Comparison of different advanced oxidation processes for phenol degradation.
Advanced Oxidation Processes (O3, O3/H2O2, UV, UV/O3, UV/H2O2, O3/UV/H2O2, Fe2+ /H2O2 and photocatalysis) for degradation of phenol in aqueous solution have been studied in earlier works. In this paper, a comparison of these techniques is undertaken: pH influence, kinetic constants, stoichiometric coefficient and optimum oxidant/pollutant ratio. Of the tested processes, Fenton reagent was found to the fastest one for phenol degradation. However, lower costs were obtained with ozonation. In the ozone combinations, the best results were achieved with single ozonation. As for the UV processes, UV/H2O2 showed the highest degradation rate.


Detection of minimally disseminated disease in the cerebrospinal fluid of children with high-risk retinoblastoma by reverse transcriptase-polymerase chain reaction for GD2 synthase mRNA.
To evaluate minimally disseminated disease (MDD) in cytologically negative cerebrospinal fluid (CSF) specimens of patients with high-risk retinoblastoma by the detection of the synthase of ganglioside GD2 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). The CSF was evaluated in 26 patients with high risk for CSF relapse: 14 with postlaminar optic nerve invasion, five of them with tumour at the resection margin, five with massive choroidal invasion, three with overt orbital extension and four patients with systemic metastasis. Serial CSF examinations were repeated at different time intervals according to stage and in the event of suspected relapse. GD2 synthase mRNA was evaluated by RT and nested PCR at each procedure. MDD was present at diagnosis in six cases (23%) and it was significantly associated to massive optic nerve involvement or history of glaucoma (p<0.05). Three of the children with positive MDD had a CSF relapse. Thirteen patients had negative MDD at diagnosis and one had a CSF relapse. In seven children no ARN could be obtained for PCR analysis and two subsequently relapsed. The probability of CSF relapse was 0.50 (95% confidence interval (CI) 0.13-0.88) for children with MDD and 0.08 (95% CI 0.02-0.46) for those with negative RT-PCR examination of the CSF at diagnosis (p=0.03). MDD in the CSF detected by RT-PCR for GD2-synthase mRNA occurred in 31.7% of evaluable high-risk children with retinoblastoma with no initial central nervous system (CNS) involvement. It was significantly associated to optic nerve involvement and glaucoma and increased risk of CSF relapse.


A facile and green pretreatment method for nonionic total organic halogen (NTOX) analysis in water - Step I. Using electrodialysis to separate NTOX and halides.
Adsorbable organic halogen (AOX) is a bulk organic parameter conventionally used to indicate all adsorbable halogenated organic disinfection byproducts formed in disinfected water. Analytically, AOX is determined by three sequential steps: 1) concentration and separation of AOX from halides with activated carbon, 2) conversion of AOX into halides with pyrolysis, and 3) quantification of halides via microcoulometry or ion chromatography (IC). Because the approach is relatively costly and cannot effectively recover non-adsorbable compounds, we herein proposed a facile and green pretreatment tool to measure the nonionic portion of total organic halogen (NTOX) with a new three-step approach: 1) separation of NTOX and halides with electrodialysis (ED), 2) conversion of NTOX into halides with ultraviolet, and 3) analysis of halides with IC. To verify this proposal, this study presented the efficiency of ED in separating halides and NTOX under a variety of operational and environmental conditions. The results showed that ED removed ≥98.5% of fluoride, chloride, bromide, and iodide from all tested waters (up to 1000 mg-X/L) within 1.5 h. Meanwhile, ED recovered an average of 87.9% of fourteen small molecular weight model compounds with each at 100 μg/L. By using electrospray ionization-triple quadrupole mass spectrometry, the whole pictures of high molecular weight compounds in a chlorinated drinking water before and after ED pretreatment were compared, which revealed 79.7% and 83.6% recoveries of overall polar chlorinated and brominated compounds, respectively. In addition, the quantity and property of the dissolved organic matter were largely maintained by ED, and the retained organics may be used for later characterization. The study hence presents a novel use of ED as a pretreatment tool to enable subsequent NTOX measurement.


Assesing the behaviour of particulate/nanoparticulate form of E171 (TiO2) food additive in colored chocolate candies before and after in vitro oral ingestion by spICP-MS, TEM and cellular in vitro models.
Potential risk of nanoparticles present in food additives should be assessed. Although food-grade additive E171 (TiO2) has been banned by European Union due to the potential occurrence of nanometric TiO2, it is still present in stock products and permitted in other countries. TiO2 (nano)particles from the outer coating of colored chocolate candies were determined by TEM (Transmission Electron Microscopy), ICP-MS (Inductively Coupled Plasma Mass Spectrometry) and spICP-MS (Single-Particle-ICP-MS). Total titanium content was in the range of 1219 ± 83 µg g-1, except for brown and white candies. Percentage of TiO2 particles bellow 100 nm was under 25% regardless the color, with most frequent size between 120 and 160 nm. In vitro gastrointestinal assays reveal differences in bioaccessibility percentages between whole candy (14%) or aqueous extracts of the coating of candy (37%). More than 90% of bioaccessible titanium was found in particulate form. Caco-2 cells viability decreased around 65% after 24 h exposed to intestinal fraction.


Protamine kinase from yeast.
A protein kinase (ATP: protein phosphotransferase, EC 18.104.22.168) which preferentially phosphorylates protamine is purified about 250-fold from the soluble fraction of baker's yeast (Saccharomyces cerevisiae). This enzyme is not sensitive to activation by cyclic nucleotides. Histone is about 5% as active as protamine in the reaction rate. Neither casein, phosvitin nor glycogen phosphorylase is active as substrate. The enzyme is distinguishable from casein kinase of the classical type (Rabinowitz, M. and Lipmann, F. (1960) J. Biol. Chem. 235, 1043-1050) and from adenoshine 3', 5'-monophosphate-dependent protein kinase described earlier (Takai, Y., Yamamura, H. and Nishizuka, Y. (1974) J. Biol. Chem. 249,530-535).


Residency Experience With Physical Examination- and Ultrasound-Indicated Cerclage: A Single Center Retrospective Study.
Background: Cervical insufficiency, the dilation of the cervix in the absence of contractions or labor, can cause second-trimester pregnancy loss or preterm birth. Cervical cerclage is a common treatment for cervical insufficiency and has 3 indications for placement: history, physical examination, and ultrasound. The purpose of this study was to compare pregnancy and birth outcomes for physical examination- and ultrasound-indicated cerclage. Methods: We conducted a retrospective observational descriptive review of second-trimester obstetric patients with transcervical cerclage performed by residents at a single tertiary care medical center from January 1, 2006, to January 1, 2020. We present data on all patients and compare outcomes between the 2 study groups: patients who received physical examination-indicated cerclage vs those who received ultrasound-indicated cerclage. Results: Cervical cerclage was placed on 43 patients at a mean gestational age of 20.4 ± 2.4 weeks (range, 14 to 25 weeks) and with a mean cervical length of 1.53 ± 0.5 cm (range, 0.4 to 2.5 cm). With a latency period of 11.8 ± 5.7 weeks, mean gestational age at delivery was 32.1 ± 6.2 weeks. Fetal/neonatal survival rates were comparable: 80% (16/20) for the physical examination group compared to 82.6% (19/23) for the ultrasound group. No differences were found between groups for gestational age at delivery-31.5 ± 6.8 in the physical examination group vs 32.6 ± 5.8 in the ultrasound group (P=0.581)-or for preterm birth <37 weeks-65.0% (13/20) in the physical examination group vs 65.2% (15/23) in the ultrasound group (P=1.000). Rates of maternal morbidity and neonatal intensive care unit morbidity were similar between the groups. No cases of immediate operative complications or maternal deaths occurred. Conclusion: Pregnancy outcomes for physical examination- and ultrasound-indicated cerclage placed by residents at a tertiary academic medical center were similar. Fetal/neonatal survival and preterm birth rates were favorable for physical examination-indicated cerclage when compared to other published studies.


A Systematic Review of Muscle Synergies during a Walking Gait to Define Optimal Donor-Recipient Pairings for Lower Extremity Functional Reconstruction.
Functional lower extremity reconstruction primarily aims to restore independent ambulation. We sought to define the synergies recruited during a walking gait to inform donor selection for various motor deficits. With these findings, we discuss the functional neuromuscular components of independent gait with the goal of informing lower extremity reconstruction. A systematic review was performed using MEDLINE for articles published between January 2000 and December 2020. Search terms included (1) "motor module(s)," "synergy," "motor pattern," or "motor primitive" and (2) "gait," "walking," "ambulation," or "locomotion." Abstracts/full texts were reviewed by two independent reviewers. A total of 38 studies were selected. The average reported number of synergies and variance accounted for was 4.5 ± 0.9 and 88.6% ± 7.7%, respectively. Four motor modules were conserved across nearly all studies. Walking can be reduced to the sequential activation of four motor modules. Activities during the stance phase are critical for both standing stability and forward progression and should be prioritized for reconstruction with the goal of preserving efficient gait. Muscles recruited during swing, except those used for ankle dorsiflexion, are less prone to injury and benefit from greater redundancy, less often necessitating reconstruction. With the emphasis on stability during stance, several synergistic or sometimes even antagonistic tendons can be used to replace their counterparts and restore efficient, independent ambulation. With a finite supply of donor tissues, and in the absence of well-defined clinical outcomes data, this research allows us to effectively prioritize reconstructive goals and maximize patient outcomes.


Combined the GABA-A and GABA-B receptor agonists attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism.
Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. In this study, we employed prenatally exposed to valproic acid (VPA) to establish a validated ASD mouse model and found impaired inhibitory gamma-aminobutyric acid (GABAergic) neurotransmission through a presynaptic mechanism in these model mice, which was accompanied with decreased GABA release and GABA-A and GABA-B receptor subunits expression. And acute administration of individual GABA-A or GABA-B receptor agonists partially reversed autistic-like behaviors in the model mice. Furthermore, acute administration of the combined GABA-A and GABA-B receptor agonists palliated sociability deficits, anxiety and repetitive behaviors in the animal model of autistic-like behaviors, demonstrating the therapeutic potential of above cocktail in the treatment of ASD.


