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A new crocodylian, Dongnanosuchus hsui n. gen. n. sp., is described mainly based on four well-preserved skulls from the Eocene Youganwo Formation of the Maoming Basin, southeastern China. It is an alligatoroid and phylogenetically nested within the Orientalosuchina. Dongnanosuchus hsui n. gen. n. sp. differs from all other orientalosuchines primarily in certain features of the skull: (1) a preorbital ridge connects posteriorly with the dorsal orbital rim and a ridge around the anteroventral margin of the orbit, (2) the palatine is short and does not reach the posterior border of the suborbital fenestra, (3) the external mandibular fenestra is closed, and (4) the splenial joins the formation of the mandibular symphysis. The discovery of Dongnanosuchus hsui n. gen. n. sp. confirms the monophyly and North American origin of the Orientalosuchina but suggests that the clade dispersed to Asia via Beringia after diverging from the mainline rather than a sub-lineage of the Alligatoroidea in the Late Cretaceous.UUID: http://zoobank.org/f8ca22f1-6323-462e-bf32-03c6a164c82e.

Intranasal insulin administration may improve cognitive function in patients with dementia and may prevent cognitive problems after surgery. Although the metabolic effects of intranasal insulin in non-surgical patients have been studied, its influence on glucose concentration during surgery is unknown.We conducted a randomized, double-blind, placebo-contolled trial in patients scheduled for elective cardiac surgery. Patients with type 2 diabetes mellitus (T2DM) and non-T2DM patients were randomly allocated to one of three groups (normal saline, 40 international units [IU] of intranasal insulin, and 80 IU intranasal insulin). Insulin was given after the induction of general anesthesia. Glucose and plasma insulin concentrations were measured in ten-minute intervals during the first hour and every 30 min thereafter. The primary outcome was the change in glucose concentration 30 min after intranasal insulin administration.A total of 115 patients were studied, 43 of whom had T2DM. In non-T2DM patients, 40 IU intranasal insulin did not affect glucose concentration, while 80 IU intranasal insulin led to a statistically significant but not clinically important decrease in blood glucose levels (mean difference, 0.4 mMol·LIn patients with and without T2DM undergoing elective cardiac surgery, intranasal insulin administration at doses as high as 80 IU did not cause clinically important hypoglycemia.www.ClinicalTrials.gov (NCT02729064); registered 5 April 2016.RéSUMé: OBJECTIF: L’administration intranasale d’insuline pourrait améliorer la fonction cognitive des patients souffrant de démence et pourrait prévenir les problèmes cognitifs après une chirurgie. Bien que les effets métaboliques de l’insuline intranasale chez les patients non chirurgicaux aient été étudiés, son influence sur la glycémie pendant une chirurgie est inconnue. MéTHODE: Nous avons réalisé une étude randomisée, à double insu, contrôlée par placebo auprès de patients devant subir une chirurgie cardiaque non urgente. Des patients atteints de diabète de type 2 et des patients non diabétiques ont été randomisés dans l’un de trois groupes (solution physiologique salée, 40 unités internationales [UI] d’insuline intranasale et 80 UI d’insuline intranasale). La solution intranasale a été administrée après l’induction de l’anesthésie générale. Les concentrations de glucose et d’insuline plasmatique ont été mesurées à des intervalles de dix minutes pendant la première heure et toutes les 30 minutes par la suite. Le critère d’évaluation principal était le changement de glycémie 30 min après l’administration intranasale d’insuline. RéSULTATS: Un total de 115 patients ont été étudiés, dont 43 souffraient de diabète de type 2. Chez les patients non diabétiques, 40 UI d’insuline intranasale n’ont pas affecté la glycémie, alors que 80 UI d’insuline intranasale ont entraîné une réduction statistiquement significative mais non cliniquement importante de la glycémie (différence moyenne, 0,4 mMol·L

Migration test of food utensils, containers, and packaging is an important test method for confirming the safety and their compliance to the standards. However, there is little report on inter-laboratory study which was performed to evaluate the entire migration test, including migration operations and quantification. An interlaboratory study was performed participating 22 laboratories using 8 types of model synthetic resin samples containing 10 substances with a wide range of Log P

