Genetic diversity of the Leptospiral immunoglobulin-like (Lig) genes in pathogenic Leptospira spp.
Recent serologic, immunoprotection, and pathogenesis studies identified the Lig proteins as key virulence determinants in interactions of leptospiral pathogens with the mammalian host. We examined the sequence variation and recombination patterns of ligA, ligB, and ligC among 10 pathogenic strains from five Leptospira species. All strains were found to have intact ligB genes and genetic drift accounting for most of the ligB genetic diversity observed. The ligA gene was found exclusively in L. interrogans and L. kirschneri strains, and was created from ligB by a two-step partial gene duplication process. The aminoterminal domain of LigB and the LigA paralog were essentially identical (98.5+/-0.8% mean identity) in strains with both genes. Like ligB, ligC gene variation also followed phylogenetic patterns, suggesting an early gene duplication event. However, ligC is a pseudogene in several strains, suggesting that LigC is not essential for virulence. Two ligB genes and one ligC gene had mosaic compositions and evidence for recombination events between related Leptospira species was also found for some ligA genes. In conclusion, the results presented here indicate that Lig diversity has important ramifications for the selection of Lig polypeptides for use in diagnosis and as vaccine candidates. This sequence information will aid the identification of highly conserved regions within the Lig proteins and improve upon the performance characteristics of the Lig proteins in diagnostic assays and in subunit vaccine formulations with the potential to confer heterologous protection.


Idazoxan treatment in progressive supranuclear palsy.
To confirm the preliminary report that increases in norepinephrine neurotransmission improve motor performance, we administered the investigational drug idazoxan (IDA) to nine patients with progressive supranuclear palsy (PSP) according to a double-blind crossover protocol. There were seven women and two men, whose mean age was 70 years and mean duration of illness 4 years. All had an advanced parkinsonian syndrome, supranuclear ocular motor palsies, and poor responses to dopaminergic drugs. During administration of 40 mg tid of IDA, the total score and the motor subscale score of the United Parkinson's Disease Rating Scale significantly decreased. Features that improved most included mobility, balance, gait, and measures of digital dexterity. There were no significant changes in any measure during placebo administration. Corticobulbar manifestations and eye movements were not significantly improved during treatment. Side effects of IDA included transient hypertension, tachycardia, action tremor, flushing, and sweating, but none was so severe that any patient withdrew from the study. Among the few attempted treatments of PSP, IDA is the first medication shown in a double-blind study to improve aspects of motor function.


Entropy generation method to quantify thermal comfort.
The present paper presents a thermodynamic approach to assess the quality of human-thermal environment interaction and quantify thermal comfort. The approach involves development of entropy generation term by applying second law of thermodynamics to the combined human-environment system. The entropy generation term combines both human thermal physiological responses and thermal environmental variables to provide an objective measure of thermal comfort. The original concepts and definitions form the basis for establishing the mathematical relationship between thermal comfort and entropy generation term. As a result of logic and deterministic approach, an Objective Thermal Comfort Index (OTCI) is defined and established as a function of entropy generation. In order to verify the entropy-based thermal comfort model, human thermal physiological responses due to changes in ambient conditions are simulated using a well established and validated human thermal model developed at the Institute of Environmental Research of Kansas State University (KSU). The finite element based KSU human thermal computer model is being utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal responses to different environmental conditions. The output from the simulation, which include human thermal responses and input data consisting of environmental conditions are fed into the thermal comfort model. Continuous monitoring of thermal comfort in comfortable and extreme environmental conditions is demonstrated. The Objective Thermal Comfort values obtained from the entropy-based model are validated against regression based Predicted Mean Vote (PMV) values. Using the corresponding air temperatures and vapor pressures that were used in the computer simulation in the regression equation generates the PMV values. The preliminary results indicate that the OTCI and PMV values correlate well under ideal conditions. However, an experimental study is needed in the future to fully establish the validity of the OTCI formula and the model. One of the practical applications of this index is that could it be integrated in thermal control systems to develop human-centered environmental control systems for potential use in aircraft, mass transit vehicles, intelligent building systems, and space vehicles.


Extradyadic sexual relationships in Norway.
The purpose of this research was to study the occurrence of extradyadic sexual relationships among Norwegians. We examined what background factors were associated with this type of relationship, and to what extent condoms were used. In 2002, a random sample of 9,852 Norwegians between the ages of 18 and 49 were asked to participate in an anonymous self-administered questionnaire survey on sexual behavior. A total of 3387 persons responded (1386 men, 1993 women, and 8 who did not indicate their gender), yielding a response rate of 34%. Of the 2807 participants who had ever been married or cohabited, 29% of the men and 23% of the women reported experience with extradyadic sexual relationships at some point during their lives. Sixteen percent of the men and 11% of the women reported extradyadic sex during their current marriage/cohabiting relationship. Women were more emotionally attached to the extradyadic partner than men. Factors that predicted occurrence of extradyadic sexual relationships were age, number of years married/cohabiting, number of sex partners, and sexual orientation. In addition, there was a correlation between low self-esteem and extradyadic sexual experience. About 50% of the participants reported no use of contraception during the most recent intercourse with an extradyadic partner. In conclusion, men's extradyadic partner seems most often to be a casual partner, whereas women prefer someone they already know. The choice of extradyadic partner is most likely associated with use of STI protection.


A new molineid (Nematoda: Trichostrongylina) parasite of Dasypus hybridus (Xenarthra: Dasypodidae) from Argentina.
Delicata abbai n. sp. collected from the small intestine of the southern long-nosed armadillo, Dasypus hybridus, from Argentina is herein described. This new species is characterized by vulvar opening within second half of body length, female tail conical, ending bluntly with a terminal spine, complex spicules, presence of a bursal membrane supported by 2 small rays, and a synlophe with bilateral symmetry and 26 cuticular ridges. By the morphology of the caudal bursa, caudal end of female, and shape of spicules, the new species resembles Delicata cameroni Travassos, 1935 and Delicata variabilis Travassos, 1935 . However, it differs from D. cameroni by having rays 5 and 6 diverging more proximally, rays 8 shorter than the dorsal ray, and spicules with a different shape. Delicata abbai n. sp. is distinguished from D. variabilis mainly by the spicules, which have a different shape and proportion of their constitutive parts. This is the first report of a species of Delicata in Argentina.


Interposition of the flexor hallucis longus tendon through the subtalar joint as a late complication of pediatric clubfoot repair: a case report.
Interposition of the flexor hallucis longus tendon through the subtalar joint was identified intraoperatively during a triple arthrodesis for a symptomatic adult clubfoot in a patient who had a posteromedial release as a child. The mechanism for this occurrence is unknown, although it is likely that the flexor hallucis longus tendon deviated into the subtalar joint during the early postoperative period. Interposition of the flexor hallucis longus tendon has not been previously reported as a late complication of pediatric clubfoot repair.


Emerging role of HMGB1 in fibrotic diseases.
High-mobility group box 1 (HMGB1) is originally identified as a DNA-binding protein that functions as a structural co-factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can be passively released from necrotic cells or actively secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 is a multifunctional cytokine that contributes to the process of infection, injury, inflammation, apoptosis, and immune responses by binding to specific cell-surface receptors. Recently, emerging studies indicate that HMGB1 is closely involved in fibrotic disorders including cystic fibrosis, liver fibrosis and pulmonary fibrosis, while HMGB1 signal inhibitions protect against the experimental models of fibrotic diseases. From a clinical perspective, HMGB1 represents a current challenge that can be exploited orchestrate reparative responses. This review focuses on the crucial role of HMGB1 in the pathogenesis of fibrotic diseases and inhibition of which may represent a promising clinical approach for treating tissue fibrosis.


Effect of Spectral Quality of Monochromatic LED Lights on the Growth of Artichoke Seedlings.
Indoor farming is becoming a popular alternative approach in food production to meet the demand of a growing world population. Under this production system, artificial light provides the main source of illumination in sustaining plant growth and development. The use of light-emitting diodes (LEDs) is a popular source of artificial light for indoor farms due to its narrow light spectra, modular design and energy efficiency. This study purposely assessed the effect of monochromatic LED light quality on the growth of three varieties of artichoke seedlings compared to greenhouse condition. Spectral quality assessment showed that photosynthetic photon flux density (PPFD) was highest under red LED light, but only a third of the total PPFD under natural light. Seedlings grown under red light showed 60-100% more shoot dry weight and were 67-115% taller than seedlings grown in the greenhouse. However, seedlings under blue or white light conditions showed 67-76% less in biomass compared to greenhouse-grown seedlings. Overall, plant response of seedlings under red light condition was much better compared to greenhouse-grown seedlings emphasizing the importance of red light spectral quality in plant growth and development.


Exonic deletions in AUTS2 cause a syndromic form of intellectual disability and suggest a critical role for the C terminus.
Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each with a breakpoint within the AUTS2 locus. Comparison of 17 well-characterized individuals enabled identification of a variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. The dysmorphic features were more pronounced in persons with 3'AUTS2 deletions. This part of the gene is shown to encode a C-terminal isoform (with an alternative transcription start site) expressed in the human brain. Consistent with our genetic data, suppression of auts2 in zebrafish embryos caused microcephaly that could be rescued by either the full-length or the C-terminal isoform of AUTS2. Our observations demonstrate a causal role of AUTS2 in neurocognitive disorders, establish a hitherto unappreciated syndromic phenotype at this locus, and show how transcriptional complexity can underpin human pathology. The zebrafish model provides a valuable tool for investigating the etiology of AUTS2 syndrome and facilitating gene-function analysis in the future.


