Text classification to streamline online wildlife trade analyses.
Automated monitoring of websites that trade wildlife is increasingly necessary to inform conservation and biosecurity efforts. However, e-commerce and wildlife trading websites can contain a vast number of advertisements, an unknown proportion of which may be irrelevant to researchers and practitioners. Given that many wildlife-trade advertisements have an unstructured text format, automated identification of relevant listings has not traditionally been possible, nor attempted. Other scientific disciplines have solved similar problems using machine learning and natural language processing models, such as text classifiers. Here, we test the ability of a suite of text classifiers to extract relevant advertisements from wildlife trade occurring on the Internet. We collected data from an Australian classifieds website where people can post advertisements of their pet birds (n = 16.5k advertisements). We found that text classifiers can predict, with a high degree of accuracy, which listings are relevant (ROC AUC ≥ 0.98, F1 score ≥ 0.77). Furthermore, in an attempt to answer the question 'how much data is required to have an adequately performing model?', we conducted a sensitivity analysis by simulating decreases in sample sizes to measure the subsequent change in model performance. From our sensitivity analysis, we found that text classifiers required a minimum sample size of 33% (c. 5.5k listings) to accurately identify relevant listings (for our dataset), providing a reference point for future applications of this sort. Our results suggest that text classification is a viable tool that can be applied to the online trade of wildlife to reduce time dedicated to data cleaning. However, the success of text classifiers will vary depending on the advertisements and websites, and will therefore be context dependent. Further work to integrate other machine learning tools, such as image classification, may provide better predictive abilities in the context of streamlining data processing for wildlife trade related online data.


Legionnaire's disease avoidance planning.
Hospital-acquired infection is the cause of about 5,000 deaths a year in the UK. In New Zealand, there are more than three times as many such deaths as from the annual road toll. The costs in loss of income, in pain and suffering and in direct costs to hospitals are staggering.


[Some problems of human gas balance].
The authors have presented gas balance in extracorporeal pulmonary. The diffusion speed by pulmonary membrane alveoli is dependent from: particles metility, surface diffusion of pulmonary alveoli, alveolocapillary thickness, hemoglobin chemical affinity is dependent from blood temperature and pH.


Determination of glucose concentrations in an aqueous matrix from NIR spectra using optimal time-domain filtering and partial least-squares regression.
We have investigated the use of a time-domain optimal filtering method to simultaneously minimize both the baseline variation and high-frequency noise in near-infrared (NIR) spectrophotometric absorption data of glucose dissolved in a simple aqueous (deionized water) matrix. By coupling a third-order (six-pole) digital Butterworth bandpass filter with partial least-squares (PLS) regression modeling, glucose concentrations were determined for a set of test data with a standard error of prediction (SEP) of 10.53 mg/dl (mean percent error: 4.24%) using seven PLS factors. Compared to the unfiltered test data for six PLS factors and a SEP = 17.00 (mean percent error: 7.38%) this results shows more than a 38% decrease in the error. The glucose concentrations ranged from 51 mg/dl to 493 mg/dl, and the NIR spectral region between 2088 nm and 2354 nm (4789 cm-1 and 4248 cm-1) was used to develop the optimal PLS model. The optimal PLS model was determined from a sequence of three-dimensional performance response maps for different numbers of PLS factors (2-10). A total of 99 NIR spectra were generated for glucose dissolved in deionized water using a NIRsystems 5000 dispersive spectrophotometer. Nine of these spectra were generated for only water, which were averaged and subtracted from the remaining 90 spectra to generate the training and test data sets, thereby, removing the intrinsic high background absorption due to the water. The training set consisted of 57 spectra and associated glucose concentration target values, and the test set was comprised of the remaining 33 spectra and target values. Performance results were compared for three different digital Butterworth bandpass filters (four-poles, six-poles, and eight-poles), and a digital Gaussian filter design approach (i.e., Fourier filtering).


Essiac tea: scavenging of reactive oxygen species and effects on DNA damage.
Essiac, a tea reportedly developed by the Ojibwa tribe of Canada and widely publicized as a homeopathic cancer treatment, is prepared from a mixture of four herbs Arctium lappa, Rumex acetosella, Ulmus rubra and Rheum officinale. Each of these herbs has been reported to possess antioxidant and anti-cancer activity. Essiac itself has also been reported to demonstrate anti-cancer activity in vitro, although its effects in vivo are still a matter of debate. We prepared an extract of Essiac tea from a concentration of 25mg/mL and boiled it for 10 min. From this preparation we used concentrations of 5, 10, 25 and 50% to measure Essiac effects. In this study, we examined the effects of Essiac on free radical scavenging and DNA damage in a non-cellular system, as well as the effects Essiac on lipid peroxidation using the RAW 264.7 cell line. We observed, using electron spin resonance, that Essiac effectively scavenged hydroxyl, up to 84% reduction in radical signal at the 50% tea preparation concentration, and superoxide radicals, up to 82% reduction in radical signal also at the 50% tea preparation concentration, as well as prevented hydroxyl radical-induced DNA damage. In addition, Essiac inhibited hydroxyl radical-induced lipid peroxidation by up to 50% at the 50% tea preparation concentration. These data indicate that Essiac tea possesses potent antioxidant and DNA-protective activity, properties that are common to natural anti-cancer agents. This study may help to explain the mechanisms behind the reported anti-cancer effects of Essiac.


Variation of urinary acid glycosaminoglycan and collagen metabolite excretion with disease activity in generalized scleroderma.
Follow-up of patients with generalized scleroderma improving during treatment with collagen biosynthesis inhibitors showed a decrease towards normalization of the elevated urinary values for acid glycosaminoglycans and collagen catabolites. The determinations supply objective evidence of the disease activity as well as of the efficacy of treatment. In the control group, relatively high urinary values for the two macromolecules were found in the second decade of life in comparison with older age groups.


"Ride-on" technique and other simple and logical solutions to counter most common complications of silicone implants in augmentation rhinoplasty.
Augmentation rhinoplasty can be carried out using a wide range of materials including autologous bone and/or cartilage as well as alloplasts. Use of biologic bone and cartilage grafts results in lower infection rates, but they are associated with long-term resorption and donor-site morbidity. Alloplastic materials, in particular silicone, have been associated in literature with extrusion, necrosis of the tip, mobility and deviation or displacement of the implant, immobile nasal tip and infection. However, they have the advantages of being readily available and easy to reshape with no requirement for harvesting autografts. To overcome these problems associated with silicone implants for which the authors have devised a novel technique, the "rideon technique". The present study was carried out on 11 patients over a period of 4 years. The authors have devised a simple technique to fix the silicone implant and retain it in place. Restricting the implant to only dorsum avoided common complications related to the silicone implant. The authors have used this technique in 11 patients with encouraging results. Follow-up ranged from 12 months to 36 months during which patients were assessed for implant mobility, implant extrusion and tip necrosis. There was no incidence of above mentioned complications in these patients. The "rideon technique" provides excellent stability to silicone implants and restricting the implant only to dorsum not only eliminates chances of tip necrosis and thus implant extrusion but also maintains natural shape, feel and mobility of the tip.