Protamine causes cardiac depression, which may be mediated by tumor necrosis factor alpha (TNF-α). Ulinastatin, a human urinary protease inhibitor, inhibits TNF-α. Here, we aimed to investigate whether ulinastatin prevented protamine-induced myocardial depression by inhibiting TNF-α. Rat hearts were perfused using a Langendorff system, and three protocols were followed. Protocol 1: The hearts were divided into saline, ulinastatin-low, and ulinastatin-high groups. Protamine was administered to each group, and myocardial contractility was the primary outcome. Protocol 2: The hearts were allotted to saline or ulinastatin group. Protamine was administered to each group. TNF-α expression in the coronary effluent and myocardial tissue was measured. Protocol 3: The hearts were allotted to saline and ulinastatin groups. Recombinant rat-TNF-α was administered to each group. Protamine alone reduced the maximum left ventricular pressure derivative (LV dP/dt max) by 45 ± 4%. In contrast, the reduction in LV dP/dt max was 4 ± 3% in the ulinastatin-high group. Compared with that in the saline group, the increase in TNF-α in the coronary effluent was attenuated in the ulinastatin group. Recombinant TNF-α alone reduced LV dP/dt max (- 21 ± 14%). In contrast, when TNF-α was added in the presence of ulinastatin, the decrease in LV dP/dt max was prevented significantly (- 3 ± 8%). We showed, for the first time, that ulinastatin protected against protamine-induced myocardial damage, both by inhibiting TNF-α synthesis and by directly preventing the cardiodepressant action of TNF-α.

Mandibular morphology is determined not only by dietary habits, but also by sexual selection and allometry in primates. It is well-known that African papionins show intra- and interspecific variations through varied extensions of a common ontogenetic allometric trajectory in the face. Here, we used geometric morphometrics to compare the ontogenetic trajectories of large-bodied Japanese macaques and small-bodied long-tailed macaques in the sister clade of African papionins. The two species showed a major common allometric trend that was comparable to that of African papionins, but the allometric trajectory was transposed parallel to each other with few interspecies differences in mandibular shape. A minor allometric trend occurred before the eruption of the first molar. During extensino of this allometric trend in Japanese macaques, mandibular shape becomes mechanically suitable for processing tough food items in their dietary repertoire in winter. The decoupling of size and shape in the major allometric trend can allow for adaptive modifications in mandibular shape, which in turn may play a central role in speciation in macaques. Compared to other African papionins, macaques are widely distributed in temperate areas and have survived in fluctuating climates and habitats. Thus, evolutionary modifications that occur in different ontogenetic bases can result in variations in size and shape that are uniquely adaptive for a given clade.

Insulin exerts positive inotropic effects on cardiac muscle; however, the relationship between cardiac contractility and phosphoinositol-3-kinase/Akt (PI3K/Akt) activation remains unclear. We hypothesized that the positive inotropic effects of insulin are dose-dependent and mediated via the PI3K/Akt pathway in isolated normal rat hearts. The Institutional Animal Investigation Committee approved the use of hearts excised from rats under pentobarbital anesthesia. The hearts were perfused at a constant pressure using the Langendorff technique. After stabilization (baseline), the hearts were randomly divided into the following four insulin (Ins) groups: 1) Ins0 (0 IU/L), 2) Ins0.5 (0.5 IU/L), 3) Ins5 (5 IU/L), and 4) Ins50 (50 IU/L) (n = 8 in each group). To clarify the role of the PI3K/Akt pathway in insulin-dependent inotropic effects, we also treated the insulin groups with the PI3K inhibitor wortmannin (InsW): 5) InsW0 (0 IU/L), 6) InsW0.5 (0.5 IU/L), 7) InsW5 (5 IU/L), and 8) InsW50 (50 IU/L). Hearts were perfused with Krebs–Henseleit buffer solution with or without wortmannin for 10 min, followed by 20 min perfusion with the solution containing each concentration of insulin. The data were recorded as the maximum left ventricular derivative of pressure development (LV dP/dt max). Myocardial p-Akt levels were measured at 3 min, 5 min, and at the end of the perfusion. In the Ins groups, LV dP/dt max in Ins5 and Ins50 increased by 14% and 48%, respectively, 3 min after insulin perfusion compared with the baseline. Tachyphylaxis was observed after 10 min in the Ins5 and Ins50 treatment groups. Wortmannin partially inhibited the positive inotropic effect of insulin; although insulin enhanced p-Akt levels at all time points compared with the control group, this increase was suppressed in the presence of wortmannin. The positive inotropic effect of insulin is dose-dependent and consistent with Akt activation. This effect mediated by high doses of insulin on cardiac tissue was temporary and caused tachyphylaxis, potentially triggered by Akt overactivation, which leads beta 1 deactivation.