Do not drop: mechanical shock in vials causes cavitation, protein aggregation, and particle formation.
Industry experience suggests that g-forces sustained when vials containing protein formulations are accidentally dropped can cause aggregation and particle formation. To study this phenomenon, a shock tower was used to apply controlled g-forces to glass vials containing formulations of two monoclonal antibodies and recombinant human growth hormone (rhGH). High-speed video analysis showed cavitation bubbles forming within 30 μs and subsequently collapsing in the formulations. As a result of echoing shock waves, bubbles collapsed and reappeared periodically over a millisecond time course. Fluid mechanics simulations showed low-pressure regions within the fluid where cavitation would be favored. A hydroxyphenylfluorescein assay determined that cavitation produced hydroxyl radicals. When mechanical shock was applied to vials containing protein formulations, gelatinous particles appeared on the vial walls. Size-exclusion chromatographic analysis of the formulations after shock did not detect changes in monomer or soluble aggregate concentrations. However, subvisible particle counts determined by microflow image analysis increased. The mass of protein attached to the vial walls increased with increasing drop height. Both protein in bulk solution and protein that became attached to the vial walls after shock were analyzed by mass spectrometry. rhGH recovered from the vial walls in some samples revealed oxidation of Met and/or Trp residues.


Cyanogenesis in animal-plant interactions.
When there is variation between individuals of the same plant species for a putative defensive chemical it is possible to prove beyond reasonable doubt that the chemical does indeed have a defence function for the plant. The polymorphism for cyanogenesis in Lotus corniculatus and Trifolium repens provides ample evidence that cyanogenesis has an important role in plant defence. This herbivore-plant interaction is, however, far from simple: the degree of selectivity varies between individuals of the same animal species and is influenced by differences in hunger and the type of food previously consumed. The primary effect of cyanogenesis is at the feeding and not at the digesting stage, although it seems that it is the carbonyl compounds released on cyanogenesis which have the deterrent effect and not hydrogen cyanide itself. Although cyanogenesis is not a particularly effective method of defence, it is a conservative system--the compounds involved are recycled and the plant has to be physically damaged before cyanogenesis occurs. Because there is no pre-damage volatile compound involved, cyanogenesis cannot be used by insects or other animals as a means of finding the plants.


The plasma catecholamine responses to ventricular pacing: implications for rate responsive pacing.
Many patients with VVI and VVIR pacemakers will alternate between periods of sinus rhythm and ventricular pacing. These rhythm shifts may be poorly tolerated by some patients. Changes in plasma catecholamine levels during these rhythm shifts may contribute to these patients' symptoms. We measured blood pressure, ejection fraction and plasma norepinephrine, epinephrine, and dopamine serially in nine patients with normal left ventricular ejection fractions and VVI pacemakers during sinus rhythm and at paced rates of 10 beats per minute (bpm) above sinus rates (10 + NSR), 100 bpm, and 130 bpm. The mean norepinephrine level at baseline was 143 +/- 16 pg/mL and increased to 166 +/- 36 pg/mL at 10 + NSR, 204 +/- 47 pg/mL at 100 bpm, and 182 +/- 34 pg/mL at 130 bpm. These increases corresponded to mean percent changes from baseline of 17% (P = 0.02), 33% (P = 0.002), and 24% (P = 0.07), respectively. The magnitude of the norepinephrine response was not correlated with the pacing rate. The mean plasma epinephrine level at baseline was 57 +/- 6 pg/mL and peaked at 51 +/- 12 pg/mL at 10 + NSR, 89 +/- 31 pg/mL at 100 bpm and 101 +/- 28 pg/mL at 130 bpm. These increases corresponded to mean percent changes from baseline of -10% (P = NS), 30% (P = 0.07), and 89% (P = 0.02), respectively. No trends in the dopamine response to pacing were noted. During ventricular pacing there were no significant changes in mean blood pressure and only slight changes in ejection fraction. The individual percent changes in plasma norepinephrine and epinephrine at 100 bpm were inversely correlated to the changes in systolic blood pressure (R = -0.68, P = 0.06, and R = -0.81, P = 0.03, respectively). These results suggest that plasma norepinephrine and epinephrine increase acutely in response to ventricular pacing at rates commonly seen during rate responsive ventricular pacing.


[Renal hyperparathyroidism's control after subtotal parathyroidectomy].
Parathyroidectomy, in any of its forms, is considered an effective short-term treatment of renal hyperparathyroidism in patients who are not being controlled with drugs. Nevertheless, the outcome in the medium and long term of the various surgical procedures is still unclear and seems a controversial issue. We conducted a prospective study of 15 patients undergoing subtotal parathyroidectomy who were followed up for a period of 48 months after surgery. All patients were included in hemodialysis programmes. Elevated levels of parathyroid hormone which did not decrease with drug therapy recommended parathyroidectomy. The aim of our study is to determine whether subtotal parathyroidectomy is an effective technique in the medium and long term. As regards the results obtained, the levels of parathyroid hormone and calcemia remarkably decreased during the follow-up period, if compared to pre-surgery levels. The level of alkaline phosphatase also showed a reduction and the "hungry bone effect" was observed. The phosphorus and Ca-P product levels only showed a significant reduction immediately after surgery but showed an increment from the first year after surgery onwards. Hemoglobin levels did not show any alteration after parathyroidectomy. In two patients we observed a relapse of hyperparathyroidism. The anatomopathological examination revealed nodular hyperplasia in most of the cases, including the two relapses. Subtotal parathyroidectomy is an effective surgical procedure in the medium-term treatment of renal hyperparathyroidism.


Molecular characterization of the minimal replicon and the unidirectional theta replication of pSCM201 in extremely halophilic archaea.
A 3,463-bp plasmid, pSCM201, was isolated from a halophilic archaeon, Haloarcula sp. strain AS7094. The minimal replicon that is essential and sufficient for autonomous replication and stable maintenance in Haloarcula hispanica was determined by deletion analysis of the plasmid. This minimal replicon ( approximately 1.8 kb) consisted of only two functionally related segments: (i) a putative origin (ori201) containing an AT-rich region and sets of repeats and (ii) an adjacent gene encoding a putative replication initiation protein (Rep201). Electron microscopic observation and Southern blotting analysis demonstrated that pSCM201 replicates via a theta mechanism. Precise mapping of the putative origin suggested that the replication initiated from a fixed site close to the AT-rich region and proceeded unidirectionally toward the downstream rep201 gene, which was further confirmed by electron microscopic analysis of the ClaI-digested replication intermediates. To our knowledge, this is the first unidirectional theta replication plasmid experimentally identified in the domain of archaea. It provides a novel plasmid system to conduct research on archaeal DNA replication.


New challenges in ageing: home care.
Most nations are undergoing two fundamental demographic changes: concentration of their population in cities and accelerated pace of population ageing. The fastest-growing population is that 85 years and over. Morbidity increases with advancing age, functional capacities decrease; this results in decreased performance of activities of daily liver and need for services. The challenge is particularly strong in urban areas. Modern societies seek solutions in maintaining the elderly in their homes through home care programmes for those who are functionally impaired, homebound, and need support in home-making and home nursing. Home care is firmly established in programmes for the elderly. In order to become a scientific discipline home care has to define its boundaries, identify clients by careful multidisciplinary assessment, provide answers regarding its cost-effectiveness, evaluate outcomes of home caring develop indicators of high-quality care and advise appropriate home care technology, which is affordable and accessible. Home care for the elderly population living in remote rural areas is one of the future challenges.


Soil-water distribution coefficients and plant transfer factors for (134)Cs, (85)Sr and (65)Zn under field conditions in tropical Australia.
Measurements of soil-to-plant transfer of (134)Cs, (85)Sr and (65)Zn from two tropical red earth soils ('Blain' and 'Tippera') to sorghum and mung crops have been undertaken in the north of Australia. The aim of the study was to identify factors that control bioaccumulation of these radionuclides in tropical regions, for which few previous data are available. Batch sorption experiments were conducted to determine the distribution coefficient (K(d)) of the selected radionuclides at pH values similar to natural pH values, which ranged from about 5.5 to 6.7. In addition, K(d) values were obtained at one pH unit above and below the soil-water equilibrium pH values to determine the effect of pH. The adsorption of Cs showed no pH dependence, but the K(d) values for the Tippera soils (2300-4100 ml/g) exceeded those for the Blain soils (800-1200 ml/g) at equilibrium pH. This was related to the greater clay content of the Tippera soil. Both Sr and Zn were more strongly adsorbed at higher pH values, but the K(d) values showed less dependence on the soil type. Strontium K(d)s were 30-60 ml/g whilst Zn ranged from 160 to 1630 ml/g for the two soils at equilibrium pH. With the possible exception of Sr, there was no evidence for downward movement of radionuclides through the soils during the course of the growing season. There was some evidence of surface movement of labelled soil particles. Soil-to-plant transfer factors varied slightly between the soils. The average results for sorghum were 0.1-0.3 g/g for Cs, 0.4-0.8 g/g for Sr and 18-26 g/g for Zn (dry weight) with the initial values relating to Blain and the following values to Tippera. Similar values were observed for the mung bean samples. The transfer factors for Cs and Sr were not substantially different from the typical values observed in temperate studies. However, Zn transfer factors for plants grown on both these tropical soils were greater than for soils in temperate climates (by more than an order of magnitude). This may be related to trace nutrient deficiency and/or the growth of fungal populations in these soils. The results indicate that transfer factors depend on climatic region together with soil type and chemistry and underline the value of specific bioaccumulation data for radionuclides in tropical soils.


Erythromycin uptake and accumulation by human polymorphonuclear leukocytes and efficacy of erythromycin in killing ingested Legionella pneumophila.
Studies were undertaken to demonstrate the efficacy of erythromycin in killing Legionella pneumophila organisms that have been ingested by human polymorphonuclear leukocytes. With use of an electron microscope-autoradiography method in conjunction with an antibiotic-uptake assay, it was shown that [3H]-labeled erythromycin A base penetrated into the cytoplasm of human polymorphonuclear leukocytes in concentrations up to 24 times higher than the extracellular drug level. Similar studies using [14C]benzyl penicillin revealed that this antibiotic penetrated human polymorphonuclear leukocytes very poorly. Removal of erythromycin from the extracellular environment resulted in rapid leakage of radioactivity from the cells; an assay for bioactivity showed that this material was unaltered drug. Human polymorphonuclear leukocytes were permitted to ingest L. pneumophila and were then treated with erythromycin A base. The erythromycin killed the ingested legionellae, as evidenced by bacterial plate counts and morphological destruction of ingested organisms. These data clearly demonstrate the efficacy of erythromycin in killing susceptible intracellular pathogens.