Mine water treatment with limestone for sulfate removal.
Limestone can be an option for sulfate sorption, particularly from neutral mine drainages because calcium ions on the solid surface can bind sulfate ions. This work investigated sulfate removal from mine waters through sorption on limestone. Continuous stirred-tank experiments reduced the sulfate concentration from 588.0mg/L to 87.0mg/L at a 210-min residence time. Batch equilibrium tests showed that sulfate loading on limestone can be described by the Langmuir isotherm, with a maximum loading of 23.7mg/g. Fixed-bed experiments were utilized to produce breakthrough curves at different bed depths. The Bed Depth Service Time (BDST) model was applied, and it indicated sulfate loadings of up to 20.0gSO(4)(2-)/L-bed as the flow rate increased from 1 to 10mL/min. Thomas, Yoon-Nelson and dose-response models, predicted a maximum particle loading of 19mg/g. Infrared spectrometry indicated the presence of sulfate ions on the limestone surface. Sulfate sorption on limestone seems to be an alternative to treating mine waters with sulfate concentrations below the 1200-2000mg/L range, where lime precipitation is not effective. In addition, this approach does not require alkaline pH values, as in the ettringite process.


Development of a novel method to measure the elastic properties of skin including subcutaneous tissue: new age-related parameters and scope of application.
We have developed a new apparatus to measure the elastic properties of skin without contact using an air blown technique. Real-time measurements of skin movement induced by air blown on the surface were measured at various times. We investigated age-related changes in the displacement of the skin surface caused by air using various parameters. Ninety-eight female Japanese volunteers, aged from 10 to 70 years, were used in this study. The maximum distance (the denting state) that cheek skin moved reached 2-5 mm within 10-15 ms. After that, the skin generally recovered to its original state within 40-50 ms. The average maximum speed of movement was 0.49+/-0.08 (average+/-SD) m/s and the average recovery speed was 0.25+/-0.06 m/s. Significant changes with age were not observed in the denting state, but significant correlations with age were observed in the recovery state. The maximum recovery speed decreased significantly with age and the time required for recovery increased significantly with age. Although similar results were obtained at the corner of the mouth or the inner upper arm, different results were obtained at the below eyes and the forehead. This apparatus differs from other conventional instruments in that it measures the elastic properties of skin including subcutaneous tissue without contact.


Physician recruitment and retention: a physician's perspective.
In order to overcome the inevitable physician shortage, physician groups and hospitals must acknowledge and incorporate effective recruiting techniques into their practices.


Preparation of DNA catenanes and observation of their topological structures by atomic force microscopy.
DNA catenanes have been prepared by the reaction of T4 DNA ligase with linear DNA in the presence of nicked DNA. Single molecular images of DNA catenanes and large circular DNAs have been clearly observed by AFM using a tapping mode at room temperature and in an ambient atmosphere.


Swim-over: an alternative method for harvesting motile spermatozoa.
An alternative method for harvesting motile spermatozoa has been developed. Two plastic chambers, one with human semen and one with Earle's medium, were connected by a glass tube filled with cervical mucus. Semen samples were obtained from 18 men. Mid-cycle, sperm-free cervical mucus was provided by 18 women. During incubation aliquots were drawn from the culture chamber every hour for analysis of sperm characteristics. A pronounced increase in motility was observed. The number of penetrated sperms averaged 1 million after 3 hr. The percentage normal morphology increased from 42 +/- 11 to 73 +/- 15 (mean +/- SD). It is suggested that "swim-over" should prove useful for obtaining sperm of high quality. Further studies for refinement and evolution of the method are currently in progress.


Structural studies of 5 S ribosomal RNAs from a thermophilic fungus, Thermomyces lanuginosus. A comparison of generalized models for eukaryotic 5 S RNAs.
The cytoplasmic ribosomes of the thermophilic fungus Thermomyces lanuginosus contain two types of 5 S RNA. The nucleotide sequence for approximately 80% of the molecules is (pp)pA-C-A-U-G-C-G-A-C-C-A-U-A-G-G-G-U-G-U-G-G-A-A-A-A-C-A-G-G-G-C-U-U-C-C-C-G-U-C-C-G-C-U-C-A-G-C-C-G-U-A-C-U-U-A-A-G-C-C-A-C-A-C-G-C-C-G-G-C-U-G-G-U-U-A-G-U-A-G-U-U-G-G-G-U-G-G-G-U-G-A-C-C-A-C-C-A-G-C-G-A-A-U-C-C-C-A-G-C-U-G-U-U-G-C-A-U-G-UOH. The remainder contains two nucleotide substitutions, C19 and G60, which preserve base complementarity. The secondary structure was probed using partial T1, pancreatic, and S1 nuclease digestion under a variety of ionic and temperature conditions and fragments were analyzed by rapid gel sequencing techniques. The results support the Y-shaped secondary structure model originally proposed by Nishikawa, K., and Takemura, S. (1974) FEBS Lett. 40, 106-109, for eukaryotic 5 S RNAs. When the thermal denaturation profile was compared with that of the yeast 5 S RNA, the thermophilic RNA exhibited not only a higher Tm but also an unusual decline in absorbency at moderate temperatures. This suggests that a functionally important structure may be maintained only at higher temperatures.


Behavioural factors underlying innovative problem-solving differences in an avian predator from two contrasting habitats.
Innovative behavior is considered one of the main factors facilitating the adaptation of animals to urban life. However, the relationship between urbanization and innovativeness is equivocal, perhaps reflecting aspects of urban environments that influence differently the behavioural traits underlying the occurrence of an innovation. In this work, we analysed the variation in innovative problem-solving performance between urban and rural individuals of the Caracara Chimango (Milvago chimango), with the goal of determining which behavioural trait (or combination) most explained such variation. We found that urban raptors outperformed rural ones in their solving speed and solving level (number of solutions) with a multiaccess box. They also showed more persistence, motor flexibility and diversity, as well as higher effectiveness in their solving attempts than rural chimangos. Sex was not an important factor. Urban chimangos showed less neophobia and spent more time exploring the box than rural birds during the initial habituation period, which probably determined the amount of information about the system that each individual had at the beginning of first problem solving trial. This difference in novelty response both directly and indirectly, through its relationship with persistence, motor flexibility and proportion of effective attempts, explained variability in solving performance. All individuals showed a decrease in solving latency, and an increase in solving level with experience, indicating that learning occurred in both raptor groups. This improvement occurred in parallel with changes in the afore-mentioned traits, though the pattern of improvement differed between urban and rural chimangos. We suggest that the characteristics of urban areas modulate the novelty response of chimangos, along with other correlated non-cognitive behavioural traits, which act in combination to increase the chances that novel problems could be quickly solved, and the resulting new behaviours established in city populations of this species.


DNA polymerases: Hoogsteen base-pairing in DNA replication?
Human polymerase-iota belongs to the error-prone Y family of polymerases, which frequently incorporate incorrect nucleotides during DNA replication but can efficiently bypass DNA lesions. On the basis of X-ray diffraction data, Nair et al. propose that Hoogsteen base-pairing is adopted by DNA during its replication by this enzyme. Here I re-examine their X-ray data and find that the electron density is very weak for a Hoogsteen base pair formed between a template adenine deoxyribonucleotide in the syn conformation and a deoxythymidine 5'-triphosphate (dTTP), and that the fit is better for a normal Watson-Crick base pair. As a guanine-cytosine (G-C) base pair has no potential to form a Hoogsteen base pair at physiological pH, Hoogsteen base-pairing is unlikely to be used in replication by this polymerase.


Fresh cheese as a vehicle for polyunsaturated fatty acids integration: effect on physico-chemical, microbiological and sensory characteristics.
Five different vegetable oils were used in the production of fresh cheese to increase the concentration of polyunsaturated fatty acids (PUFAs), particularly α-linolenic acid (ALA), the most important omega-3 fatty acid of vegetable origin. Physico-chemical and microbiological characteristics of functionalized cheeses were evaluated after 1 and 3 days of ripening at 4 °C while the consumer appreciation was evaluated in the final product at 3 days of ripening. After 3 days, the cheeses with Camelina sativa and Echium plantagineum oils added exhibited the highest retention of PUFAs (mostly ALA) compared to those with flaxseed, raspberry and blackcurrant oils. The addition of oil showed little effects on physico-chemical characteristics and also consumers' evaluation highlighted that all of the fresh cheeses were considered acceptable although those with flaxseed and raspberry oils were the most appreciated.


5-Aminosalicylic acid suppositories in the management of ulcerative colitis.
5-aminosalicylic acid (5-ASA) suppositories have been used in the author's out-patient clinic in Bologna for the treatment of distal ulcerative colitis (UC). One hundred fifty-six patients with mild or moderate attacks of UC were treated using different protocols for controlling active disease. Improvement was observed in 88.5 percent of the therapeutic cycles after one month. A small preliminary maintenance study using only 400-mg suppositories of 5-ASA twice a day for 6 or 12 months showed a remission percentage similar to salicylazosulfapyridine (SASP).


Glucose stimulation of testosterone-maintained protein synthesis in the rat ventral prostate.
The stimulatory effect of exogenous glucose on protein synthesis maintained by testosterone was studied by measuring the in vitro incorporation of amino acids into proteins in the rat ventral prostate. The addition of glucose did not influence the specific activity of the extracellular or intracellular amino acid pools. The amount of newly-synthetized proteins was increased in the presence of glucose. Mannose was as effective as glucose, whereas a variety of other substrates (e.g. pyruvate, lactate, amino acids, acetate) which are readily metabolized by the prostate, failed to support to the same extent hormone-activated protein synthesis. None of the substrates increased protein synthesis in the prostate of castrated rats. The incubation of the prostate without any substrate led to a decline in the level of ATP, the ATP/ADP ratio and the adenylate energy charge and to a rise in the levels of ADP and AMP irrespective of the hormonal state of the tissue. The addition of glucose restored the levels and ratios of the adenine nucleotides, but several other substrates were also able to maintain the initial ATP levels in the prostate of castrated, as well as castrated, testosterone-treated rats. The stimulatory effect of glucose on hormone-maintained protein synthesis cannot be explained by changes in the adenine nucleotides. Nevertheless, the activation of glucose metabolism may play an important role by providing energy for increased synthetic reactions. Moreover, glucose and mannose molecules themselves or a glycolytic metabolite (proximal to pyruvate) may be required for the full expression of the transcriptional effect of testosterone on protein synthesis in the ventral prostate of castrated rats.