Background: Lactoferrin, an iron-binding glycoprotein, is known to have protective effects against intestinal and cerebral ischemia-reperfusion (IR) injuries; however, its cardioprotective effects against the stunned myocardium are unknown. This study aimed to test the hypothesis that lactoferrin has cardioprotective effects against stunned myocardium. Methods: Using isolated rat hearts (Langendorff system), we determined the effects of lactoferrin administered enterally and by direct cardiac perfusion. Rat hearts were perfused using the Langendorff system, and two experiments were performed. In experiment 1, the hearts were divided into the enteral lactoferrin (E-LF) 7.5 m, 15 m, 30 m, and 60 m groups, where lactoferrin (1000 mg/kg) was administered enterally 7.5, 15, 30, and 60 min, respectively, before perfusion; and a control group, where saline was administered 30 min before perfusion. In experiment 2, hearts were allocated to the perfusate lactoferrin (P-LF) 15 and 100 groups, where 15 mg/L and 100 mg/L lactoferrin were respectively added to the perfusate, and a control group. Each group was perfused for 20 min prior to 15 min of no-flow ischemia with pacing, followed by 20 min of reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (LV dP/dt max) 15 min after reperfusion. Myocardial phospho-protein kinase B (p-Akt) was assayed using western blotting. Results: The LV dP/dt max 15 min after reperfusion in the E-LF 15 and 30 m groups was significantly higher than that in the control group. However, the effects disappeared in the E-LF 60 m group. In the second experiment, there were no significant differences in LV dP/dt max. Myocardial p-Akt was not significantly activated in any lactoferrin group. Conclusion: Cardioprotection was observed 15–30 min after enteral lactoferrin but not by direct cardiac perfusion with lactoferrin. Myocardial p-Akt was not associated with the cardioprotective effect. The cardioprotective effect may be induced by enteral lactoferrin-induced substances.

A fossil specimen of the jumping plant-louse genus Cacopsylla (Insecta, Hemiptera, Psylloidea) is described from lacustrine sediments of the middle Pleistocene Miyajima Formation of the Shiobara Group in Tochigi Prefecture, central Japan. It is the first report of a psylloid fossil from Japan. The specimen is a compression fossil of almost whole insect body, and the superb preservation of forewings with delicate veins and membrane tissues strongly suggests that it can be most probably identified as Cacopsylla abieti (Kuwayama), which is a common extant psyllid species in the fossil locality, or possibly its most closely relative of continental east Asia, Cacopsylla pseudosieboldiani (Konovalova and Loginova). The fossil-yielding stratum is a Lagerstatte known for the abundant fossil leaves and other fossil organisms. Extant C. abieti feeds on Siebold’s maple Acer sieboldianum, and remains of various species of Acer including A. sieboldianum are common components of Shiobara fossil biota.

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The Nova StatStrip® Glucose Hospital Meter System (Nova Biomedical, Waltham, MA, USA) is United States Food and Drug Administration approved for point-of-care use in critically ill patients, but its use during cardiac surgery has not been evaluated. In this study, we compare glucose values obtained during cardiac surgery by StatStrip® with values obtained by a blood gas analyzer. Blood glucose concentrations were analyzed in 121 patients by the StatStrip point- of-care test (POCT) glucose monitor and the GEM® Premier™ 3000 blood gas analyzer (Instrumentation Laboratory Company, Bedford MA, USA). Arterial blood samples were taken at baseline (before surgery), before cardiopulmonary bypass (CPB), during early and late CPB, and 30 min after CPB. Accuracy of the StatStrip glucometer was analyzed using the Clinical and Laboratory Standards Institute (CLSI) POCT12-A3 criteria (criterion 1; 95% of samples should be ± 0.66 mMol·L−1 of reference glucose values 5.5 mMol·L−1, criterion 2; 98% of samples should be ± 0.83 mMol·L−1 of reference glucose values 4.1 mMol·L−1). The accuracy of StatStrip glucose measurements at baseline (99%, 100%) and before CPB (95%, 98%), but not during (early: 84%, 97%; late: 83%, 96%) and after (92%, 100%) CPB, satisfied the CLSI POCT12-A3 criteria. Arterial blood glucose measurement by StatStrip was accurate before CPB, but lacked accuracy during and after CPB. Glucose values should be interpreted with caution when intensive glucose control protocols are being used during cardiac surgery. ClinicalTrials.gov (NCT02729064); registered 5 April, 2016.