The p53 family member genes are involved in the Notch signal pathway.
The p53 tumor suppressor is a transcription factor that regulates cell growth and death in response to environmental stimuli such as DNA damage. p63/p51 and p73 were recently identified as members of the p53 gene family. In contrast to p53 however, p63 and p73 are rarely mutated in human cancers. Mice that lack p53 are developmentally normal, while p63 and p73 appear to play critical roles in normal development. To determine how p63 and p73 are involved in normal development, we attempted to identify target genes that are specifically regulated by p63 and/or p73 but not by p53. We found that the Jagged1 (JAG1) and Jagged2 (JAG2) genes, encoding ligands for the Notch receptors, are up-regulated by p63 and p73. Furthermore, we identified a p63-binding site in the second intron of the JAG1 gene, which can directly interact with the p63 protein in vivo, as assessed by a chromatin immunoprecipitation assay. A heterologous reporter assay revealed that this p63-binding site is a functional response element and is specific for p63. We also found a target of Notch signaling, HES-1 was up-regulated in Jurkat cells, in which Notch1 is highly expressed, when co-cultured with p63-transfected cells, suggesting that p63 can trigger the Notch signal pathway in neighboring cells. Our findings show an association between the p53 family genes and Notch signaling and suggest a potential molecular mechanism for the involvement of the p53 family genes in normal development.


Design of an Adaptive Human-Machine System Based on Dynamical Pattern Recognition of Cognitive Task-Load.
This paper developed a cognitive task-load (CTL) classification algorithm and allocation strategy to sustain the optimal operator CTL levels over time in safety-critical human-machine integrated systems. An adaptive human-machine system is designed based on a non-linear dynamic CTL classifier, which maps a set of electroencephalogram (EEG) and electrocardiogram (ECG) related features to a few CTL classes. The least-squares support vector machine (LSSVM) is used as dynamic pattern classifier. A series of electrophysiological and performance data acquisition experiments were performed on seven volunteer participants under a simulated process control task environment. The participant-specific dynamic LSSVM model is constructed to classify the instantaneous CTL into five classes at each time instant. The initial feature set, comprising 56 EEG and ECG related features, is reduced to a set of 12 salient features (including 11 EEG-related features) by using the locality preserving projection (LPP) technique. An overall correct classification rate of about 80% is achieved for the 5-class CTL classification problem. Then the predicted CTL is used to adaptively allocate the number of process control tasks between operator and computer-based controller. Simulation results showed that the overall performance of the human-machine system can be improved by using the adaptive automation strategy proposed.


The process utility of thermotolerant methylotrophic bacteria: I. An evaluation in chemostat culture.
In Part l, the process utility of a thermotolerant methylotrophic bacterium is evaluated in chemostat culture under conditions where methanol, methanol/formaldehyde mixtures and dual methanol/ammonia limitation occurred. The results show that the bacterium studied was nonfastideous under steady-state operation, in contrast to results obtained in batch culture. For application in industrial wastewater treatment processes the bacterium should be employed in systems where the biomass residence time exceeds 5 h, i. e., dilution rates < O.2 h(-1). Under such conditions, methanol was essentially exhausted and the biomass yield coefficient was lowered.


[Anorexia nervosa is frequently associated with psychiatric co-morbidity].
Recent literature is explored focusing on the relationship between symptoms of anorexia nervosa (AN) and other psychiatric disorders and lines of treatment. In AN, restrictive subtype, anxiety and obsessive-compulsive disorders are the most frequent co-morbidities. In AN, bulimic subtype, depression, emotional instability/borderline and dependency disorders are most frequent. Psychopharmacological treatment could be tried in cases with AN and co-morbid depression, but otherwise the evidence base is lacking and pharmacological treatment relies on case stories and experience.


Rhizobium multihospitium sp. nov., isolated from multiple legume species native of Xinjiang, China.
Thirty-one rhizobial strains isolated from nodules of legumes native of Xinjiang, China, were characterized. These strains were classified as belonging to the genus Rhizobium based on amplified 16S rDNA restriction analysis (ARDRA). The strains were distinguished from recognized Rhizobium species using analysis of 16S-23S rDNA intergenic spacers (IGS-RFLP), SDS-PAGE analysis of whole proteins and BOX-PCR; the test strains always formed a distinct cluster with patterns that were quite different from those of the reference rhizobial strains used. According to the phylogenetic analysis based on the 16S rRNA gene, the test strains belonged to the genus Rhizobium, with Rhizobium tropici, Rhizobium rhizogenes and Rhizobium lusitanum as the closest related species, with 99.6, 99.2 and 99.4 % sequence similarities, respectively, between the type strains of the three Rhizobium species and strain CCBAU 83401(T). Phylogenetic analyses of the representative strains using IGS and atpD, recA and glnII genes all confirmed the phylogenetic arrangements obtained using the 16S rRNA gene. The DNA-DNA relatedness values between strain CCBAU 83401(T) and strains CCBAU 83364, CCBAU 83345 and CCBAU 83523 ranged from 80.8 to 100 %, showing that they belong to the same species. The DNA-DNA relatedness between strain CCBAU 83401(T) and R. tropici IIB CIAT 899(T), R. tropici IIA CFN 299, R. rhizogenes LMG 150(T) and R. lusitanum P1-7(T) were 26.9, 27.7, 38.2 and 22.6 %, respectively, clearly indicating that strain CCBAU 83401(T) represents a novel species. Phenotypic characterization of four representative strains, CCBAU 83401(T), CCBAU 83364, CCBAU 83345 and CCBAU 83523, showed several distinctive features that differentiated them from closely related species. The 31 strains had identical nodD and nifH genes, which were very similar to those of the bean-nodulating R. lusitanum, Devosia neptuniae and R. tropici IIB. Based upon these results, the strains from this study are considered to represent a novel species, for which the name Rhizobium multihospitium sp. nov. is proposed. The DNA G+C content ranged from 65.3 to 66.0 mol% (T(m)). The type strain is CCBAU 83401(T) (=LMG 23946(T)=HAMBI 2975(T)), which nodulates Robinia pseudoacacia, but not Leucaena leucocephala, Phaseolus vulgaris, Pisum sativum or Medicago sativa.


