Endoscopic endonasal approach to the ethmoidal planum: anatomic study.
The endoscopic endonasal technique is currently used by otolaryngologists for the management of different extradural lesions located below the ethmoidal planum. The cooperation between ENTs and neurosurgeons has recently pushed the use of such approach also in the removal of some intradural lesions, which has promoted the interest for an anatomic study to identify the anatomical landmarks and the dangerous points during the endoscopic approach to this area. In six fresh cadaver heads, unilateral and bilateral measurements between the main landmarks of the approach were performed by means of an endoscopic endonasal approach. A wide exposure of the midline anterior skull base was realized. The maximum of lateral extension was obtained between the two medial orbital walls, at the middle of the cribriform plate (mean distance 25,33 mm), while the mean distance between the anterior and posterior ethmoidal arteries at the level of the lamina papyracea was 16 mm. The endoscopic endonasal route can be considered a minimally invasive technique to approach the ethmoidal planum. It requires adequate anatomical knowledge and endoscopic skill for its realization. Due to the wide window realizable through this corridor, it could be considered in selected cases for the removal of intradural lesions such as meningiomas or estesioneuroblastomas.


Procedures to characterize in vivo and in vitro enantioselective glucuronidation properly: studies with benoxaprofen glucuronides.
The diastereoisomeric glucuronic acid conjugates of R/S-benoxaprofen are the major benoxaprofen metabolites and are found in urine at high concentrations. The conjugates of R- and S-benoxaprofen can be separated directly on a C18 reversed-phase column using a mixture of acetonitrile and tetrabutylammonium hydroxide buffer, pH 2.5 (28:72, v/v), as the mobile phase. The k' values of S- and R-benoxaprofen glucuronides are 57.5 and 63.0, respectively. Diluted urine or deproteinized plasma samples were injected without further treatment. With fluorescence detection at 313/365 nm, quantifiable limits of 50 ng equiv./ml were found for the conjugates. The intra- and interday variability was below 12%. Utilizing this analytical procedure it is possible to characterize enantioselective glucuronidation both in vivo and in vitro. For in vitro procedures, apparent rates of formation and the R/S ratio may be substrate (benoxaprofen) and cosubstrate (UDPGA) dependent. Moreover, enantioselective cleavage of the formed benoxaprofen glucuronides by alkaline hydrolysis, hydrolytic enzymes, and acyl migration must be controlled for both in vitro and in vivo studies since R-benoxaprofen glucuronide is degraded faster than the S-diastereomer under certain conditions.


Sex-specific differences in transcriptomic profiles and cellular characteristics of oligodendrocyte precursor cells.
The susceptibility to neurological and psychiatric disorders reveals sexual dimorphism in the structure and function of human brains. Recent evidence has also demonstrated the sex-related differences in cellular components of the brain, including neurons, microglia, astrocytes, and endothelial cells. Oligodendrocyte precursor cells (OPCs) regulate the neuronal system in various ways and play crucial roles in brain homeostasis beyond their well-known role as a reservoir for mature oligodendrocytes. Although recent studies have shown regional diversities and heterogeneities of OPCs, sex-related differences in OPCs are largely unknown. Here, we revealed transcriptomic differences in OPCs isolated from male and female neonatal rat brains. Furthermore, we demonstrated sex-dependent differences in OPCs regarding proliferation, migration, differentiation, tolerance against ischemic stress, energy metabolism, and the ability to regulate the blood-brain barrier integrity.


mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats with both Tsc2 haploinsufficiency and developmental status epilepticus.
Epilepsy is a major risk factor for autism spectrum disorder (ASD) and complicates clinical manifestations and management of ASD significantly. Tuberous sclerosis complex (TSC), caused by TSC1 or TSC2 mutations, is one of the medical conditions most commonly associated with ASD and has become an important model to examine molecular pathways associated with ASD. Previous research showed reversal of autism-like social deficits in Tsc1 +/- and Tsc2 +/- mouse models by mammalian target of rapamycin (mTOR) inhibitors. However, at least 70 % of individuals with TSC also have epilepsy, known to complicate the severity and treatment responsiveness of the behavioural phenotype. No previous study has examined the impact of seizures on neurocognitive reversal by mTOR inhibitors. Adult Tsc2 +/- (Eker)-rats express social deficits similar to Tsc2 +/- mice, with additive social deficits from developmental status epilepticus (DSE). DSE was induced by intraperitoneal injection with kainic acid at post-natal days P7 and P14 (n = 12). The experimental group that modelled TSC pathology carried the Tsc2 +/- (Eker)-mutation and was challenged with DSE. The wild-type controls had not received DSE (n = 10). Four-month-old animals were analysed for social behaviour (T1), then treated three times during 1 week with 1 mg/kg everolimus and finally retested in the post-treatment behavioural analysis (T2). In the experimental group, both social interaction and social cognition were impaired at T1. After treatment at T2, behaviour in the experimental group was indistinguishable from controls. The mTOR inhibitor, everolimus, reversed social deficit behaviours in the Tsc2 haploinsufficiency plus DSE animal model to control levels.


Protein disulfide isomerase regulation by nitric oxide maintains vascular quiescence and controls thrombus formation.
Essentials Nitric oxide synthesis controls protein disulfide isomerase (PDI) function. Nitric oxide (NO) modulation of PDI controls endothelial thrombogenicity. S-nitrosylated PDI inhibits platelet function and thrombosis. Nitric oxide maintains vascular quiescence in part through inhibition of PDI. SUMMARY: Background Protein disulfide isomerase (PDI) plays an essential role in thrombus formation, and PDI inhibition is being evaluated clinically as a novel anticoagulant strategy. However, little is known about the regulation of PDI in the vasculature. Thiols within the catalytic motif of PDI are essential for its role in thrombosis. These same thiols bind nitric oxide (NO), which is a potent regulator of vessel function. To determine whether regulation of PDI represents a mechanism by which NO controls vascular quiescence, we evaluated the effect of NO on PDI function in endothelial cells and platelets, and thrombus formation in vivo. Aim To assess the effect of S-nitrosylation on the regulation of PDI and other thiol isomerases in the vasculature. Methods and results The role of endogenous NO in PDI activity was evaluated by incubating endothelium with an NO scavenger, which resulted in exposure of free thiols, increased thiol isomerase activity, and enhanced thrombin generation on the cell membrane. Conversely, exposure of endothelium to NO+ carriers or elevation of endogenous NO levels by induction of NO synthesis resulted in S-nitrosylation of PDI and decreased surface thiol reductase activity. S-nitrosylation of platelet PDI inhibited its reductase activity, and S-nitrosylated PDI interfered with platelet aggregation, α-granule release, and thrombin generation on platelets. S-nitrosylated PDI also blocked laser-induced thrombus formation when infused into mice. S-nitrosylated ERp5 and ERp57 were found to have similar inhibitory activity. Conclusions These studies identify NO as a critical regulator of vascular PDI, and show that regulation of PDI function is an important mechanism by which NO maintains vascular quiescence.


Correlations between the time-intensity parameters of contrast-enhanced ultrasound and clinical prognosis of hepatocellular carcinoma.
The purpose of the study was to detect the correlation between the time-intensity parameters of contrast-enhanced ultrasound (CEUS) and the clinical prognosis of hepatocellular carcinoma (HCC). A total of 73 HCC patients were analyzed with the time-intensity curve of CEUS. The expression of vascular endothelial factor (VEGF) and CD34 in different differentiation-staged HCC specimens was observed using immunohistochemistry. A positive correlation was found between the VEGF expression and microvessel density. The time-intensity parameters were not correlated with the HCC size. CEUS time-intensity parameters are inducive for assessing the prognosis of HCC with revealed intratumoral microvessel perfusion in different differentiation stages.


High E/e' disrupts the rapid lowering of blood glucose in response to exercise training.
No relationship between the ratio of peak early velocity of left ventricular inflow to peak systolic longitudinal velocity of the mitral annulus velocity (E/e') and insulin resistance has yet been shown in patients with cardiac disease. We hypothesized that patients with high E/e' values would tend not to show the rapid blood glucose-lowering in response to exercise training characteristic of impaired glucose tolerance (IGT) or diabetes mellitus (DM) patients. The subjects were continuous IGT/DM patients (n = 27) participating in cardiac rehabilitation. All patients' E/e' values were measured by echocardiography. The patients' blood glucose levels (mg/dl) were measured just before (pre-BS) and after (post-BS) exercise training. Post-BS was subtracted from pre-BS to obtain ΔBS, and the relationship between E/e' and ΔBS was investigated. E/e' correlated negatively with ΔBS. Moreover, E/e' was a significant predictor of ΔBS and as such was independent of hemoglobin A1c (HbA1c), pre-BS, and presence of atrial fibrillation on multivariate analysis. Patients with high E/e', indicating high left ventricular filling pressure, were unlikely to exhibit the rapid glucose-lowering response.


NMDA and non-NMDA receptors on rat supraoptic nucleus neurons activated monosynaptically by olfactory afferents.
The recently discovered efferent projections from the main and accessory olfactory bulbs to the supraoptic nucleus (SON) were further investigated. Intracellular electrophysiological methods were used to determine (a) if these projections are monosynaptic, (b) which excitatory amino acid (EAA) receptor subtypes mediate responses to activation of these pathways and (c) whether the same receptor subtypes mediate responses of phasically firing (vasopressin) and continuously firing (putative oxytocin) neurons. Recordings were made from SON neurons in large explants and 500 microns thick horizontal slices, containing 2-6 mm of the piriform cortex and lateral olfactory tract (LOT). This allowed recording of synaptic responses to selective stimulation of the LOT. EPSPs in SON neurons faithfully followed stimulus frequencies of 50-100 Hz, indicating that these inputs were monosynaptic. Stimulus-evoked EPSPs were blocked by the non-specific EAA antagonist, kynurenate. Perifusion of the slice with Mg(2+)-free medium revealed the presence of NMDA receptors in addition to the non-NMDA receptors on both phasically and continuously firing cells, indeed, on all cells tested. Partial blockade of these EPSPs in Mg(2+)-free medium could be achieved with either the NMDA antagonist, AP5, or the non-NMDA antagonist, CNQX or NBQX. Full blockade of the stimulus-evoked EPSPs was effected by adding both types of antagonists to the medium, although spontaneous EPSPs were still observed in several cells. These results are consistent with prior studies showing both receptor subtypes in the SON. This is the first demonstration that afferent stimulation activates both subtypes in the same SON neuron regardless of its peptide content.