Identification of glucoselysine-6-phosphate deglycase, an enzyme involved in the metabolism of the fructation product glucoselysine.
The metabolism of the glycation product fructose-epsilon-lysine in Escherichia coli involves its ATP-dependent phosphorylation by a specific kinase (FrlD), followed by the conversion of fructoselysine 6-phosphate into glucose 6-phosphate and lysine by fructoselysine-6-phosphate deglycase (FrlB), which is distantly related to the isomerase domain of glucosamine-6-phosphate synthase. As shown in the present work, several bacterial operons comprise: (1) a homologue of fructoselysine-6-phosphate deglycase; (2) a second homologue of the isomerase domain of glucosamine-6-phosphate synthase, more closely related to it; and (3) components of a novel phosphotransferase system, but no FrlD homologue. The FrlB homologue (GfrF) and the closer glucosamine-6-phosphate synthase homologue (GfrE) encoded by an Enterococcus faecium operon were expressed in E. coli and purified. Similar to FrlB, GfrF catalysed the reversible conversion of fructoselysine 6-phosphate into glucose 6-phosphate and lysine. When incubated with fructose 6-phosphate and elevated concentrations of lysine, GfrE catalysed the formation of a compound identified as 2-epsilon-lysino-2-deoxy-6-phospho-glucose (glucoselysine 6-phosphate) by NMR. GfrE also catalysed the reciprocal conversion, i.e. the formation of fructose 6-phosphate (but not glucose 6-phosphate) from glucoselysine 6-phosphate. The equilibrium constant of this reaction (0.8 M) suggests that the enzyme serves to degrade glucoselysine 6-phosphate. In conclusion, GfrF and GfrE serve to metabolize glycation products formed from lysine and glucose (fructoselysine) or fructose (glucoselysine), via their 6-phospho derivatives. The latter are presumably formed by the putative phosphotransferase system encoded by gfrA-gfrD. The designation gfr (glycation and fructation product degradation) is proposed for this operon. This is the first description of an enzyme participating in the metabolism of fructation products.


Learning Adversarial Transformer for Symbolic Music Generation.
Symbolic music generation is still an unsettled problem facing several challenges. The complete music score is a quite long note sequence, which consists of multiple tracks with recurring elements and their variants at various levels. The transformer model, benefiting from its self-attention has shown advantages in modeling long sequences. There have been some attempts at applying the transformer-based model to music generation. However, previous works train the model using the same strategy as the text generation task, despite the obvious differences between the pattern of texts and musics. These models cannot consistently produce music samples of high quality. In this article, we propose a novel adversarial transformer to generate transformer to generate music pieces with high musicality. The generative adversarial learning and the self-attention networks are combined creatively. The generation of long sequence is guided by the adversarial objectives, which provides a strong regularization to enforce the transformer to focus on learning of the global and local structures. Instead of adopting the time-consuming Monte Carlo (MC) search method that is commonly used in the existing sequence generative models, we propose an effective and convenient method to compute the reward for each generated step (REGS) for the long sequence. The discriminator is trained to optimize the elaborately designed global and local loss objective functions simultaneously, which enables the discriminator to give reliable REGS for the generator. The adversarial objective combined with the teacher forcing objective is used to guide the training of the generator. The proposed model can be used to generate single-track or multitrack music pieces. Experiments show that our model can generate long music pieces with the improved quality compared with the original music transformers.


Time-course effects of aerobic physical training in the prevention of cigarette smoke-induced COPD.
A previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke). Mice were exposed to CS and ET for 4, 8, or 12 wk. Exercise protected mice exposed to CS from emphysema and reductions in tissue damping and tissue elastance after 12 wk (P < 0.01). The total number of inflammatory cells in the bronchoalveolar lavage increased in the Smoke group, mainly due to the recruitment of macrophages after 4 wk, neutrophils and lymphocytes after 8 wk, and lymphocytes and macrophages after 12 wk (P < 0.01). Exercise attenuated this increase in mice exposed to CS. The protection conferred by exercise was mainly observed after exercise adaptation. Exercise increased IL-6 and IL-10 in the quadriceps and lungs (P < 0.05) after 12 wk. Total antioxidant capacity and SOD was increased and TNF-α and oxidants decreased in lungs of mice exposed to CS after 12 wk (P < 0.05). The protective effects of exercise against lung injury induced by cigarette smoke exposure suggests that anti-inflammatory mediators and antioxidant enzymes play important roles in chronic obstructive pulmonary disease development mainly after the exercise adaptation.NEW & NOTEWORTHY These experiments investigated for the first time the temporal effects of regular moderate exercise training in cigarette smoke-induced chronic obstructive pulmonary disease. We demonstrate that aerobic conditioning had a protective effect in emphysema development induced by cigarette smoke exposure. This effect was most likely secondary to an effect of exercise on oxidant-antioxidant balance and anti-inflammatory mediators.


Extracellular phosphorylation of a receptor tyrosine kinase controls synaptic localization of NMDA receptors and regulates pathological pain.
Extracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate. More recently, extracellular kinases that phosphorylate extracellular serine, threonine, and tyrosine residues of numerous proteins have been identified. However, the functional significance of extracellular phosphorylation of specific residues in the nervous system is poorly understood. Here we show that synaptic accumulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) and pathological pain are controlled by ephrin-B-induced extracellular phosphorylation of a single tyrosine (p*Y504) in a highly conserved region of the fibronectin type III (FN3) domain of the receptor tyrosine kinase EphB2. Ligand-dependent Y504 phosphorylation modulates the EphB-NMDAR interaction in cortical and spinal cord neurons. Furthermore, Y504 phosphorylation enhances NMDAR localization and injury-induced pain behavior. By mediating inducible extracellular interactions that are capable of modulating animal behavior, extracellular tyrosine phosphorylation of EphBs may represent a previously unknown class of mechanism mediating protein interaction and function.


Imaging evaluation of laparoscopic greater curvature plication: preliminary observations.
The purpose of this article is to assess normal imaging findings and complications after laparoscopic greater curvature plication on luminal upper gastrointestinal studies and CT. This was a retrospective chart review of 24 adults who underwent laparoscopic greater curvature plication between 2008 and 2011. Seventeen patients (70.8%) underwent postoperative luminal upper gastrointestinal studies, and four (16.7%) underwent postoperative CT. Normal imaging features and complications were recorded. The percentage of intraluminal gastric diameter occupied by the plicated segment and the percentage of greater curvature involved on postoperative upper gastrointestinal luminal studies were determined. A multilobular intraluminal filling defect reflecting the surgical plication occupied the proximal third of the greater curvature in 16 of 17 patients (94%), extending to the mid portion in 10 of 17 patients (59%) and to the distal third in one of 17 patients (6%). There was luminal narrowing of 50-75% in 14 of 17 patients (82%) and narrowing of 25-50% in two patients (12%). In 14 of 17 patients (82%), the plication involved 50-75% of the greater curvature length and 25-50% in the remaining three patients (18%). In four patients who underwent CT, a central low-attenuation stripe accompanied the plication. Five of 24 patients (21%) had complications, including extraluminal gastric leak (n = 1), gastric outlet obstruction (n = 2), and plication suture failure (n = 2). Laparoscopic greater curvature plication is seen as multilobular filling defects most commonly along the proximal greater curvature with 50-75% narrowing of the gastric lumen. A linear low-attenuation stripe accompanies the filling defect on CT.


Coracoclavicular ligament reconstruction: a systematic review and a biomechanical study of a triple endobutton technique.
Operative intervention is recommended for complete acromioclavicular (AC) joint dislocation to restore AC stability, but the best operative technique is still controversial. Twelve fresh-frozen male cadaveric shoulders (average age, 62.8±7.8 years) were equally divided into endobutton versus the modified Weaver-Dunn groups. Each potted scapula and clavicle was fixed in a custom made jig to allow translation and load to failure testing using a Zwick BZ2.5/TS1S material testing machine (Zwick/Roell Co, Germany). A systematic review of 21 studies evaluating reconstructive methods for coracoclavicular or AC joints using a cadaveric model was also performed. From our biomechanical study, after ligament reconstruction, the triple endobutton technique demonstrated superior, anterior, and posterior displacements similar to that of the intact state (P>0.05). In the modified Weaver-Dunn reconstruction group, however, there was significantly greater anterior (P<0.001) and posterior (P=0.003) translation after ligament reconstruction. In addition, there was no significant difference after reconstruction between failure load of the triple endobutton group and that of the intact state (686.88 vs 684.9 N, P>0.05), whereas the failure load after the modified Weaver-Dunn reconstruction was decreased compared with the intact state (171.64 vs 640.86 N, P<0.001). From our systematic review of 21 studies, which involved comparison of the modified Weaver-Dunn technique with other methods, the majority showed that the modified Weaver-Dunn procedure had significantly (P<.05) greater laxity than other methods including the endobutton technique. The triple endobutton reconstruction proved superior to the modified Weaver-Dunn technique in restoration of AC joint stability and strength. Triple endobutton reconstruction of the coracoclavicular ligament is superior to the modified Weaver-Dunn reconstruction in controlling both superior and anteroposterior displacements with a failure load that approximates the intact ligament.


Exclusions and limitations in children's behavioral health care coverage.
The objective of this study was to identify benefit limits, diagnostic exclusions, and service exclusions of private behavioral health care plans that can influence the delivery of care to children. A total of 128 commercial, employment-based behavioral health plans were examined for types of benefit limits, service exclusions, and diagnostic exclusions applicable to children. Almost half of the plans had restrictions on the number of outpatient visits, with limits ranging from 12 to 60 clinic visits a year. More than half of the plans had limitations on the number of inpatient days, ranging from 20 to 60 days a year. Diagnoses excluded from coverage included autism, mental retardation, problems related to child abuse, and impulse control disorders, such as kleptomania and pyromania. Half of the services excluded could be categorized as either social and human services or complementary medicine rather than as mental health care. Plans commonly had service and diagnostic exclusions that could disrupt children's health care. The results of the study emphasize a need to address the types of treatment covered by mental health insurance.