Messenger RNA in early sea-urchin embryos: cytoplasmic particles.
Three structures containing messenger RNA can be demonstrated in the cytoplasm of early sea-urchin embryos: (i) particles that sediment more slowly than ribosomes and contain newly synthesized DNA-like RNA, (ii) light polyribosomes, which also contain this newly synthesized RNA, and (iii) heavy polyribosomes, which seemingly contain only already existing or "maternal" messenger RNA and account for the bulk of the synthesis of protein.


New Answers to Old Conundrums: What Antibodies, Exosomes and Inflammasomes Bring to the Conversation. Canadian National Transplant Research Program International Summit Report.
Antibody-mediated injury is a major cause of allograft dysfunction and loss. Antibodies to ABH(O) blood group antigens are classic mediators of ABO-incompatible graft rejection, whereas donor-specific anti-HLA antibodies and, more recently, autoantibodies are appreciated as important contributors to allograft inflammation and dysfunction. In August 2016, the International Summit of the Canadian National Transplant Research Program focused on recent advances in the field of antibody-mediated rejection. Here, we describe work presented and discussed at the meeting, with a focus on 3 major themes: the importance of (1) natural antibodies and autoantibodies, (2) tissue injury-derived exosomes and autoimmunity, (3) inflammasome activation and innate immune responses in regulating allograft inflammation and dysfunction. Finally, we explore novel areas of therapeutic intervention that have recently emerged from these 3 major and overlapping fields of transplantation research.


Fourteen-year evaluation of posterior zirconia-based three-unit fixed dental prostheses: A Prospective clinical study of all ceramic prosthesis.
the purpose of the present prospective trial was to evaluate the clinical performance of posterior 3-unit zirconia-based fixed dental prostheses (FDPs) after 14 years of clinical function. thirty-seven patients needing to replace either premolars or molars were involved and 48 FDPs were fabricated (Procera Zirconia, Nobel Biocare AB). Frameworks with a9 mm2 cross section of the connectors and 0.6 mm minimum thickness of the retainers were made by means of Procera Forte CAD-CAM System (Nobel Biocare AB). The patients were recalled after 6 and 12 months and then yearly up to a total follow-up of 14 years. Two independent survival curves for patients wearing 1 or 2 FDPs were calculated by means of Kaplan-Meier analysis and a log-rank test was performed in order to compare these curves. The United States Public Health Service criteria were used to examine technical and esthetic outcomes. The biological examination was performed evaluating plaque control, pocket depth, attachment level, bleeding on probing at both abutments and contralateral teeth and evaluated by means of the Wilcoxon test (p < 0.05) between the baseline and the 14-year follow-up. descriptive statistics resulted in 91 % and 99 % cumulative survival rates for patients wearing 1 and 2 FDPs, respectively. There were no significant differences in periodontal parameters between control and test teeth. Both function and esthetic results were successful for FDPs over a 14-year follow-up period. the results of this prospective clinical study confirmed the effectiveness of zirconia as a clinical option to fabricate short-span posterior FDPs. within the limitations of the present prospective clinical study, zirconia-based three-unit fixed dental prostheses perform satisfactorily on long term, in posterior areas and in patients with standard biomechanical conditions.


Angiotensin converting enzymes in fish venom.
Animal venoms are multifaceted mixtures, including proteins, peptides and enzymes produced by animals in defense, predation and digestion. These molecules have been investigated concerning their molecular mechanisms associated and possible pharmacological applications. Thalassophryne nattereri is a small venomous fish inhabiting the northern and northeastern coast of Brazil, and represents a relatively frequent cause of injuries. Its venom causes severe inflammatory response followed frequently by the necrosis of the affected area. Scorpaena plumieri is the most venomous fish in the Brazilian fauna and is responsible for relatively frequent accidents involving anglers and bathers. In humans, its venom causes edema, erythema, ecchymoses, nausea, vomiting, and syncope. Recently, the presence of a type of angiotensin converting enzyme (ACE) activity in the venom of Thalassophryne nattereri and Scorpaena plumieri, endemic fishes in northeastern coast of Brazil, has been described. The ACE converts angiotensin I (Ang I) into angiotensin II (Ang II) and inactivates bradykinin, there by regulating blood pressure and electrolyte homeostasis, however, their function in these venoms remains an unknown. This article provides an overview of the current knowledge on ACE in the venoms of Thalassophryne nattereri and Scorpaena plumier.


Potential Effects of Boldine on Oxidative Stress, Apoptosis, and Inflammatory Changes Induced by the Methylprednisolone Hepatotoxicity in Male Wistar Rats.
Synthetic glucocorticoid therapeutic agent methylprednisolone (MPL), when used for an extended period of time at high dose, promotes the development of reactive oxygen species (ROS)-induced liver toxicity. This study investigated the role of boldine, a natural antioxidant with anti-apoptotic and anti-inflammatory properties, against MPL-induced hepatoxicity in male Wistar rats. 120 rats were divided into eight equal groups: G1 (control), G2, 3, and 4 (rats orally administered 5, 10, and 50 mg boldine/kg b.w./day; respectively, for 28 days), G5 (rats intramuscularly injected with 100 mg MPL/kg b.w. only on the last three days), G6, 7, and 8 (rats administered boldine + MPL). After the last MPL injection, rats were sacrificed at intervals of 1, 24, and 48 h. There was a significant decrease in WBCs, RBCs count, and HGB levels, as well as an increase in PLT count, ALT, AST, TG, and LDL levels, and a decrease in HDL level in serum. Oxidative stress markers levels increased at all times, and gene expression of antioxidant enzymes increased at 24h. Immunohistochemical analysis revealed that cytochrome c levels significantly increased after MPL treatment. The COMET assay revealed detectable DNA lesions. There was no immune reactivity of IL-6 expressions as an inflammatory response marker. Oral administration of boldine has a modulatory protective, antioxidant, and anti-apoptotic effect against free radicals.


Accuracy and Safety Study of Intracavitary Electrocardiographic Guidance for Peripherally Inserted Central Catheter Placement in Neonates.
The purpose of this study is to investigate the accuracy and safety of intracavitary electrocardiogram (IC-ECG) guidance for the localization of peripherally inserted central catheter (PICC) in neonatal patients. A total of 160 neonatal patients were randomly assigned to receive either anthropometric measurement combined with IC-ECG guidance (n = 80) or conventional anatomical landmark guidance (n = 80) for PICC catheter tip positioning. The catheter tip position was confirmed by postinsertion radiograph and data were interpreted by independent radiologists. Subsequent catheter-related complications of neonates between 2 groups were also compared. The first-attempt target rate was 95.0% (95% confidence interval, 90.1%-99.9%) in IC-ECG-guided PICCs, significantly higher than 78.8% (95% confidence interval, 69.6%-87.9%) in the anatomical landmark guidance group (P < .05). In contrast, IC-ECG-guided PICCs provided a significantly lower overall incidence of the catheter-related complications (3.75%), compared with those guided by anatomical landmarks only (23.75%). Thus, combined use of anatomical landmark and IC-ECG guidance improved the first-attempt target rate of PICC placement and decreased catheter-related complications. These findings indicated a superior accuracy and safety of IC-ECG guidance to conventional anatomical landmark method in neonatal PICC practice.