Changes in cytosolic calcium during cholinergic and adrenergic stimulation of the parotid salivary gland.
Ca-selective microelectrodes were used to examine calcium transport during acetylcholine (ACh) and Epinephrine (Ep) stimulation of amylase secretion in the parotid gland. The cytosolic concentration of free ionized Ca2+ ( [Ca]i) determined in unstimulated cells was 0.44 +/- 0.04 microM. By measuring the induced changes in intracellular electrode potentials (ECa, EM) we were able to demonstrate that ACh at 10(-9), 10(-8), 10(-7), 10(-6), and 10(-5) M increased [Ca]i by 0.20 +/- 0.02, 0.61 +/- 0.04, 0.53 +/- 0.02, 0.30 +/- 0.05, and 0.14 +/- 0.03 microM. Similarly, Ep increased [Ca]i by 0.14 +/- 0.01, 0.42 +/- 0.06, 0.31 +/- 0.04, 0.15 +/- 0.03, and 0.05 +/- 0.04, respectively. Removal of extracellular Ca2+ significantly (P less than 0.001) altered the changes in ECa in response to ACh and Ep stimulation, thereby demonstrating that the induced increases in [Ca]i must be due to a transmembrane movement of Ca2+. Enzyme secretion was found to vary with the concentration of the stimulus used. Maximal secretion occurred during stimulation using 10(-7) M and 10(-8) M Ep with a suppression of release at supramaximal concentrations. The dose-response curve for ACh differed in that there were two concentrations of stimulus (2 X 10(-9) and 1 X 10(-6) M ACh) in which the greatest rate of secretion occurred. Concentrations of stimulus which increase [Ca]i between 0.86 +/- 0.06 microM and 0.74 +/- 0.05 appeared to produce optimal amylase secretion, indicating that salivary secretion in the mouse parotid is regulated within a narrow concentration range of cytosolic Ca2+.


Sex- and strain-dependent hepatic microsomal ethylmorphine N-demethylation in mice: the roles of type I binding and NADPH-cytochrome P-450 reductase.
The roles of type I binding and NADPH-cytochrome P-450 reductase in ethylmorphine demethylation were investigated in two strains of mice, using sex differences in these activities as a tool. In the CPB-SE strain, females metabolize ethylmorphine faster than males. Sex differences in cytochrome P-450 content and endogenous NADPH-cytochrome P-450 reductase activity were too small to account for this. On the other hand, the differences in the magnitudes of type I spectra and ethylmorphine-induced enhancement of cytochrome P-450 reduction were considerable larger than those in the rates of demethylation. All parameters, except endogenous cytochrome P-450 reduction, were modified in a similar way by testosterone pretreatment: in females they were depressed to the male level, whereas in males they remained unchanged. Castration had no effect in females and enhanced the activities in males. The CPB-V strain exhibited little or no sex differences in ethylmorphine demethylation, cytochrome P-450 content and endogenous cytochrome P-450 reduction. Testosterone pretreatment had little or no influence on these activities. Type I binding and reductase stimulation, however, showed sex differences, comparable to those observed in the CPB-SE strain, which were also abolished by testosterone. A relationship between reductase stimulation and type I binding was observed, which was, apparently, independent of sex or strain. It is concluded that androgen primarily influences the amount of cytochrome P-450-substrate complex formed, but that the reduction of this complex is not rate-limiting in the demethylation of ethylmorphine.


A family outbreak of gastroenteritis caused by group C rotavirus.
A family outbreak of gastroenteritis caused by group C rotavirus is described. All five members of the family, with children between 8 and 15 years of age, fell ill with diarrhea. The diagnosis was initially based on the detection of rotavirus RNA showing a typical group C profile in gel electrophoresis in stool samples, and it was serologically verified from patient sera using a cell culture adapted porcine group C rotavirus as a source of standard antigen. All collected serum samples from the family contained IgM and/or IgG class antibodies to group C rotavirus measurable by immunofluorescence antibody test (IFAT). Group C rotavirus specific IgM class antibodies were present in the early serum samples in 3/4 patients. A roller tube neutralization test (NT) was established to demonstrate neutralizing antibodies to porcine group C rotavirus in human sera. These methods can be used to detect serologically group C rotavirus infections.


Design and fabrication of high-performance injectable self-setting trimagnesium phosphate.
Magnesium phosphate bone cement has become a widely used orthopedic implant due to the advantages of fast-setting and high early strength. However, developing magnesium phosphate cement possessing applicable injectability, high strength, and biocompatibility simultaneously remains a significant challenge. Herein, we propose a strategy to develop high-performance bone cement and establish a trimagnesium phosphate cement (TMPC) system. The TMPC exhibits high early strength, low curing temperature, neutral pH, and excellent injectability, overcoming the critical limitations of recently studied magnesium phosphate cement. By monitoring the hydration pH value and electroconductivity, we demonstrate that the magnesium-to-phosphate ratio could manipulate the components of hydration products and their transformation by adjusting the pH of the system, which will influence the hydration speed. Further, the ratio could regulate the hydration network and the properties of TMPC. Moreover, in vitro studies show that TMPC has outstanding biocompatibility and bone-filling capacity. The facile preparation properties and these advantages of TMPC render it a potential clinical alternative to polymethylmethacrylate and calcium phosphate bone cement. This study will contribute to the rational design of high-performance bone cement.


Regulation of tumorigenesis and ferroptosis in non-small cell lung cancer by a novel BBOX1-AS1/miR-326/PROM2 axis.
Dysregulation of long non-coding RNAs (lncRNAs) is associated with the tumorigenesis and ferroptosis of non-small cell lung cancer (NSCLC). BBOX1 antisense RNA 1 (BBOX1-AS1) functions as an oncogenic driver in NSCLC. Here, we aim to investigate the regulation effect and underlying mechanism of BBOX1-AS1 in NSCLC progression and ferroptosis. RNA expression was detected by quantitative real-time PCR (qRT-PCR), and protein expression was measured by immunoblotting. Cell growth was assessed by CCK-8 and colony formation assays. Transwell assay was applied to evaluate cell invasion and migration. RNA pull-down and dual-luciferase reporter assays were applied to verify the relationship between miR-326 and BBOX1-AS1 or prominin 2 (PROM2). The role of BBOX1-AS1 in NSCLC tumorigenicity was also analyzed by xenograft assays. Silencing BBOX1-AS1 or PROM2 impeded NSCLC cell growth, migration, and invasion. Silencing BBOX1-AS1 induced cell apoptosis and ferroptosis. BBOX1-AS1 up-regulated PROM2 expression, and re-expression of PROM2 reversed the effects of BBOX1-AS1 depletion on cell malignant phenotypes and ferroptosis. BBOX1-AS1 post-transcriptionally modulated PROM2 expression by sponging miR-326. MiR-326 was validated as a mediator of BBOX1-AS1 in regulating NSCLC cell malignant phenotypes and ferroptosis. Additionally, BBOX1-AS1 deficiency in vivo resulted in the suppression of xenograft tumor growth. Together, our study defines a novel BBOX1-AS1/miR-326/PROM2 axis in regulating NSCLC malignant progression and ferroptosis, offering new evidence for the oncogenic role of BBOX1-AS1 in NSCLC. These findings may provide a basis for the future usage of targeting BBOX1-AS1 in NSCLC treatment.


Antimicrobial resistance in major pathogens of hospital-acquired pneumonia in Asian countries.
Antimicrobial resistance is a worldwide problem. For patients with hospital-acquired or ventilator-associated pneumonia, resistant pathogens pose a significant challenge to successful treatment outcomes and to the cost-effective delivery of health care. In the developing world, antibiotic resistance may be relatively more prevalent compared with Western countries. Common resistant pathogens include methicillin-resistant Staphylococcus aureus, multidrug resistant Pseudomonas aeruginosa, multidrug resistant Acinetobacter species, and extended-spectrum beta-lactamase-producing strains of Escherichia coli and Klebsiella pneumoniae. The emergence of these strains has provided a major impetus toward development of the present consensus treatment recommendations of the Asian HAP Working Group. The following review provides summary data regarding the incidence and prevalence of antibiotic-resistant pathogens in 10 Asian countries.


Structural units of reovirus ribonucleic acid and their possible functional significance.
Reovirus contains ribonucleic acid (RNA) equivalent in amount to a molecular weight of approximately 10(7) daltons. On isolation, this RNA is invariably broken into fragments of three different sizes. The three pieces have been separated from each other by chromatography on methylated albumin-kieselguhr columns. Denaturation of the three fragments of RNA in dimethyl sulfoxide led to separation of the strands, as suggested by sucrose gradient sedimentation patterns and by the second-order kinetics of reannealing. Molecular weights of 0.8 x 10(6), 1.4 x 10(6), and 2.4 x 10(6) were determined for the double-stranded fragments from the sedimentation rates of the single-stranded RNA obtained by denaturation. There was little or no homology among the three classes of denatured RNA when taken in pairs in hybridization tests. The three pieces of double-stranded RNA, therefore, did not result from random breaks in the original viral RNA molecule. Virusspecific single-stranded RNA formed in infected cells, and previously found to be largely if not entirely messenger RNA transcribed from the viral genome, was also separated into three size classes by sedimentation through sucrose gradients. Each class of single-stranded RNA corresponded in size to one of the three fragments of double-stranded RNA. The largest piece of single-stranded RNA hybridized uniquely with the largest fragment of denatured viral RNA. By whatever means this fragment of double-stranded RNA may be joined into the viral RNA molecule, it seems to act as a specific unit for transcription of an uninterrupted messenger RNA of equivalent length.


Effect of batch and continuous thermosonication on the microbial and physicochemical quality of pumpkin juice.
The study investigated the use of batch and continuous thermosonication for pasteurization of pumpkin (Cucurbita moschata) juice emphasizing on its microbial, physicochemical and sensorial quality parameters. Batch thermosonication (40, 50, 60 °C, 37 kHz, 150 W) of pumpkin juice was compared with the ultrasonication (23 °C) and conventional heat treatments (40, 50, 60 °C). For batch thermosonication, maximum inactivation of Escherichia coli K-12 was 6.62 ± 0.00 log cfu/mL, meanwhile, it was 3.64 ± 0.19 log cfu/mL for heat treatment. In addition, only 0.37 ± 0.21 log cfu/mL inactivation in E. coli K-12 was obtained by ultrasonication. The designed continuous thermosonication system (0.029 L/min, 60 °C) reduced E. coli K-12 by 6.23 ± 0.34 cfu/mL log after cycle 3 (34.15 min of processing). Color properties (L*, a*, b*, ∆E), pH, total titratable acidity, total soluble solids content, turbidity and non-enzymatic browning index were determined for batch and continuously thermosonicated, ultrasonicated and heat-treated pumpkin juices. Total color change of continuously thermosonicated samples were higher than the batch thermosonicated (60 °C) ones but, lower than the conventional heat treated (60 °C) samples. Sensory panel showed general acceptance scores of fresh, batch (60 °C) and continuously thermosonicated pumpkin juice samples have no significant (P < 0.05) difference. Continuous treatment results supported by the batch ones revealed that thermosonication could be effectively used for pasteurization of pumpkin juice producing a safe product with minimum changes in physicochemical and sensorial properties.