Infectious speciation revisited: impact of symbiont-depletion on female fitness and mating behavior of Drosophila paulistorum.
The neotropical Drosophila paulistorum superspecies, consisting of at least six geographically overlapping but reproductively isolated semispecies, has been the object of extensive research since at least 1955, when it was initially trapped mid-evolution in flagrant statu nascendi. In this classic system females express strong premating isolation patterns against mates belonging to any other semispecies, and yet uncharacterized microbial reproductive tract symbionts were described triggering hybrid inviability and male sterility. Based on theoretical models and limited experimental data, prime candidates fostering symbiont-driven speciation in arthropods are intracellular bacteria belonging to the genus Wolbachia. They are maternally inherited symbionts of many arthropods capable of manipulating host reproductive biology for their own benefits. However, it is an ongoing debate as to whether or not reproductive symbionts are capable of driving host speciation in nature and if so, to what extent. Here we have reevaluated this classic case of infectious speciation by means of present day molecular approaches and artificial symbiont depletion experiments. We have isolated the α-proteobacteria Wolbachia as the maternally transmitted core endosymbionts of all D. paulistorum semispecies that have coevolved towards obligate mutualism with their respective native hosts. In hybrids, however, these mutualists transform into pathogens by overreplication causing embryonic inviability and male sterility. We show that experimental reduction in native Wolbachia titer causes alterations in sex ratio, fecundity, and mate discrimination. Our results indicate that formerly designated Mycoplasma-like organisms are most likely Wolbachia that have evolved by becoming essential mutualistic symbionts in their respective natural hosts; they have the potential to trigger pre- and postmating isolation. Furthermore, in light of our new findings, we revisit the concept of infectious speciation and discuss potential mechanisms that can restrict or promote symbiont-induced speciation at post- and prezygotic levels in nature and under artificial laboratory conditions.


Long-read-based Genome Assembly of Drosophila gunungcola Reveals Fewer Chemosensory Genes in Flower-breeding Species.
Drosophila gunungcola exhibits reproductive activities on the fresh flowers of several plant species and is an emerging model to study the co-option of morphological and behavioral traits in male courtship display. Here, we report a near-chromosome-level genome assembly that was constructed based on long-read PacBio sequencing data (with ∼66× coverage) and annotated with the assistant from RNA-seq transcriptome data of whole organisms at various developmental stages. A nuclear genome of 189 Mb with 13,950 protein-coding genes and a mitogenome of 17.5 kb were acquired. Few interchromosomal rearrangements were found in the comparisons of synteny with Drosophila elegans, its sister species, and Drosophila melanogaster, suggesting that the gene compositions on each Muller element are evolutionarily conserved. Loss events of several OR and IR genes in D. gunungcola and D. elegans were revealed when orthologous genomic regions were compared across species in the D. melanogaster species group. This high-quality reference genome will facilitate further comparative studies on traits related to the evolution of sexual behavior and diet specialization.


Integrated Characterization of Cassava (Manihot esculenta) Pectin Methylesterase (MePME) Genes to Filter Candidate Gene Responses to Multiple Abiotic Stresses.
Plant pectin methylesterases (PMEs) play crucial roles in regulating cell wall modification and response to various stresses. Members of the PME family have been found in several crops, but there is a lack of research into their presence in cassava (Manihot esculent), which is an important crop for world food security. In this research, 89 MePME genes were identified in cassava that were separated into two types (type-Ⅰ and type-Ⅱ) according to the existence or absence of a pro-region (PMEI domain). The MePME gene members were unevenly located on 17 chromosomes, with 19 gene pairs being identified that most likely arose via duplication events. The MePMEs could be divided into ten sub-groups in type-Ⅰ and five sub-groups in type-Ⅱ. The motif analysis revealed 11 conserved motifs in type-Ⅰ and 8 in type-Ⅱ MePMEs. The number of introns in the CDS region of type-Ⅰ MePMEs ranged between one and two, and the number of introns in type-Ⅱ MePMEs ranged between one and nine. There were 21 type-Ⅰ and 31 type-Ⅱ MePMEs that contained signal peptides. Most of the type-Ⅰ MePMEs had two conserved "RK/RLL" and one "FPSWVS" domain between the pro-region and the PME domain. Multiple stress-, hormone- and tissue-specific-related cis-acting regulatory elements were identified in the promoter regions of MePME genes. A total of five co-expressed genes (MePME1, MePME2, MePME27, MePME65 and MePME82) were filtered from different abiotic stresses via the use of UpSet Venn diagrams. The gene expression pattern analysis revealed that the expression of MePME1 was positively correlated with the degree of cassava postharvest physiological deterioration (PPD). The expression of this gene was also significantly upregulated by 7% PEG and 14 °C low-temperature stress, but slightly downregulated by ABA treatment. The tissue-specific expression analysis revealed that MePME1 and MePME65 generally displayed higher expression levels in most tissues than the other co-expressed genes. In this study, we obtain an in-depth understanding of the cassava PME gene family, suggesting that MePME1 could be a candidate gene associated with multiple abiotic tolerance.


VNTR (CAG)n polymorphism of the ATXN2 gene and metabolic parameters of cardiovascular risk associated with the degree of obesity in the Amerindian population of Oaxaca.
The ATXN2 gene has a VNTR (CAG)n with locus in exon1. Long alleles within the normal range (22-29 repeats) are associated with severe obesity in people from the United Kingdom, Indonesia and the Caribbean. To analyse the influence of VNTR (CAG)n on metabolic profile in adults with obesity and pre-obesity, as well as to estimate its effect on the risk of developing diabetes. 255 adults of Chinantec Amerindian ethnic origin were included, who underwent anthropometric and biochemical evaluation. The VNTR was amplified by end-point PCR and by 8% PAGE electrophoresis. Differences were found in the waist/hip circumference index and body mass index in the carriers of genotypes different to the one homozygous for 22 repeats with a Student's t test value of 0.0041 and 0.0334, respectively. We also found an association with a family history of chronic disease. The VNTR of ATXN2 is associated with obesity in Mexican adults of Chinantec ancestry.


Factors predisposing to suspected offending by adults with self-reported learning disabilities.
This study investigated factors contributing to suspected offending behaviour by adults with a history of learning disabilities taken into custody at a city police station. Adults charged with offences, and/or leaving custody, during a defined period, were identified as having a possible learning disability using a four-item questionnaire (Lyall et al. 1995 a). A comparison group, of similar age, sex and IQ, was identified from a database of young people with learning difficulties. Information was obtained on interview about each individual's medical, psychiatric, social and family histories and psychological assessments were undertaken. In contrast to the comparison group, those in the 'offending' group were more likely to have a history of the following: losing contact with their father, forensic contact in one or more family members, past homelessness, illicit drug use, experiencing an excess of recent life events, self-reported behavioural problems at school, truancy, childhood police contact and contact with probation services. All had histories of repeated offending. There was also an increased rate of drug/alcohol dependence. Only two subjects in the study group had a full-scale IQ below 70. These differences would suggest that the presence of childhood behavioural problems, offending behaviour by other family members, family separation and other social disruption and the development of drug and alcohol related problems are potentially the most important factors in trying to understand why one group engaged in criminal behaviour. The offending group had many characteristics in common with general offending populations.


Stereocontrolled synthesis of heterocyclic C-nucleosides. Protecting group effect and molecular modeling studies.
We report herein a short stereocontrolled synthesis of heterocyclic C-nucleosides (indole, imidazole, benzimidazole, and 6-iodobenzimidazole). First, condensation of 2-lithiated heterocycles 2-5 with 5-(tert-butyldiphenylsilyl)-2,3-O-isopropylidene-D-gamma-ribonolactone (1) afforded the hemiacetals 6-9 in good yields. Then, borohydride reduction (NaBH(4)) of the protected hemiacetals proceeded stereoselectively to give predominantly the S diols 10-13, which upon Mitsunobu cyclization afforded the alpha-C-nucleosides 14-17. In contrast, the same PPh(3)/DEAD treatment of the 1:1 diastereomeric mixture of the free heterocyclic diols 10d and 11d gave exclusively the beta-anomers 14dbeta and 15dbeta, respectively, by a stereocontrolled process. The mechanisms of these stereocontrolled steps are discussed with the support of molecular modeling studies.


The Epstein-Barr virus BARF1 gene encodes a novel, soluble colony-stimulating factor-1 receptor.
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with infectious mononucleosis and several tumors. The BARF1 gene is transcribed early after EBV infection from the BamHI A fragment of the EBV genome. Evidence shown here indicates that the BARF1 protein is secreted into the medium of transfected cells and from EBV-carrying B cells induced to allow lytic replication of the virus. Expression cloning identified colony-stimulating factor-1 (CSF-1) as a ligand for BARF1. Computer-assisted analyses indicated that subtle amino acid sequence homology exists between BARF1 and c-fins, the cellular proto-oncogene that is the receptor for CSF-1. Recombinant BARF1 protein was found to be biologically active, and it neutralized the proliferative effects of human CSF-1 in a dose-dependent fashion when assayed in vitro. Since CSF-1 is a pleiotropic cytokine best known for its differentiating effects on macrophages, these data suggest that BARF1 may function to modulate the host immune response to EBV infection.


A case report on rare finding of microfilaria in pus sample of an ulcer over elephantiasis leg.
Skin ulcerations are a significant cause of morbidity and can be challenging to manage. Among the various causes of chronic non-healing ulcers, lymphedema is also considered a possible diagnosis in countries such as Nepal. Lymphatic filariasis has been a significant public health issue in endemic areas. Wuchereria bancrofti is a common nematode parasite that causes lymphatic filariasis. Excessive retention of lymphatic fluid in the interstitial compartment can cause localized tissue swelling, known as lymphedema, which is caused by impaired lymphatic drainage. Microfilariae can be detected in peripheral blood, body fluids, and needle aspirates. Microfilaria is not commonly found in ulcers on elephantiasis legs. We discuss here a case of 73-year-old women with elephantiasis legs with pus discharging ulcers in the thighs. Microscopic examination of pus discharge revealed microfilaria which highlights the importance of pus examination as diagnostic modality in endemic countries.