Structure, dynamics and topology of membrane polypeptides by oriented 2H solid-state NMR spectroscopy.
Knowledge of the structure, dynamics and interactions of polypeptides when associated with phospholipid bilayers is key to understanding the functional mechanisms of channels, antibiotics, signal- or translocation peptides. Solid-state NMR spectroscopy on samples uniaxially aligned relative to the magnetic field direction offers means to determine the alignment of polypeptide bonds and domains relative to the bilayer normal. Using this approach the (15)N chemical shift of amide bonds provides a direct indicator of the approximate helical tilt, whereas the (2)H solid-state NMR spectra acquired from peptides labelled with 3,3,3-(2)H(3)-alanines contain valuable complimentary information for a more accurate analysis of tilt and rotation pitch angles. The deuterium NMR line shapes are highly sensitive to small variations in the alignment of the C(alpha)-C(beta) bond relative to the magnetic field direction and, therefore, also the orientational distribution of helices relative to the membrane normal. When the oriented membrane samples are investigated with their normal perpendicular to the magnetic field direction, the rate of rotational diffusion can be determined in a semi-quantitative manner and thereby the aggregation state of the peptides can be analysed. Here the deuterium NMR approach is first introduced showing results from model amphipathic helices. Thereafter investigations of the viral channel peptides Vpu(1-27) and Influenza A M2(22-46) are shown. Whereas the (15)N chemical shift data confirm the transmembrane helix alignments of these hydrophobic sequences, the deuterium spectra indicate considerable mosaic spread in the helix orientations. At least two peptide populations with differing rotational correlation times are apparent in the deuterium spectra of the viral channels suggesting an equilibrium between monomeric peptides and oligomeric channel configurations under conditions where solid-state NMR structural studies of these peptides have previously been performed.


[Therapeutic use of aromatic substances in al-Andalus ].
Aromatic substances were used for therapeutic purposes in the ancient Arabic world, as they were in other contemporary and earlier cultures. By the Tenth Century, the Oriental Islamic culture had developed a solid corpus on aromatic substances that were selected for that purpose. This paper is an introduction to the knowledge of these substances that had been attained in al-Andalus in the Eleventh Century (considered the "Golden Age" of Andalusian pharmacology), based on the comparative study of the Kitāb ŷawāhir al-tīb al-mufrada, by Ibn Māsawayh, and the Kitāh al-adwiya al-mufrada, by Ibn Wāfid.


Growth, Biochemical Characteristics, Flesh Quality, and Gut Microbiota of the Pacific White Shrimp (Penaeus vannamei) Fed a Defatted Superworm (Zophobas atratus) Larvae Meal.
This study evaluated the effects of defatted superworm (Zophobas atratus) larvae meal (DBWLM) as an alternative protein ingredient for juvenile Pacific white shrimp (Penaeus vannamei). Six isonitrogenous and isolipidic experimental diets were characterized by replacing 0%, 15%, 30%, 45%, 60%, and 75% fish meal (DBWLM0, DBWLM15, DBWLM30, DBWLM45, DBWLM60, and DBWLM75, respectively) with DBWLM on a w/w basis and feeding them to juvenile shrimp (0.34 ± 0.04 g) for 56 days. The results showed that the replacement of up to 75% fish meal by DBWLM had no negative effect on the growth performance of P. vannamei. The survival of shrimp in the DBWLM30 group was the highest, and the weight gain, specific growth rate, feed conversion ratio, condition factor, and apparent digestibility coefficients of dry matter in the DBWLM15 group were the highest. The substitution of DBWLM for fish meal significantly increased the elasticity of flesh, improved the total content of umami amino acids in flesh (aspartic acid, glutamic acid, glycine, and alanine), promoted lipid metabolism in shrimp, and reduced serum lipid levels. With the increase in DBWLM level, serum acid phosphatase, alkaline phosphatase activity, and intestinal inflammatory gene expression (IGF-1 and IL-6) were inhibited, malondialdehyde content decreased, and total antioxidant capacity level and superoxide dismutase activity increased significantly. Histological sections of the hepatopancreas showed that when 60% or more fish meal was replaced, the hepatopancreas atrophied and had irregular lumen distortion, but the cell membrane was not damaged. Microbiome analysis showed that the abundance of Bacteroidetes and Firmicutes increased and the abundance of Proteobacteria decreased in the DBWLM replacement group, and it was rich in "metabolism"-related functional pathways. It is worth mentioning that the expression of amino-acid-related enzymes was upregulated in the DBWLM15 and DBWLM30 groups, and the DBWLM75 group inhibited the biosynthesis of steroids and hormones. To conclude, the replacement of 15%-45% fish meal with DBWLM can result in better growth and immune status, improved meat elasticity, and reduced inflammation in P. vannamei. However, it is recommended that the replacement level should not exceed 60%, otherwise it will cause atrophy of hepatopancreas cells.


Recognizing and Predicting Thioether Bridges Formed by Lanthionine and β-Methyllanthionine in Lantibiotics Using a Random Forest Approach with Feature Selection.
Lantibiotics, which are usually produced from Gram-positive bacteria, are regarded as one type of special bacteriocins. Lantibiotics have unsaturated amino acid residues formed by lanthionine (Lan) and β-methyllanthionine (MeLan) residues as a ring structure in the peptide. They are derived from the serine and threonine residues and are essential to preventing the growth of other similar strains. In this pioneering work, we firstly proposed a machine learning method to recognize and predict the Lan and MeLan residues in the protein sequences of lantibiotics. We adopted maximal relevance minimal redundancy (mRMR) and incremental feature selection (IFS) to select optimal features and random forest (RF) to build classifiers determining the Lan and MeLan residues. A 10- fold cross-validation test was performed on the classifiers to evaluate their predicted performances. The Matthew's correlation coefficient (MCC) values for predicting the Lan and MeLan residues were 0.813 and 0.769, respectively. Our constructed RF classifiers were shown to have a reliable ability to recognize Lan and MeLan residues from lantibiotic sequences. Furthermore, three other methods, Dagging, the nearest neighbor algorithm (NNA) and sequential minimal optimization (SMO) were also utilized to build classifiers to predict Lan and MeLan residues for comparison. Analysis was also performed on the optimal features, and the relationships between the optimal features and their biological importance were provided. The selected optimal features and analysis in this work will contribute to a better understanding of the sequence and structural features around the Lan and MeLan residues. It could provide useful information and practical suggestions for experimental and computational methods toward exploring the biological features of such special residues in lantibiotics.