Left atrium in cardiac resynchronization therapy: Active participant or innocent bystander.
Cardiac resynchronization therapy (CRT) is an established treatment for patients with advanced heart failure that results in improvement of left ventricle (LV) systolic function and LV reverse remodeling. This may have a positive effect on the size and the function of the left atrium (LA). We assessed the LA function, dimensions, and volumes before and after CRT implantation. A total of 37 patients with mean age of 55.3 ± 9.64 years including 11 (29.7%) females, having symptomatic heart failure [ejection fraction (EF) <35%, left bundle branch block >120 ms, with New York Heart Association III or ambulatory class IV] were enrolled, and underwent CRT implantation. M-mode, two-dimensional (2D) echocardiography, tissue Doppler imaging, and 2D strain (ɛ) imaging were done assessing LV volumes, ejection fraction, and diastolic function, LA diameter, area, maximal and minimal volumes, LA EF, and longitudinal strain (ɛ). Patients were reassessed after 3 months. A reduction in LV end-systolic volume of ≥10% was defined as volumetric responders to CRT. Patients with decompensated New York Heart Association class IV, sustained atrial arrhythmias, rheumatic or congenital heart diseases, nonleft bundle branch block, and those who were poorly echogenic, were excluded. Twenty-four (64.8%) patients were volumetric responders (group A). Both groups were matched regarding demographic, clinical, electrocardiographic, and echocardiographic criteria apart from the LA dimension and volumes which were significantly lower in the responders group prior to CRT. At the end of the follow-up, only the responders group had further significant reduction in LA diameter (41.6 ± 1.67 vs. 43.88 ± 1.82 mm, p < 0.01), maximal volume (62.2 ± 18.3 vs. 73.04 ± 21.78 ml, p < 0.01), minimal volume (32.6 ± 12.3 vs. 41.8 ± 13.97, p < 0.01), together with a significant increase in LA EF (48.3 ± 11.3 vs. 41.99 ± 13.9, p < 0.01), positive longitudinal strain (16.59% ± 5.89 vs. 12.45% ± 6.12, p < 0.01), and negative longitudinal strain (-3.3 ± 1.9 vs. -1.62 ± 1.2, p < 0.01) compared to baseline readings, a finding that was not present in the nonresponders group. In addition, atrial fibrillation was significantly higher in the nonresponders group. Baseline LA diameter and volumes were found to be independent predictors of response to CRT by multivariate analysis. CRT induces LA anatomic, electrical, and structural reverse remodeling that could be assessed by conventional 2D echocardiography and 2D (ɛ) strain imaging. LA dimension and volumes were independent predictors of response to CRT and can help in selection of candidates for it.


The structure of natively iodinated bovine thyroglobulin.
Thyroglobulin is a homodimeric glycoprotein that is essential for the generation of thyroid hormones in vertebrates. Upon secretion into the lumen of follicles in the thyroid gland, tyrosine residues within the protein become iodinated to produce monoiodotyrosine (MIT) and diiodotyrosine (DIT). A subset of evolutionarily conserved pairs of DIT (and MIT) residues can then engage in oxidative coupling reactions that yield either thyroxine (T4; produced from coupling of a DIT `acceptor' with a DIT `donor') or triiodothyronine (T3; produced from coupling of a DIT acceptor with an MIT donor). Although multiple iodotyrosine residues have been identified as potential donors and acceptors, the specificity and structural context of the pairings (i.e. which donor is paired with which acceptor) have remained unclear. Here, single-particle cryogenic electron microscopy (cryoEM) was used to generate a high-resolution reconstruction of bovine thyroglobulin (2.3 Å resolution in the core region and 2.6 Å overall), allowing the structural characterization of two post-reaction acceptor-donor pairs as well as tyrosine residues modified as MIT and DIT. A substantial spatial separation between donor Tyr149 and acceptor Tyr24 was observed, suggesting that for thyroxine synthesis significant peptide motion is required for coupling at the evolutionarily conserved thyroglobulin amino-terminus.


Antibody-mediated rejection of a unilateral donor lung in bilateral living-donor lobar lung transplantation: report of a case.
We report a case of antibody-mediated rejection (AMR) of a unilateral donor lung in the presence of newly formed donor-specific antibodies, 10 months after living-donor lobar lung transplantation (LDLLT). Of note is that the AMR occurred in the unilateral lung. Furthermore, the lung graft was from her husband and HLA analysis on the recipient's daughter revealed the same donor-specific HLA antigens, which strongly suggested pre-sensitization before lung transplantation. Fortunately, we could perform direct crossmatch even 1 year after lung transplantation because of the living donors.


Herbivore deme formation on individual trees: a test case.
We examined the deme-formation hypothesis, which states that sessile herbivores on long-lived hosts become locally adapted to the defensive phenotypes of individual trees. We showed a five-fold increase in resistance by individual pinyon pines (Pinus edulis) to the pinyon pine needle scale (Matsucoccus acalyptus). Although such variation could represent a significant selection pressure favoring deme formation, two lines of evidence led to rejection of the hypothesis. First, there were no significant differences in mortality among scale populations in a reciprocal transfer experiment. Second, a seven-year experiment showed that mortality of newly founded, incipient scale populations was similar to established scale populations. While our experiments fail to support the deme-formation hypothesis, they do demonstrate significant variation in the resistance traits of a natural tree population. Although we feel that demeformation is still probable in this system, it is likely to occur on a larger geographic scale than individual trees as proposed by Edmunds and Alstad.


An odorant-binding protein required for suppression of sweet taste by bitter chemicals.
Animals often must decide whether or not to consume a diet that contains competing attractive and aversive compounds. Here, using the fruit fly, Drosophila melanogaster, we describe a mechanism that influences this decision. Addition of bitter compounds to sucrose suppressed feeding behavior, and this inhibition depended on an odorant-binding protein (OBP) termed OBP49a. In wild-type flies, bitter compounds suppressed sucrose-induced action potentials, and the inhibition was impaired in Obp49a mutants. However, loss of OBP49a did not affect action potentials in sugar- or bitter-activated gustatory receptor neurons (GRNs) when the GRNs were presented with just one type of tastant. OBP49a was expressed in accessory cells and acted non-cell-autonomously to attenuate nerve firings in sugar-activated GRNs when bitter compounds were combined with sucrose. These findings demonstrate an unexpected role for an OBP in taste and identify a molecular player involved in the integration of opposing attractive and aversive gustatory inputs.


Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta.
In the arterial circulation, regions of disturbed flow (DF), which are characterized by flow separation and transient vortices, are susceptible to atherogenesis, whereas regions of undisturbed laminar flow (UF) appear protected. Coordinated regulation of gene expression by endothelial cells (EC) may result in differing regional phenotypes that either favor or inhibit atherogenesis. Linearly amplified RNA from freshly isolated EC of DF (inner aortic arch) and UF (descending thoracic aorta) regions of normal adult pigs was used to profile differential gene expression reflecting the steady state in vivo. By using human cDNA arrays, approximately 2,000 putatively differentially expressed genes were identified through false-discovery-rate statistical methods. A sampling of these genes was validated by quantitative real-time PCR and/or immunostaining en face. Biological pathway analysis revealed that in DF there was up-regulation of several broad-acting inflammatory cytokines and receptors, in addition to elements of the NF-kappaB system, which is consistent with a proinflammatory phenotype. However, the NF-kappaB complex was predominantly cytoplasmic (inactive) in both regions, and no significant differences were observed in the expression of key adhesion molecules for inflammatory cells associated with early atherogenesis. Furthermore, there was no histological evidence of inflammation. Protective profiles were observed in DF regions, notably an enhanced antioxidative gene expression. This study provides a public database of regional EC gene expression in a normal animal, implicates hemodynamics as a contributory mechanism to athero-susceptibility, and reveals the coexistence of pro- and antiatherosclerotic transcript profiles in susceptible regions. The introduction of additional risk factors may shift this balance to favor lesion development.


Long non-coding RNA MALAT1 promotes angiogenesis and immunosuppressive properties of HCC cells by sponging miR-140.
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer in adults. Previous studies in our laboratory found that long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was upregulated in HCC cells, which could affect the metastasis and invasion of HCC. However, the underlying mechanism remains unknown. Herein, we studied the interaction between MALAT1 and miR-140 on the regulation of angiogenesis and immunosuppressive properties. We revealed that the expression of MALAT1 and VEGF-A was significantly increased in HCC cells. Knockdown of MALAT1 in HCC cells suppressed the production of VEGF-A, impaired the angiogenesis of HUVECs, and facilitated the polarization of macrophage toward the M1 subset. Mechanistically, the interaction between MALAT1 and miR-140 or between miR-140 and VEGF-A was confirmed by multiple assays. Besides, a negative correlation between MALAT1 and miR-140 was found in HCC tissues. Furthermore, miR-140 inhibition significantly increased VEGF-A expression, promoted angiogenesis of HUVECs, and redirected the polarization of macrophages toward the M2 subset. In addition, in vivo studies also verified the regulatory network of the MALAT1/miR-140 axis on VEGF-A in HCC progression. In summary, this study revealed the mechanism that MALAT1 worked as a putative HCC promotor via inhibiting miR-140. Therefore, targeting MALAT1 or miR-140 might alleviate the progression of HCC in the future.


Steroid-pulse therapy in pemphigus vulgaris long term follow-up.
Patients with pemphigus vulgaris may occasionally present the highly active, widespread form of the disease, and/or maybe resistant to conventional oral steroid therapy, and/or manifest significant side effects from the prolonged use of high oral prednisone dosage. Our purpose was to evaluate the efficacy of steroid "pulse" therapy (PT) in these patients. Eight patients were given alternate-day, one hour, infusions of 8, 9, or 10 mg/kg methylprednisolone Na succinate. Oral prednisone and a second immunosuppressive agent were simultaneously administered; these were rapidly decreased when control of the disease was achieved. All patients initially responded well to therapy. The disease recurred in four patients after 3, 4, 9, and 16 months of remission, respectively. Three of these patients were treated again with PT and went into remission. None of the patients who received cyclophosphamide had a recurrence. One patient died of cardiac arrest, 12 days after PT. On a follow-up of 59 +/- 25 months since the last relapse, patients continue in remission. Pulse therapy is recommended as an adjunct to the total management plan of severely affected patients with pemphigus vulgaris. The addition of cyclophosphamide may prevent the disease from recurring. Alternate-day small-quantity bolus infusions over 16-20 days, may be equally effective as the administration of 15 mg/kg/daily for 3-5 days. The risk of cardiac arrest exists even with this, less aggressive form of PT therapy. A medical history of supraventricular arrhythmias may be considered a risk factor.