Background While lactoferrin, an iron-binding glycoprotein, has protective effects on intestinal and cerebral ischemia-reperfusion injuries, its cardioprotective effects against stunned myocardium are unknown. This study aimed to test the hypothesis that lactoferrin has cardioprotective effects against stunned myocardium. Methods Rat hearts were perfused using the Langendorff system, and two experiments were performed. In experiment 1, the hearts were divided into the enteral lactoferrin (E-LF) 7.5 m, 15 m, 30 m, and 60 m groups, where lactoferrin (1000 mg/kg) was administered enterally for 7.5, 15, 30, and 60 min, respectively, before perfusion; and a control group, where saline was administered 30 min before perfusion. In experiment 2, hearts were allocated to the perfusate lactoferrin (P-LF) 15 and 100 groups, where 15 mg/L and 100 mg/L lactoferrin were respectively added to the perfusate, and a control group. Each group was perfused for 20 min prior to 15 min of no-flow ischemia with pacing, followed by 20 min of reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (LV dP/dt max) 15 min after reperfusion. Myocardial phospho-protein kinase B (p-Akt) was assayed by western blotting. Results LV dP/dt max in the E-LF 15 m and 30 m groups was significantly higher than in the control group. In the second experiment, there were no significant differences in LV dP/dt max. Myocardial p-Akt was not significantly activated in any lactoferrin group. Conclusion Cardio-protection was observed with enteral but not parenteral lactoferrin administration, and myocardial p-Akt was not involved in this effect.

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The Polycotylidae are short-necked plesiosaurs known from the Cretaceous in various parts of the world, but only a few occurrences have been documented in Japan, where elasmosaurid remains are much more common. An indeterminate polycotylid specimen from the Upper Cretaceous in Obira Town, Hokkaido, is described. Characteristics of the vertebrae and clavicular arch support its taxonomic affinity. The Turonian occurrence of the specimen indicates the continuous presence of the Polycotylidae across the Cenomanian-Turonian boundary in the northwestern Pacific. Macroscopic osteological features of the vertebrae and clavicular arch indicate an advanced stage of ossification, and there are histological characteristics suggesting slowed growth. The osteoporotic-like condition implies a high degree of aquatic adaption.

Background Hyperinsulinemic normoglycemia augments myocardial glucose uptake and utilization. We tested the hypothesis that hyperinsulinemic normoglycemia reduces 30-day mortality and morbidity after cardiac surgery. Methods This dual-center, parallel-group, superiority trial randomized cardiac surgical patients between August 2007 and March 2015 at the Cleveland Clinic, Cleveland, Ohio, and Royal Victoria Hospital, Montreal, Canada, to intraoperative glycemic management with (1) hyperinsulinemic normoglycemia, a fixed high-dose insulin and concomitant variable glucose infusion titrated to glucose concentrations of 80 to 110 mg · dl–1; or (2) standard glycemic management, low-dose insulin infusion targeting glucose greater than 150 mg · dl–1. The primary outcome was a composite of 30-day mortality, mechanical circulatory support, infection, renal or neurologic morbidity. Interim analyses were planned at each 12.5% enrollment of a maximum 2,790 patients. Results At the third interim analysis (n = 1,439; hyperinsulinemic normoglycemia, 709, standard glycemic management, 730; 52% of planned maximum), the efficacy boundary was crossed and study stopped per protocol. Time-weighted average glucose concentration (means ± SDs) with hyperinsulinemic normoglycemia was 108 ± 20 versus 150 ± 33 mg · dl–1 with standard glycemic management, P < 0.001. At least one component of the composite outcome occurred in 49 (6.9%) patients receiving hyperinsulinemic normoglycemia versus 82 (11.2%) receiving standard glucose management (P < efficacy boundary 0.0085); estimated relative risk (95% interim-adjusted CI) 0.62 (0.39 to 0.97), P = 0.0043. There was a treatment-by-site interaction (P = 0.063); relative risk for the composite outcome was 0.49 (0.26 to 0.91, P = 0.0007, n = 921) at Royal Victoria Hospital, but 0.96 (0.41 to 2.24, P = 0.89, n = 518) at the Cleveland Clinic. Severe hypoglycemia (less than 40 mg · dl–1) occurred in 6 (0.9%) patients. Conclusions Intraoperative hyperinsulinemic normoglycemia reduced mortality and morbidity after cardiac surgery. Providing exogenous glucose while targeting normoglycemia may be preferable to simply normalizing glucose concentrations.

A basal mosasauroid specimen, including a rib and a vertebra from the middle to posterior portion of the trunk, is reported from the lower Campanian Inoceramus (Platyceramus) japonicus Zone in Obira Town, northern Hokkaido, northern Japan. It is the second occurrence of basal mosasauroids sensu lato in Japan after the halisaurine Phosphorosaurus ponpetelegans, but represents a larger individual than the P. ponpetelegans holotype. The Obira specimen predates the early Maastrichtian P. ponpetelegans by about 10 million years, indicating colonization by basal mosasauroids of the northwestern Pacific by at latest the early Campanian age. While the overall morphology of the Obira specimen agrees well with that of a halisaurine vertebra, the presence of well developed zygantra (zygosphenes missing postmortem if present), the inclined condyle, and a distinct precondylar constriction uniquely align the specimen with Pannoniasaurus inexpectatus, a Santonian-aged basal mosasauroid from freshwater deposits...