Identification of Regulatory Molecular "Hot Spots" for LH/PLOD Collagen Glycosyltransferase Activity.
Hydroxylysine glycosylations are post-translational modifications (PTMs) essential for the maturation and homeostasis of fibrillar and non-fibrillar collagen molecules. The multifunctional collagen lysyl hydroxylase 3 (LH3/PLOD3) and the collagen galactosyltransferase GLT25D1 are the human enzymes that have been identified as being responsible for the glycosylation of collagen lysines, although a precise description of the contribution of each enzyme to these essential PTMs has not yet been provided in the literature. LH3/PLOD3 is thought to be capable of performing two chemically distinct collagen glycosyltransferase reactions using the same catalytic site: an inverting beta-1,O-galactosylation of hydroxylysines (Gal-T) and a retaining alpha-1,2-glucosylation of galactosyl hydroxylysines (Glc-T). In this work, we have combined indirect luminescence-based assays with direct mass spectrometry-based assays and molecular structure studies to demonstrate that LH3/PLOD3 only has Glc-T activity and that GLT25D1 only has Gal-T activity. Structure-guided mutagenesis confirmed that the Glc-T activity is defined by key residues in the first-shell environment of the glycosyltransferase catalytic site as well as by long-range contributions from residues within the same glycosyltransferase (GT) domain. By solving the molecular structures and characterizing the interactions and solving the molecular structures of human LH3/PLOD3 in complex with different UDP-sugar analogs, we show how these studies could provide insights for LH3/PLOD3 glycosyltransferase inhibitor development. Collectively, our data provide new tools for the direct investigation of collagen hydroxylysine PTMs and a comprehensive overview of the complex network of shapes, charges, and interactions that enable LH3/PLOD3 glycosyltransferase activities, expanding the molecular framework and facilitating an improved understanding and manipulation of glycosyltransferase functions in biomedical applications.


Polyunsaturated fatty acids in inflammatory bowel diseases: a reappraisal of effects and therapeutic approaches.
Recent epidemiological studies highlight the key role of the type of consumed unsaturated fatty acid and the development of ulcerative colitis (UC). We aimed to review the potential mechanisms behind the antiinflammatory effects of unsaturated fatty acids on intestinal inflammation, to discuss their potential limitations, and to propose a new reappraisal of polyunsaturated fatty acids (PUFAs) in the pathophysiology of inflammatory bowel disease (IBD). A literature search using PubMed was carried out to identify relevant studies (basic science, epidemiological studies, or clinical trials) with unsaturated fatty acids and IBD. Only articles published in English were included. IBD patients exhibit an altered lipid metabolism. While in vitro and in vivo studies have demonstrated the antiinflammatory properties of n-3 polyunsaturated fatty acids in experimental models IBD, results of clinical trials have been disappointing. In addition, the impact of fatty acid on innate immunity as an alternative therapeutic approach is explored. This may offer insight into therapeutic avenues for designing n-3 PUFA diet therapy for IBD.


Suppression of the transforming growth factor-β signaling pathway produces a synergistic effect of combination therapy with programmed death receptor 1 blockade and radiofrequency ablation against hepatic carcinoma in mice.
Primary liver cancer (PLC) significantly affects the health of patients globally owing to its high morbidity and low survival rate. Radiofrequency ablation (RFA) has recently been introduced for the clinical treatment of PLC. However, significant immunosuppressive effects are induced by RFA, which limits its application. This study aimed to explore the potential of combination therapy with RFA by investigating the effects of siRNAs against programmed death receptor 1 (PD-1) and transforming growth factor-β (TGF-β) on the antitumor effect induced by RFA. We observed that compared with si-NC, cell viability was reduced, apoptosis rate was elevated, release of inflammatory factors and percentage of CD3+CD8+ cells were increased, and the PI3K/AKT/mTOR pathway was repressed in the co-culture of RFA-treated H22 cells and CD8+ T cells by transfection with si-PD-1 and si-TGF-β; these effects were further enhanced by co-transfection with si-PD-1 and si-TGF-β. Additionally, in H22 cell xenograft-bearing mice treated with RFA, compared with the si-NC group, repressed tumor growth, prolonged survival, increased production of inflammatory factors and expression of CD3 and CD8 in tumor tissues, and downregulation of the PI3K/AKT/mTOR pathway were observed in the si-PD-1 and si-TGF-β groups; these effects were further enhanced in the si-PD-1 + si-TGF-β group. Taken together, our data revealed that suppression of the TGF-β signaling pathway produced a synergistic antitumor effect of combination therapy with PD-1 blockade and RFA against PLC. [Figure: see text].


LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma.
To examine the expression and function of long non-coding RNA taurine up-regulated 1 (TUG1) in human osteosarcoma cells. Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection efficient as well as the expression of other molecules. Compared to the normal cell line, TUG1 exhibited a significant upregulation in osteosarcoma cells. Phenotyping analysis showed the growth-promotion activity of TUG1, since knockdown of TUG1 resulted in declined proliferation. We also found that AKT phosphorylation was impaired after TUG1 was inhibited, suggesting that the AKT pathway was involved in the regulation of TUG1 in U2OS cells. Our data provided evidence that TUG1 was upregulated and acted as a possible oncogene via positively regulating cell proliferation in osteosarcoma cells.


Tutorial on Biostatistics: Statistical Analysis for Correlated Binary Eye Data.
To describe and demonstrate methods for analyzing correlated binary eye data. We describe non-model based (McNemar's test, Cochran-Mantel-Haenszel test) and model-based methods (generalized linear mixed effects model, marginal model) for analyses involving both eyes. These methods were applied to: (1) CAPT (Complications of Age-related Macular Degeneration Prevention Trial) where one eye was treated and the other observed (paired design); (2) ETROP (Early Treatment for Retinopathy of Prematurity) where bilaterally affected infants had one eye treated conventionally and the other treated early and unilaterally affected infants had treatment assigned randomly; and (3) AREDS (Age-Related Eye Disease Study) where treatment was systemic and outcome was eye-specific (both eyes in the same treatment group). In the CAPT (n = 80), treatment group (30% vision loss in treated vs. 44% in observed eyes) was not statistically significant (p = 0.07) when inter-eye correlation was ignored, but was significant (p = 0.01) with McNemar's test and the marginal model. Using standard logistic regression for unfavorable vision in ETROP, standard errors and p-values were larger for person-level covariates and were smaller for ocular covariates than using models accounting for inter-eye correlation. For risk factors of geographic atrophy in AREDS, two-eye analyses accounting for inter-eye correlation yielded more power than one-eye analyses and provided larger standard errors and p-values than invalid two-eye analyses ignoring inter-eye correlation. Ignoring inter-eye correlation can lead to larger p-values for paired designs and smaller p-values when both eyes are in the same group. Marginal models or mixed effects models using the eye as the unit of analysis provide valid inference.