Relation of left ventricular infarct transmurality and infarct size after primary percutaneous coronary angioplasty to time from symptom onset to balloon inflation.
This study was performed to evaluate the impact of time to reperfusion on infarct size and transmurality after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). In 73 patients undergoing primary PCI for STEMI, contrast-enhanced magnetic resonance imaging was performed. Infarct size and transmurality on delayed-enhancement imaging were measured. Infarct size was not associated with symptom onset-to-balloon time (23 +/- 9% for <180 minutes, 22 +/- 9% for 180 to 360 minutes, and 24 +/- 11% for >360 minutes, p = 0.62) or door-to-balloon time (23 +/- 8% for <90 minutes, 23 +/- 10% for 90 to 120 minutes, and 22 +/- 11% for >120 minutes, p = 0.88). Infarct transmurality increased significantly with a delay of symptom onset-to-balloon time (73 +/- 22% for <180 minutes, 78 +/- 14% for 180 to 360 minutes, and 86 +/- 14% for >360 minutes, p = 0.04), but not for door-to-balloon time (79 +/- 15% for <90 minutes, 76 +/- 19% for 90 to 120 minutes, and 81 +/- 18% for >120 minutes, p = 0.62). In multivariate analysis, anterior infarction (odds ratio 4.15, 95% confidence interval 1.31 to 13.18, p = 0.02) and myocardial blush grade 0/1 (odds ratio [OR] 3.89, 95% confidence interval [CI] 1.13 to 13.51, p = 0.03) independently predicted a large infarct (infarct size > or =25%). Symptom onset-to-balloon time (OR per 30 minutes 1.26, 95% CI 1.04 to 1.53, p = 0.02) was an independent predictor of transmural infarct (average transmural extent > or =75%) and use of glycoprotein IIb/IIIa inhibitors showed a protective effect (OR 0.09, 95% CI 0.02 to 0.53, p = 0.007). In conclusion, symptom onset-to-balloon time was significantly associated with infarct transmurality but not infarct size in patients undergoing primary PCI for STEMI.


A pilot study of an online workplace nutrition program: the value of participant input in program development.
Tailored nutrition Web programs constitute an emerging trend in obesity prevention. Initial investment in innovative technology necessitates that the target population be well understood. This pilot study's purpose was to determine the feasibility of a workplace nutrition Web program. Formative research was conducted with gaming industry employees and benefits managers to develop a consensus on workplace-specific nutrition needs. A demonstration Web program was piloted with stakeholders to determine feasibility. Indiana, Mississippi, Nevada, and New Jersey gaming establishments. 86 employees, 18 benefits managers. Prototype Web program. Concept mapping; 16-item nutrition knowledge test; satisfaction. Concept mapping was used to aggregate importance ratings on programmatic content, which informed Web program curriculum. Chi-square tests were performed postintervention to determine knowledge improvement. (1) Employees and benefits managers exhibited moderate agreement about content priorities for the program (r = 0.48). (2) There was a significant increase in employees' nutrition knowledge scores postintervention (t = 7.16, df = 36, P < .001); those with less knowledge exhibited the greatest gains in knowledge scores (r = -0.647, P < .001). Employees and benefit managers do not necessarily agree on the priority of nutrition-related content, suggesting a need for programs to appeal to various stakeholders. Computer-based approaches can address various stakeholder health concerns via tailored, customized programming.


Ultrasound-Assisted Anthocyanins Extraction from Pigmented Corn: Optimization Using Response Surface Methodology.
This study aimed to determine the optimal UAE conditions for extracting anthocyanins from pigmented corn using the Box-Behnken design (BBD). Six anthocyanins were identified in the samples and were used as response variables to evaluate the effects of the following working variables: extraction solvent pH (2-7), temperature (10-70 °C), solvent composition (0-50% methanol in water), and ultrasound power (20-80%). The extraction time (5-25 min) was evaluated for complete recovery. Response surface methodology suggested optimal conditions, specifically 36% methanol in water with pH 7 at 70 °C using 73% ultrasound power for 10 min. The method was validated with a high level of accuracy (>90% of recovery) and high precision (CV < 5% for both repeatability and intermediate precision). Finally, the proposed analytical extraction method was successfully applied to determine anthocyanins that covered a wide concentration range (36.47-551.92 mg kg-1) in several pigmented corn samples revealing potential varieties providing more health benefits.


The Rice Transcription Factor WRKY53 Suppresses Herbivore-Induced Defenses by Acting as a Negative Feedback Modulator of Mitogen-Activated Protein Kinase Activity.
The mechanisms by which herbivore-attacked plants activate their defenses are well studied. By contrast, little is known about the regulatory mechanisms that allow them to control their defensive investment and avoid a defensive overshoot. We characterized a rice (Oryza sativa) WRKY gene, OsWRKY53, whose expression is rapidly induced upon wounding and induced in a delayed fashion upon attack by the striped stem borer (SSB) Chilo suppressalis. The transcript levels of OsWRKY53 are independent of endogenous jasmonic acid but positively regulated by the mitogen-activated protein kinases OsMPK3/OsMPK6. OsWRKY53 physically interacts with OsMPK3/OsMPK6 and suppresses their activity in vitro. By consequence, it modulates the expression of defensive, MPK-regulated WRKYs and thereby reduces jasmonic acid, jasmonoyl-isoleucine, and ethylene induction. This phytohormonal reconfiguration is associated with a reduction in trypsin protease inhibitor activity and improved SSB performance. OsWRKY53 is also shown to be a negative regulator of plant growth. Taken together, these results show that OsWRKY53 functions as a negative feedback modulator of MPK3/MPK6 and thereby acts as an early suppressor of induced defenses. OsWRKY53 therefore enables rice plants to control the magnitude of their defensive investment during early signaling.


A Population-Based Retrospective Analysis of Post-In-Hospital Cardiac Arrest Survival after Modification of the Chain of Survival.
In 2010, the American Heart Association recommended that postcardiac arrest care should be included in the chain of survival to reduce permanent neurological damage, improve quality of life, and reduce health care expenses of postcardiac arrest care. To investigate post-in-hospital cardiac arrest (IHCA) survival prior to and after modification of the chain of survival in 2010, with subgroup analyses per age and concomitant coronary heart disease (CHD). We retrospectively searched the National Health Insurance Research Database for the 2007-2015 period to collect case data coded as "427.41" or "427.5" per International Classification of Disease Clinical Modification, Ninth revision codes and analyzed the data with SPSS v22.0. The 1-day survival rate in the 2011-2015 period was 2% higher than that in the 2007-2010 period (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04). Moreover, in the 2011-2015 period, the survival-to-discharge rate was increased by 1% in patients under 65 years (OR 1.01, 95% CI 1.00-1.02) and 1% in CHD patients (OR 1.01, 95% CI 1.01-1.02) compared with that in the 2007-2010 period. For patients with IHCA, the overall short-term survival improved significantly after modification of the chain of survival. Younger patients and patients with CHD had better long-term survival.


Acute coronary syndrome, right ventricular dysfunction and cardiogenic shock: a diagnostic challenge.
Right ventricular infarction is uncommon in isolation but can be observed in 50% of cases of inferior wall myocardial infarction. Diagnosis is difficult and suspicion of this condition should always be borne in mind. Progression to cardiogenic shock is not uncommon, when the outcome is similar to left ventricular infarction; mortality can reach 60%. We present the case of a 64-year-old woman with known coronary disease who was admitted to our coronary care unit after an anterior myocardial infarction. Cardiac catheterization showed diffuse stenosis of the left descending and 70% stenosis of the posterior descending arteries. She was surgically revascularized with a favorable evolution, but was later readmitted for acute decompensated heart failure with cardiogenic shock. She was refractory to medical therapy, with biventricular dysfunction on echocardiographic examination. Cardiac magnetic resonance imaging confirmed the diagnosis of right ventricular infarction.


Structural features of potent inhibitors of rat kidney histamine N-methyltransferase.
Three antimalarial drugs amodiaquine, quinacrine and chloroquine were compared side-by-side with the antiseptic agent chlorhexidine and the neuromuscular blocker alcuronium for their capacity to competitively inhibit in vitro the activity of the enzyme histamine N-methyltransferase (HMT) from rat kidney over the concentration range 10(-3)-10(-8). Amodiaquine was clearly the most potent HMT inhibitor followed by quinacrine, chlorhexidine, alcuronium and chloroquine. Investigation of the structure-activity relationships by examining space-filling models revealed marked similarities in the conformations of the arrangement of three N atoms in histamine and in each of the compounds tested.


Small-angle neutron scattering from native and irradiated superoxide dismutase in aqueous solution.
The approximate size and shape of holo and apo forms of bovine cupro-zinc erythrocyte superoxide dismutase (EC 22.214.171.124) were determined by small-angle neutron scattering from aqueous solutions at neutral pH. A model assuming a cylindrical shape gave the best fit to the data for both forms of the enzyme. The radius of gyration, Rg, of the apoenzyme was found to be marginally larger than that of the holoenzyme. Scattering from the protein vanished for H2O/2H2O mixtures containing 42(+/- 2)% 2H2O, and the negligible dependence of Rg on the 2H2O fraction indicated uniform scattering density. Irradiation with 60Co gamma-rays resulted in aggregation of superoxide dismutase molecules; scattering at small doses was interpreted in terms of pairwise side-by-side aggregation. For large doses (approx. 3.8 X 10(3) Gy) and at relatively high enzyme concentrations (320 microM), the interpretation of the neutron scattering data is ambiguous. The value of Rg suggests that end-to-end stacking of the cylindrical molecules is one possibility. The equilibrium concentration of separated subunits was found to be unobservable and calculations showed that denaturation did not contribute significantly to our neutron scattering measurements for the radiation doses employed (maximum 3.8 X 10(5) Gy). High-performance liquid chromatography (HPLC) data showed that in mixtures the apo and holo forms of superoxide dismutase interact with one another, and that the side-by-side aggregates, induced by irradiation of the enzyme, are readily dissociated, resulting in a single elution peak that is resolved from the later peak common to both the apo and holo forms.


An Escherichia coli DNA topoisomerase I mutant has a compensatory mutation that alters two residues between functional domains of the DNA gyrase A protein.
Nucleotide sequence analysis revealed that the compensatory gyrA mutation in Escherichia coli DM750 affects DNA supercoiling by interchanging the identities of Ala-569 and Thr-586 in the DNA gyrase A subunit. These residues flank Arg-571, a site for trypsin cleavage that splits gyrase A protein between DNA breakage-reunion and DNA-binding domains. The putative interdomain locations of the DM750 mutation and that of E. coli DM800 (in gyrase B protein) suggests that these compensatory mutations may reduce DNA supercoiling activity by altering allosteric interactions in the gyrase complex.


Clastogenic and cytotoxic effects of spermine oxidation products in mouse lymphoma L5178Y cells.
Treatment of mouse lymphoma L5178Y cells with spermine in Fischer's medium containing bovine serum lead to formation of chromatid aberrations. The cause of this effect seems to be that bovine serum contains spermine oxidase which catalyzes oxidation of spermine to unstable aldehyde derivatives (oxidized spermine) and hydrogen peroxide. Fraction of chromatid aberrations induced by oxidized spermine was estimated in experiments in which the cells were treated with spermine or a stoichiometric amount of hydrogen peroxide in the presence and in the absence of catalase. Cytotoxicity of oxidized spermine was evaluated by clonogenic assay.