Tomistoma petrolica Yeh, 1958 is restudied here based on 18 new specimens from the same horizon of the type and a previously referred specimen (IVPP V 5015) in Maoming, Guangdong Province. Our restudy reveals that ‘T.’ petrolica is morphologically incomparable with the extant species Tomistoma schlegelii and other species referred to Tomistoma in a number of osteological features, such as the penetration by the first dentary tooth in the anterior tip of the rostrum, the premaxilla-maxillary suture on the palate with a strong anterior projection, the jugal-quadratojugal suture starting from the posteroventral corner of the infratemporal fenestra, the sharp anterior process of the palatine relatively long, the palatine-pterygoid suture anteriorly positioned, and the broad tip of the neural spine of the third cervical vertebra. Therefore, a new genus, Maomingosuchus, is erected to include Maomingosuchus petrolica. This study also supports the previous view that a common pattern of the phylogenetic relationships among the Tomistominae cannot be established before collecting more specimens of the fragmentary taxa and sampling a suitable set of characters for the phylogenetic analysis of the group. However, this study suggests that M. petrolica may be grouped in a lineage also including Tomistoma lusitanica (Portugal), Gavialosuchus eggenburgensis (Austria), the living species T. schlegelii, Paratomistoma courti (northern Africa), and Tomistoma coppensi (central Africa). Within the lineage, M. petrolica appears to be more closely related to T. schlegelii than to the P. courti-T. coppensi clade and T. schlegelii is most probably related to the T. lusitanica-G. eggenburgensis clade rather than to M. petrolica. With the addition of M. petrolica, our phylogenetic results indicate that the origin and dispersal history of the extant species were much more complicated than what we previously thought.

Ordering and disordering electrons When a liquid is cooled rapidly, it can form a glass, a state stuck between liquid and solid. Two groups looked in detail into analogous dynamics in electronic systems. Sato et al. and Sasaki et al. studied layered organic materials with a triangular in-plane lattice. These materials can assume a state in which their charge distribution has a regular pattern—an electronic or charge crystal. When the materials were cooled rapidly, a charge glass was formed instead and then allowed to crystallize. The dynamics of crystallization showed similarities to the analogous processes in conventional glasses. Science , this issue p. 1378 , p. 1381

Background While acute hyperglycemia has been shown to mitigate the beneficial effects of ischemic preconditioning, its effect on insulin-induced preconditioning remains unclear. Methods The study was designed to test the hypothesis that acute hyperglycemia diminishes the cardioprotective effects following a 20-min pre-ischemic pre-conditioning with insulin in the isolated rat heart using the Langendorff system. Forty hearts were assigned to receive modified Krebs–Henseleit (KH) buffer containing 0.5 U/L insulin and 100 mg/dL glucose (InsG100, n = 10), KH buffer with 100 mg/dL glucose (G100, n = 10), KH buffer supplemented with 0.5 U/L insulin and 600 mg/dL glucose (InsG600, n = 10), or with 600 mg/dL glucose (G600, n = 10). To match the osmotic pressure of the InsG600 group, 27.5 mmol/L of mannitol was added to KH solution in the InsG100 and G100 group. The four groups were perfused with each solution for 20 min prior to 15 min of no-flow ischemia, and during 20 min of reperfusion. Only during the ischemic period the heart was paced at 222 beats/min. Measurements of heart rate, coronary flow and maximum of LV derivative of pressure development (dP/dt max) were recorded. Myocardial phospho-protein kinase B (p-Akt) and tumor necrosis factor-α (TNF-α) levels were assayed by enzyme-linked immunosorbent assay and sandwich ELISA, respectively following reperfusion. Results After reperfusion, LV dP/dt max and heart rate in the InsG100 group was significantly higher than that in the other three groups. The myocardial p-Akt level in the InsG100 group was significantly elevated when compared to the InsG600 group at the end of reperfusion. The p-Akt levels in the InsG600 and InsG100 group were significantly higher than in the corresponding non-insulin groups. Conclusions Acute hyperglycemia diminishes the cardioprotective effects of insulin preconditioning in the isolated rat heart, possibly mediated through the suppression of myocardial Akt phosphorylation.