Effects of Bariatric Surgeries on Fetuin-A, Selenoprotein P, Angiopoietin-Like Protein 6, and Fibroblast Growth Factor 21 Concentration.
Obesity is a civilization disease representing a global health problem. Excessive body weight significantly reduces the quality of life. It is also associated with the leading causes of death, including type 2 diabetes mellitus, cardiovascular diseases, and numerous types of cancer. The mainstay of therapy is a dietary treatment. However, in morbidly obese patients, dietary treatment is often insufficient. In these patients, the most effective procedure is bariatric surgery, but it is still difficult to predict its outcome and metabolic changes. Hepatokines are proteins secreted by hepatocytes. Many of them, including fetuin-A, selenoprotein P, angiopoietin-like protein 6, and fibroblast growth factor 21, have been linked to metabolic dysfunctions. In this context, hepatokines may prove helpful. This review investigates the possible changes in hepatokine profiles after selected bariatric surgery protocols. In this regard, Roux-en-Y gastric bypass is the most studied type of surgery. The overall analysis of published research identified fetuin-A as a potential marker of metabolic alternations in patients after bariatric surgery.


Vasodilatation and the discovery of endothelium-derived relaxing factor.
Whether endothelium-derived relaxing factor (EDRF) is important in the physiology and pathology of vascular reactivity must await the discovery of the nature of the factor and an appropriate antagonist substance. Nevertheless the demonstration that EDRF is powerful, short-lived and can be released by a wide variety of stimuli adds a new dimension to our knowledge of the control of the circulation. The macroenvironment of the vessel wall is influenced by nerves, blood-borne factors and the architecture of the wall. The discovery of a role of the endothelial cell has for the first time forced pharmacologists to consider cell-cell interactions in the micro-environment of the blood-vessel wall. This is a potentially important target for new therapy.


The role of CNS tumor location in health-related quality of life outcomes: A systematic review of supratentorial vs infratentorial tumors in childhood survivorship.
Continued advancements in the treatment of pediatric brain tumors have resulted in a growing proportion of children surviving previously incurable diagnoses. However, survivors of pediatric brain tumors show reduced Health-Related Quality of Life (HRQoL) compared to healthy populations and non-CNS childhood cancer survivors. This review systematically evaluates the existing literature on the influence of supratentorial and infratentorial brain tumor locations on Health-Related Quality of Life outcomes in survivors of pediatric brain tumors. Five electronic databases were searched for relevant articles published between their inception and January 2022. A purpose-developed evaluative tool was constructed to assess the quality of eligible studies. 16 of the 5270 identified articles were included in this review (n = 1391). This review found little evidence relating to the impact of brain tumor location on HRQoL, with only one study finding a significant difference between supratentorial and infratentorial tumor survivors. Key limitations of the current evidence include poor statistical reporting, ambiguous construct definitions, and insufficient adjustment for confounds. Findings from this review show that recovery from a pediatric brain tumor extends beyond recovery post-treatment and that further study into the factors influencing survivor HRQoL, including the influence of tumor location, is necessary.


The Women's Health Questionnaire (WHQ): Frequently Asked Questions (FAQ).
The Women's Health Questionnaire (WHQ) is a measure of mid-aged women's emotional and physical health. Since its publication in 1992 the WHQ has been widely used in multinational clinical trials, in epidemiological studies as well as in the evaluation of non-medical treatments. In particular the WHQ has been included as a quality of life measure in trials of hormonal preparations for peri and post menopausal women and in studies using a variety of preventative interventions for mid-aged and older women. The questionnaire was developed in English and standardised on a sample of women aged 45-65 years. It is reliable, has good concurrent validity and is sensitive to detecting change, and is available in 27 languages. The range of subscales included in the WHQ enable a detailed assessment of dimensions of emotional and physical health, such as depression, anxiety, sleep problems, somatic symptoms, with optional subscales for menstrual problems and sexual difficulties. The WHQ is the first measure to be included in the MAPI Research Institute's database, the International Health-related Quality of Life Outcomes Database (IQOD). Drawing upon data from international studies this project aims to produce reference values for cross-culturally valid, reliable and responsive quality of life instruments. In addition to this work, a revised shorter version of the WHQ is currently being developed.


Direct and maternal genetic effects on growth, reproduction, and ultrasound traits in zebu Brahman cattle in Colombia.
Covariance components and genetic parameters were estimated for birth weight (BiW); adjusted weights at 4, 7, 12, and 18 mo; and ADG between 0 and 4 mo, between 4 and 7 mo, between 7 and 12 mo, and between 12 and 18 mo. Additionally, reproductive traits, calving interval, and age at first calving were analyzed, together with traits measured by ultrasound: loin eye area, deep fat mean, back fat, and rump fat. Analyses were performed using an animal model, considering the fixed effects of the farm ( = 37), year and month of birth, sex, calving number (1 to 7), season (dry and rainy seasons), region (North Coast, Andean Region, and Oriental Savannas), and conception (natural mating or AI), whereas the age of the cows at calving was considered a polynomial covariate with linear and quadratic effects. Three different models were used to find the one with the best fit for each trait: a single-trait model with an additive direct genetic effect, a single-trait model with additive direct and maternal genetic effects, and finally, a multitrait model with an additive direct genetic effect. For the growth traits, the heritability was between 0.24 and 0.47, with the lowest value for weight at 7 mo and the greatest value for BiW, and the maternal heritability was found to be between 0.15 and 0.21 but did not decrease later on. The correlation between direct and maternal effects was high and negative (-0.59 to -0.76). With ultrasound traits, a model with only direct effects was used. The heritability was between 0.13 and 0.28 for back fat and loin eye area, respectively. The heritabilities for deep fat mean and rump fat were similar, being 0.19 and 0.21, respectively. The reproductive traits showed high residual variance. In particular, the heritability of calving interval was low (0.06). The results showed that the growth traits have an important genetic component, which is a favorable indicator for obtaining improvement progress in the zebu Brahman breed for beef production in tropical regions of Colombia. The maternal effects influenced the weight performance from 4 to 18 mo and should be taken into account in genetic analyses. In general, the direct heritability of medium magnitude estimated for growth and traits measured by ultrasound suggests that individual selection for these traits will be effective.


Do obstacles affect the selection of grasping points?
The selection of grasping points, the positions at which the digits make contact with an object's surface in order to pick it up, depends on several factors. In this study, we examined the influence of obstacles on the selection of grasping points. Subjects reached to grasp a sphere placed on a table. Obstacles were placed either near the anticipated grasping points or near the anticipated elbow position at the time of contact with the object. In all cases, subjects adjusted the way they moved when there was an obstacle nearby, but only obstacles near the thumb had a consistent influence across subjects. In general, the influence of the obstacle increased as it was placed closer to the digit or elbow, rather than the subject grasping in a manner that would be appropriate for all conditions. This suggests that under these circumstances the configuration of the arm and hand at the moment of contact was a critical factor when selecting at which points to grasp the objects.