[Supression of angiotensin II-induced contraction of the isolated guinea pig ileum by alveolar surfactants (author's transl)].
The guinea pig alveolar surfactant reduces the contraction of the isolated guinea pig ileum, induced by Angiotensin II. It is tentatively proposed, that the surfactant system suppresses the reactivity of lung blood vessels towards contacting stimuli.


Individuals with incident accelerated knee osteoarthritis have greater pain than those with common knee osteoarthritis progression: data from the Osteoarthritis Initiative.
We evaluated whether accelerated knee osteoarthritis (AKOA) was associated with greater pain and other outcomes and if outcomes varied over time differently among those with incident AKOA or common knee osteoarthritis (KOA), which we defined as a gradual onset of disease. We conducted longitudinal analyses among participants in the Osteoarthritis Initiative who had no radiographic KOA at baseline (Kellgren-Lawrence [KL] <2). Participants were considered AKOA if ≥1 knees progressed to KL grade ≥3 and common KOA if ≥1 knees increased in radiographic scoring within 48 months. We defined the index visit as the study visit when they met the AKOA or common KOA criteria. Our observation period included up to 3 years before and after the index visit. Our primary outcome was WOMAC pain converted to an ordinal scale: none (pain score = 0/1 out of 20), mild (pain score = 2/3), and moderate-severe pain (pain score >3). We explored 11 other secondary outcome measures. We performed an ordinal logistic regression or linear models with generalized estimating equations. The predictors were group (AKOA or common KOA), time (seven visits), and a group-by-time interaction. Overall, individuals with AKOA (n = 54) had greater pain, functional disability, and global rating scale as well as slower chair-stand and walking pace compared with those with common KOA (n = 187). There was no significant interaction between group and time for knee pain; however, there was for chair-stand pace and global rating scale. In conclusion, AKOA may be a painful and disabling phenotype that warrants more attention by clinicians and researchers.


Regulation of central cholecystokinin recognition sites by guanyl nucleotides.
Guanyl nucleotides affected the binding of radiolabeled cholecystokinin (CCK) octapeptide to rodent cortical binding sites. Micromolar quantities of a stable GTP analogue, guanylyl-imidodiphosphate (GppNp), resulted in a plateau where binding was decreased by 30%. In the presence of 25 microM GppNp, binding analysis revealed a decrease in affinity (increase in KD), without an apparent effect on the maximal number of binding sites. Ki values for CCK-related peptides shifted up to 1.6-fold. The rate of peptide association decreased by threefold, and the rapid component of peptide dissociation increased. The collective data suggest that a class of central CCK binding sites is linked to nucleotide regulatory proteins. The evidence is discussed with regard to multiple receptor populations and to possible interconversions between receptor types.


Identification and molecular analysis of glgS, a novel growth-phase-regulated and rpoS-dependent gene involved in glycogen synthesis in Escherichia coli.
The putative stationary-phase sigma factor (sigma S) encoded by rpoS is essential for glycogen synthesis, but is not required for the transcription of glgC and glgA, which encode ADP-glucose-pyrophosphorylase and glycogen synthase, respectively. Using a mini-Mu random chromosomal library and a screen for glycogen overproduction, we identified a novel gene (glgS) involved in glycogen synthesis. glgS maps at 66.6 min (3247 kb) on the chromosome and constitutes a monocistronic operon. It encodes a hydrophilic and highly charged small protein, with a molecular weight of 7886, which is strongly expressed in minicells. Experiments with single-copy chromosomal glgS::lacZ gene fusions indicated that glgS expression is controlled by sigma S as well as by cAMP. Two transcriptional start sites were mapped in the upstream regulatory region of glgS. The glgSp1 transcript was absent in a cya mutant, whereas an rpoS mutant did not synthesize the glgSp2 transcript. Although glycogen synthesis is strongly stimulated by overproduction of GlgS and is inhibited by a glgS null mutation, glgS does not affect the expression of the glgCAP operon. Its potential role in the metabolic control of glycogen synthesis is discussed. Also, evidence is presented to show that the amount of glycogen accumulated in vivo in early stationary-phase cells is mainly determined by sigma S-controlled gene expression and allosteric activation of GlgC, whereas the absolute levels of expression of glgCAP as well as the intracellular concentration of cAMP are of minor importance.


Risk factors for bad outcome in pediatric epidural hematomas: a systemic review.
Pediatric epidural hematomas (EDH) represent a neurosurgical emergency. Both surgical and conservative treatment can lead to a good clinical outcome. The aim of the study was to review our series of pediatric EDH and to determine the clinical and radiologic factors, which can influence the final outcome. All children aged from 0 to 16 that have been treated between 2013 and 2017 for cranial EDH have been selected. Thirty children have been included in the study. Seventeen cases have been treated with surgical evacuation and 13 conservatively. Six months after the trauma, the outcome was excellent (mRS 0) in 25/30 (83.3%) cases, mild deficits (mRS 1-2) were present in 4/30 (13.3%), and severe deficits (mRS 3-5) in 1/30 (3.3%) cases. Only a GCS (Glasgow Coma Scale) below 8 at admission was significantly related to the presence of a neurologic deficit at 6 months (p = 0.048). EDH can be managed with excellent outcomes. Even in the presence of bad initial clinical and radiologic conditions, a correct treatment strategy can lead to a good recovery. In our series, only a GCS below 8 at admission was significantly related to the presence of neurological sequelae.


Controlling the Magnetic Anisotropy of the van der Waals Ferromagnet Fe3GeTe2 through Hole Doping.
Identifying material parameters affecting properties of ferromagnets is key to optimized materials that are better suited for spintronics. Magnetic anisotropy is of particular importance in van der Waals magnets, since it not only influences magnetic and spin transport properties, but also is essential to stabilizing magnetic order in the two-dimensional limit. Here, we report that hole doping effectively modulates the magnetic anisotropy of a van der Waals ferromagnet and explore the physical origin of this effect. Fe3-xGeTe2 nanoflakes show a significant suppression of the magnetic anisotropy with hole doping. Electronic structure measurements and calculations reveal that the chemical potential shift associated with hole doping is responsible for the reduced magnetic anisotropy by decreasing the energy gain from the spin-orbit induced band splitting. Our findings provide an understanding of the intricate connection between electronic structures and magnetic properties in two-dimensional magnets and propose a method to engineer magnetic properties through doping.


Chemoprevention of experimental carcinogenesis in animals.
Retinoids are well-established chemopreventive agents for experimental carcinogenesis of many target organs including mammary glands, urinary bladder, lung, skin, liver, pancreas, colon, and esophagus. Modification of the basic retinoid structure has produced analogs with enhanced target organ specificity, increased inhibitory activity, and reduced toxicity. N-(4-hydroxyphenyl)retinamide (4-HPR) currently appears to be the most efficacious retinoid against carcinogen-induced breast, urinary bladder, and lung cancer in rodents. Retinoids are most effective when administered shortly after the carcinogen treatment; however, the treatment can be delayed significantly while maintaining its chemopreventive effect. Under various experimental conditions combining retinoid treatment with other modifiers of growth enhances its chemopreventive activity; for example retinoid plus hormonal modulation can provide better protection against mammary cancer than either treatment alone. More recently chemopreventive activity of various other classes of agents, such as thiols, phenols, antioxidants, inhibitors of prostaglandin synthesis, etc., have been investigated in experimental mammary, urinary bladder, and lung cancer models.


PEG-Ara-C conjugates for controlled release.
The antitumour agent 1-beta-D arabinofuranosilcytosyne (Ara-C) was covalently linked to poly(ethylene glycol) (PEG) in order to improve the in vivo stability and blood residence time. Eight PEG conjugates were synthesised, with linear or branched PEG of 5000, 10000 and 20000 Da molecular weight through an amino acid spacer. Starting from mPEG-OH or HO-PEG-OH, conjugation was carried out to the one or two available hydroxyl groups at the polymer's extreme. Furthermore, to increase the drug loading of the polymer, the hydroxyl functions of PEG were functionalised with a bicarboxylic amino acid yielding a tetrafunctional derivative and, by recursive conjugation with the same bicarboxylic amino acid, products with four or eight Ara-C molecules for each PEG chain were prepared. A computer graphic investigation demonstrated that aminoadipic acid was a suitable bicarboxylic amino acid to overcome the steric hindrance between the vicinal Ara-C molecules in the dendrimeric structure. In this paper we report the optimised conditions for synthesis and purification of PEG-Ara-C products with a low amount of remaining free drug, studies toward the hydrolysis of PEG-Ara-C and the Ara-C deamination by cytidine deaminase, pharmacokinetics in mice and cytotoxicity towards HeLa human cells were also investigated. Increased stability towards degradation of the conjugated Ara-C products, in particular for the highly loaded ones, improved blood residence time in mice and a reduced cytotoxicity with respect to the free Ara-C form was demonstrated.


The metabolic disposition of 14C-labelled Ponceau 4R in the rat, mouse and guinea-pig.
The absorption, metabolism and excretion of 14C-labelled Ponceau 4R has been studied in the rat, mouse and guinea-pig. Following administration of a single oral dose of 0.5 or 50 mg/kg body weight substantially all of the dose was excreted in the urine and faeces within 72 hr, with the majority being accounted for in the faeces. In all three species, naphthionic acid was the major urinary metabolite, whereas in the faeces naphthionic acid, 7-hydroxy-8-aminonaphthalene-1,3-disulphonic acid and unchanged dye were found. Pretreating male rats with unlabelled Ponceau 4R in the diet (50 mg/kg/day) for 28 days prior to dosing with the 14C-labelled colouring had no effect on the route of excretion or the time taken to eliminate the majority of the label. Following a single dose of 14C-labelled colouring to previously untreated rats, mice and guinea-pigs or to rats pretreated as above, no marked accumulation of radioactivity in any tissue was found, although tissue levels of radioactivity at 72 hr after dosing were higher in the pretreated rats than in those that were not pretreated. Pregnant rats eliminated a single oral dose of 14C-labelled colouring at a similar rate to non-pregnant females; however, some retention of radioactivity in the foetuses was found. In studies of absorption from isolated loops of small intestine containing 50, 500 or 5000 ppm Ponceau 4R, no significant absorption was detected in rats, but some absorption was seen in mice at the lowest concentration, and in the guinea-pig at the two higher concentrations.