A new group of species within the bee genus Ruizantheda, with a revised key to the males of the genus (Hymenoptera: Halictidae: Caenohalictini).
Males of the neotropical bee genus Ruizantheda Moure sensu lato (Halictinae: Caenohalictini) differ from those of other caenohalictine genera in having the outer gonostylar plate with a large membranous region that extends to the ventral region, and the ventral gonostylar lobe retrorse. These features permit the placement of six additional species described here, four of which are new, in the genus in this broader sense. The males of these six species share the following characteristics: profemur swollen; mesofemur exceedingly swollen; mesotibia slightly swollen with flat, minutely ridged ventral area and small apical tooth; S4 shortened medially, commonly largely hidden under S3, with transverse median depression and apical margin emarginate; apicolateral lobes of S4 with tuft of branched setae and stout, simple, recurved setae on margin; S5 with U-shaped gradulus and setal patch, sometimes inconspicuous; outer lateral expansion of penis valve bilobed, and median posterior margin of volsella strongly angulate. Together, these species constitute a new group within Ruizantheda and share with the previously known Ruizantheda inca Coelho, Felizardo, Engel, R. aerugineus Coelho, Felizardo, Engel, and R. kallos Coelho, Felizardo, Engel, a short outer gonostylar plate, terminating before the apex of the main gonostylar lobe as well as the presence of long setae on its dorsal surface. In other species of Ruizantheda the outer gonostylar plate extends beyond the apex of the main gonostylar lobe and lacks setae. The species comprising this distinctive subgroup of Ruizantheda, and treated herein, are: R. nigra n. sp., R. colombiana n. sp., R. venezuelana n. sp., R. baeri (Vachal) n. comb., R. pilosa n. sp., and R. gaullei (Vachal) n. comb. Two of the new species expand the distribution of the genus northward into Colombia and Venezuela. In addition to the description and illustration of the species, an updated key to the species of Ruizantheda s. l. is provided.


Helical tomotherapy for brain metastases: dosimetric evaluation of treatment plans and early clinical results.
The purpose of this study was to evaluate the feasibility and treatment plans of intensity-modulated radiation therapy using helical tomotherapy (HT) for brain metastases. Twenty-three patients with 1 to 4 brain metastases were treated with HT. In combination with whole-brain radiotherapy (simultaneous plans), metastatic lesions, and the whole brain were treated with 50 Gy and 30 Gy, respectively, in 10 fractions, with a simultaneous integrated boost technique. In patients treated for brain metastases alone (focal plans), metastatic lesions were treated with 35 or 37.5 Gy in 5 fractions. The treatment plans were compared regarding the conformation number (CN) and homogeneity index (HI), and differences in these indexes between simultaneous and focal plans were examined by Student's t-test. Seven and 16 patients were treated with simultaneous plans and focal plans, respectively. The mean +/- SD of CN and HI values were 0.75 +/- 0.13 and 0.063 +/- 0.042, respectively, for simultaneous plans, and 0.73 +/- 0.12 and 0.052 +/- 0.023, respectively, for focal plans. The CN and HI between the two plans were not significantly different. Response rates in 13 patients with follow-up imaging were approximately 90% for both plans and the local control rate at 1 year was 69%. One patient with a huge tumor (34.0 cc) and WHO performance status 3 treated with focal plans experienced severe headache, requiring prolongation of the treatment time, and died at 8 days after completion of treatment. The exact cause of deterioration was uncertain as no radiological investigation was performed in this patient. No late complications were observed during follow-up periods up to 20 months. HT is a viable non-invasive technique for treatment of brain metastases and achieves high accuracy in terms of dose conformity and homogeneity.


Surgical treatment of flail chest and rib fractures.
Despite significant advances in critical care management, flail chest remains a clinically significant finding, with a mortality rate of up to 33%. Nonsurgical management is associated with prolonged ventilator support, pneumonia, respiratory difficulties, and lengthy stays in the intensive care unit, as well as chronic pain from nonunion and malunion of the bony thorax. Treatment with aggressive pulmonary toilet, ventilator support, and different modalities of pain control remains the benchmark of care. However, several recent randomized controlled studies of surgical intervention of flail chest have demonstrated an improvement in the number of ventilator days, intensive care unit and hospital stays, incidence of pneumonia, and respiratory function and hospital costs, as well as faster return to work. The success of these surgical constructs compared with those of historical attempts at open fixation is largely the result of modern plating technology and improvement in surgical approaches. Clinical evidence continues to grow regarding proper indications and techniques for surgical stabilization of flail chest.


Multivariate statistical characterization of water quality in Lake Lanier, Georgia, USA.
Watershed monitoring programs depend on water quality characterization data collected for many parameters, at many times and places, and with limited resources. Our objective is to present a strategy that reduces the measured parameters, locations, and frequency without compromising the quality of the monitoring program. One year of twice-monthly (growing season) and monthly (dormant season) water quality data collected from 17 lake and 10 tributary sites are used in conjunction with multivariate statistical techniques to improve the utility of collected data by identifying key parameters and monitoring locations. Factor analysis shows that tributary water quality data consists of three components-stormwater runoff, municipal and industrial discharges, and ground water-which can be distinguished using total suspended solids, total dissolved solids, and alkalinity plus soluble reactive P, respectively. Lake water quality characterization is more ambiguous than tributary water quality characterization, but factor analysis indicates that anoxia associated with lake stratification is the largest source of lake water quality variation, followed by nutrient abundance, and finally by biomass abundance. Cluster analysis suggests that tributary and lake monitoring stations can be consolidated. Reducing the number of parameters and stations frees up resources for increased monitoring elsewhere.


Electron-phonon coupling on the surface of the topological insulator Bi2Se3 determined from surface-phonon dispersion measurements.
In this Letter, we report measurements of the coupling between Dirac fermion quasiparticles (DFQs) and phonons on the (001) surface of the strong topological insulator Bi2Se3. While most contemporary investigations of this coupling have involved examining the temperature dependence of the DFQ self-energy via angle-resolved photoemission spectroscopy measurements, we employ inelastic helium-atom scattering to explore, for the first time, this coupling from the phonon perspective. Using a Hilbert transform, we are able to obtain the imaginary part of the phonon self-energy associated with a dispersive surface-phonon branch identified in our previous work [Phys. Rev. Lett. 107, 186102 (2011)] as having strong interactions with the DFQs. From this imaginary part of the self-energy we obtain a branch-specific electron-phonon coupling constant of 0.43, which is stronger than the values reported from the angle-resolved photoemission spectroscopy measurements.


Synapse formation changes the rules for desensitization of PKC translocation in Aplysia.
Protein kinase Cs (PKCs) are activated by translocating from the cytoplasm to the membrane. We have previously shown that serotonin-mediated translocation of PKC to the plasma membrane in Aplysia sensory neurons was subject to desensitization, a decrease in the ability of serotonin to induce translocation after previous application of serotonin. In Aplysia, changes in the strength of the sensory-motor neuron synapse are important for behavioral sensitization and PKC regulates a number of important aspects of this form of synaptic plasticity. We have previously suggested that the desensitization of PKC translocation in Aplysia sensory neurons may partially explain the differences between spaced and massed training, as spaced applications of serotonin, a cellular analog of spaced training, cause greater desensitization of PKC translocation than one massed application of serotonin, a cellular analog of massed training. Our previous studies were performed in isolated sensory neurons. In the present study, we monitored translocation of fluorescently-tagged PKC to the plasma membrane in living sensory neurons that were co-cultured with motor neurons to allow for synapse formation. We show that desensitization now becomes similar during spaced and massed applications of serotonin. We had previously modeled the signaling pathways that govern desensitization in isolated sensory neurons. We now modify this mathematical model to account for the changes observed in desensitization dynamics following synapse formation. Our study shows that synapse formation leads to significant changes in the molecular signaling networks that underlie desensitization of PKC translocation.


Using the Alcohol, Smoking and Substance Involvement Screening Test to predict substance-related hospitalisation after release from prison: A cohort study.
Poor substance use-related health outcomes after release from prison are common. Identifying people at greatest risk of substance use and related harms post-release would help to target support at those most in need. The Alcohol Smoking and Substance Involvement Screening Test (ASSIST) is a validated substance use screener, but its utility in predicting substance-related hospitalisation post-release is unestablished. We measured whether screening for moderate/high-risk substance use on the ASSIST was associated with increased risk of substance-related hospitalisation. A prospective cohort study. Prisons in Queensland and Western Australia. Participants were incarcerated and within 6 weeks of expected release when recruited. A total of 2585 participants were followed up for a median of 873 days. Baseline survey data were combined with linked unit record administrative hospital data. We used the ASSIST to assess participants for moderate/high-risk cannabis, methamphetamine and heroin use in the 3 months prior to incarceration. We used International Classification of Diseases (ICD) codes to identify substance-related hospitalisations during follow-up. We compared rates of substance-related hospitalisation between those classified as low/no-risk and moderate/high-risk on the ASSIST for each substance. We estimated adjusted hazard ratios (aHR) by ASSIST risk group for each substance using Weibull regression survival analysis allowing for multiple failures. During follow-up, 158 (6%) participants had cannabis-related, 178 (7%) had opioid-related and 266 (10%) had methamphetamine-related hospitalisation. The hazard rates of substance-related hospitalisation after prison were significantly higher among those who screened moderate/high-risk compared with those screening low risk on the ASSIST for cannabis (aHR 2.38, 95% confidence interval [CI] 1.74, 3.24), methamphetamine (aHR 2.23, 95%CI 1.75, 2.84) and heroin (aHR 5.79, 95%CI 4.41, 7.60). Incarcerated people with an Alcohol Smoking and Substance Involvement Screening Test (ASSIST) screening of moderate/high-risk substance use appear to have a significantly higher risk of post-release substance-related hospitalisation than those with low risk. Administering the ASSIST during incarceration may inform who has the greatest need for substance use treatment and harm reduction services in prison and after release from prison.