[3H]etorphine binding in rat striatum following lesions of the raphe nuclei.
Following 5,7-dihydroxytryptamine lesions of the rat raphe nuclei a significant reduction in striatal serotonin concentrations was observed. However, with [3H]etorphine as ligand no change in opiate receptor binding was observed in striatal membranes. Moreover, when [3H]etorphine binding was resolved into its mu- and delta + kappa-components no change in either component was observed compared with controls. It is concluded that opiate receptors are not on striatal serotonergic nerve terminals whose cell bodies are located in the raphe nuclei.


In vitro study of the aromatic hydroxylation of 1-methyltetrahydro-beta-carboline (methtryptoline) in rat.
The incubation of 1-methyltetrahydro-beta-carboline (1-MeTHBC) with hepatocytes isolated from 3-methylcholanthrene-treated rats led to formation of the 5-, 6- and 7-hydroxylated products. The hydroxylating activity was associated with the microsomal fraction as indicated by testing different subcellular fractions. The highest activity for hydroxylating 1-MeTHBC was found in liver which was about ten times as active as lung. Only a trace amount of hydroxylating activity was present in brain and kidney tissue. Analysis using chiral gas chromatography revealed an unequal abundance of enantiomers in all three products. The formation of the 5-, 6- and 7-hydroxylated products was confirmed in vivo by analysis of 24 h urine samples after intraperitoneal administration of 1-MeTHBC to 3-methylcholanthrene-treated rats.


Development of a Cell Line Containing the Chimeric ETV6-NTRK3 Gene. The Search for Mutations of the Tyrosine Kinase Chimeric Domain That Cause Resistance to Larotrectinib.
The development, registration, and further use of entrectinib and larotrectinib for the treatment of tumors resulting from oncogenic stimulation of chimeric neurotrophin receptors (TRK) attracted much interest to the mechanisms of tumor cells resistance to TRK inhibitors during treatment. In the presented study, a cell line carrying the chimeric gene ETV6-NTRK3 (HFF-EN) was created on the basis of human fibroblasts. The transcription level of the chimeric ETV6-NTRK3 gene in HFF-EN was comparable to the transcription level of the household ACTB gene, the expression of the ETV6-NTRKA protein was confirmed by immunoblotting. A comparison of the dose-effect curves of fibroblasts and HFF-EN cells showed a ~38-fold increase in the sensitivity of HFF-EN to larotrectinib. To obtain a cell model of the resistance to larotrectinib in NTRK-dependent cancer, we used cell passages with a gradually increasing concentration of larotrectinib and obtained six resistant clones. p.G623E c.1868G>A mutation was found in five clones, and p.R582W c.1744C>T mutation, previously not described as a resistance mutation, was found in one clone showing significantly less resistance. These results can be further used for more complete understanding of the mechanisms of the resistance to TRK inhibitors and for the development of new drugs.


Impact of Soil Rhizobacteria Inoculation and Leaf-Chewing Insect Herbivory on Mentha piperita Leaf Secondary Metabolites.
Secondary metabolites commonly play important physiological roles in plants and can be modified quantitatively and qualitatively by exposure to biotic and abiotic interactions. Plant growth promoting rhizobacteria (PGPR) and herbivory induce systemic resistance. In the present study, we analyzed the induction of secondary metabolites in peppermint plants in response to chewing insect herbivory on PGPR-inoculated Mentha piperita plants. The secondary metabolites of M. piperita plants were increased when plants were inoculated with PGPR and also exposed to caterpillar herbivory. It was found that the total essential oil yield in inoculated plants with insect damage was ~2.6-fold higher than in controls. The yield was similar to that of plants either damaged by insects or inoculated, indicating that there was no synergism. The same trend was observed for phenolic compounds. In contrast, VOC emissions were significantly higher in plants infested by insects, independent of whether they were inoculated. Insect damaged plants had 5.5 times higher monoterpene emissions than control plants, and ~ 2-fold higher emissions than on PGPR-inoculated plants without insects. To gain a better understanding of how herbivory on PGPR-inoculated plants can cause an increase in secondary metabolites of peppermint, we examined changes in plant defense hormones in inoculated plants after herbivory. We found that the combination of both treatments increased the endogenous jasmonic and salicylic acid levels to the same extent as in plants only inoculated or only insect-damaged. Because different interactions can alter the phytochemistry of plants such as M. piperita, this topic is both ecologically and economically relevant.


Circularly Polarized Light-Driven Supramolecular Chirality.
Introduction of asymmetry into a supramolecular system via external chiral stimuli can contribute to the understanding of the intriguing homochirality found in nature. Circularly polarized light (CPL) is regarded as a chiral physical force with right- or left-handedness. It can induce and modulate supramolecular chirality due to preferential interaction with one enantiomer. Herein, this review focuses on the photon-to-matter chirality transfer mechanisms at the supramolecular level. Thus, asymmetric photochemical reactions are reviewed, and the creation of a chiral bias upon CPL irradiation is discussed. Furthermore, the possible mechanisms for the amplification and propagation of the bias into the supramolecular level are outlined based on the nature of the photochromic building block. Representative examples, including azobenzene derivatives, polydiacetylene, bicyclic ketone, polyfluorenes, Cn -symmetric molecules, and inorganic nanomaterials, are presented.


Endolymphatic subarachnoid shunt operation for idiopathic endolymphatic hydrops.
In 1974 we reported on 92 patients who had endolymphatic subarachnoid shunt surgery for idiopathic endolymphatic hydrops. That group had a follow-up of at least 5 years, and only 41% had satisfactory control of vertigo. The purpose of this paper is to describe the results after a larger postoperative follow-up (12 1/2 years, with a range of 68 to 182 months), and to discuss some additional observations regarding endolymphatic sac operations. Two patients have died of unrelated causes, one in the 115th postoperative month and the other in the 124th postoperative month. Eight patients have been lost to follow-up. Our data show that 35% of the patients have had satisfactory control of their vertigo: 23% have had no vertigo, and 12% have had the vertigo improved by at least 75%. The remaining patients had improvement in vertigo, but not to a satisfactory degree, had pronounced improvement in vertigo, but with subsequent recurrence of severe attacks of dizziness, or had no improvement at all. In addition, there has been a steady deterioration in the success rate with increased time of observation. Nineteen percent of the patients showed significant improvement in hearing after surgery, 47% demonstrated no change in hearing, and 34% had a moderate to profound decline in hearing postoperatively. Of 17 patients who had socially adequate hearing in the afflicted ear preoperatively, 12 showed deterioration in hearing to the point that air-conduction thresholds were below the socially adequate level. Six patients with bilateral endolymphatic hydrops who had almost identical auditory acuity in each ear underwent a unilateral shunt operation. In each of these patients, the unoperated-on ear had better results from the hearing standpoint. The data show, therefore, that control of vertigo with the endolymphatic subarachnoid shunt operation was not only disappointing initially, but as the patients were followed over a longer time, the percentage of patients with satisfactory vertigo control declined. Additionally, one-third of the patients experienced further moderate to profound sensorineural deafness, either as a result of surgery or because the operation failed to control the disease process. Last, it is obvious that the endolymphatic subarachnoid shunt operation did not preserve hearing, even when the operation was performed early in the course of the disease.


Clinical application of the P3 component of event-related potentials. I. Normal aging.
Normal adult volunteer subjects ranging in age from 18 to 90 years participated in a study in which analogous auditory and visual paradigms, with infrequently occurring target and non-target events, were used to elicit event-related potentials (ERPs) with a prominent P3 component. Of the 135 subjects participating, 66 completed both auditory and visual paradigms. The amplitude and latency of P3 were analyzed using average ERPs, single trials (adaptive filter) and principal components analysis (PCA). Age regressions were calculated using measures derived from average ERPs and single trials. Single trial measures were better than average ERP measures in demonstrating age-related changes in P3 latency. There was a significant increase in P3 latency with age of 1-1.5 msec/year. The range of normal P3 latency for a given age (1 S.E. of the regression = 40 msec for the visual target stimuli) was much larger than obtained by other investigators. The visual paradigm produced higher P3 latency/age correlations than the auditory paradigm (visual target r = 0.52, non-target r = 0.42; auditory target r = 0.32, non-target r = 0.33). Within individuals, the amplitude and latency of P3 generated by auditory and visual stimuli were highly correlated, though the visual paradigm produced larger and later P3s than the auditory paradigm. There is an apparent change in the scalp topography of P3 with age. In young adults, P3s to target stimuli have a markedly parietal distribution. The distribution of P3 becomes more uniformly distributed from Pz to Fz with age. This may be due to changes in overlapping components such as the slow wave (SW) rather than to changes in the amplitude of P3 per se.


Representation of visual space in area 7a neurons using the center of mass equation.
The firing rate of neurons in parietal area 7a of the behaving Rhesus monkey with its head fixed incorporates both visual and eye position information. This neural tuning is not in an ego-centered coordinate space. This physiological result was unexpected as behavioral deficits following parietal damage in human and monkey subjects suggested the existence of egocentric representations. A formulation to extract a world-centered system from area 7a neurons is presented that depends on the linearity of the eye position signal and the similarity of the equation describing the tuning of these neurons to the center of mass equation. This formulation permits the computation of the location of objects in world coordinates using either serial analysis of a single neuron's activity or parallel processing of a collection of neurons. Experimental predictions are made for the relationship between different parameters of angle of gaze neurons.


First record of a mosquito iridescent virus in Culex pipiens L. (Diptera: Culicidae).
The mosquito iridescent viruses (MIVs) are large icosahedral DNA viruses that replicate and assemble in the cytoplasm of the host. Paracrystalline arrangements of virions that accumulate in the cytoplasm produce an iridescent color that is symptomatic of acute infections. In August 2010, we found larvae of Culex pipiens with these symptoms in suburban ditches around the city of La Plata, Argentina. Electron microscope studies, DNA sequencing, and phylogenetic analysis of the major capsid protein confirmed this as the first record of an MIV in C. Pipiens.