Mood and affect during detoxification of opiate addicts: a comparison of buprenorphine versus methadone.
Twenty-six in-patients with Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were selected at random to receive either a combination of an 11-day low-dose buprenorphine and a 14-day carbamazepine regimen (n = 14) or a combination of an 11-day methadone and a 14-day carbamazepine regimen (n = 12) in a double-blind, randomized 14-day in-patient detoxification treatment. Patients with buprenorphine and carbamazepine showed a significantly better psychological state after the first and second weeks of treatment. Above all, the buprenorphine-treated patients demonstrated a less marked tiredness, sensitiveness and depressive state as well as a more prominent elevated mood during the detoxification process. Seven non-completers (after 7 days: four of 12 = 33.3%; after 14 days: seven of 12 = 58.3%) were treated with methadone and carbamazepine and five non-completers (after 7 days: two of 14 = 14.3%; after 14 days: five of 14 = 35.7%) received buprenorphine and carbamazepine. The difference in the overall dropout rate after day 14 was not significant. The present study supports the hypothesis that the combination of buprenorphine and carbamazepine leads to a better clinical outcome than does a combination of methadone and carbamazepine in the detoxification of opioid addicts with additional multiple drug abuse. The buprenorphine and carbamazepine-regimen provides a more effective short-term relief of affective disturbances than does methadone and carbamazepine. No severe side effects occurred during the treatment period in both groups.


Multiphasic bone-ligament-bone integrated scaffold enhances ligamentization and graft-bone integration after anterior cruciate ligament reconstruction.
The escalating prevalence of anterior cruciate ligament (ACL) injuries in sports necessitates innovative strategies for ACL reconstruction. In this study, we propose a multiphasic bone-ligament-bone (BLB) integrated scaffold as a potential solution. The BLB scaffold comprised two polylactic acid (PLA)/deferoxamine (DFO)@mesoporous hydroxyapatite (MHA) thermally induced phase separation (TIPS) scaffolds bridged by silk fibroin (SF)/connective tissue growth factor (CTGF)@Poly(l-lactide-co-ε-caprolactone) (PLCL) nanofiber yarn braided scaffold. This combination mimics the native architecture of the ACL tissue. The mechanical properties of the BLB scaffolds were determined to be compatible with the human ACL. In vitro experiments demonstrated that CTGF induced the expression of ligament-related genes, while TIPS scaffolds loaded with MHA and DFO enhanced the osteogenic-related gene expression of bone marrow stem cells (BMSCs) and promoted the migration and tubular formation of human umbilical vein endothelial cells (HUVECs). In rabbit models, the BLB scaffold efficiently facilitated ligamentization and graft-bone integration processes by providing bioactive substances. The double delivery of DFO and calcium ions by the BLB scaffold synergistically promoted bone regeneration, while CTGF improved collagen formation and ligament healing. Collectively, the findings indicate that the BLB scaffold exhibits substantial promise for ACL reconstruction. Additional investigation and advancement of this scaffold may yield enhanced results in the management of ACL injuries.


Myogenesis in Wilms' tumors is associated with mutations of the WT1 gene and activation of Bcl-2 and the Wnt signaling pathway.
Wilms tumors with WT1 mutations [ WT1(-)] have a stromal-predominant histology with varying extents of rhabdomyogenesis. These tumors also frequently have mutations in the beta-catenin gene ( CTNNB1). We have investigated the molecular events that may explain the origins of rhabdomyogenesis in WT1(-) tumors. Of 35 Wilms tumors, we identified 12 with WT1 mutations, of which 9 carried CTNNB1 mutations. We compared WT1 wild-type tumors [ WT1(+)] with WT1(-) tumors for histological features, localization of beta-catenin, Bcl-2 expression, and apoptosis using an in-situ end-labeling technique. WT1(+) tumors showed triphasic and blastemal- and epithelial predominant-histology. Expression of WT1, beta-catenin, and Bcl-2 recapitulated those of normal kidney epithelial development. Localization of beta-catenin was observed in the cytoplasm and cytoplasmic membrane of early glomerular epithelial structures. Bcl-2 is also expressed in condensing blastema and early glomerular epithelial structures which had little apoptosis. WT1(-) tumors, regardless of whether CTNNB1 mutations were detected or not, showed a stromal-rich phenotype with abundant expression of beta-catenin in the nucleus of the rhabdomyoblasts. Bcl-2 was expressed in rhabdomyoblasts, but not in blastemal cells undergoing apoptosis, suggesting that WT1 regulates Bcl-2 positively in the epithelial pathway, but negatively in the myogenic pathway. These data indicate that mutations in WT1 might alter the Wnt signaling pathway and Bcl-2 related-apoptosis. In WT1(-) tumors, the nuclear accumulation of beta-catenin and Bcl-2 expression are associated with rhabdomyogenesis, and dysregulation of Bcl-2 may be a mechanism by which the histogenesis (loss of blastemal component, muscle differentiation) may be explained.


Detection and Molecular Characterization of Aichivirus 1 in Wastewater Samples from Uruguay.
Aichivirus 1 (AiV-1) is an enteric virus with 30 nm in diameter, belonging to the genus Kobuvirus in the Picornaviridae family being a causative agent of gastroenteritis in humans. The transmission is via the fecal-oral route, through person to person contact, recreation in contaminated waters, or through the consumption of contaminated food or water. The aim of this study was to determine the frequency and the molecular characterization of AiV-1 in wastewater from Uruguay. Biweekly collections from March 2011 to February 2012 were performed in the cities of Bella Unión, Salto, Paysandú, and Fray Bentos, northwestern region of Uruguay. A total of 96 samples were collected; viruses were concentrated by ultracentrifugation, and AiV-1 was detected by using a nested PCR with primers directed to a conserved region (3CD junction) of the viral genome. A high frequency of AiV-1 (n = 54) was observed at all the cities analyzed mainly in the colder months of the year. AiV-1 was not evidenced as an appropriate viral fecal indicator since when compared with other previously detected enteric viruses, no correlation was observed. All 13 characterized AiV-1 belonged to the genotype B after the phylogenetic analysis performed with the sequences obtained from the first round PCR amplicon. This study demonstrates that AiV-1 is a frequently detected enteric viruses present in wastewater and excreted by infected persons in the northwestern region of Uruguay.


Commentary - A comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars and Intended Copy Biologics in treating chemotherapy associated febrile neutropenia.
Filgrastim, human white cell growth factor, Granulocyte colony-stimulating factor (G-CSF), is a core medicine in the WHO list of Essential Medicines. For this reason, recent reporting of statistically significant safety and efficacy differences between reference and Biosimilar brands of filgrastim by Rastogi and the Indian Pharmacopoeia Commission in Toxicology and Applied Pharmacology in 2020 is of great concern [Shruti Rastogi et al. Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data. Toxicology and Applied Pharmacology Volume 395, 15 May 2020, 114,976. https://doi.org/10.1016/j.taap.2020.114976]. This commentary shows that the alarming report is a result of incorrect statistical tests misapplied to inappropriate data sets compounded by a further problem relating to the strict regulatory definition of a Biosimilar Medicine as opposed that of an Intended Copy Biologic. In contrast, the body of evidence from more than seven and a half thousand participants in Confirmatory Clinical Studies and Post Approval Clinical Studies as well as the Periodic Safety Update Reports confirms that European approved filgrastim Biosimilars show no meaningful difference in quality, safety or efficacy compared to the reference brand.


Differences of the growth of mouse teratocarcinoma OTT6050 induced by various sex hormone treatments in vivo.
To study why the tumor growth rate was different among host mice of different sexes and ages, we examined the role of sex hormones in the growth and development of mouse teratocarcinoma OTT6050 in vivo. Estrogen and progesterone showed enhancement of tumor growth, while ovariectomy resulted in partial growth inhibition. Testosterone, orchiectomy, and antiestrogen had no effects. We concluded that the differences in tumor growth rate in females of different ages were due to changes in serum estrogen and progesterone levels and that the constancy of the growth in adult males was due to absent effects of testosterone.


Large-scale testing of human serum to determine cytomegalovirus neutralising antibody.
Complement (C')-dependent neutralising cytomegalovirus (CMV) antibody titres were determined in 4150 serum samples obtained from infants and children, as well as women of childbearing age. In a smaller group of samples, C'-independent neutralising antibody titres were also measured together with their reactivity to each individual CMV structural polypeptide in addition to total CMV antibody concentration. Results showed that primary CMV infection takes place mainly in early infancy and that 30-40% women of childbearing age do not have any or have very low titres of CMV neutralising antibody. Since poor correlation was found between the results of neutralisation tests and those of enzyme immunoassay, routine testing of neutralising antibody is warranted in those subjects, such as pregnant women, at risk of CMV infection. Results of immunoblotting suggest a correlation between high titres of neutralising antibody and antibody reactivity with three proteins of MW 86, 65, 60 kDa.


Resistance May Be Futile: Gut Spatial Heterogeneity Supports Bacteria-Phage Co-existence.
How do we explain the co-existence of bacteria and bacteriophages in complex environments? In this issue of Cell Host & Microbe, Lourenço et al. highlight the importance of spatial structure in facilitating the persistence of sensitive bacterial hosts and their virulent bacteriophages in the mammalian gut.


2,3-Diamino-pyridinium sorbate-sorbic acid (1/1).
In the title mol-ecular salt-adduct, C(5)H(8)N(3) (+)·C(6)H(7)O(2) (-)·C(6)H(8)O(2), the 2,3-diamino-pyridinium cation is essentially planar, with a maximum deviation of 0.013 (2) Å, and is protanated at its pyridine N atom. The sorbate anion and sorbic acid mol-ecules exist in extended conformations. In the crystal, the protonated N atom and one of the two amino-group H atoms are hydrogen bonded to the sorbate anion through a pair of N-H⋯O hydrogen bonds, forming an R(1) (2)(6) ring motif. The carboxyl groups of the sorbic acid mol-ecules and the carboxyl-ate groups of the sorbate anions are connected via O-H⋯O hydrogen bonds. Furthermore, the ion pairs and neutral mol-ecules are connected via inter-molecular N-H⋯O hydrogen bonds, forming sheets lying parallel to (100).


A new nucleic acid-protein cross-linking reagent.
A new photoactivable reagent is described, which allows the formation of RNA-protein cross-links via disulfide bridges in combination with mercaptobutyrimidate. The reconstituted L24 protein-23S RNA complex from the large subunit of E. coli ribosomes has been used as a model system for the cross-linking. The main advantages of the reagent are the absence of U.V. generated cross-links, since photoactivation is carried out at 360 nm, on one hand and the ease of cleavage of the cross-link by mild reduction (beta-mercaptoethanol) on the other.


Extremely high electron mobility in a phonon-glass semimetal.
The electron mobility is one of the key parameters that characterize the charge-carrier transport properties of materials, as exemplified by the quantum Hall effect as well as high-efficiency thermoelectric and solar energy conversions. For thermoelectric applications, introduction of chemical disorder is an important strategy for reducing the phonon-mediated thermal conduction, but is usually accompanied by mobility degradation. Here, we show a multilayered semimetal β-CuAgSe overcoming such a trade-off between disorder and mobility. The polycrystalline ingot shows a giant positive magnetoresistance and Shubnikov de Haas oscillations, indicative of a high-mobility small electron pocket derived from the Ag s-electron band. Ni doping, which introduces chemical and lattice disorder, further enhances the electron mobility up to 90,000 cm(2) V(-1) s(-1) at 10 K, leading not only to a larger magnetoresistance but also a better thermoelectric figure of merit. This Ag-based layered semimetal with a glassy lattice is a new type of promising thermoelectric material suitable for chemical engineering.