Nerve fibers in breast cancer tissues indicate aggressive tumor progression.
Emerging evidence has indicated nerve fibers as a marker in the progression of various types of cancers, such as pancreatic cancer and prostate cancer. However, whether nerve fibers are associated with breast cancer progression remains unclear. In this study, we evaluated the presence of nerve fibers in 352 breast cancer specimens and 83 benign breast tissue specimens including 43 cases of cystic fibrosis and 40 cases of fibroadenoma from 2 independent breast tumor center using immunohistochemical staining for specific peripheral nerve fiber markers.In all, nerve fibers were present in 130 out of 352 breast cancer tissue specimens, while none were detected in normal breast tissue specimens. Among 352 cases, we defined 239 cases from Sun Yat-Sen Memorial Hospital, Guangzhou, China, as the training set, and 113 cases from the First Affiliated Hospital of Shantou University, Guangdong, China, as the validation set. The thickness of tumor-involving nerve fibers is significantly correlated with poor differentiation, lymph node metastasis, high clinical staging, and triple negative subtype in breast cancer. More importantly, Cox multifactor analysis indicates that the thickness of tumor-involving nerve fibers is a previously unappreciated independent prognostic factors associated with shorter disease-free survival of breast cancer patients. Our findings are further validated by online Oncomine database. In conclusion, our results show that nerve fiber involvement in breast cancer is associated with progression of the malignancy and warrant further studies in the future.


The relation of infants' home environments to achievement test performance in first grade: a follow-up study.
In 2 earlier investigations, we found that scores on the HOME Inventory administered during the first 2 years of life were substantially correlated with intelligence test scores at ages 3 and 4 1/2. In the current investigation, HOME scores in first 2 years showed similar relations to SRA Achievement Test scores during the first grade. In general, findings from this study were like those from the earlier investigations except that the subscale, "maternal responsivity," showed a weaker relation to achievement than IQ; while the "variety of stimulation" scale showed a stronger relation. Of all the HOME subscales, "play materials" revealed the strongest correlation with first-grade achievement. When 12-month Bayley MDI scores were partialed out of the HOME/achievement relation, little reduction was noted in the magnitude of the correlation; however, when 3-year IQ or subsequent HOME scores were partialed out, little residual correlation was noted.


[Analysis of the dopamine D4 receptor gene variants in attention deficit hyperactivity disorder].
The human dopamine D4 receptor (DRD4) gene has been extensively studied as a candidate gene for attention deficit hyperactivity disorder (ADHD). Both the 5' regulatory region and the coding sequence contain a number of polymorphisms. The most widely investigated polymorphism of the DRD4 gene is the 48 bp VNTR (Variable Number of Tandem Repeats) in the third exon. The promoter variants have received particular attention in the past few years due to their possible role in the regulation of gene expression. In this study we describe an association analysis of the 120 bp duplication and three sequence variations (SNPs, Single Nucleotide Polymorphism; -616 C/G, -615 A/G, -521 C/T) in the 5' region of the DRD4 gene is presented among children with ADHD. In case-control approach, the 1-repeat form of the 120 bp duplication had a significantly higher frequency among ADHD children than controls, both in allele-(p=0.047), and genotype (p=0.019) distributions. There was no significant difference between the ADHD and control groups in the allele or genotype frequencies of the investigated SNPs. The transcriptional effect of the 120 bp duplication was analysed in luciferase reporter system. The different 120 bp duplication alleles (1-repeat, 2-repeat and the newly identified 4-repeat allele) was found to have an effect on transcriptional activity of the DRD4 gene in both neuroblastoma and retinoblastoma cell lines in a dose-dependent manner. The higher was the repeat number of the 120 bp sequence in the promoter, the stronger was the decrease of the gene transcription (1-repeat > 2-repeat > 4-repeat; p<0.01). These results of association and functional analyses suggest that the 1-repeat form of the 120 bp duplication might be a risk factor of ADHD.


Effect of Hydrofluoric Acid Concentration and Etching Time on Bond Strength to Lithium Disilicate Glass Ceramic.
The aim of this study was to evaluate the influence of different concentrations of hydrofluoric acid (HF) associated with varied etching times on the microshear bond strength (μSBS) of a resin cement to a lithium disilicate glass ceramic. Two hundred seventy-five ceramic blocks (IPS e.max Press [EMX], Ivoclar Vivadent), measuring 8 mm × 3 mm thickness, were randomly distributed into five groups according to the HF concentrations (n=50): 1%, 2.5%, 5%, 7.5%, and 10%. Further random distribution into subgroups was performed according to the following etching times (n=10): 20, 40, 60, 120, and 20 + 20 seconds. After etching, all blocks were treated with a silane coupling agent followed by a thin layer of an unfilled resin. Three resin cement cylinders (∅=1 mm) were made on each EMX surface, which was then stored in deionized water at 37°C for 24 hours before testing. The μSBS was in a universal testing machine at a crosshead speed of 1 mm/min until failure. Data were submitted to two-way analysis of variance, and multiple comparisons were performed using the Tukey post hoc test (α=0.05). One representative EMX sample was etched according to the description of each subgroup and evaluated using scanning electron microscopy for surface characterization. The HF concentrations of 5%, 7.5%, and 10% provided significantly higher μSBS values than 1% and 2.5% (p<0.05), regardless of the etching times. For 1% and 2.5% HF, the etching times from 40 to 120 seconds increased the μSBS values compared with 20 seconds (p<0.05), but etching periods did not differ within the 5%, 7.5%, and 10% HF groups (p>0.05). The effect of re-etching was more evident for 1% and 2.5% HF (p<0.05). Different HF concentrations/etching times directly influenced the bond strength and surface morphology of EMX.


Modular Synthesis of Furans with up to Four Different Substituents by a trans-Carboboration Strategy.
Propargyl alcohols, on treatment with MHMDS (M=Na, K), B2 (pin)2 , an acid chloride and a palladium/copper co-catalyst system, undergo a reaction cascade comprised of trans-diboration, regioselective acylation, cyclization and dehydration to give trisubstituted furylboronic acid pinacol ester derivatives in good yields; subsequent Suzuki coupling allows a fourth substituent of choice to be introduced and hence tetrasubstituted (arylated) furans to be formed. In terms of modularity, the method seems unrivaled, not least because each product can be attained by two orthogonal but convergent ways ("diagonal split"). This asset is illustrated by the "serial" formation of a "library" of all twelve possible furan isomers that result from systematic permutation of four different substituents about the heterocyclic core.