Differential uptake of silver, copper and zinc suggests complementary species-specific phytoextraction potential.
The aim of our study, conducted as a pot experiment, was to assess the potential of willow (Salix miyabeana), alfalfa (Medicago sativa), tall fescue (Festuca arundinacea), and Indian mustard (Brassica juncea) to remediate two brownfield soils differentially contaminated with Ag, Cu and Zn (up to 113.60, 47.50, and 117.00 mg kg(-1) respectively). While aboveground Ag accumulation was highest in B. juncea (4.60 ± 2.58 mg kg(-1)), lower levels were also measured in M. sativa and F. arundinacea. Cu accumulation was observed in all species, but only in underground parts, and was highest in F. arundinacea (269.20 ± 74.75 mg kg(-1)), with a bioconcentration factor of 13.85. Salix miyabeana was found to have the highest Zn aerial tissue concentration (119.96 ± 20.04 mg kg(-1)). Because of its high Ag uptake, the remediation potential of B. juncea should be evaluated more extensively on the site from which we excavated the soil for this study. Given the multiple forms of contamination on the site and the differential specie-related uptake evident in our findings, we hypothesize that an optimal plantation allowing expression of complementary remediation functions would include B. juncea for extraction of Ag, in combination with F. arundinacea for stabilization of Cu and S. miyabeana for extraction of Zn.


Estimated Glomerular Filtration Rate Trajectories in HIV-Infected Subjects Treated With Different Ritonavir-Boosted Protease Inhibitors and Tenofovir Disoproxil Fumarate or Abacavir.
The aim of the study was to evaluate in human immunodeficiency virus (HIV)-infected patients estimated glomerular filtration rate (eGFR) trajectories during treatment with different protease inhibitors (PIs) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus tenofovir (TDF) or abacavir (ABC) and lamivudine or emtricitabine (xTC).Retrospective study of patients followed at a single clinical center; all patients who started TDF or ABC for the first time with a NNRTI or lopinavir/r (LPV/r) or atazanavir/r (ATV/r) or darunavir/r (DRV/r), for whom at least 1 eGFR value before the start and during the studied treatment was known, were included in this analysis. eGFR was calculated by means of the CKD-EPI formula. Univariate and multivariate mixed linear model (MLM) was applied to estimate eGFR slope with the considered antiretroviral treatment.In the 1658 patients treated with TDF/xTC (aged 43 [37-48] years, with an eGFR of 105 [96; 113] mL/min/1.73 m, 80% males, 92% Caucasians, 10% coinfected with HCV, 4% with diabetes, 11% with hypertension, 38% naive for antiretroviral therapy (ART), 37% with HIV-RNA <50 copies/mL) the median follow-up was 2.5 (1.2-4.6) years. Their adjusted eGFR slopes (95% CI) were -1.26 (-1.58; -0.95), -0.43 (-1.20; +0.33), -0.86 (-1.28; -0.44), and -0.20 (-0.42; +0.02) mL/min/1.73 m per year in patients treated with ATV/r, DRV/r, LPV/r, and NNRTI, respectively. Patients receiving ATV/r or LPV/r had a greater adjusted decline in eGFR compared with those receiving NNRTIs (difference -1.06 [-1.44; -0.69] mL/min/1.73 m per year, P <0.001; and -0.66 [-1.13; -0.20] mL/min/1.73 m per year, P = 0.005, respectively); adjusted eGFR slopes were similar in patients receiving DRV/r and in those receiving NNRTIs. Patients receiving ATV/r had a greater adjusted eGFR decline than those treated with DRV/r (difference -0.83 [-1.65; -0.02] mL/min/1.73 m per year; P = 0.04), but not than those receiving LPV/r; no significant difference was observed in adjusted eGFR slopes between patients receiving DRV/r and those receiving LPV/r. In the 286 patients treated with ABC and lamivudine, eGFR slopes were similar, independent of the PI.In patients receiving TDF/xTC, eGFR trajectories were small for all regimens and declined less in patients receiving DRV/r or NNRTIs than in those treated with ATV/r or LPV/r.


Studies on cell surface antigens of mouse leukemic and normal lymphocytes. II. Relationships between mammary leukemia, gross virus related and major histocompatibility antigens on L1210 leukemic lymphocytes.
The presence of ML antigen on leukemia L1210 cells was confirmed by different procedures. In addition, by applying appropriate absorptions and blocking techniques combined with ferritin labelled antibodies in electron microscopy (EM), the independent localization of ML antigen and murine leukemia virus Gross (MuLV-Gross) cellular antigen on L1210 cells was demonstrated. The ferritin labeled antigenic sites appeared to be free from budding viral particles. In further studies the 3M KCI extracts of L1210 leukemia cells purified by polyacrylamide gel electrophoresis (PAGE) and the antigenic material from leukemia L1210 cells purified by affinity chromatography were characterized. Their identity was verified by anti ML-sera. Using the modified lyso-strip method, the presence of ML antigen and H-2K and H-2D gene products on independent molecules on the surface of L1210 cells was shown. In addition, in preparative polyacrylamide gel electrophoresis (PAGE) of 3M KCL extracts of L1210 cells, ML and H-2d antigenic products were found in separate fractions.


Effect of socioeconomic status on exposures to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) among pregnant African-American women.
In this study, the authors investigated the associations between socioeconomic status and exposures to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) in a cohort of inner-city African-American pregnant women. Data for this study were derived from the Columbia Presbyterian Medical Center subcohort of the National Collaborative Perinatal Project. African-American women from whom venous blood had been collected during their third trimester of pregnancy during the time period between 1960 and 1965 were included in the current study (n = 152). Prenatal samples were assayed for PCB and DDE concentrations. The authors used linear-regression analysis to explore the association between socioeconomic indicators and PCB and DDE concentrations. Mean concentrations of the 4 most abundant congeners (i.e., PCB4) and total DDE were 3.9 microg/l and 37.2 microg/l, respectively. In adjusted analyses, income was associated significantly with an increase in serum concentrations of PCBs, whereas education was not. Neither income nor education was associated with concentrations of DDE. The authors concluded that maternal socioeconomic indicators may influence the effects of exposure to PCBs among African-American pregnant women.


Status and transition of normal-weight central obesity and the risk of cardiovascular diseases: A population-based cohort study in China.
Cardiovascular disease (CVD) has become a growing public health concern. Normal weight central obesity (NWCO) has emerged as a potential risk factor for cardiometabolic dysregulation. To date, the association between NWCO and new-onset CVDs remains unclear. We aimed to evaluate the associations of NWCO and its longitudinal transitions with cardiovascular risks in middle-aged and older Chinese. Data were from the China Health and Retirement Longitudinal Study 2011-2018. NWCO was defined as the combination of a body mass index (BMI) of <24.0 kg/m2 and a waist circumference (WC) of >85 cm in males or >80 cm in females. CVDs included heart diseases and stroke. Cause-specific hazard models and subdistribution hazard models with all-cause death as the competing event were applied. In 2011, 9856 participants without prior CVDs were included, of whom 1814 developed CVDs during a 7-year follow-up. Compared to normal weight and non-central obesity (NWNCO), NWCO was significantly associated with new-onset CVDs, with cause-specific hazard ratios (cHRs) and 95% confidence intervals (CIs) of 1.21 (1.04-1.41) for heart diseases and 1.40 (1.11-1.76) for stroke. From 2011 to 2013, 571 NWNCO participants developed NWCO who subsequently demonstrated a 45% higher risk of CVDs than those with maintained NWNCO. NWCO and transition from NWNCO to NWCO are associated with higher risks of CVDs. Identification and prevention of NWCO may be useful in the management of CVDs.


The metabolic potential of plastics as biotechnological carbon sources - Review and targets for the future.
The plastic crisis requires drastic measures, especially for the plastics' end-of-life. Mixed plastic fractions are currently difficult to recycle, but microbial metabolism might open new pathways. With new technologies for degradation of plastics to oligo- and monomers, these carbon sources can be used in biotechnology for the upcycling of plastic waste to valuable products, such as bioplastics and biosurfactants. We briefly summarize well-known monomer degradation pathways and computed their theoretical yields for industrially interesting products. With this information in hand, we calculated replacement scenarios of existing fossil-based synthesis routes for the same products. Thereby, we highlight fossil-based products for which plastic monomers might be attractive alternative carbon sources. Notably, not the highest yield of product on substrate of the biochemical route, but rather the (in-)efficiency of the petrochemical routes (i.e., carbon, energy use) determines the potential of biochemical plastic upcycling. Our results might serve as a guide for future metabolic engineering efforts towards a sustainable plastic economy.


"Emerging unwanted side effects of quality control, or the value of the immeasurable qualities of medical care".
The author reviews briefly the sociocultural aspects of the quality control movements and how they relate to the medical profession. The "ethos" of the neurosurgical practice and the way to harmonize the new paradigms of modern medicine and the need to define parameters to evaluate quality are discussed.


Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) - Feasibility testing, pilot randomised controlled trial and mixed methods process evaluation.
Treatment decision-making is complex for people with multiple sclerosis. Profound information on available options is virtually not possible in regular neurologist encounters. The "nurse decision coach model" was developed to redistribute health professionals' tasks in supporting immunotreatment decision-making following the principles of informed shared decision-making. To test the feasibility of a decision coaching programme and recruitment strategies to inform the main trial. Feasibility testing and parallel pilot randomised controlled trial, accompanied by a mixed methods process evaluation. Two German multiple sclerosis university centres. People with suspected or relapsing-remitting multiple sclerosis facing immunotreatment decisions on first line drugs were recruited. Randomisation to the intervention (n = 38) or control group (n = 35) was performed on a daily basis. Quantitative and qualitative process data were collected from people with multiple sclerosis, nurses and physicians. We report on the development and piloting of the decision coaching programme. It comprises a training course for multiple sclerosis nurses and the coaching intervention. The intervention consists of up to three structured nurse-led decision coaching sessions, access to an evidence-based online information platform (DECIMS-Wiki) and a final physician consultation. After feasibility testing, a pilot randomised controlled trial was performed. People with multiple sclerosis were randomised to the intervention or control group. The latter had also access to the DECIMS-Wiki, but received otherwise care as usual. Nurses were not blinded to group assignment, while people with multiple sclerosis and physicians were. The primary outcome was 'informed choice' after six months including the sub-dimensions' risk knowledge (after 14 days), attitude concerning immunotreatment (after physician consultation), and treatment uptake (after six months). Quantitative process evaluation data were collected via questionnaires. Qualitative interviews were performed with all nurses and a convenience sample of nine people with multiple sclerosis. 116 people with multiple sclerosis fulfilled the inclusion criteria and 73 (63%) were included. Groups were comparable at baseline. Data of 51 people with multiple sclerosis (70%) were available for the primary endpoint. In the intervention group 15 of 31 (48%) people with multiple sclerosis achieved an informed choice after six months and 6 of 20 (30%) in the control group. Process evaluation data illustrated a positive response towards the coaching programme as well as good acceptance. The pilot-phase showed promising results concerning acceptability and feasibility of the intervention, which was well perceived by people with multiple sclerosis, most nurses and physicians. Delegating parts of the immunotreatment decision-making process to trained nurses has the potential to increase informed choice and participation as well as effectiveness of patient-physician consultations.