Total synthesis of 25-hydroxy-16,23E-diene vitamin D3 and 1 alpha,25-dihydroxy-16,23E-diene vitamin D3: separation of genomic and nongenomic vitamin D activities.
Separation of genomic and nongenomic vitamin D activities was achieved by structural modification of 1,25-dihydroxy vitamin D3 by introduction of 16 and 23E double bonds. The modified compound 3, lacking a 1 alpha-hydroxy group, exhibits only nongenomic activity. Its 1 alpha-hydroxy relative 4 expresses fully both genomic and non-genomic activities. A total synthesis of analogues 3 and 4 is described.


Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin.
Our objective was to assess the contribution of CYP2C9 genotype, age, body size, and vitamin K and lipid status to warfarin dose requirements. Patients with stable warfarin dose requirements and an international normalized ratio (INR) of the prothrombin time within the target range of 2.0 to 3.0 were recruited to the study. On arrival at the clinic in the morning, after an overnight fast, a blood sample was taken from each patient for CYP2C9 genotyping and for determination of venous INR and plasma vitamin K, R- and S-warfarin, and triglyceride concentrations. A total of 121 patients were recruited to the study. CYP2C9 genotyping showed that 74 patients were homozygous wild-type (*1/*1), 30 were heterozygous *1/*2, and 15 were heterozygous *1/*3 genotype. One patient was found to have the genotype *2/*3, and another was found to have the genotype *3/*3. The mean warfarin daily dose requirement in milligrams fell from 4.06 +/- 1.72 mg in homozygous wild-type patients to 3.63 +/- 1.78 mg for *1/*2-positive patients and 2.70 +/- 1.36 mg for *1/*3-positive patients. The multiple linear regression model for warfarin dose indicated significant contributions from age (r = 0.41, P <.001), genotype (r = 0.24, P <.005), and age and genotype together (r = 0.45, P <.005). Although there were significant linear correlations between warfarin dose and body surface area (r = 0.21, P =.02), body weight (r = 0.25, P =.005), and plasma vitamin K concentration (r = 0.18, P <.05), none of these variables made a significant contribution to the regression model for warfarin dose. CYP2C9 genotype had a significant effect on S-warfarin clearance (r = 0.34, P <.0001) but none on R-warfarin clearance. This study showed that age and CYP2C9 polymorphism affect warfarin dose requirements in patients receiving long-term therapy and having stable control of anticoagulation. It is anticipated that using dosing regimens modified to take into account the contribution of age and CYP2C9 genotype has the potential to improve the safety of warfarin therapy.


Predictors for intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease.
To assess the predictors for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD). A total of 560 KD patients were reviewed retrospectively, including 410 complete KD (cKD) and 150 incomplete KD (iKD) patients. The laboratory data were compared between the IVIG-resistant and IVIG-responsive groups, as well as between the coronary artery lesions (CALs+) and without coronary artery lesions (CALs-) groups. In the cKD patients, C-reactive protein (CRP) levels had a sensitivity of 65.52% and a specificity of 62.7% for predicting IVIG-resistance at a cutoff point of >100 mg/L. When albumin <32 g/L, the sensitivity and specificity for predicting IVIG-resistance were 72 and 83.19%, respectively. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels had a sensitivity of 73.91% and a specificity of 76.43% for predicting IVIG-resistance at a cutoff point of >1300 pg/ml. Interleukin-6 levels had a sensitivity of 76.19% and a specificity of 61.59% at a cutoff value of >45 pg/ml. Erythrocyte sedimentation rate (ESR) levels had a sensitivity of 53.26% and a specificity of 64.14% for predicting CALs at a cutoff point of >75 mm/h. In the iKD patients, the sensitivity and specificity for predicting IVIG-resistance were 80 and 54.1% when hemoglobin <110 g/L. When proportion of neutrophils >70%, the sensitivity and specificity for predicting IVIG-resistance were 68 and 66.94%, respectively. ESR levels had a sensitivity of 70.83% and a specificity of 65.81% for predicting IVIG-resistance at a cutoff point of >80 mm/h. NT-proBNP levels had a sensitivity of 78.57% and a specificity of 56.67% for predicting IVIG-resistance at a cutoff point of >360 pg/ml. Interleukin-6 levels had a sensitivity of 70.59% and a specificity of 66.28% at a cutoff value of >25 pg/ml. Interleukin-10 levels had a sensitivity of 64.71% and a specificity of 74.42% for predicting IVIG-resistance at a cutoff value of >8 pg/ml. ESR levels had a sensitivity of 61.82% and a specificity of 65.12% for predicting CALs at a cutoff point of >75 mm/h. The white blood cell count, proportion of neutrophils, hemoglobin, CRP, ESR, albumin, NT-proBNP, interleukin-6 and 10 may be effective predictors for IVIG resistance and CALs in KD patients.


Neurological outcome in surgically treated patients with incomplete closed traumatic cervical spinal cord injury.
Retrospective study based on a reference paper. Neurological outcome in patients who were managed surgically with closed traumatic cervical spine injury was evaluated using the ASIA motor scoring system and Frankel grading. To assess the accuracy of motor charting and Frankel grading as tools to evaluate neurological outcome in closed traumatic cervical spine injury, and also to evaluate how the surgically treated patients fared in their neurological recovery by measurement tools as in the reference paper. National Spinal Injuries Centre, Stoke Mandeville Hospital, Aylesbury, UK. Fifty-seven patients were admitted within 2 days of the injury with closed traumatic cervical spine injuries (1997-2004). Thirty-seven (65%) met the inclusion criteria as per the referenced paper, that is, were treated surgically, were Frankel grade B and above and had at least 12 months follow up. The remaining 20 patients were not included as they did not meet the inclusion criteria. The breakdown of the 20 patients is given in Table 1. The mean recovery percentage (MRP) and mean deficit percentage (MDP) were calculated as per the referenced paper. An evaluation of 37 patients surgically treated, who had follow up of at least 12 months, showed that preservation of pin prick below the level of lesion, and preservation of anal tone and perianal sensation were good prognostic indicators. There was no correlation between degree of encroachment of canal or the degree of kyphosis to MDP or MRP. The mean time from injury to mobilization was 7.6 days in 25 out of 37 patients. Twelve of the 37 patients had prolonged immobilization because of ITU stay or because they were initially treated conservatively. Three out of the 37 patients developed DVT/PE. Mean hospital stay was 6.4 months. The neurological outcome in surgically treated patients is comparable to the conservatively treated patients. The Frankel grading and ASIA motor charting combined is a powerful tool in assessing the neurological outcome in closed traumatic cervical spinal injured patients. Until now there has been no evidence to suggest that the obvious advantages of surgical management of closed cervical spine injuries (better alignment, easier manual handling and early mobilization) is traded for poorer neurological outcome.


Risk reduction in pediatric procedural sedation by application of an American Academy of Pediatrics/American Society of Anesthesiologists process model.
Guidelines for risk reduction during procedural sedation from the American Academy of Pediatrics (AAP) and the American Society of Anesthesiologists (ASA) rely on expert opinion and consensus. In this article, we tested the hypothesis that application of an AAP/ASA-structured model would reduce the risk of sedation-related adverse events. Prospectively coded sedation records were abstracted by a hospital quality improvement specialist with practical and administrative experience in pediatric sedation. Process variables included notation of nulla per os (NPO) status, performance of a guided risk assessment, assignment of ASA physical status score, obtaining informed consent, generation of a sedation plan, and assessment of sedation level using a quantitative scoring system. Content variables included adherence to AAP NPO guidelines, ASA class, target sedation level, actual sedation level, age, procedure, and drugs used. Complication risk was assessed by logistic regression and Mantel-Haenszel odds ratios (OR). Complications were identified in 40 of 960 records (4.2%). The complication rate was 34 of 895 (3.8%) with planned conscious sedation and 6 of 65 (9.2%) with planned deep sedation ([DS]; OR: 2.6). Complications were reduced by performance of structured risk assessment (OR: 0.10), adherence to all process guidelines (OR: 0), and avoiding actual DS (OR: 0.4). The only drug associated with higher risk was chloral hydrate (OR: 2.1). Failure to adhere to NPO guidelines did not increase risk in this assessment; however, the adverse event rate was 0 if all process guidelines were followed. Presedation assessment reduces complications of DS. Repeated assessment of sedation score reduces the risk of inadvertent DS. The data provide direct evidence that AAP/ASA guidelines can reduce the risk of pediatric procedural sedation.


Human malignant lymphomas in vitro. Characterization of biopsy cells and establishment of permanent cell lines.
A series of 55 biopsies from different types of malignant lymphomas were characterized in short-term culture experiments and during prolonged growth in vitro. The majority of the lymphocytic lymphomas and half of the histiocytic lymphomas expressed surface immunoglobulin, either in monoclonal or polyclonal form, indicating B-lymphocyte derivation. No lysozyme production was noted in either type of lymphoma, giving further support to the notion that histiocytic lymphomas are not truly histiocytic. Production of beta2-microglobulin was higher in histiocytic than in lymphocytic lymphoma and Hodgkin's disease but did not significantly differ from the production observed in non-neoplastic lymph node disorders. Incorporation of 3H-thymidine varied greatly within each category of lymphoma; the highest mean labelling index was noted in histiocytic lymphoma, possibly reflecting the generally more malignant course in such cases. Epstein-Barr virus-associated nuclear antigen was observed in one case of Hodgkin's disease. Attempts to establish permanent tumor cell lines were successful only from two explants of lymphocytic lymphoma and one pleural effusion from histiocytic lymphoma. The two cell lines derived from lymphocytic lymphomas both exhibited B-lymphocyte characteristics. The histiocytic lymphoma line lacked lymphocyte markers, produced lysozyme and was found to be rich in cytoplasmic esterases. These features are consistent with a "true" histiocytic derivation of this line. Lymphoblastoid cell lines representing non-neoplastic EBV-carrying lymphocytes contaminating the biopsies were derived from 19 biopsies, with the highest frequency noted in cultures of biopsies from Hodgkin's disease. The tumor lines were all EBV-genome negative.