Topological quantum similarity indices based on fitted densities: theoretical background and QSPR application.
A novel methodology to derive adjacency matrices for 3-dimensional molecules is presented in this work. These matrices, which are derived from atomic quantum similarity calculations, allow redefining several adjacency matrix-based topological indices, such as Randić, Zagreb or Chi's. The present derivation is built upon a previous work, where a simpler class of density function was used to describe the atoms composing the molecule, and the present proposal suggests using fitted atomic densities from the Atomic Shell Approximation procedure, which has been proved to appropriately reproduce, in its application space, atomic ab initio densities. The construction of such matrices as well as the derived indices are presented, along with some QSPR, where these topological indices are used as molecular descriptors for heat of formation, inhibition, and toxicity with promising results.


Therapeutic potential in rheumatic diseases of extracellular vesicles derived from mesenchymal stromal cells.
The incidence of rheumatic diseases such as rheumatoid arthritis and osteoarthritis and injuries to articular cartilage that lead to osteochondral defects is predicted to rise as a result of population ageing and the increase in high-intensity physical activities among young and middle-aged people. Current treatments focus on the management of pain and joint functionality to improve the patient's quality of life, but curative strategies are greatly desired. In the past two decades, the therapeutic value of mesenchymal stromal cells (MSCs) has been evaluated because of their regenerative potential, which is mainly attributed to the secretion of paracrine factors. Many of these factors are enclosed in extracellular vesicles (EVs) that reproduce the main functions of parental cells. MSC-derived EVs have anti-inflammatory, anti-apoptotic as well as pro-regenerative activities. Research on EVs has gained considerable attention as they are a potential cell-free therapy with lower immunogenicity and easier management than whole cells. MSC-derived EVs can rescue the pathogenetic phenotypes of chondrocytes and exert a protective effect in animal models of rheumatic disease. To facilitate the therapeutic use of EVs, appropriate cell sources for the production of EVs with the desired biological effects in each disease should be identified. Production and isolation of EVs should be optimized, and pre-isolation and post-isolation modifications should be considered to maximize the disease-modifying potential of the EVs.


Rapid Maize Leaf and Immature Ear Responses to UV-B Radiation.
Because of their sessile lifestyle, plants have evolved adaptations to environmental factors, including UV-B present in solar radiation. To gain a better understanding of the initial events in UV-B acclimation, we have analyzed a 10 min to 1 h time course of transcriptome responses in irradiated and shielded leaves, and immature maize ears to unravel the systemic physiological and developmental responses in exposed and shielded organs. After 10 min of UV-B exposure, 262 transcripts are changed by at least two-fold in irradiated leaves, and this number doubles after 1 h. Indicative of the rapid modulation of transcription, 130 transcripts are only changed after 10 min. This is true not only in irradiated leaves, but also in shielded tissues. After 10 min of exposure, the overlap in transcriptome changes in irradiated and shielded organs is significant; however, after 30 min of UV-B, there are only two transcripts showing similar UV-B regulation between the three organs; 35 are similarly regulated in both IL and SL. Therefore, at longer irradiation times, there is more specificity of responses, and these are organ-specific. We suggest that early signaling in different tissues may be elicited by common signaling pathways, while at longer exposure times responses become more specific. To identify metabolites as possible signaling molecules, we looked for compounds that increased within 5-90 min in both irradiated and shielded leaves, to explain the kinetics of profound transcript changes within 1 h. We found that myoinositol is one such candidate metabolite; and we also demonstrate that if 0.1 mM myoinositol is applied to leaves of greenhouse maize, some metabolites that are changed by UV-B are also changed similarly by the chemical treatment. Therefore, this metabolite can partially mimic UV irradiation.


A rapid and efficient way to dynamic creation of cross-reactive sensor arrays based on ionic liquids.
Based on the simple counterion exchange of ionic liquids, a rapid, facile, and efficient strategy to create a cross-reactive sensor array with a dynamic tunable feature was developed, and exemplified by the construction of a sensor array for the identification and classification of nitroaromatics and explosives mimics. To achieve a good sensing system with fast response, good sensitivity, and low detection limit, the synthesized ionic liquid receptors were tethered onto a silica matrix with a macro-mesoporous hierarchical structure. Through the facile anion exchange approach, abundant ionic-liquid-based individual receptors with diversiform properties, such as different micro-environments, diverse molecular interactions, and distinctive physico-chemical properties, were easily and quickly synthesized to generate a distinct fingerprint of explosives for pattern recognition. The reversible anion exchange ability further endowed the sensor array with a dynamic tunable feature as well as good controllability and practicality for real-world application. With the assistance of statistical analysis, such as principal component analysis (PCA) and linear discrimination analysis (LDA), an optimized-size array with a good resolution was rationally established from a large number of IL-based receptors. The performed experiments suggested that the ionic-liquid-based sensing protocol is a general and powerful strategy for creating a cross-reactive sensor array that could find a wide range of applications for sensing various analytes or complex mixtures.


Application of single-cell RNA sequencing in probing oligodendroglia heterogeneity and neurological disorders.
In the central nervous system, oligodendrocytes are highly specialized myelinating glial cells that originate from oligodendrocyte precursor cells. In the past, research centered on the oligodendrocyte development, myelination, and the role of oligodendrocyte lineage in neurological disorders. The emerging single-cell RNA sequencing technology is a new tool to specifically identify cell-types at the transcriptome level, and recently have also been used to investigate oligodendrocyte lineage-related issues. In this review, we summarize the recent developments of single-cell RNA sequencing technologies and their application in the oligodendroglia heterogeneity and neurological disorders, thereby providing new ideas and references for the utilization of single-cell RNA sequencing technology in the research field of oligodendrocyte lineage and neurological disorders.


Towards the Experimentally-Informed In Silico Nozzle Design Optimization for Extrusion-Based Bioprinting of Shear-Thinning Hydrogels.
Research in bioprinting is booming due to its potential in addressing several manufacturing challenges in regenerative medicine. However, there are still many hurdles to overcome to guarantee cell survival and good printability. For the 3D extrusion-based bioprinting, cell viability is amongst one of the lowest of all the bioprinting techniques and is strongly influenced by various factors including the shear stress in the print nozzle. The goal of this study is to quantify, by means of in silico modeling, the mechanical environment experienced by the bioink during the printing process. Two ubiquitous nozzle shapes, conical and blunted, were considered, as well as three common hydrogels with material properties spanning from almost Newtonian to highly shear-thinning materials following the power-law behavior: Alginate-Gelatin, Alginate and PF127. Comprehensive in silico testing of all combinations of nozzle geometry variations and hydrogels was achieved by combining a design of experiments approach (DoE) with a computational fluid dynamics (CFD) of the printing process, analyzed through a machine learning approach named Gaussian Process. Available experimental results were used to validate the CFD model and justify the use of shear stress as a surrogate for cell survival in this study. The lower and middle nozzle radius, lower nozzle length and the material properties, alone and combined, were identified as the major influencing factors affecting shear stress, and therefore cell viability, during printing. These results were successfully compared with those of reported experiments testing viability for different nozzle geometry parameters under constant flow rate or constant pressure. The in silico 3D bioprinting platform developed in this study offers the potential to assist and accelerate further development of 3D bioprinting.


[Relationship between HLA-DR4/1 subtypes and T cell response to influenza virus hemagglutinin or anti-HA308-317 antibodies in rheumatoid arthritis].
To investigate the relationship between HLA-DR4/1 subtypes and T cell response to influenza virus hemagglutinin (HA) as well as anti-HA308-317 antibodies in rheumatoid arthritis (RA). The peripheral blood mononuclear cells (PBMCs) from 70 RA patients were cultured with HA308-317 for 5 days. T cell proliferative responses to HA308-317 were evaluated by [3H] thymidine incorporation assay. ELISA was used to detect the antibodies to HA308-317. HLA-DR4/1 subtypes were analyzed by PCR with sequence-specific primers. Twenty-seven of the 70 RA patients (38.6%) were positive for HLA-DR4/1 subtypes and 43 patients (61.4%) were negative for HLA-DR4/1 subtypes. In the HLA-DR4/1 positive group, T cell proliferative response to HA308-317 was observed in 17 (62.9%) RA patients and anti-HA308-317 antibodies were present in 15 RA patients (55.6%). In the HLA-DR4/1 negative group, T cell proliferative response to HA308-317 was observed in 10 (23.3%) patients and anti-HA308-317 antibodies were present in 25 (58.1% ) patients. T cell proliferative response to HA308-317 in the HLA-DR4/1 positive group was higher than in the negative group (P<0.01). However, there was no significant difference in production of antibodies to HA308-317 between the HLA-DR4/1 positive and negative groups (P>0.05). There is a relationship between HLA-DR4/1 subtypes and T cell response to HA308-317. Antibodies to HA308-317 are not associated with HLA-DR4/1 phenotype. HA308-317 peptide may be involved in the pathogenesis of RA through activating HLA-DR4/1 specific T cells.


Rhinorrhea triggered by obturator prosthesis after surgical intervention of partial maxillary resection: a clinical report.
This clinical report describes a case of rhinorrhea that arose after surgical intervention of partial maxillary resection and obturator prosthesis positioning. Ultimately, the diagnosis was that rhinorrhea was induced by mechanical irritation of the nasal mucosa determined by the nasal part of the obturator prosthesis. The differential diagnosis of nasal irritation, vasomotor rhinitis, gustatory rhinorrhea are presented and discussed, as well as the technical notes and measures taken to reach the final diagnosis and a satisfactory functional and aesthetic result for the patient.


[Windmill principle versus clockwork principle--tradition and interaction in academic lectures. A. N. S. A. Radiologica].
In reply to depersonalization of teaching, students hiding behind anonymity and their decreasing effective presence in campus life, academic teaching has to become practice-oriented, attractive and at least more effective. The traditional teacher-based lecture competes with student-centered and issue-related academic events like problem-based learning, thus, concerning student-teacher interaction. The model of a clockwork represents the components of a traditional lecture. The model of a windmill is suitable for explaining synergistic effects in scope and experience during an interaction concerned lecture. An example of student-teacher interaction and students' activation even in a preclinical course of lectures on anatomy and radiology is given. A high response and acceptance of the lecture is assured by structure-and process-oriented features.