Characterization of oil spills in the environment using parallel factor multiway analysis.
The aim of this study was to characterize samples of petroleum spills derived from the oily free-phase zone located in the subsurface of a petroleum refinery and to reveal the contained distinct petroleum fractions, thus enabling the identification of the spill origin. The samples were collected from different monitoring wells and were analyzed using gel permeation chromatography (GPC) combined with a UV-diode array detector. The PARAFAC algorithm was employed for the analysis of the 3-D experimental data matrix, which contained the areas under the chromatographic trace, measured for distinct time slices over the 270-440 nm UV range for the whole sample population. The application of the PARAFAC method revealed two significant elution profiles possessing characteristic UV signals, which were attributed to the gasoline and diesel fractions, respectively. A third elution profile was also identified which corresponded to biodegraded heavy fractions. The relative contribution of these compositional features to the oil spill samples was also identified. The presented method can be employed as a rapid and reliable fingerprinting tool in environmental studies, where petroleum pollutants of unknown composition are expected.


Evaluation of pediatric intensive care scoring systems.
There is no report analysing pediatric severity scoring systems in British Intensive Therapy Units (ICUs). Two previously reported pediatric severity scoring systems, the Admission Physiologic Stability Index (APSI) and the Organ System Failure (OSF) score were evaluated for 151 patients. The APSI was higher for children who died than for those who lived (p less than 0.001). This difference reflected the sharp distinction between the APSI for children who left intensive care within 24 h and those remaining in ICU longer than 24 h (p less than 0.001). For children remaining in ICU longer than 24 h, there was a large overlap of APSI scores, and the APSI did not discriminate between children in the overlap region who lived and those who died (p = 0.054). There was underscoring of neurological patients; the APSI did not differentiate neurological patients whole lived and those who died (p greater than 0.10). The OSF also underscored neurological patients. Increasing number of organ systems failed was associated with increasing mortality. In contrast to previous reports, however, the mortality rate was unaffected by whether the total number of systems failed simultaneously or non-simultaneously. There is still a need for a comprehensive yet simple pediatric scoring system for comparing the efficacy and outcome of pediatric intensive care in different ICUs in different countries.


A Case Report: Point-of-care Ultrasound in the Diagnosis of Post-Myocardial Infarction Ventricular Septal Rupture.
Ventricular septal rupture (VSR) is a rare complication of ST-elevation myocardial infarction (STEMI), typically discovered post-revascularization. We present the first case of VSR detected on point-of-care ultrasound (POCUS) in the emergency department immediately prior to emergent angiography, with management positively affected by this discovery. The VSR was quickly confirmed via right heart catheterization. Subsequently, hemodynamic stability was achieved using an intra-aortic balloon pump. A delayed surgical VSR repair, with concomitant coronary artery bypass grafting, was implemented for definitive management. This case highlights the utility of POCUS in a STEMI patient with a suspected mechanical complication.


Comparison of early postoperative period electrophysiological and clinical findings following carpal tunnel syndrome: is EMG necessary? [Retraction].
[This retracts the article on p. 10011 in vol. 8, PMID: 26309691.].


Adhesion, proliferation, and adipogenesis in primary rat cell cultures: effects of collagenous substrata, fibronectin, and serum.
The effects of collagenous substrata, fibronectin, and fetal bovine serum on the adhesion, proliferation, and adipogenesis of rat stromal-vascular cells are reported. There was no effect on initial stromal-vascular cell-attachment by fetal bovine serum or fibronectin. The number of cells attached to a hydrated collagen-gel was almost twice (P less than 0.04) the number attached to dried collagen-gel or dried denatured collagen-gel. Total number of cells after 5 days in culture was similar among the collagenous substrata and among the treatments with or without fibronectin in the growth media. Total number of cells increased significantly (P less than 0.02) with 10% FBS. Adipocytic formation was inhibited by hydrated collagen-gel (P less than 0.02) compared to dried collagen-gel or dried, denatured collagenous substrata. An interaction occurred between dried, denatured gel and fetal bovine serum so that total formation of adipocytes increased by increasing the level of fetal bovine serum (P less than 0.07). Adipocytic formation was inhibited by hydrated collagen-gel at all levels of fetal bovine serum. The percentage of cells that converted to adipocytes was significantly lower (P less than 0.01) on hydrated collagen-gel compared to dried, denatured or dried collagen-gel. Percentage of conversion was not significantly different among levels of fetal bovine serum, although this percentage increased as fetal bovine serum level increased. Adipocytic conversion was not different between fibronectin-treated or untreated cells. Morphology of stromal vascular cells was similar on dried collagen and dried, denatured collagen-gel, but tended to remain bipolar on hydrated collagen-gel.(ABSTRACT TRUNCATED AT 250 WORDS)


Decreased corticotropin-releasing factor receptor expression and adrenocorticotropic hormone responsiveness in anterior pituitary cells of Wistar-Kyoto rats.
The Wistar-Kyoto (WKY) rat shows signs of persistent activation of the hypothalamic-pituitary-adrenal axis, but the cause and site of this activation is not yet known. Chronically activated corticotrophs generally show blunted adrenocorticotropic hormone (ACTH) response to corticotropin releasing factor (CRF); therefore, the anterior pituitary responsiveness to ACTH secretagogues, CRF and vasopressin, was compared in male WKY and Wistar rats. Anterior pituitary CRF binding and CRF receptor mRNA expression was significantly decreased in WKY rats. ACTH response to CRF or vasopressin was markedly impaired, and vasopressin failed to potentiate the CRF-stimulated ACTH release in cultured WKY anterior pituitary cells. In contrast, CRF and vasopressin alone and in combination stimulated large, concentration-dependent increases in ACTH release in Wistar anterior pituitary cells. By contrast to the decreased ACTH secretory responses, steady-state anterior pituitary pro-opiomelanocortin mRNA levels were approximately 12-fold greater in WKY rats compared to Wistar rats, and they further increased in response to CRF stimulation. These findings suggest that, although the WKY rat corticotroph is under a chronic state of activation or disinhibition, the in vitro secretory responses to classic ACTH secretagogues are impaired.


Glycemic response after glucose oral administration of wild juvenile red grouper Epinephelus morio fed two different diets.
Epinephelus morio is a large carnivorous species of the Caribbean Sea under reproduction in captivity and nutritional physiology. A diet with raw cornstarch (RCS) was compared to a basal diet without starch (basal) to measure plasma glucose, liver glycogen, and intermediary metabolism. Glucose level did not change (p > 0.05) whereas liver glycogen was significantly higher in fish fed the RCS diet (137.2 ± 14.5 mg g-1) than in fish fed the basal diet (87.4 ± 14.5 mg g-1). Oral glucose administration (170 mg glucose per 100 g body weight) yielded a slight change; two peaks of plasma glucose were recorded with basal (5.6 mM L-1) 2 h after oral administration and at 12 h (6.4 mM L-1). After 24 h, with 1.7 mM L-1, fish returned to initial stage (2.4 mM L-1). RCS diet produced the highest level (6.3 mM L-1) 2 h after oral administration; lowest level observed at 24 h after oral administration (1.0 mM L-1). A significant effect was detected with the presence or absence of dietary carbohydrates (CBH) on hepatic fructose 1,6-bisphosphatase and pyruvate kinase activity. Grouper used two strategies to maintain glucose homeostasis: CBH present in the diet oriented towards gluconeogenesis, whereas no dietary CBH enhanced glycolytic route to liberate glucose and increase liver glycogen.


Na-ion batteries based on the inorganic BN nanocluster anodes: DFT studies.
It has been recently indicated that the Li-ion batteries may be replaced by Na-ion batteries because of their low safety, high cost, and low-temperature performance, and lack of the Li mineral reserves. Here, using density functional theory calculations, we studied the potential application of B12N12 nanoclusters as anode in Na-ion batteries. Our calculations indicate that the adsorption energy of Na+ and Na are about -23.4 and -1.4kcal/mol, respectively, and the pristine BN cage to improve suffers from a low cell voltage (∼0.92V) as an anode in Na-ion batteries. We presented a strategy to increase the cell voltage and performance of Na-ion batteries. We showed that encapsulation of different halides (X=F-, Cl-, or Br-) into BN cage significantly increases the cell voltage. By increasing the atomic number of X, the Gibbs free energy change of cell becomes more negative and the cell voltage is increased up to 3.93V. The results are discussed based on the structural, energetic, frontier molecular orbital, charge transfer and electronic properties and compared with the performance of other nanostructured anodes.


Expression of alpha subunit and luteinizing hormone beta genes in the ovine anterior pituitary. Estradiol suppresses accumulation of mRNAS for both alpha subunit and luteinizing hormone beta.
Bovine cDNA clones containing coding sequences for growth hormone, prolactin, alpha subunit, and luteinizing hormone beta (LH beta) have been used to quantitate their respective mRNA concentrations in anterior pituitary glands isolated from ovariectomized ewes, or from ovariectomized ewes treated for three weeks with estradiol. Concentrations of mRNAs for prolactin or growth hormone remained unchanged in either physiological state. In contrast, treatment with estradiol resulted in a 98% decrease of mRNA for LH beta, relative to untreated animals. This change in mRNA was associated with a similar decrease in the concentrations of pituitary and serum LH. Administration of estradiol also led to a reduction (86%) of alpha subunit mRNA. These results suggest that estrogen regulates the expression of the genes encoding both the alpha and LH beta subunit prior to translation. Furthermore, the pronounced effect of estradiol on the concentrations of mRNAs for alpha subunit and LH beta suggest that the assembly of mature glycoprotein hormones may not be limited solely by the rate of accumulation of the beta subunit.


