[Immediate postoperative color Doppler ultrasonography on the diagnosis of hemorrhagic complications of liver biopsy and its directed compression hemostasis].

Objective: To study the diagnostic value of immediate color Doppler ultrasonography on traumatic hepatic hemorrhage after tissue sampling with ultrasound-guided liver biopsy and the clinical effect of its-directed local compression hemostasis at puncture-site. Methods: 132 hospitalized patients with various liver diseases underwent ultrasound-guided hepatic puncture-biopsies, including 61 cases with diffuse parenchymal and 71 cases with focal liver lesions. Immediate postoperative color Doppler ultrasonography was performed following liver biopsy. Abnormal blood flow signal was observed at hepatic puncture biopsy site, and if there were hemorrhagic signals, ultrasound-directed local compression hemostasis was performed until the bleeding signal disappeared. F-test and Chi-square test were used for statistical analysis. Results: Immediate color Doppler ultrasonography showed traumatic hemorrhage in 36.1% (22/61) and 40.8% (29/71) cases of diffuse liver disease and focal liver disease group, respectively. All hemorrhagic signals were eventually disappeared after ultrasound-directed local compression hemostasis. The median hemostasis time was 2 min in both groups, and there was no statistically significant difference in bleeding rate and hemostasis time between the two groups (P>0.05). There were no serious complications and deaths. Conclusion: Traumatic hepatic hemorrhage along the needle puncture tract is a common accompanying condition during liver biopsy. Immediate postoperative color Doppler ultrasonography can trace bleeding signals in timely manner and direct effective compression hemostasis, so it should be used routinely to help avoid occurrence of severe hemorrhagic complications.

Dynamic assembly of liquid crystalline graphene oxide gel fibers for ion transport.

Colloidal dispersions with liquid crystallinity hold great promise for fabricating their superstructures. As an example, when graphene oxide (GO) sheets are assembled in the liquid crystalline state, they can turn into ordered macroscopic forms of GO such as fibers via the wet spinning process. Here, we report that by reinforcing intersheet interactions, GO liquid crystals (LCs) turn into mechanically robust hydrogels that can be readily drawn into highly aligned fibrillar structures. GO hydrogel fibers with highly aligned sheets (orientation factor, f = 0.71) exhibit more than twice the ionic conductivity compared to those with partially aligned structures (f = 0.01). The hierarchically interconnected two-dimensional nanochannels within these neatly aligned GOLC hydrogel fibers may facilitate controlled transport of charge carriers and could be potentially explored as cables for interconnecting biosystems and/or human-made devices.

Influence of various levels of milk by-products in weaner diets on growth performance, blood urea nitrogen, diarrhea incidence, and pork quality of weaning to finishing pigs.

OBJECTIVE: This study was conducted to evaluate various levels of milk by-product in weaning pig diet on growth performance, blood profiles, carcass characteristics and economic performance for weaning to finishing pigs. METHODS: A total of 160 weaning pigs ([Yorkshire×Landrace]×Duroc), average 7.01±1.32 kg body weight (BW), were allotted to four treatments by BW and sex in 10 replications with 4 pigs per pen in a randomized complete block design. Pigs were fed each treatment diet with various levels of milk by-product (Phase 1: 0%, 10%, 20%, and 30%, Phase 2: 0%, 5%, 10%, and 15%, respectively). During weaning period (0 to 5 week), weaning pigs were fed experimental diets and all pigs were fed the same commercial feed during growing-finishing period (6 to 14 week). RESULTS: In the growth trial, BW, average daily gain (ADG), and average daily feed intake (ADFI) in the nursery period (5 weeks) increased as the milk by-product level in the diet increased (linear, p<0.05). Linear increases of pig BW with increasing the milk product levels were observed until late growing period (linear, p = 0.01). However, there were no significant differences in BW at the finishing periods, ADG, ADFI, and gain:feed ratio during the entire growing-finishing periods. The blood urea nitrogen concentration had no significant difference among dietary treatments. High inclusion level of milk by-product in weaner diet decreased crude protein (quadratic, p = 0.05) and crude ash (Linear, p = 0.05) of Longissimus muscle. In addition, cooking loss and water holding capacity increased with increasing milk product levels in the weaner diets (linear, p<0.01; p = 0.05). High milk by-product treatment had higher feed cost per weight gain compared to non-milk by-products treatment (linear, p = 0.01). CONCLUSION: Supplementation of 10% to 5% milk by-products in weaning pig diet had results equivalent to the 30% to 15% milk treatment and 0% milk by-product supplementation in the diet had no negative influence on growth performance of finishing pigs.