Heart transplantation experiences: a phenomenological approach.
The aim of this study was to understand the heart transplantation experience based on patients' descriptions. To patients with heart failure, heart transplantation represents a possibility to survive and improve their quality of life. Studies have shown that more quality of life is related to patients' increasing awareness and participation in the work of the healthcare team in the post-transplantation period. Deficient relationships between patients and healthcare providers result in lower compliance with the postoperative regimen. A phenomenological approach was used to interview 26 patients who were heart transplant recipients. Patients were interviewed individually and asked this single question: What does the experience of being heart transplanted mean? Participants' descriptions were analysed using phenomenological reduction, analysis and interpretation. Three categories emerged from data analysis: (i) the time lived by the heart recipient; (ii) donors, family and caregivers and (iii) reflections on the experience lived. Living after heart transplant means living in a complex situation: recipients are confronted with lifelong immunosuppressive therapy associated with many side-effects. Some felt healthy whereas others reported persistence of complications as well as the onset of other pathologies. However, all participants celebrated an improvement in quality of life. Health caregivers, their social and family support had been essential for their struggle. Participants realised that life after heart transplantation was a continuing process demanding support and structured follow-up for the rest of their lives. The findings suggest that each individual has unique experiences of the heart transplantation process. To go on living participants had to accept changes and adapt: to the organ change, to complications resulting from rejection of the organ, to lots of pills and food restrictions. Stimulating a heart transplant patients spontaneous expression about what they are experiencing and granting them the actual status of the main character in their own story is important to their care.


Secretory Phospholipases A2 in Durum Wheat (Triticum durum Desf.): Gene Expression, Enzymatic Activity, and Relation to Drought Stress Adaptation.
Phospholipases A2 (PLA2s) are known to mediate signaling cascades during plant growth and development, as well as biotic and abiotic stress responses. In this context, the present study provides extensive characterization of specific PLA2s in durum wheat, and assesses their involvement in durum wheat response to drought stress. In durum wheat leaves, four full-length expressed sequences encoding putative PLA2s were isolated and characterized as belonging to the class of secretory PLA2s (sPLA2s): TdsPLA2I, TdsPLA2II, TdsPLA2III and TdsPLA2IV. PLA2 activity was also detected, the characteristics of which resemble those of previously characterized plant sPLA2s: strong preference for phospholipids; requirement for millimolar Ca2+ concentrations; optimal activity at basic pH; heat stability; and inhibition by the reducing agent dithiothreitol. With drought stress imposed at both the vegetative and reproductive stages, accumulation of TdsPLA2I and TdsPLA2III transcripts, and to a lesser extent of TdsPLA2IV transcript, paralleled increased PLA2 activity; both transcript levels and enzymatic activity decreased as a consequence of stress recovery. Consistently, free fatty acid analysis of drought-stressed leaves revealed increased linoleate, linolenate and palmitate contents, which were reversed by plant re-watering. Overall, these findings strongly suggest that there are inducible sPLA2 isoforms in durum wheat that have roles in orchestrating the plant response to drought stress.


[The role of the neurophysiological methods in the assessment of the effectiveness of the rehabilitation of sensorimotor disturbances associated with the lesions of the central nervous system at the spinal cord level].
The objective of the present study was the evaluation and comparison of the effectiveness of the differential approaches to the neurorehabilitation of the somatosensory disturbances in the patients presenting with the spinal cord lesions. A total of 68 patients with spinal cord lesions were enrolled in the study, including 38 suffering from vascular myelopathy, 18 with the consequences of extramedullar meningioma surgery, 12 with the sequelae of acute transverse myelitis. The control groups was comprised of were 55 subjects. All the participants of the study underwent rehabilitation which included robotized mechanotherapy, stabilography, neuro-muscular stimulation, kinesiotherapy, physical therapy, ergotherapy, massage, etc. Transcranial magnetic stimulation (TMS) and evaluation of somatosensory evoked potentials (SSEP) were carried out before and after the therapy. In those patients who received personalized therapy, significant changes of TMS parameters (central motor conduction time at rest and in facilitation probe), but not SSEP ones were registered. Moreover, the patients who had undergone personalized therapy exhibited better clinical results than in the absence of such treatment. The results of the study gave evidence that neurorehabilitation had produced the more pronounced beneficial influence as regards the correction of motor disturbances even though the disturbances of the somatosensory functions proved to be more resistant to therapy. The data obtained suggest that taking into consideration the afferent deficit has to be mandatory for the purpose of planning the neurorehabilitative treatment of the patients suffering from sensorimotor disturbances associated with the lesions of the central nervous system at the spinal cord level. TMS and SSEP have to be utilized as the tools for the objective evaluation of the effectiveness of the neurorehabilitation process in such patients.


FBXW7 is involved in the acquisition of the malignant phenotype in epithelial ovarian tumors.
FBXW7 is a ubiquitin ligase that mediates ubiquitylation of oncoproteins, such as c-Myc, cyclin E, Notch and c-Jun. FBXW7 is a known tumor-suppressor gene, and mutations in FBXW7 have been reported in various human malignancies. In this study, we examined the sequences of the FBXW7 and p53 genes in 57 ovarian cancer clinical samples. Interestingly, we found no FBXW7 mutations associated with amino acid changes. We also investigated FBXW7 expression levels in 126 epithelial ovarian tumors. FBXW7 expression was negatively correlated with the malignant potential of ovarian tumors. That is to say, FBXW7 expression levels in ovarian cancer samples were significantly lower than those in borderline and benign tumors (P < 0.01). FBXW7 expression levels in serous carcinoma samples were the lowest among four major histological subtypes. In addition, p53-mutated ovarian cancer samples showed significantly lower levels of FBXW7 expression compared with p53 wild-type cancer samples (P < 0.001). DNA methylation arrays and bisulfite PCR sequencing experiments revealed that 5'-upstream regions of FBXW7 gene in p53-mutated samples were significantly higher methylated compared with those in p53 wild-type samples (P < 0.01). This data indicates that p53 mutations might suppress FBXW7 expression through DNA hypermethylation of FBXW7 5'-upstream regions. Thus, FBXW7 expression was downregulated in ovarian cancers, and was associated with p53 mutations and the DNA methylation status of the 5'-upstream regions of FBXW7.


ApoB and apoM - New aspects of lipoprotein biology in uremia-induced atherosclerosis.
Chronic kidney disease affects as much as 13% of the population, and is associated with a markedly increased risk of developing cardiovascular disease. One of the underlying reasons is accelerated development of atherosclerosis. This can be ascribed both to increased occurrence of traditional cardiovascular risk factors, and to risk factors that may be unique to patients with chronic kidney disease. The latter is reflected in the observation that the current treatment modalities, mainly directed against traditional risk factors, are insufficient to prevent cardiovascular disease in the patient with chronic kidney disease. This review discusses mechanisms accelerating uremic atherosclerosis with a specific focus on the putative roles of apolipoprotein(apo)s B and M that may be particularly important in patients with chronic kidney disease.


Reproductive health service use and associated factors among youths in Becho district, southwest Ethiopia.
Young people are less informed, less experienced, and less at ease when it comes to accessing reproductive health services than adults. Though youth-friendly services are designed to accommodate the unique needs of youth, in developing countries like Ethiopia, studies on the level of utilization of reproductive health services are limited. This study determined the level of reproductive health (RH) service use and associated factors among youths. A community-based cross-sectional study was conducted in Becho district, Illubabor zone, southwest Ethiopia. A multistage random sampling technique was used to select 702 youths, regardless of their marital status. A pre-tested interviewer-administered questionnaire was used to collect data. The questionnaire includes questions on socio-demographic characteristics, sexual and reproductive health characteristics, knowledge, and components of RH assessment. The data was entered into Epidata version 3.1 and analyzed using SPSS version 22. Multivariable binary logistic regression analysis was used to identify factors associated with the utilization of reproductive health services at a p < 0.05. A total of 647 youths participated in the study, constituting a response rate of 92.1%. Male youths made up 51.5% of the respondents, with an average (±SD) age of 19.38 (±2.69) years. Reproductive health (RH) services were utilized by 43.9% of youths. Knowledge of RH services (AOR = 4.11; 95% CI: 2.77, 6.09), discussion with family (AOR = 2.18; 95% CI: 1.38, 3.45), history of sexual exposure (AOR = 2.94; 95% CI: 1.95, 4.43), shorter distance from a health facility (AOR = 2.42; 95% CI: 1.63, 3.57), and history of reproductive health problems (AOR = 2.4; 95% CI: 1.34, 4.31) were associated with RH service utilization. The use of reproductive health services among youths is found to be low. Knowledge about reproductive health services, discussion with parents, sexual exposure, distance, and previous experience with reproductive health problems shaped the utilization of RH services by youth. Improving knowledge through information dissemination, creating awareness to increase parent-child intimacy, and expanding health services should be emphasized.


Are optic disc haemorrhages a common finding in all glaucoma patients?
Disc haemorrhages are an important risk factor in development and progression of glaucomatous damage, but it is not known whether such bleedings can be found in all glaucoma patients. In this retrospective study of 1506 patients with manifest or suspected glaucoma, sequential optic disc stereophotographs revealed a disc haemorrhage in 94 cases. Distribution of the haemorrhagic and non-haemorrhagic patients according to the frequency of photography indicates that the 2 groups of patients represent different glaucoma populations. Furthermore, patients who do not show a haemorrhage in 1 or 2 random examinations probably will not show a bleeding in the later follow-up, either.