A historical collection of hesperornithiform fossils from the Gammon Ferruginous, Pembina, and Millwood members of the Pierre Shale (Campanian, Upper Cretaceous) in southern Manitoba, Canada, was examined to revise their taxonomy. Only two species of Hesperornis have been recognized in previous studies on the Pierre Shale in Manitoba, but our study recognizes six species of two genera, including H. lumgairi sp. nov. H. regalis is the most common species but absent in the uppermost unit within the studied sequence. The result of this study supports the paleobiogeographic subdivision of the Campanian vertebrate fauna within the Western Interior Seaway, but not the faunal boundary that distinguishes the avian fauna of Manitoba from that of South Dakota and Kansas.

A nearly complete pinniped skeleton from the middle Miocene Okoppezawa Formation ( ca 16.3–13.9 Ma), Hokkaido, northern Japan, is described as the holotype of Allodesmus uraiporensis sp. nov. The new species is distinguishable from other species of the genus by having the palatine fissure (incisive foramen) that is located anterior to the canine, an anteriorly located supraorbital process of the frontal, and by having the calcaneum with a developed peroneal tubercle. Our phylogenetic analysis suggests that the subfamily Allodesminae are represented by two genera, Atopotarus and Allodesmus , and the latter genus is represented by at least six species; Al . kernensis , Al . sinanoensis , Al . naorai , Al . packardi, Al. demerei and Al. uraiporensis sp. nov. Allodesmus uraiporensis sp. nov. is one of the oldest and the northernmost record of the genus in the western North Pacific, and it suggests that the diversification of the genus in the western North Pacific was synchronous to the time of their diversification in the eastern North Pacific.

Hyperinsulinemic normoglycemia augments myocardial glucose uptake and utilization. We tested the hypothesis that hyperinsulinemic normoglycemia reduces 30-day mortality and morbidity after cardiac surgery.This dual-center, parallel-group, superiority trial randomized cardiac surgical patients between August 2007 and March 2015 at the Cleveland Clinic, Cleveland, Ohio, and Royal Victoria Hospital, Montreal, Canada, to intraoperative glycemic management with (1) hyperinsulinemic normoglycemia, a fixed high-dose insulin and concomitant variable glucose infusion titrated to glucose concentrations of 80 to 110 mg · dl; or (2) standard glycemic management, low-dose insulin infusion targeting glucose greater than 150 mg · dl. The primary outcome was a composite of 30-day mortality, mechanical circulatory support, infection, renal or neurologic morbidity. Interim analyses were planned at each 12.5% enrollment of a maximum 2,790 patients.At the third interim analysis (n = 1,439; hyperinsulinemic normoglycemia, 709, standard glycemic management, 730; 52% of planned maximum), the efficacy boundary was crossed and study stopped per protocol. Time-weighted average glucose concentration (means ± SDs) with hyperinsulinemic normoglycemia was 108 ± 20 versus 150 ± 33 mg · dl with standard glycemic management, P0.001. At least one component of the composite outcome occurred in 49 (6.9%) patients receiving hyperinsulinemic normoglycemia versus 82 (11.2%) receiving standard glucose management (Pefficacy boundary 0.0085); estimated relative risk (95% interim-adjusted CI) 0.62 (0.39 to 0.97), P = 0.0043. There was a treatment-by-site interaction (P = 0.063); relative risk for the composite outcome was 0.49 (0.26 to 0.91, P = 0.0007, n = 921) at Royal Victoria Hospital, but 0.96 (0.41 to 2.24, P = 0.89, n = 518) at the Cleveland Clinic. Severe hypoglycemia (less than 40 mg · dl) occurred in 6 (0.9%) patients.Intraoperative hyperinsulinemic normoglycemia reduced mortality and morbidity after cardiac surgery. Providing exogenous glucose while targeting normoglycemia may be preferable to simply normalizing glucose concentrations.

Hupehsuchus nanchangensis has been known from five specimens from the Triassic of China since its type was found in 1972. However, our knowledge of its morphology is still limited because of the po...

Taking into account the previously described link between body weight and diabetes mellitus (DM) in non-surgical patients, and the understanding that the degree of intraoperative insulin resistance is a predictor of adverse clinical outcomes, we investigated the relationship between body mass index (BMI) and insulin sensitivity during cardiac surgery. We prospectively enrolled 400 patients scheduled for elective cardiac surgery and divided them into groups based on the presence or absence of type-2 DM. They were further categorized into four subgroups based on their BMI: group 1- normal weight, BMI 18.5-24.9 kg·m−2; group 2 - overweight, BMI 25-29.9 kg·m−2; group 3 - obese, BMI 30-34.9 kg·m−2; group 4 - morbidly obese, BMI ≥ 35 kg·m−2. Insulin sensitivity was assessed using the hyperinsulinemic-normoglycemic clamp technique during surgery. We also analyzed the association of BMI, quality of postoperative glycemic control, and postoperative outcomes. A linear negative relationship between BMI and insulin sensitivity (r = 0.42, P < 0.001) was observed, independent of the patients’ diabetic state. There was also a positive correlation between BMI and postoperative glycemia (r = 0.30, P < 0.001) though the relationship between BMI and major and infectious complication was not significant (P = 0.56, P = 0.10, respectively). Patient BMI may be used as a simple predictor of insulin sensitivity during cardiac surgery and as a predictor of the quality of postoperative glycemic control. A larger cohort will be necessary to evaluate the association of BMI, perioperative insulin resistance, and clinical outcomes.