Modelling drug-related morbidity in Sweden using an expert panel of pharmacists'.
Drug-related morbidity (DRM) is common and to some extent preventable, and associated with considerable costs in patients attending hospital. In outpatients and in the general public corresponding data are limited, but pharmacists' expert opinion has suggested high rates of DRM also in US ambulatory care. It is unknown if the results are applicable in Sweden today. To estimate the proportions of patients with DRM and preventable DRM and the cost-of-illness (COI) of DRM in Sweden based on pharmacists' expert opinion. Swedish healthcare. The study applied a conceptual model of DRM based on a decision tree. An expert panel of pharmacists determined the probabilities of therapeutic outcomes of medication therapy. The COI analysis included direct costs from the healthcare perspective. Sensitivity analyses were performed for variations in probabilities and pathway costs. DRM included new medical problems (adverse drug reactions, drug dependence and intoxications) and therapeutic failures (insufficient effects of medicines and morbidity due to untreated indication). The expert panel estimated that 61 ± 14 % (mean ± SD) of all patients attending healthcare suffered from DRM, of which 29 ± 8 % suffered from new medical problems, 18 ± 6 % from therapeutic failures, and 15 ± 7 % from a combination of both. The DRM was considered preventable in 45 ± 15 % of the patients with DRM. The estimated COI was EUR 997 per patient attending healthcare, corresponding to an annual cost of EUR 6,600 million to the Swedish healthcare system. The COI ranged from EUR 490 to EUR 1,314 when varying the participants' probabilities of DRM and clinical outcomes from the first to the third quartile. Of the pathway costs, the COI was most sensitive to variation in the cost of prolonged hospital stay (COI range EUR 953-1,306). According to pharmacists' expert opinion, a large proportion of patients in Sweden experience DRM and preventable DRM, and the estimated COI of DRM is extensive. Since observational studies have not addressed the burden of DRM to the general public, this study adds the pharmacists' perception on DRM. Other healthcare professionals' perceptions on DRM need to be investigated in future studies.


Monitoring of scoliosis surgery with epidurally recorded motor evoked potentials (D wave) revealed false results.
To elucidate the mechanism behind D wave amplitude changes after surgical correction of scoliosis. We collected D wave and muscle MEP data from 93 patients (78 female, 15 male, age range 4-19 years, mean age 15.9 years), who underwent surgical correction of scoliosis. D waves were recorded via a catheter electrode inserted epidurally through the flavectomy. Muscle MEPs from lower limb muscles were also recorded. Muscle MEPs/D wave were elicited by short trains/single transcranial electrical stimuli. SEPs were elicited through bilateral percutaneous stimulation of the tibial nerves at the ankle and an averaged response from 100 to 200 single sweeps were recorded over the scalp at Cz'/Fz. In addition, we analyzed intraoperatively obtained X-ray images of the spine in 9 patients and preoperative spinal MRI in two of those nine. After surgical correction of scoliosis in 25 of 93 (27%) patients, the D wave amplitude changed by more than 20% of its baseline value. A decremental change occurred in 21 (84%) and an incremental change in 4 (16%) patients. D wave decrements of more than 50% were observed in 5 patients without significant SEP changes in any of these cases. In 9 patients, intraoperatively obtained X-rays of the spine (before and after correction of spine curvature) showed no catheter displacement. Muscle MEPs did not change and postoperative sensory-motor status was normal. In 2 patients, preoperative MRI revealed displacement of the spinal cord towards the concave side of the scoliotic curvature. During scoliosis surgery, D wave amplitude changes should be interpreted cautiously until the definitive cause(s) of these changes are found. One possible mechanism to explain D wave changes during scoliosis correction could involve rotation of the spinal cord within the spinal canal, and the relative position of the epidural recording catheter (ERC). Rotation of the spinal cord after correction of scoliosis could introduce a new relationship between the ERC and the corticospinal tracts (CTs). Due to high incidence of false D wave amplitude changes we suggest that this methodology should not be used to assess the functional integrity of the CTs during scoliosis surgery. This study provides new insight into the methodology of D wave monitoring as well as strong evidence of a high incidence of false positive results using D wave monitoring during surgical correction of scoliosis.


Visual and haptic responses as measures of word comprehension and speed of processing in toddlers: Relative predictive utility.
Early vocabulary knowledge and speed of word processing are important foundational skills for the development of preschool and school-age language and cognition. However, the variance in outcomes accounted for by parent-reported receptive or expressive vocabulary is generally modest. Recent research suggests that directly assessed, decontextualized vocabulary predicts developmental outcomes, including general language ability and kindergarten readiness, accounting for additional variance above and beyond parent-reported vocabulary. The current research extends this finding by exploring prediction from both decontextualized vocabulary and speed of word processing at 2 years of age to vocabulary during the preschool period. At age 2, children completed a two-alternative forced-choice task that yielded a measure of decontextualized vocabulary (number of correct touch responses) and two measures of speed of processing: latency to fixate the target (visual response latency) and latency to touch (haptic response latency). Results reveal that age 2 vocabulary and visual response latency, but not haptic response latency, independently predict vocabulary at ages 3 and 4. Furthermore, only decontextualized vocabulary remains a significant predictor when controlling for speed of processing, but not vice versa. This suggests that the number of early, stable word-referent associations and the efficiency with which these are processed are important to vocabulary outcomes. However, it also suggests that decontextualized vocabulary may be a more robust unique predictor of downstream outcomes.


Differences in Pharmacokinetic/Pharmacodynamic Parameters of Tedizolid Against VRE and MRSA.
Vancomycin-resistant enterococci (VRE) have recently become a major cause of nosocomial infections and a global public health concern. Tedizolid exhibits powerful antibacterial activity against VRE in vitro, but its pharmacokinetic/pharmacodynamic (PK/PD) parameters remain unclear. Therefore, we aimed to determine the PK/PD indices of tedizolid action on VRE and the mechanisms underlying the PK/PD indices differences of tedizolid against VRE and methicillin-resistant Staphylococcus aureus (MRSA). Optimal PK/PD target values of tedizolid were determined in vitro, based on time-kill curves and post-antibiotic effects (PAEs), and in vivo, using mouse models of thigh infection with VRE and MRSA strains. The tedizolid bactericidal activity on VRE and MRSA was time-dependent. Correlations were closest between fAUC24/MIC and the tedizolid PK/PD index against MRSA and VRE. To achieve 1 log10 kill tedizolid fAUC24/MIC in neutropenic mouse models of thigh infection with VRE and MRSA should be 14.2 and 138.5, respectively. The PAEs of tedizolid against VRE and MRSA were 2.39 and 0.99 h, respectively. Tedizolid showed bactericidal effects against VRE even in neutropenic mice unlike MRSA, which could be attributed to its longer PAE against VRE. Hence, we hypothesize that tedizolid treatment against VRE infections is promising for achieving therapeutic success in clinical.


Mental health, social functioning, and feelings of hatred and revenge of Kosovar Albanians one year after the war in Kosovo.
A cross-sectional cluster sample survey was conducted in June 2000 in Kosovo to assess the prevalence of mental health problems associated with traumatic experiences, feelings of hatred and revenge, and the level of social functioning among Kosovar Albanians approximately 1 year after the end of the war. Findings of the second cross-sectional survey were compared with those from our 1999 mental health survey in Kosovo. Included in the survey were 1399 Kosovar Albanians aged 15 years or older living in 593 randomly selected households across Kosovo. Twenty-five percent of respondents reported PTSD symptoms, compared with 17.1% in 1999. The MOS-20 social functioning score improved to 69.8 from 29.5 in 1999. In the 2000 survey 54% of men felt hatred toward the Serbs, compared with 88.7% in 1999.


Breast cancer radiotherapy treatments calculated to have environmental impact.
Giving radiotherapy during surgery to early-stage breast cancer patients could save millions of travel miles and carbon dioxide emissions, according to a study.


Renal arteriovenous fistula discovered ~2 years after renal biopsy: A case report.
Although percutaneous renal biopsy is considered safe, this invasive procedure has complications such as renal arteriovenous fistula (RAVF). Even if complications such as RAVFs are not observed early after renal biopsy, considering the possibility of delayed renal hemorrhage, follow-up with ultrasound after renal biopsy even in asymptomatic cases could be important. Although percutaneous renal biopsy is considered safe, this invasive procedure can lead to complications such as renal arteriovenous fistula (RAVF). RAVF occurs when some arteries and veins communicate in the absence of capillaries in the renal hilum or renal parenchyma. It was previously thought to be relatively rare; however, with advances in imaging diagnostics, it is sometimes found asymptomatically. In addition, renal biopsy is the most common cause of acquired RAVF. In this case, RAVF was discovered 2 years after renal biopsy. Late-onset RAVF is scarce. This case highlights that even if complications such as RAVFs are not observed early after renal biopsy, considering the possibility of delayed RAVF, follow-up with ultrasound could be important.


Diode laser in management of loss of taste sensation in patients with post-COVID syndrome: a randomized clinical trial.
Loss of taste (ageusia) is a symptom observed following recovery from COVID-19 infection. The loss of taste and smell sensation may negatively affect patients' quality of life (QoL). The present study aimed to evaluate the effectiveness of the Diode Laser in managing loss of taste sensation in patients with post-COVID syndrome versus the placebo. The study sample was 36 patients who complained of persistent loss of taste sensation following COVID-19. The patients were randomly assigned to one of the two groups according to the received treatment: Group I (laser treatment) and Group II (light treatment), with each patient receiving a diode laser treatment or placebo from the same operator. Taste sensation was subjectively measured after treatment for four weeks. The results demonstrated a significant difference between both groups regarding taste restoration after one month (p = 0.041), with Group II having a significantly higher percentage of cases 7 (38.9%) with partial taste restoration. In contrast, a significantly higher proportion of Group I 17 cases (94.4%) had complete taste restoration (p < 0.001). The present study concluded that using a Diode laser 810 nm aided in a more rapid recovery from loss of taste dysfunction.


Treatment of Liver Metastases With Focused Ultrasound and Microbubbles in Patients With Colorectal Cancer Receiving Chemotherapy.
Pre-clinical trials have obtained promising results that focused ultrasound (FUS) combined with microbubbles (MBs) increases tumor uptake and the therapeutic effect of drugs. The aims of the study described here were to investigate whether FUS and MBs could improve the effect of chemotherapy in patients with liver metastases from colorectal cancer and to investigate the safety and feasibility of using FUS + MBs. We included 17 patients with liver metastases from colorectal cancer, selected two lesions in each patient's liver and randomized the lesions for, respectively, treatment with FUS + MBs or control. After chemotherapy (FOLFIRI or FOLFOXIRI), the lesions were treated with FUS (frequency = 1.67 MHz, mechanical index = 0.5, pulse repetition frequency = 0.33 Hz, 33 oscillations, duty cycle = 0.2%-0.4% and MBs (SonoVue) for 35 min). Nine boluses of MBs were injected intravenously at 3.5 min intervals. Patients were scheduled for four cycles of treatment. Changes in the size of metastases were determined from computed tomography images. Treatment with FUS + MBs is safe at the settings used. There was considerable variation in treatment response between lesions and mixed response between lesions receiving only chemotherapy. There is a tendency toward larger-volume reduction in lesions treated with FUS + MBs compared with control lesions, but a mixed response to chemotherapy and lesion heterogeneity make it difficult to interpret the results. The combination of FUS and MBs is a safe, feasible and available strategy for improving the effect of chemotherapy in cancer patients. Therapeutic effect was not demonstrated in this trial. Multicenter trials with standardized protocols should be performed.