Dengue virus infections among travelers returning from Haiti--Georgia and Nebraska, October 2010.
In October 2010, a Nebraska clinician notified the state's Central District Health Department (CDHD) of a cluster of dengue-like illnesses in six of 28 missionary workers from Nebraska and Georgia who recently had returned after 7-11 days in Haiti. Infection with the mosquito-transmitted dengue virus (DENV) later was confirmed by laboratory testing in seven persons, five of whom were hospitalized. CDHD, the Nebraska Department of Health and Human Services (NDHHS), the Georgia Department of Public Health (GDPH), and CDC conducted a retrospective cohort study to assess the pretravel dengue knowledge and mosquito-avoidance practices of those with and without laboratory-confirmed infection. This report describes the results of that study, which indicated that 90% of those in the study had a pretravel health-care appointment, 57% sought travel advice on the Internet, and 24% used mosquito repellent several times a day; neither pretravel knowledge nor mosquito-avoidance practices were significantly associated with absence of DENV infection. Clinicians should be vigilant for dengue among travelers returning from Haiti and other areas where DENV is endemic or likely to be endemic and should report suspected cases of dengue to public health authorities.


Effect of cyclic loading on microleakage of silorane based composite compared with low shrinkage methacrylate-based composites.
There are many concerns regarding the marginal seal of composite restorations, especially when composite restorations are subjected to cyclic loading. The aim of this study was to evaluate the effect of cyclic loading on the microleakage of silorane based composite compared with low shrinkage methacrylate-based composites in class V cavities. In this in vitro study, class V cavities were prepared on the facial and lingual surfaces of 48 human premolars (96 cavities). The teeth were randomly divided into four groups of 12 teeth (24 cavities) each and restored as follows: Group 1 (Siloran System Adhesive + Filtek P90), Group 2 (All Bond SE + Aelite LS Posterior), Group 3 (Futurabond NR + Grandio), and Group 4 (G-Bond + Kalore-GC). All the specimens were thermocycled for 2000 cycles (5-55°C) and then half of the specimens from each group, were Load cycled. All teeth were immersed in 0.5% basic fuchsine dye, sectioned, and observed under a stereomicroscope. Data were analyzed using Wilcoxon test, Kruskal-Wallis, and Mann-Whitney U-tests. P < 0.05 was considered as significant. In both unloaded and loaded groups, no statistically significant differences were observed among four composites at the occlusal margin, but a significant difference in gingival microleakage was found between Aelite and silorane. Occlusal and gingival microleakage was not affected by cyclic loading in none of the four restorative materials. Silorane did not provide better marginal seal than the low shrinkage methacrylate-based composites (except Aelite). In addition, cyclic loading did not affect the marginal microleakage of evaluated composite restorations.


Autologous Induced Pluripotent Stem Cell-Based Cell Therapies: Promise, Progress, and Challenges.
The promise of human induced pluripotent stem cells (iPSCs) lies in their ability to serve as a starting material for autologous, or patient-specific, stem cell-based therapies. Since the first publications describing the generation of iPSCs from human tissue in 2007, a Phase I/IIa clinical trial testing an autologous iPSC-derived cell therapy has been initiated in the U.S., and several other autologous iPSC-based therapies have advanced through various stages of development. Three single-patient in-human transplants of autologous iPSC-derived cells have taken place worldwide. None of the patients suffered serious adverse events, despite not undergoing immunosuppression. These promising outcomes support the proposed advantage of an autologous approach: a cell therapy product that can engraft without the risk of immune rejection, eliminating the need for immunosuppression and the associated side effects. Despite this advantage, there are currently more allogeneic than autologous iPSC-based cell therapy products in development due to the cost and complexity of scaling out manufacturing for each patient. In this review, we highlight recent progress toward clinical translation of autologous iPSC-based cell therapies. We also highlight technological advancements that would reduce the cost and complexity of autologous iPSC-based cell therapy production, enabling autologous iPSC-based therapies to become a more commonplace treatment modality for patients. © 2021 The Authors.


Purification and biochemical characterization of a human autocrine growth factor produced by Epstein-Barr virus-transformed B cells.
Autocrine growth factor for Epstein-Barr virus-transformed human B cells (aBGF), a protein that is constitutively produced by the human EBV-transformed B cell line 5/2, has been purified from serum-free conditioned medium. The purification involved sequential ammonium sulfate precipitation, ion exchange chromatography, gel filtration, and reversed-phase high performance liquid chromatography. The purified protein has a m.w. of 16,000 in NaDodSO4/polyacrylamide gel electrophoresis and an isoelectric point between 7.0 and 8.0. The relative molecular mass 16,000 form exists in equilibrium with dimeric and tetrameric forms. aBGF supports the growth of EBV-transformed B cells, which have been deprived of their own conditioned medium. The purified aBGF is fully effective at 0.5 ng/ml and has no interleukin 1 activity in the lymphocyte activation factor assay. Because several randomly selected lines of EBV-transformed cells and one EBV-negative lymphoma cell line both produce aBGF activity and show growth dependency on aBGF and because stimulation of normal B cells with anti-immunoglobulin M is increased by aBGF, we propose that aBGF has general significance for growth control of human B cells.


Enhanced hepatic adenylate cyclase activity in rats with portacaval shunt.
Male Wistar rats were submitted to a portacaval anastomosis (PCA). Control rats were sham operated and pair fed. After 20 days, PCA led to a decrease in liver weight (-40%) and fasting blood glucose (-35%) and to an increase in fasting glucagonemia (+65%). The in vitro response of adenylate cyclase in hepatic membranes to GTP, Gpp(NH)p, fluoride, and forskolin (in the absence of GTP), and to glucagon (in the presence of GTP) was greater in PCA rats than in controls (by 30-54%) whereas the response to L-isoproterenol (in the presence of GTP) was only slightly increased (by 8%) and that to vasoactive intestinal peptide (in the presence of GTP) was similar in both groups of rats. The binding of [125I]glucagon and [125I]VIP to liver membranes did not differ in both groups of animals. It is concluded that the hepatic adenylate cyclase system from PCA rats responded better to stimuli involving efficiently the guanyl nucleotide stimulatory site Ns. This implies that the fasting hypoglycemia observed in these animals, in spite of the hyperglucagonemia, was due to either the refractoriness of a step distal to adenylate cyclase activation or to limited glucose production by an atrophic liver.


A Fatal Case of Candida auris and Candida tropicalis Candidemia in Neutropenic Patient.
We report a fatal case of Candida auris that was involved in mixed candidemia with Candida tropicalis, isolated from the blood of a neutropenic patient. Identification of both isolates was confirmed by amplification and sequencing of internal transcribed spacer and D1/D2 domain of large subunit in rRNA gene. Antifungal susceptibility test by E-test method revealed that C. auris was resistant to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole and voriconazole. On the other hand, C. tropicalis was sensitive to all antifungal tested. The use of chromogenic agar as isolation media is vital in detecting mixed candidemia.


[Complications After Transcatheter Aortic Valve Implantation].
to assess rate of complications after transcatheter aortic valve implantation (TAVI). Our study included 99 patients who underwent TAVI. Frequent complications were: bleeding not requiring surgical hemostasis (17.2%), hemopericardium (6%), novel cardiac rhythm disturbances requiring permanent pacemaker implantation (15.1%), delirium in early postoperative period (10.7%), acute kidney injury (8.0%), stroke (7%), ventricular fibrillation (5.1%), myocardial infarction (2%). There were no significant differences in rate and type of complications between transapical and transfemoral TAVI. Comparison of general and local anesthesia showed that rate of ventricular fibrillation was significantly higher among patients subjected to transfemoral TAVI under local anesthesia (p less or equal 0.012).


Combining Bulk RNA-seq and scRNA-seq data to identify RNA m5C methyltransferases NSUN1: a rising star as a biomarker for cancer diagnosis, prognosis and therapy.
RNA 5-methylcytosine (m5C) methyltransferases NSUN1 is a member of the NOP2/SUN (NSUN) RNA methyltransferase family. Studies have found that the expression of NSUN1 is elevated in breast and colon cancer and can predict poor prognosis. However, the NSUN1 gene has only been studied in a few tumors. Single-cell RNA sequencing (scRNA-seq) and Bulk RNA-seq data were used for comprehensive analysis of NSUN1 in cancers. The Human Protein Atlas (HPA) database was used to identify the gene location. Immunofluorescence staining was used to detect NSUN1 subcellular distribution within the nucleus, endoplasmic reticulum (ER), and microtubules of A-431, U-2, U-251 cells. The cBioPortal tool was used to analyze the alteration frequency and mutation type. The epigenetic profile of NSUN1 also was analyzed by using the University of Alabama at Birmingham CANcer data analysis Portal (UCLCAN). Tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint expression in cancers were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to perform enrichment and visualization. The study was based on online resources and public databases. Elevated NSUN1 expression had been observed in most human cancers. Analysis of scRNA-seq data showed that NSUN1 was highly expressed in immune cells such as T cells, B cells, and dendritic (DC) cells. High NSUN1 expression indicated poor overall survival (OS) and disease-free survival (DFS). The characteristics of genetic alteration, methylation and phosphorylation of NSUN1 were analyzed and higher levels of phosphorylation in tumor tissues were found. In addition, the expression of NSUN1 was closely related to tumor-infiltrating immune cells. At the same time, the expression of NSUN1 was positively correlated with the expression of multiple immune checkpoints. The gene expression profile, survival status, genetic alteration, methylation, phosphorylation and infiltrating immune cells of NSUN1 in human cancers were comprehensively analyzed. The results herein implied that NSUN1 may be an effective biomarker for early cancer diagnosis, prognosis and therapy.


Regulatory T cell activity specific to human type II and III collagens in rheumatoid arthritis.
Fifty-one patients with rheumatoid arthritis (RA) were examined for their immune response potential to human collagen type II and III. It was found that T cells of 57% of patients with RA proliferated to collagen type III whereas only 27% of T cells of patients with osteoarthritis (OA) and healthy controls responded to this antigen by proliferation (p less than 0.04). A lower percentage (38%) of patients with RA had proliferative responses to collagen type II in comparison to 17% of responders in healthy controls. The capability to produce T cell helper factors specific to collagen type III was found to be significantly higher in patients treated with nonsteroidal antiinflammatory drugs (NSAID) (60%) in comparison to patients with OA (16%) and healthy controls (13%). Immunoregulatory drugs affected the specific T helper function in response to collagen type III but did not change the proliferative responses to collagen type II and III in patients with RA. HLA analyses revealed a significant difference in the frequency of HLA-DRw10 between our sample of patients with RA and healthy controls.