The ichthyopterygian Utatsusaurus hataii Shikama et al. 1978 is the only valid reptilian taxon known from the Lower Triassic Osawa Formation in Minamisanriku Town, Miyagi Prefecture, which records the recovery of the marine ecosystem shortly after the end-Permian mass extinction. In this paper, we describe a fragmentary specimen of an indeterminate ichthyopterygian which is distinguished from Utatsusaurus hataii based on rib morphology. The discovery of a previously unknown ichthyopterygian implies that the taxonomic diversity of the reptilian fauna of this formation is higher than previously assumed.

A nearly complete skeleton of a new hadrosaurid, Kamuysaurus japonicus gen. et sp. nov., was discovered from the outer shelf deposits of the Upper Cretaceous Hakobuchi Formation of the Yezo Group in Hobetsu area of Mukawa town in Hokkaido, Japan. Kamuysaurus belongs to the sub-clade of Hadrosaurinae, Edmontosaurini, and forms a monophyly with Laiyangosaurus and Kerberosaurus from the northern Far East. Kamuysaurus has a long anterior platform for the nasofrontal sutural surface, which may indicate the presence of a small supracranial crest, similar to a sub-adult form of Brachylophosaurus based on the extension of the nasofrontal sutural surface. The Dispersal Extinction Cladogenesis analysis with the 50% Majority Rule consensus tree suggests that the clade of Kamuysaurus, Laiyangosaurus, and Kerberosaurus may have dispersed into Asia prior to the late Campanian and the potential endemism of this clade during the late Campanian and early Maastrichtian in the northern Far East. The results of both Dispersal Extinction Cladogenesis and Ancestral State Reconstruction analyses imply that the marine-influenced environment in North America during the Campanian may have played an important role for the hadrosaurid diversification in its early evolutionary history.

Insulin induces cardioprotection partly via an antiapoptotic effect. However, the optimal timing of insulin administration for the best quality cardioprotection remains unclear. We tested the hypothesis that insulin administered prior to ischemia provides better cardioprotection than insulin administration after ischemia. Isolated rat hearts were prepared using Langendorff method and divided into three groups. The Pre-Ins group (Pre-Ins) received 0.5 U/L insulin prior to 15 min no-flow ischemia for 20 min followed by 20 min of reperfusion. The Post-Ins group (Post-Ins) received 0.5 U/L insulin during the reperfusion period only. The control group (Control) was perfused with KH buffer throughout. The maximum of left ventricular derivative of pressure development (dP/dt(max)) was recorded continuously. Measurements of TNF-αand p-Akt in each time point were assayed by ELISA. After reperfusion, dP/dt(max) in Pre-Ins was elevated, compared with Post-Ins at 10 minutes after reperfusion and Control at all-time points. TNF-αlevels at 5 minutes after reperfusion in the Pre-Ins were lower than the others. After 5 minutes of reperfusion, p-Akt was elevated in Pre-Ins compared with the other groups. Insulin administration prior to ischemia provides better cardioprotection than insulin administration only at reperfusion. TNF-αsuppression is possibly mediated via p-Akt leading to a reduction in contractile myocardial dysfunction.

Diandongosaurus acutidentatus Shang, Wu & Li, 2011 is restudied on the basis of a new specimen. The new specimen provides further information on the palate of the skull, the shoulder girdle, the gastralia and hind limbs, and permits revision of the diagnosis. Newly added or modified diagnostic characters include the presence of a few small vomerine teeth, the presence of an ectopterygoid, lateral elements of gastralia distally swollen and curving dorsally, boomerang-shaped interclavicle and clavicle with a distinct anterolateral process. Slight variations in the vertebral counts, girdle morphology, and phalangeal formulae are attributed to the intraspecific variations. A revised phylogenetic analysis demonstrates that Diandongosaurus is closely related to the Nothosauroidea and that certain Chinese taxa (e.g. Keichousaurus ) previously affiliated with the Pachypleurosauridae are more closely related to the Nothosauroidea. The effect of inclusion or exclusion of fragmentary taxa in the phylogenetic analysis is observed in the branching pattern of the cladogram, but it has little effect on the morphological characterization of the major clades.

