure free. Complete resection of the epileptogenic area (p = 0.02), and the presence of dysmorphic neurons or balloon cells on histopathology (p = 0.01) were associated with favorable surgical outcomes. Patients who underwent hippocampal resection were more likely to have a favorable surgical outcome (p = 0.02). CONCLUSIONS: We show that patients with complete resection of epileptogenic area, the presence of dysmorphic neurons or balloon cells on histopathology, or resection of hippocampus have a higher chance of a favorable surgical outcome. We believe that this observation is useful in planning of surgical procedures and predicting the prognoses of individual patients with FCD patients accompanied by HS.

How Much Value Would a Treatment for Alzheimer's Disease Offer? Cost-Effectiveness Thresholds for Pricing a Disease-Modifying Therapy.

BACKGROUND: Recent trials suggest that disease-modifying therapy (DMT) for Alzheimer's disease may become available soon. With the expected high price and a large patient pool, the budget impact will be substantial. OBJECTIVE: We explore combinations of effectiveness and price under which a DMT is cost-effective. METHODS: We used an open-source model to conduct two-way scenario analyses for both payer and societal perspectives, varying price, and treatment effect size simultaneously. The analysis generates costeffectiveness threshold prices over a potential range of DMT effectiveness in patients aged 65+ with mild cognitive impairment due to Alzheimer's disease in the US. RESULTS: Under the willingness-to-pay a threshold of $150,000 per quality-adjusted life year and assuming 30% risk reduction relative to the standard of care, the maximum cost-effective price of a DMT per patient per year is ~$22,000 and ~$15,000 from societal and payer perspectives, respectively. CONCLUSION: Joint variation of price and treatment effect size can help assess the cost-effectiveness of a potential Alzheimer's disease treatment.

A mortality analysis of septic shock, vasoplegic shock and cryptic shock classified by the third international consensus definitions (Sepsis-3).

INTRODUCTION: This study aimed to compare the 28-day mortality of patients with septic shock, defined by Sepsis-3 criteria and patients with vasoplegic or cryptic shock who are excluded from this new definition. OBJECTIVES: This retrospective observational study was performed using a tertiary emergency department's septic shock registry and investigated the records of patients managed between January 2010 and December 2015. In 2,138 total patients, 1004 (47.0%) had septic shock, 476 (22.2%) had vasoplegic shock and 655 (30.6%) had cryptic shock. RESULTS: There was significant variation in 28-day mortality among the three groups: 23.4% for septic shock, 8.8% for vasoplegic shock and 12.2% for cryptic shock (P < .001). In subgroup analysis of cryptic shock or septic shock according to lactate levels (2-3, 3-4 and >4 mmol/L), the mortality rate increased as lactate increased (cryptic shock: 9.5%, 14.8% and 18.0%; septic shock: 18.6%, 22.6% and 27.0%, respectively; P < .001). Multivariable analysis revealed odds ratios for mortality of 0.31 (95% CI 0.22-0.44; P < .001) for vasoplegic shock and 0.46 (95% CI 0.35-0.61; P < .001) for cryptic shock relative to septic shock. Survival curve analysis showed significant differences among patients with septic shock, vasoplegic shock and cryptic shock (Log rank test: P < .0001). CONCLUSION: The new septic shock definition may be useful for identifying high-risk patients requiring intensive care. However, cryptic shock-associated mortality increased to 18.0% as serum lactate increased, which suggests that some cryptic shock patients may also require intensive management.

Ethanol-induced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice.

BACKGROUND/AIMS: Oxidative stress via generation of reactive oxygen species is suggested to be the major mechanism of alcohol-induced liver injury. We investigated the effects of glutathione peroxidase-1 and catalase double deficiency (Gpx-1(-/-)/Cat(-/-)) on liver injury and changes in the sulfur amino acid metabolism induced by binge ethanol administration. METHODS: Ethanol (5 g/kg) was administered orally to the wild-type and the Gpx-1(-/-)/Cat(-/-) mice every 12 h for a total of three doses. Mice were sacrificed 6 h after the final dose. RESULTS: The Gpx-1/Cat deficiency alone increased malondialdehyde levels in liver significantly. Hepatic methionine adenosyltransferase (MAT) activity and S-adenosylmethionine levels were decreased, however, glutathione contents were not changed. Ethanol administration to the Gpx-1(-/-)/Cat(-/-) mice increased the elevation of serum alanine aminotransferase activity, plasma homocysteine levels, hepatic fat accumulation and lipid peroxidation compared with the wild-type animals challenged with ethanol. Also the reduction of MAT activity and S-adenosylmethionine levels was enhanced, but MATI/III expression was increased significantly. CONCLUSIONS: The results indicate that Gpx-1 and Cat have critical roles in the protection of liver against binge ethanol exposure. Augmentation of ethanol-induced oxidative stress may be responsible for the impairment of the transsulfuration reactions and the aggravation of acute liver injury in the Gpx-1(-/-)/Cat(-/-) mice.

Technetium-99m-GSA clearance in mice under long-term dietary restriction.