Ru(II)-Catalyzed Synthesis of Substituted Furans and Their Conversion to Butenolides.
The synthesis of densely functionalized trisubstituted and tetrasubstituted furans via a novel Ru(II)-catalyzed intramolecular cyclization of vinyl diazoesters is reported. The synthetic utility of these furans is further demonstrated through a simple acid-mediated reaction to access highly substituted Δα,β-butenolides.


Formaldehyde degradation by UV/TiO2/O3 process using continuous flow mode.
The degradation of formaldehyde gas was studied using UV/TiO2/O3 process under the condition of continuous flow mode. The effects of humidity, initial formaldehyde concentration, residence time and ozone adding amount on degradation of formaldehyde gas were investigated. The experimental results indicated that the combination of ozonation with photocatalytic oxidation on the degradation of formaldehyde showed a synergetic action, e.g., it could considerably increase decomposing of formaldehyde. The degradation efficiency of formaldehyde was between 73.6% and 79.4% while the initial concentration in the range of 1.84-24 mg/m3 by O3/TiO2/UV process. The optimal humidity was about 50% in UV/TiO2/O3 processs and degradation of formaldehyde increases from 39.0% to 94.1% when the ozone content increased from 0 to 141 mg/m3. Furthermore, the kinetics of formaldehyde degradation reaction could be described by Langmuir-Hinshelwood model. The rate constant k of 46.72 mg/(m3 x min) and Langmuir adsorption coefficient K of 0.0268 m3/mg were obtained.


Discovery of a Small Molecule Drug Candidate for Selective NKCC1 Inhibition in Brain Disorders.
Aberrant expression ratio of Cl- transporters, NKCC1 and KCC2, is implicated in several brain conditions. NKCC1 inhibition by the FDA-approved diuretic drug, bumetanide, rescues core symptoms in rodent models and/or clinical trials with patients. However, bumetanide has a strong diuretic effect due to inhibition of the kidney Cl- transporter NKCC2, creating critical drug compliance issues and health concerns. Here, we report the discovery of a new chemical class of selective NKCC1 inhibitors and the lead drug candidate ARN23746. ARN23746 restores the physiological intracellular Cl- in murine Down syndrome neuronal cultures, has excellent solubility and metabolic stability, and displays no issues with off-target activity in vitro. ARN23746 recovers core symptoms in mouse models of Down syndrome and autism, with no diuretic effect, nor overt toxicity upon chronic treatment in adulthood. ARN23746 is ready for advanced preclinical/manufacturing studies toward the first sustainable therapeutics for the neurological conditions characterized by impaired Cl- homeostasis.


Multiple bilateral oncocytomas of the native kidneys following renal transplantation: report of a rare case and review of the literature.
Renal oncocytomas are benign tumors of the kidneys, which are usually diagnosed postoperatively, due to differential diagnostic problems, from a sample of a renal cell carcinoma. The development of a renal oncocytoma in the native kidneys following renal transplantation is a very rare condition and only a few cases have been published in the world literature. In this case report we present a unique case of bilateral multifocal renal oncocytomas of the native kidneys in a female transplant recipient 6 years after renal transplantation. The patient's postoperative clinical course was uneventful and no local recurrence or distant metastasis has been found so far. The pathology, clinical characteristics, and treatment of renal oncocytomas are also reviewed.


Needle-like Zn-doped SnO2 nanorods with enhanced photocatalytic and gas sensing properties.
Zn-doped SnO(2) nanorods have been prepared by a simple hydrothermal method on a large scale. The as-prepared samples were characterized by x-ray powder diffraction, scanning electron microscope, transmission electron microscope, energy dispersive spectrometer, x-ray photoelectron spectroscopy, UV-vis absorption spectra and photoluminescence spectra. Studies found that the products are needle-like single-crystalline nanorods grown along the [[Formula: see text]] orientation. The photocatalytic properties of the synthesized Zn-doped SnO(2) were investigated by decomposing acid fuchsine, showing much higher photocatalytic activity than pure SnO(2) nanorods and bulk SnO(2) powders. An enhanced gas sensing ability toward methanal, ethanol and acetone gases is also achieved in high sensitivity and fast response. The origins of the enhanced performances are discussed.


Nanodiamond-based nanostructures for coupling nitrogen-vacancy centres to metal nanoparticles and semiconductor quantum dots.
The ability to control the interaction between nitrogen-vacancy centres in diamond and photonic and/or broadband plasmonic nanostructures is crucial for the development of solid-state quantum devices with optimum performance. However, existing methods typically employ top-down fabrication, which restrict scalable and feasible manipulation of nitrogen-vacancy centres. Here, we develop a general bottom-up approach to fabricate an emerging class of freestanding nanodiamond-based hybrid nanostructures with external functional units of either plasmonic nanoparticles or excitonic quantum dots. Precise control of the structural parameters (including size, composition, coverage and spacing of the external functional units) is achieved, representing a pre-requisite for exploring the underlying physics. Fine tuning of the emission characteristics through structural regulation is demonstrated by performing single-particle optical studies. This study opens a rich toolbox to tailor properties of quantum emitters, which can facilitate design guidelines for devices based on nitrogen-vacancy centres that use these freestanding hybrid nanostructures as building blocks.


Data set of balance of Russia's regional economy in 2005-2024 based on the methodology of calculation of "underdevelopment whirlpools".
The article shows the possibilities of Data Set "Interactive Statistics and Intelligent Analytics of the Balanced State of the Regional Economy of Russia in Terms of Big Data and Blockchain - 2020". For creation of the data set, we formed time rows of the values of the selected indicators, which characterize the balance of Russia's regional economy. The indicators are systematized and classified into two categories. The first category includes the indicators of the level of socio-economic development: GDP per capita and "underdevelopment whirlpools", balanced financial result of companies' activities, population's employment level, and balance of the regional budget, calculated by finding the difference between revenues and expenditures. The second category includes the indicators of potential of socio-economic development: investments into fixed capital per capita, share of innovations-active organizations, share of innovative products, and digitization level. The data are collected in a table, based on which - with the help of programming and web-design - a data set is created - an interactive platform for working with data. The data set is available in Russian and English at the official web-site of the Institute of Scientific Communications [12]. The data set unifies and transfers into the digital form the data on the level and potential of Russia's regions' potential of socio-economic development. The data set allows for flexible setting of data for any research. The data set allows - based on the statistics of a region's socio-economic development - determining its position in the Russian national ranking, category by the "TRMS" matrix, calculating the integral index for each region, and comparing its values. Using the proprietary methodology of calculation of "underdevelopment whirlpools" of Prof. Popkova, the data set reflects the balance of Russia's regional economy in 2005-2024. The data set allows for automatic visualization of data by creating a blockchain polygon of region's socio-economic development, which includes the chronogram of the region's development and the process of region's pulling into an "underdevelopment whirlpool". The data set's data are presented in the form of an interactive map of Russia's regional economy. Map's color shows categories that are assigned to regions and the borders of regions, as well as information on each region's position in the 2020 rating. The data set allows for large-scale studies of Russia's regional economy with application of technologies of Big Data processing, machine learning, and intellectual analytics.


Neutron and hard X-ray diffraction studies of the isothermal transformation kinetics in the research reactor fuel candidate U-8 wt%Mo.
Exposing uranium-molybdenum alloys (UMo) retained in the γ phase to elevated temperatures leads to transformation reactions during which the γ-UMo phase decomposes into the thermal equilibrium phases, i.e. U2Mo and α-U. Since α-U is not suitable for a nuclear fuel exposed to high burn-up, it is necessary to retain the γ-UMo phase during the production process of the fuel elements for modern high-performance research reactors. The present work deals with the isothermal transformation kinetics in U-8 wt%Mo alloys for temperatures between 673 and 798 K and annealing durations of up to 48 h. Annealed samples were examined at room temperature using either X-ray or neutron diffraction to determine the phase composition after thermal treatment, and in situ annealing studies disclosed the onset of phase decomposition. While for temperatures of 698 and 673 K the start of decomposition is delayed, for higher temperatures the first signs of transformation are already observable within 3 h of annealing. The typical C-shaped curves in a time-temperature-transformation (TTT) diagram for both the start and the end of phase decomposition could be determined in the observed temperature regime. Therefore, a revised TTT diagram for U-8 wt%Mo between 673 and 798 K and annealing durations of up to 48 h is proposed.


Rotational motion of dimers of Janus particles.
We theoretically study the motion of a rigid dimer of self-propelling Janus particles. In a simple kinetic approach without hydrodynamic interactions, the dimer moves on a helical trajectory and, at the same time, it rotates about its center of mass. Inclusion of the effects of mutual advection using superposition approximation does not alter the qualitative features of the motion but merely changes the parameters of the trajectory and the angular velocity.


The effect of active carbon on the reduction of concentrated nitric acid by HCOOH.
In nuclear industry, removal of nitric acid from solutions is required in the course of chemical separation and waste treatment procedure as well as in chemical conversion steps. The reduction of HNO3 by HCOOH to gaseous products such as nitrogen, nitrogen oxides, and carbon dioxide is an attractive way to accomplish the denitration. A typical problem for the denitration is the existence of the induction period. The induction period has been explained as the time necessary to increase the concentration of HNO2, which is an important reaction intermediate, above a threshold value. In this study, adsorption sites on the surface of active carbon were found to promote HNO2 formation and efficiently suppress the induction period. Induction time was shortened by increasing the amount of active carbon in the solution. When the solution contains 3 M HNO3 and 1 M HCOOH, 10 g/L of active carbon was enough to eliminate the induction period at 50 degrees C. The catalytic effect exhibited by active carbon was similar to that reported for Pt/SiO2. Therefore, on the surface of active carbon, there is a redox cycle, where HNO3 is reduced to HNO2 and then the oxidized surface site will be reduced by HCOOH.


Suppression of agonist induced Ca2+ oscillations in cultured hepatocytes by nafenopin: possible involvement of protein kinase C.
The alpha 1-agonist phenylephrine (5 microM) induces an increase in the free cytosolic Ca2+ concentration, followed by repetitive transients of the cytoplasmic Ca2+ concentration, in single Fura-2 loaded hepatocytes. The tumor promoting, hypolipidemic drug nafenopin suppressed the cellular Ca2+ response to phenylephrine. The effect of nafenopin on the Ca2+ increase and Ca2+ oscillations was largely prevented by the specific protein kinase C inhibitor Gö 6976. This finding suggests involvement of protein kinase C in the action of nafenopin on phenylephrine induced Ca2+ mobilization.


Benign neoplasms of the larynx.
In a 45-year period (from 1948 to 1992) 291 patients with histologically proved benign neoplasms of the larynx were observed and treated. The most frequently occurring tumors were papillomas, being 95.2% in whole material. In most cases of benign tumors of the larynx intralaryngeal excision of the tumor was used. Clinical data and results of treatment were presented and discussed.