An adult skeleton of the pistosauroid sauroptery- gian Yunguisaurus liae reveals a number of morphological fea- tures not observed in the holotype, such as the complete morphology of the skull roof, stapes, atlas and axis, ventral view of the postcranium, and nearly complete limbs and tail. Size and morphological differences between the two specimens are mostly regarded as ontogenetic variation, and newly added data did not affect the phylogenetic relationships with other pistosauroids significantly. The number of mesopodia (11 car- pals and 8 tarsals) exceeds that known in any other Triassic marine reptiles and does not serve as a precursor of the plesio- saurian pattern with fewer mesopodia of different topology; it demonstrates variability of the limb morphology among the Triassic pistosauroids. The pectoral girdles of Corosaurus, Augustasaurus and Yunguisaurus may indicate early stages of the adaptation towards the plesiosaurian style of paraxial limb movements with ventroposterior power stroke.

A new Middle Triassic sauropterygian, Qianxisaurus chajiangensis, gen. et sp. nov., is described on the basis of a skeleton from the Zhuganpo Member (Ladinian) of the Falang Formation, Xingyi, southwestern Guizhou Province, China. It is primarily characterized by a premaxilla with eight teeth, marginal teeth with a slightly constricted peduncle and short conical crown, snout longer than the rest of skull, postorbital with a truncated dorsal process and forked posterior process, a very small supratemporal fenestra, a short retroarticular process posteriorly truncated and lacking a dorsal concavity, an elongate trunk with 28 vertebrae, a stout sacrum with four vertebrae, a longitudinal groove on proximodorsal surface of the dorsal ribs, and a coracoid with a narrow lateral portion and a foot-shaped medial portion. Q. chajiangensis appears similar to the European pachypleurosaurs, but a global phylogenetic analysis failed to support close relationships with these taxa. Instead, Q. chajiangensis is a...

A new Middle Triassic archosaur, Diandongosuchus fuyuanensis, gen. et sp. nov., is described on the basis of a skeleton from the Zhuganpo Member (Ladinian) of the Falang Formation, eastern Yunnan Province, China. It is primarily characterized by the nasal process of the premaxilla extending posteriorly well beyond the external naris, the super-sized coracoid foramen laterally bordered by the scapula, the ischium with a strongly expanded medial portion anteroposteriorly longer than the proximodistal height of the bone, and anteriorly notched cervical osteoderms. D. fuyuanensis is a pseudosuchian on the basis of the crocodile-normal tarsal joint and other features, such as the distal end of the ulna in posterolateral view squared off, osteoderms with a distinct anterior process, the presacral vertebrae dorsally covered by more than one osteoderm, dorsal osteoderm alignment dorsal to presacrals 10–24 staggered, the pubis-ischium contact reduced to a thin proximal contact, and the medial contact of t...

Objective To test the hypothesis that the intravenous administration of high doses of insulin while maintaining normoglycemia (GIN therapy) improves myocardial function after coronary artery bypass graft (CABG) surgery. Design A prospective, randomized clinical trial. Setting A university hospital. Participants Forty patients undergoing elective CABG surgery. Interventions Patients were randomized to the GIN or control group. Applying the principles of the hyperinsulinemic-normoglycemic clamp technique in the GIN group, insulin was administered at 5 mU/kg/min during surgery. Glucose 20% was infused at a rate adjusted to maintain blood glucose (BG) between 4.0 and 6.0 mmol/L. Patients in the control group received insulin on a sliding scale, also aiming at normoglycemia. Measurements and Main Results Systemic hemodynamic parameters included heart rate, mean arterial pressure, pulmonary artery wedge pressure, vascular resistance index, and cardiac index (CI). Left ventricular function was assessed by transesophageal echocardiography using the myocardial performance index (MPI) as a parameter of global left ventricular function, the fractional area change (FAC) for systolic function, and flow propagation velocity for diastolic function before and after surgery. All patients receiving GIN therapy were hyperinsulinemic (3,474 ± 1,204 pmol/L) and normoglycemic, showing a lower mean BG concentration (4.9 ± 0.5 mmol/L) than patients in the control group (8.2 ± 2.0 mmol/L). Patients receiving GIN therapy had an increased CI after surgery compared with the control group (p = 0.005). The GIN therapy was associated with improved MPI and FAC values when compared with standard care. Also, there was no difference in the parameters indicating left ventricular diastolic function. Conclusions Intraoperative GIN therapy improves global and systolic left ventricular function after CABG surgery.