Mechanisms of iron and copper-frataxin interactions.

Frataxin is a mitochondrial protein whose deficiency is the cause of Friedreich's ataxia, a hereditary neurodegenerative disease. This protein plays a role in iron-sulfur cluster biosynthesis, protection against oxidative stress and iron metabolism. In an attempt to provide a better understanding of the role played by metals in its metabolic functions, the mechanisms of mitochondrial metal binding to frataxin in vitro have been investigated. A purified recombinant yeast frataxin homolog Yfh1 binds two Cu(ii) ions with a Kd1(CuII) of 1.3 × 10-7 M and a Kd2(CuII) of 3.1 × 10-4 M and a single Cu(i) ion with a higher affinity than for Cu(ii) (Kd(CuI) = 3.2 × 10-8 M). Mn(ii) forms two complexes with Yfh1 (Kd1(MnII) = 4.0 × 10-8 M; Kd2(MnII) = 4.0 × 10-7 M). Cu and Mn bind Yfh1 with higher affinities than Fe(ii). It is established for the first time that the mechanisms of the interaction of iron and copper with frataxin are comparable and involve three kinetic steps. The first step occurs in the 50-500 ms range and corresponds to a first metal uptake. This is followed by two other kinetic processes that are related to a second metal uptake and/or to a change in the conformation leading to thermodynamic equilibrium. Frataxin deficient Δyfh1 yeast cells exhibited a marked growth defect in the presence of exogenous Cu or Mn. Mitochondria from Δyfh1 strains also accumulated higher amounts of copper, suggesting a functional role of frataxin in vivo in copper homeostasis.

Vecuronium pharmacokinetics in patients with major burns.

BACKGROUND: Burn patients develop resistance to non-depolarizing neuromuscular blocking agents (NDNMBAs) and require a significantly large dose to produce a desired clinical response. Pathophysiological changes related to burn injury may alter pharmacokinetics (PK) and pharmacodynamics of NDNMBAs. The purpose of this study was to compare vecuronium PK in burns vs non-burns. METHODS: Twenty adults, aged 23-58 yr, with 27-81% total body surface area (TBSA) burn, were studied at 4-57 post-burn days and compared with age- and sex-matched, non-burn controls. Vecuronium 0.12 mg kg(-1) was given i.v. as a single bolus within 10 s. Blood samples (n=20) were collected over 12 h at predetermined time points. NONMEM was used to describe plasma drug concentration-time profiles for burns and non-burns. RESULTS: A three-compartment model best described vecuronium concentration-time profiles. Burn patients showed enhanced distributional clearance at the terminal phase (0.12 vs 0.095 litre min(-1), P<0.0001), which yielded shorter elimination half-life for vecuronium (5.5 vs 6.6 h, P<0.001). BURN was the single most significant covariate that explained the altered vecuronium disposition in burns. CONCLUSIONS: The altered drug distribution between tissues may partially explain the known resistance to vecuronium in patients with major burns.

Spin-induced optical conductivity in the spin-liquid candidate herbertsmithite.