First successful case of simultaneous liver and kidney transplantation for patients with chronic liver and renal failure in Japan.
Establishment of a preferential liver allocation rule for simultaneous liver and kidney transplantation (SLK) and revisions of laws regarding organ transplants from deceased donors have paved the way for SLK in Japan. Very few cases of SLK have been attempted in Japan, and no such recipients have survived for longer than 40 days. The present report describes a case of a 50-year-old woman who had undergone living donor liver transplantation at the age of 38 years for management of post-partum liver failure. After the first transplant surgery, she developed hepatic vein stenosis and severe hypersplenism requiring splenectomy. She was then initiated on hemodialysis (HD) due to the deterioration of renal function after insertion of a hepatic vein stent. She was listed as a candidate for SLK in 2011 because she required frequent plasma exchange for hepatic coma. When her Model for End-stage Liver Disease score reached 46, the new liver was donated 46 days after registration. The reduced trisegment liver and the kidney grafts were simultaneously transplanted under veno-venous bypass and intraoperative HD. The hepatic artery was reconstructed prior to portal reconstruction in order to shorten anhepatic time. Although she developed subcapsular bleeding caused by hepatic contusion on the next day, subsequent hemostasis was obtained by transcatheter embolization. Thereafter, her recovery was uneventful, except for mild rejection and renal tubular acidosis of the kidney graft. This case highlights the need to establish Japanese criteria for SLK.


Cupriavidus necator isolates are able to fix nitrogen in symbiosis with different legume species.
The aim of the present study was to identify a collection of 35 Cupriavidus isolates at the species level and to examine their capacity to nodulate and fix N(2). These isolates were previously obtained from the root nodules of two promiscuous trap species, Phaseolus vulgaris and Leucaena leucocephala, inoculated with soil samples collected near Sesbania virgata plants growing in Minas Gerais (Brazil) pastures. Phenotypic and genotypic methods applied for this study were SDS-PAGE of whole-cell proteins, and 16S rRNA and gyrB gene sequencing. To confirm the ability to nodulate and fix N(2), the presence of the nodC and nifH genes was also determined, and an experiment was carried out with two representative isolates in order to authenticate them as legume nodule symbionts. All 35 isolates belonged to the betaproteobacterium Cupriavidus necator, they possessed the nodC and nifH genes, and two representative isolates were able to nodulate five different promiscuous legume species: Mimosa caesalpiniaefolia, L. leucocephala, Macroptilium atropurpureum, P. vulgaris and Vigna unguiculata. This is the first study to demonstrate that C. necator can nodulate legume species.


Innovative drug delivery systems in cardiovascular medicine: nifedipine-GITS and clonidine-TTS.
Innovative drug delivery systems have been developed for nifedipine and clonidine that prolong the pharmacologic activity of the medications, allowing once daily dosing. The nifedipine-GITS (gastrointestinal therapeutic system) tablet formulation and the clonidine-TTS (transcutaneous delivery system) patch may also reduce side effects in patients while preserving the therapeutic efficacy of the origin drug formulations (nifedipie capsule, clonidine tablet).


Application of a factorial design to the study of the flow behavior, spreadability and transparency of a Carbopol ETD 2020 gel. Part II.
A factorial design (2(3)) is applied to study the influence of three of the components of a cosmetic gel (the concentrations of Carbopol ETD 2020, ethanol and glycerine) on flow parameters (Casson's yield value (tau(c)), Casson's viscosity (eta(c)) and apparent viscosity at 125 s-1 (eta(ap.) 125 s-1), spreadability, and transparency. The first-order polynomial equation allowed by the model suitably accounts for the tau(c) and spreadability. Both depend on the concentrations of Carbopol and ethanol, and tau(c) also depends on the ethanol-glycerine interaction. The model explains to a certain extent the complex relationships that are established between the components and that influence eta(c) y eta(ap.) 125 s-1. Transparency is independent of the Carbopol concentration and it is also thought to be independent of the ethanol concentration. In addition, a high linear correlation has been found between the tau(c) and spreadability and other viscoelastic parameters of the gels that were previously determined (Int. J. Pharm. (2001)). The application of the technique of experimental design has been shown to be a very useful tool for formulating gels.


Effects of race, ethnicity, and gender on surgical mortality in hypoplastic left heart syndrome.
Information is limited regarding the effect of race, ethnicity, and gender on the outcomes of the three palliative procedures for hypoplastic left heart syndrome (HLHS). This study examined the effects of race, ethnicity, gender, type of admission, and surgical volume on in-hospital mortality associated with palliative procedures for HLHS between 1998 and 2007 using data from the University HealthSystem Consortium. According to the data, 1,949 patients underwent stage 1 palliation (S1P) with a mortality rate of 29 %, 1,279 patients underwent stage 2 palliations (S2P) with a mortality rate of 5.4 %, and 1,084 patients underwent stage 3 palliation (S3P) with a mortality rate of 4.1 %. The risk factors for increased mortality with S1P were black and "other" race, smaller surgical volume, and early surgical era. The only risk factors for increased mortality with S2P were black race (11 % mortality; odds ratio [OR], 3.19; 95 % confidence interval [CI] 1.69-6.02) and Hispanic ethnicity (11 % mortality; OR 3.30; 95 % CI 1.64-6.64). For S2P, no racial differences were seen in the top five surgical volume institutions, but racial differences were seen in the non-top-five surgical volume institutions. Mortality with S1P was significantly higher for patients discharged after birth (37 vs 24 %; p = 0.004), and blacks were more likely to be discharged after birth (12 vs 5 % for all other races; p < 0.001). No racial differences with S3P were observed. The risk factors for increased mortality at S1P were black and "other" race, smaller surgical volume, and early surgical era. The risk factors for increased in-hospital mortality with S2P were black race and Hispanic ethnicity.


Zinc toxicity in ruminants.
Four natural occurrences of zinc toxicity in sheep and one in calves were studied. To assist in the confirmation of a diagnosis of zinc toxicity, 2 experiments were conducted in which sheep were given toxic amounts of zinc. The clinical findings, clinical pathology, and gross and microscopic pathology are given. Clinical manifestations included inappetance, loss of condition, diarrhoea with dehydration or subcutaneous oedema, profound weakness and jaundice. Significant rises in the concentration of zinc were usually found in the liver, kidney and pancreas, but occasionally in only 1 or 2 of these organs. Many affected sheep were anaemic. Pathological changes were found in the pancreas, kidney, liver, rumen, abomasum, small intestine and adrenal gland. Lesions in the kidney and abomasum apparently made the most significant contribution to the deterioration in health of affected animals, but the pancreas was the only organ consistently affected. The degenerative changes in the pancreas were mainly restricted to the exocrine portion of the organ, and regeneration of the damaged tissue was observed although exposure to toxic amounts of zinc continued. Attention is drawn to the importance of the pancreas in the diagnosis of zinc toxicity and in estimating the period of exposure.


Circulating activated protein C is reduced in young survivors of myocardial infarction and inversely correlates with the severity of coronary lesions.
Cardiovascular risk factors for myocardial infarction (MI) are less frequent in younger than in older MI survivors. Therefore, the thrombotic component of MI may play a more important role at a young age. As activated protein C (APC) provides systemic anticoagulant and anti-inflammatory protection, a low plasma APC level may be an arterial thrombotic risk factor. To determine whether there is an association between reduced APC levels and early MI and severe coronary lesions. APC was measured in 231 young MI survivors and 231 controls. Low APC levels were significantly associated with MI. Compared with the fourth quartile, the odds ratio (OR) for APC values in the first quartile was 3.7 [95% confidence interval (CI) = 2.1-6.4], and 3.2 (1.5-7.0) after adjustment for cardiovascular risk factors. Moreover, each decrease of 0.43 ng mL(-1) (1 SD) in APC increased the OR 1.7 times (1.4-2.2), and 1.5 times (1.2-1.9) after adjustment for cardiovascular risk factors. Low APC levels were also associated with the number of coronary arteries affected and with the severity of coronary lesions (P < 0.001). There is a significant association between low circulating APC levels and both early MI and the extent and severity of coronary atherosclerosis, which might be related to the anticoagulant and anti-inflammatory properties of APC.


Toxic epidermal necrolysis with a rare long-term oral complication requiring surgical intervention.
Toxic epidermal necrolysis (TEN) is a rare and potentially fatal adverse dermatologic reaction, often secondary to drug intake. We report a case of an adult male who developed TEN that was complicated by a sepsis-induced coma lasting a period of 3 months. Although the patient eventually recovered, severe oral mucosal involvement during the course of disease resulted in frenum-like fibrotic bands that connected movable oral mucosa (tongue and lips) to attached oral mucosa (gingiva). This complication was painful and also affected his ability to speak and maintain adequate oral hygiene, requiring surgical intervention to restore structure and function. This oral manifestation in relation to TEN is rarely reported in the literature and represents a preventable complication.


Structures of two new "minimalist" modified nucleosides from archaeal tRNA.
The wyeosine (or wye) family of tricyclic ribonucleosides from archaeal and eukaryal tRNA(Phe) constitutes one of the most complex and interesting series of posttranscriptional RNA modifications, and has been the object of numerous studies of their chemical and biological synthesis and distribution. We report the structures of two minimally elaborated wye derivatives from archaea, raising the known number of wye nucleosides to eight: 3,4-dihydro-6-methyl-3-beta-d-ribofuranosyl-9H-imidazo[1,2-a]purine-9-one (symbol imG-14), and 3,4-dihydro-6,7-dimethyl-3-beta-d-ribofuranosyl-9H-imidazo[1,2-a]purine-9-one (symbol imG2). Structures were determined primarily by mass spectrometry, and confirmed by comparison of physicochemical properties with those of chemically synthesized nucleosides. The nucleosides contain no amino acid side chains at C-7 (1H-imidazo[1,2-a]purine nomenclature) and are the only wye derivatives not methylated at N-4. These features suggest a minimal role for wye methyl groups and side chains in maintenance of anticodon stem-loop structures, and support the concept that archaeal tRNA nucleoside modification motifs are generally simpler than those of their counterparts in eukarya and bacteria.


The synthesis of 2'-methylseleno adenosine and guanosine 5'-triphosphates.
Modified nucleoside triphosphates (NTPs) represent powerful building blocks to generate nucleic acids with novel properties by enzymatic synthesis. We have recently demonstrated the access to 2'-SeCH(3)-uridine and 2'-SeCH(3)-cytidine derivatized RNAs for applications in RNA crystallography, using the corresponding nucleoside triphosphates and distinct mutants of T7 RNA polymerase. In the present note, we introduce the chemical synthesis of the novel 2'-methylseleno-2'-deoxyadenosine and -guanosine 5'-triphosphates (2'-SeCH(3)-ATP and 2'-SeCH(3)-GTP) that represent further candidates for the enzymatic RNA synthesis with engineered RNA polymerases.


Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model.
We investigated the efficacy and optimal dosage of recombinant Bacillus Calmette-Guérin-dltA (rBCG-dltA) in a high-throughput 3D bio-printed bladder cancer-on-a-chip (BCOC) and orthotopic bladder cancer mouse model. We fabricated high-throughput BCOC with microfluidic systems, enabling efficient drug screening. The efficacy of rBCG-dltA was evaluated using BCOC by the cell viability assay, monocyte migration assay, and measuring cytokine levels. The anti-tumor effect was compared using the orthotopic bladder cancer mouse model. The cell proliferation rates of T24 and 253J bladder cancer cell lines (mean±standard error) were measured at three days after treatment. In T24 cell line, there was significantly decreased T24 cells compared to control at rBCG 1 multiplicity of infection (MOI) and 10 MOI (30 MOI: 63.1±6.4, 10 MOI: 47.4±5.2, 1 MOI: 50.5±7.5, control: 100.0±14.5, p<0.05). In 253J cell line, a statistically significant decrease in 253J cell count compared to control and mock BCG 30 MOI (30 MOI: 11.2±1.3, 10 MOI: 22.5±2.3, 1 MOI: 39.4±4.7, Mock: 54.9±10.8, control: 100.0±5.6, p<0.05). The migration rates of THP-1 cells showed increased patterns after rBCG-dltA treatment in BCOC. The concentration of tumor necrosis factor-α and interleukin-6 after rBCG-dltA 30 MOI treatment was higher than control in T24 and 253J cell line. In conclusion, rBCG-dltA has the potential to have better anti-tumor activity and immunomodulatory effects than BCG. Furthermore, high-throughput BCOCs have potential to reflect the bladder cancer microenvironment.


Comparative evaluation of the resolution of hydronephrosis in children who underwent open and robotic-assisted laparoscopic pyeloplasty.
To assess long-term postoperative ultrasonographic outcomes of robotic-assisted laparoscopic pyeloplasty (RALP) and of conventional open pyeloplasty (COP) in pediatric patients with ureteropelvic junction obstruction. Retrospective review of 312 patients who underwent RALP or COP in a single institution. Preoperative and postoperative ultrasounds were used to determine the grade of hydronephrosis. Postoperative assessment included 3 ultrasounds at 0-6, 6-12 and >12 months intervals. Patients were matched by age, etiology of obstruction, grade of preoperative hydronephrosis and gender for case-matched analysis. We identified 212 pyeloplasties that met inclusion criteria, being 58 RALP and 154 COP. Groups were different in age, gender and etiology, but similar in severity of hydronephrosis and follow-up time. At the end of follow-up, complete resolution and success rates were 62% and 74% in RALP and 45% and 70% in COP, respectively. Matching included 105 patients. Complete resolution was higher in RALP (p = 0.004), while median time before improvement was lower (12.3 months RALP vs 29.9 months COP). There was no difference in success rate at the end of follow-up between the groups. RALP shows satisfactory long-term outcomes, comparable to COP. In our cohort, patients who underwent robotic pyeloplasty showed faster resolution of hydronephrosis on ultrasound.


Assessment of the fecal lactobacilli population in patients with hepatitis B virus-related decompensated cirrhosis and hepatitis B cirrhosis treated with liver transplant.
This study aims to provide an overview of the diversity of intestinal Lactobacillus among Chinese patients with hepatitis B virus (HBV)-related decompensated cirrhosis and who received liver transplant for hepatitis B cirrhosis. Fecal samples were collected from 38 healthy volunteers, 61 patients with HBV-related decompensated cirrhosis (group LC) and 74 patients who had liver transplant for hepatitis B cirrhosis (group LT). Quantitative polymerase chain reaction technology with species-specific primers was applied to investigate lactobacilli 16S rDNA in crude DNA, extracted from fecal samples. Software package Statistical Package for the Social Sciences and Palaeontological Statistics for Windows was used to analyze the data. Lactobacilli population of the two patient groups was different from the healthy control subjects, principal differences being marked decrease in the population of Lactobacillus rhamnosus (p < 0.001 for both patient groups) and reduction in the frequency of Lactobacillus fermentus (p < 0.001 for group LC and p < 0.01 for group LT). Our findings on the frequency of lactobacilli population suggested decreased diversity in groups LC and LT (compared with the healthy controls (p < 0.001 and p < 0.01, respectively)). Patients tended to have less complex fecal lactobacilli composition than the healthy controls, especially in the group LC.


Large-scale dynamics have greater role than thermodynamics in driving precipitation extremes over India.
The changing characteristics of precipitation extremes under global warming have recently received tremendous attention, yet the mechanisms are still insufficiently understood. The present study attempts to understand these processes over India by separating the 'dynamic' and 'thermodynamic' components of precipitation extremes using a suite of observed and reanalysis datasets. The former is mainly due to changes in atmospheric motion, while the latter is driven mainly by the changes associated with atmospheric moisture content. Limited studies have attributed dynamic and thermodynamic contributions to precipitation extremes, and their primary focus has been on the horizontal atmospheric motion component of the water budget. Our study, on the other hand, implements the decomposition of vertical atmospheric motion, based on the framework proposed by Oueslati et al. (Sci Rep 9: 2859, 2019), which has often been overlooked, especially for India. With the focus on two major and recent extreme events in the Kerala and Uttarakhand regions of India, we show that the vertical atmospheric motion has a more significant contribution to the events than the horizontal atmospheric motion. Further, decomposition of the vertical atmospheric motion shows that the dynamic component overwhelms the thermodynamic component's contribution to these extreme events, which is found to be negligible. Using a threshold method to define extreme rainfall, we further extended our work to all India, and the results were consistent with those of the two considered events. Finally, we evaluate the contributions from the recently made available CMIP6 climate models, and the results are interestingly in alignment with the observations. The outcomes of this study will play a critical role in the proper prediction of rainfall extremes, whose value to climate adaptation can hardly be overemphasised.


Behavioral Response of Reef Fish and Green Sea Turtles to Midfrequency Sonar.
There is growing concern over the potential effects of high-intensity sonar on wild fish populations and commercial fisheries. Acoustic telemetry was employed to measure the movements of free-ranging reef fish and sea turtles in Port Canaveral, FL, in response to routine submarine sonar testing. Twenty-five sheepshead (Archosargus probatocephalus), 28 gray snapper (Lutjanus griseus), and 29 green sea turtles (Chelonia mydas) were tagged, with movements monitored for a period of up to 4 months using an array of passive acoustic receivers. Baseline residency was examined for fish and sea turtles before, during, and after the test event. No mortality of tagged fish or sea turtles was evident from the sonar test event. There was a significant increase in the daily residency index for both sheepshead and gray snapper at the testing wharf subsequent to the event. No broad-scale movement from the study site was observed during or immediately after the test.


Targeting protein kinase C and "non-kinase" phorbol ester receptors: emerging concepts and therapeutic implications.
Phorbol esters, natural compounds that mimic the action of the lipid second messenger diacylglycerol (DAG), are known to exert their biological actions through the activation of classical and novel protein kinase C (PKC) isozymes. Phorbol esters, via binding to the PKC C1 domains, cause major effects on mitogenesis by controlling the activity of cyclin-cdk complexes and the expression of cdk inhibitors. In the last years it became clear that phorbol esters activate other molecules having a C1 domain in addition to PKCs. One of the most interesting families of "non-kinase" phorbol ester receptors is represented by the chimaerins, lipid-regulated Rac-GAPs that modulate actin cytoskeleton reorganization, migration, and proliferation. The discovery of the chimaerins and other "non-kinase" phorbol ester receptors has major implications in the design of agents for cancer therapy.


First Ever Whole Genome Sequencing and De Novo Assembly of the Freshwater Angelfish, Pterophyllum scalare.
This research work is the first to ever sequence and perform a de novo assembly of the genome of the freshwater angelfish, Pterophyllum scalare . The final genome assembly consisted of 15,486 contigs and was 734.79 Mb in size with an 86.5% BUSCO score. Functional annotation of the genome revealed 24,247 protein-coding sequences related to other fish species. 14,329 (59%) of the identified genes were orthologous to Archocentrus centrarchus , a closely related South American cichlid.


Low-dose radiosurgery or hypofractionated stereotactic radiotherapy as treatment option in refractory epilepsy due to epileptogenic lesions in eloquent areas - Preliminary report of feasibility and safety.
The eradication of epileptogenic lesions (e.g. focal cortical dysplasia) can be used for treatment of drug-resistant focal epilepsy, but in highly eloquent cortex areas it can also lead to a permanent neurological deficit. In such cases the neuromodulation effect of low-dose high-precision irradiation of circumscribed lesions may represent an alternative therapy. A total of 10 patients with eloquent localized lesions causing pharmacoresistant focal epilepsy were prospectively identified. After informed consent, six patients agreed and were treated with risk adapted low-dose radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (hfSRT). Comprehensive data concerning treatment modalities and outcome after short-term follow up (mean=16.3 months) were prospectively collected and evaluated. From the six patients, two patients were treated with hfSRT (marginal dose 36 Gy) and four with SRS (marginal dose 13 Gy). Clinical target volume (CTV) ranged from 0.70 ccm to 4.32 ccm. The short-term follow-up ranged from 6 to 27 months. There were no side effects or neurological deficits after treatment. At last available follow-up two patients were seizure-free, one of them being off antiepileptic drugs. The seizure frequency improved in one and remained unchanged in three patients. Treatment of eloquent localized epileptogenic lesions by SRS and hfSRT showed no adverse events and an acceptable seizure outcome in this small prospective patient series. The relatively short-term follow-up comprises one of the study's drawbacks and therefore a longer follow-up should be awaited in order to evaluate the neuromodulation effect of the treatment. These preliminary results may however justify the initiation of a larger prospective trial investigating whether focused low-dose stereotactic irradiation could be an option for lesions in eloquent brain areas.


Molecular dynamics simulations of simple fluids confined in realistic models of nanoporous carbons.
We present molecular dynamics simulations in the micro-canonical ensemble of a Lennard-Jones model of nitrogen confined in realistic models for saccharose-based carbons developed in our previous work. We calculate the velocity autocorrelation function and mean-squared displacement, and the self-diffusivities from the latter. We observe that the self-diffusivity increases with temperature and exhibits a maximum with loading or adsorbate density. To the best of our knowledge, a maximum in self-diffusivities has not been observed in molecular dynamics simulations of fluids confined in slit pores.