OBJECTIVE: Dietary restriction (DR) without malnutrition is widely acknowledged to prolong lifespan in laboratory animals. Evidence suggests that DR retards age-related decline in protein turnover of most organs. However, there has been no report about hepatic serum glycoprotein catabolism under DR. In the current study, we evaluate the hepatic uptake of asialoglycoprotein in ICR mice with DR by measuring the plasma clearance of technetium-99m galactosyl human serum albumin (Tc-GSA). METHODS: The amount of food supplied to the restricted mice was 70% of that consumed by the mice fed ad libitum (AL). The regimen was initiated at the age of 7 weeks and terminated after the age of 44 weeks. The plasma clearance of Tc-GSA was measured at the age of 7 weeks, 14 weeks, 28 weeks, and 42 weeks. RESULTS: The restricted animals showed a marked decrease in their body and liver weight, and hepatic uptake of Tc-GSA per liver weight in the restricted mice was greater than that in the mice fed AL. On the other hand, the Tc-GSA plasma clearance in the mice fed AL was stable during the study period, and that in the restricted mice showed no change with age either, and those in the two groups were similar. In addition to the receptor function, there was no difference in the expression of mRNAs of the asialoglycoprotein receptor between the two groups. Serum concentrations of cholinesterase and hepatic mRNAs of glutamine synthetase in the restricted mice were higher than those in the mice fed AL. Serum levels of amino acids in the restricted mice were lower than those in the mice fed AL. CONCLUSIONS: The data presented here show that the DR did not affect the capacity of hepatic serum glycoprotein catabolism, whereas several protein metabolic pathways were affected.

The role of intracellular signaling in insulin-mediated regulation of drug metabolizing enzyme gene and protein expression.

Endogenous factors, including hormones, growth factors and cytokines, play an important role in the regulation of hepatic drug metabolizing enzyme expression in both physiological and pathophysiological conditions. Diabetes, fasting, obesity, protein-calorie malnutrition and long-term alcohol consumption produce changes in hepatic drug metabolizing enzyme gene and protein expression. This difference in expression alters the metabolism of xenobiotics, including procarcinogens, carcinogens, toxicants and therapeutic agents, potentially impacting the efficacy and safety of therapeutic agents, and/or resulting in drug-drug interactions. Although the mechanisms by which xenobiotics regulate drug metabolizing enzymes have been studied intensively, less is known regarding the cellular signaling pathways and components which regulate drug metabolizing enzyme gene and protein expression in response to hormones and cytokines. Recent findings, however, have revealed that several cellular signaling pathways are involved in hormone- and growth factor-mediated regulation of drug metabolizing enzymes. Our laboratory has reported that insulin and growth factors regulate drug metabolizing enzyme gene and protein expression, including cytochromes P450 (CYP), glutathione S-transferases (GST) and microsomal epoxide hydrolase (mEH), through receptors which are members of the large receptor tyrosine kinase (RTK) family, and by downstream effectors such as phosphatidylinositol 3-kinase, mitogen activated protein kinase (MAPK), Akt/protein kinase B (PKB), mammalian target of rapamycin (mTOR), and the p70 ribosomal protein S6 kinase (p70S6 kinase). Here, we review current knowledge of the signaling pathways implicated in regulation of drug metabolizing enzyme gene and protein expression in response to insulin and growth factors, with the goal of increasing our understanding of how disease affects these signaling pathways, components, and ultimately gene expression and translational control.

Experiences with acute kidney injury complicating non-fulminant hepatitis A.

AIM: To describe the clinical features and to identify factors related to development of acute kidney injury in acute hepatitis A patients. METHODS: The study and control groups consisted of 21 and 425 patients who did or did not develop acute kidney injury, respectively, after acute hepatitis A from January 1997 to May 2007. RESULTS: There were 13 men and eight women; their mean age at diagnosis was 28.8 +/- 8.2 years in the study group. Peak values for renal and liver function impairment consisted of a median serum creatinine of 4.6 mg/dL (range, 1.5-15.3 mg/dL) on day 6 (range, days 1-20) and a median total bilirubin of 10.7 mg/dL (range, 2.6-57.5 mg/dL) on day 8 (range, day 1-19). Serum creatinine concentrations returned to baseline level by a median of 16 days and total bilirubin levels returned to normal by a median of 62 days. Six of 21 (29%) patient underwent haemodialysis. Renal biopsies performed in two patients showed acute tubular necrosis and interstitial nephritis, respectively. Logistic regression analysis showed that a lower haematocrit, the presence of coagulopathy and high C-reactive protein concentration on admission, and higher peak bilirubin value during the illness were associated with development of acute kidney injury. CONCLUSION: Acute hepatitis A should be considered in the differential diagnosis of patients with acute kidney injury, even without fulminant hepatic failure. A lower haematocrit, the presence of coagulopathy and high C-reactive protein level at presentation, and higher peak bilirubin level during the illness were associated with development of acute kidney injury in acute hepatitis A patients.

Ureteral nephrogenic adenoma in a renal allograft patient.

A 56-year-old male who had renal transplants at the age of 34 and 49 years, presented with painless gross hematuria six years after the second renal transplantation. An abdominal computed tomography scan revealed diffuse wall thickening of the distal ureter of the failed first allograft and a bulging lesion about 1.2 cm in size on the lower pole of the right native kidney. Both lesions were suspected for tumors, but they showed a ureteral nephrogenic adenoma and a renal hemorrhagic simple cyst.

Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not in GLUT1 Deficiency.

OBJECTIVE: Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. METHODS: We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. RESULTS: In GLUT1-DS patients, we observed clinical deterioration including increased frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed clinical improvement as dystonic crises and fatigability decreased under basal metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has largely replaced the ketogenic diet, with the latter that is mostly resumed only during febrile illness. Positive direct effects on energy metabolism in PDHD patients were suggested by negative correlation between ketonemia and lactatemia (r 2 = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of CO2 production after 14C-labeled 3-hydroxybutyrate supplementation was consistent with improved Krebs cycle activity. However, except in one patient, ketonemia tended to be lower with 3-hydroxybutyrate administration compared to ketogenic diet. CONCLUSION: 3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.