We report a direct measurement of the low-frequency optical conductivity of large-area single-crystal herbertsmithite, a promising spin-liquid candidate material, by means of terahertz time-domain spectroscopy. In the spectral range below 1.4 THz, we observe a contribution to the real part of the in-plane conductivity σ(ab)(ω) from the spin degree of freedom. This spin-induced conductivity exhibits a power-law dependence on frequency σ(ab)(ω) ~ ω(ß) with ß ≈ 1.4. Our observation is consistent with the theoretically predicted low-frequency conductivity arising from an emergent gauge field of a gapless U(1) Dirac spin liquid.

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies.

PURPOSE: Brentuximab vedotin (ADCETRIS®), an antibody-drug conjugate, comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). In vitro studies showed that MMAE does not interfere with hERG K+ channels at clinically relevant concentrations. In pivotal phase 2 clinical trials in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin has shown substantial efficacy and an acceptable safety profile. This phase 1 open-label study was designed to evaluate the effect of brentuximab vedotin on the duration of cardiac ventricular repolarization. METHODS: Patients with CD30-positive hematologic malignancies were treated with 1.8 mg/kg brentuximab vedotin by intravenous infusion every 3 weeks for up to 16 cycles. The primary endpoint was the change from baseline to Cycle 1 Days 2, 3, and 4 in the duration of ventricular repolarization using Fridericia's corrected QT interval (QTcF). RESULTS: There was no clinically meaningful change from baseline in the duration of ventricular repolarization as measured by QTcF in the 46 evaluable patients out of 52 total patients treated with brentuximab vedotin. There was no evidence of treatment-emergent cardiac safety abnormalities. Brentuximab vedotin was generally well tolerated with a response rate and an adverse event profile consistent with prior studies. CONCLUSION: There is no significant prolongation of the QT/QTc interval with brentuximab vedotin in patients with CD30-positive hematologic malignancies.

Neuromuscular pharmacodynamics of mivacurium in adults with major burns.

BACKGROUND: Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns. METHODS: Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured. RESULTS: Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre(-1); P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=-0.6; P<0.001). The dibucaine numbers were not different. CONCLUSIONS: The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.

Analysis of FcgammaRIIA cytoplasmic tail requirements in signaling for serotonin secretion: evidence for an ITAM-dependent, PI3K-dependent pathway.

The human Fc receptor, FcgammaRIIA, is known to mediate phagocytosis and endocytosis, yet the greatest numbers of these receptors are expressed on the surface of non-phagocytic platelets, where they are involved in serotonin secretion. FcgammaRIIA harbours three tyrosine (Y) residues within its cytoplasmic domain. Y1 is upstream of both Y2 and Y3, which are contained within an immunoreceptor tyrosine-based activation motif (ITAM), required for many signaling events. We have demonstrated that the two ITAM tyrosines are required for phagocytic signaling and that mutation of a single ITAM tyrosine decreases but does not abolish phagocytic signaling. Furthermore, we have identified that the YMTL motif is required for endocytosis. These observations suggest that FcgammaRIIA utilizes different sequences for various signaling events. Therefore, we investigated the sequence requirements for another important FcgammaRIIA-mediated signaling event, serotonin secretion, using Rat Basophilic Leukemia (RBL-2H3) cells transfected with wildtype (WT) FcgammaRIIA or mutant FcgammaRIIA. Stimulation of cells expressing WT FcgammaRIIA induced release of serotonin at a level 7-fold greater than that in nonstimulated WT FcgammaRIIA-transfected cells or nontransfected RBL cells. Mutation of either ITAM tyrosine (Y2 or Y3) to phenylalanine was sufficient to abolish serotonin secretion. Further, while inhibition of Syk with piceatannol blocked phagocytosis as expected, it did not inhibit serotonin secretion. Additionally, inhibition of phosphoinositol-3-kinase (PI3K) with wortmannin only had a partial effect on serotonin signaling, despite the fact that the concentrations used completely abolished phagocytic signaling. These data suggest that the requirements for serotonin secretion differ from those for phagocytosis mediated by FcgammaRIIA.