The supernumerary lateral incisors--morphology and concomitant abnormalities.
To assess the morphology of supernumerary lateral incisors and describe the concomitant malocclusion. Intraoral examination and analysis of panoramic views as well as study casts has been proceeded in 18 patients with supernumerary laterals. The widths of the normal and supernumerary laterals were measured. 20 supernumerary incisors were found (in 2 patients - bilateral). In 1 patient - the width of the supernumerary tooth was the same as this of the adjacent normal teeth and in 12 patients - the widths were lower. In cases of unilateral hyperdontia, 4 of the laterals adjacent to supernumerary teeth were of the same, 9 were of lower and 1 was of higher widths than the contralateral ones. Supernumerary teeth were causing midline shift in 10 patients, significant space deficiency - in 4, ectopic eruption - in 1 and excessive overjet - in 4. In 3 patients the permanent supernumerary incisors were not yet erupted and in 1 patient the tooth was retained. The supernumerary lateral incisors were smaller than the adjacent ones, whereas the normal lateral incisors adjacent to supernumerary ones were smaller than the contralateral incisors. The concomitant occlusal anomalies were: excessive overjet, crowding or ectopic eruption and midline shift.


Activity of the basolateral K+ channels is coupled to the Na+-K+-ATPase in the cortical collecting duct.
Microelectrode and patch-clamp techniques were used in the isolated cortical collecting duct to study the effects of stimulating Na+-K+-ATPase by raising bath K+ (Fujii Y and Katz AI. Am J Physiol Renal Fluid Electrolyte Physiol 257: F595-F601, 1989 and Muto S, Asano Y, Seldin D, and Giebisch. Am J Physiol Renal Physiol 276: F143-F158, 1999) on the transepithelial (VT) and basolateral membrane (VB) voltages and basolateral K+ channel activity. Increasing bath K+ from 2.5 to 8.5 mM resulted in an initial hyperpolarization of both VT and VB followed by a delayed depolarization. The effects of raising bath K+ on VT and VB were attenuated by decreasing luminal Na+ from 146.8 to 14.0 mM and were abolished by removal of luminal Na+, whereas those were magnified in desoxycorticosterone acetate (DOCA)-treated rabbits. Increasing bath K+ also led to a significant reduction of the intracellular Na+ and Ca2+ concentrations. The transepithelial conductance (GT) or fractional apical membrane resistance (fRA) were unaltered during the initial hyperpolarization phase, whereas, in the late depolarization phase, there were an increase in GT and a decrease in fRA, both of which were attenuated in the presence of low luminal Na+ (14.0 mM). In tubules from DOCA-treated animals, bath Ba2+ not only caused a significantly larger initial hyperpolarization of VT and VB but also blunted the late depolarization by high bath K+. Nomega-nitro-l-arginine methyl ester (l-NAME) partially mimicked the effect of Ba2+ and decreased the amplitude of the late depolarization. Patch-clamp experiments showed that raising bath K+ from 2.5 to 8.5 mM resulted in an increased activity of the basolateral K+ channel, which was absent in the presence of l-NAME. We conclude that stimulation of Na+-K+-ATPase increases the basolateral K+ conductance and that this effect involves suppression of nitric oxide-dependent inhibition of K+ channels.


Building and developing realistic simulation scenarios on safe drug administration.
To describe the construction of the scenarios and the development of the realistic simulation technique in health on safe administration of drugs for nursing professionals. Report of experience developed from October 2017 to May 2018 involving the steps of training of the facilitators, construction of the scenarios, development of the realistic simulation with nursing staff of a teaching hospital in the southern region of Brazil. The best simulation practice guidelines used from the International Nursing Association for Clinical Simulation and Learning. Four practice-based scenarios were constructed based on adverse events. The nurses educators trained the facilitators participating in all stages. There was concern about the fidelity of the scenarios, as well as the execution of the briefing and debriefing stages. The simulation allowed the reflection of the "way of doing" of the teams adjusting the process of preparation and administration of medicines to the institutional recommendations and, thus, promoting the safety of the process.


The Diagnostic and Prognostic Values of HOXA Gene Family in Kidney Clear Cell Renal Cell Carcinoma.
Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers with high mortality worldwide. As members of the homeobox (HOX) family, homeobox-A (HOXA) genes have been reported to play an increasingly important role in tumorigenesis and the progression of multiple cancers. However, limited studies have investigated the potential diagnostic and prognostic roles of HOXA genes in KIRC. In this research, we explored the expression pattern of the HOXA gene family in KIRC progression by differential analysis of expression profiles from The Cancer Genome Atlas (TCGA). By using univariate Cox analysis and lasso regression analysis, we comprehensively evaluated the prognostic value of HOXA genes and eventually identified a prognostic risk model consisting of five HOXA genes (HOXA2, HOXA3, HOXA7, HOXA11, and HOXA13). The risk model was further validated as a novel independent prognostic factor for KIRC patients based on the calculated risk score by Kaplan-Meier analysis, univariate and multivariate Cox regression analyses, and time-dependent receiver operating characteristic (ROC) curve analysis. Moreover, to explore the potential mechanism of tumorigenesis and clinical application of KIRC, we also developed the HOXA-based competing endogenous RNA (ceRNA) regulatory network and machine learning classification model. Valproic acid and tretinoin were predicted to be the most promising small molecules to adjuvant treatment of KIRC by mining the CMAP and DGIdb drug database. Subsequently, pathway and functional enrichment analyses provided us with new ways to search for a possible mechanism of action of drugs. Taken together, our study demonstrated the nonnegligible role of HOXA genes in KIRC and constructed an effective prognostic and diagnostic model, which offers novel insights into KIRC prognosis.


Toxoplasma gondii: differential location of antigens secreted from encysted bradyzoites.
Since we have previously demonstrated the protective role against infection played by Toxoplasma excreted-secreted antigens (Darcy et al. Parasite Immunology, 10, 553-567, 1988), the aim of the present work was an attempt to precisely define the location of GRA1, GRA2, and GRA5 in both the tachyzoite and the bradyzoite stages from distinct strains, in order to explore the mechanisms of secretion by Toxoplasma gondii. Three monoclonal antibodies (Charif et al. 1990) and colloidal immunogold labeling were used to localize the 27-, 28.5-, and 21-kDa target antigens to the matrix of the dense granules of tachyzoites and bradyzoites. They were, moreover, detected in the parasitophorous vacuole and in the cyst ground substance after host cell invasion. Our data suggest that a selective sorting mechanism for dense-granule contents exists at least in encysted bradyzoites. GRA2 was found preferentially associated with the ground substance of the cyst wall and the tubular elements of the network of the modified host cell phagosome, whereas GRA5 was located on the delimiting membrane of both the cyst wall and the parasitophorous vacuole. These observations reveal the selective targeting of dense-granule molecules, which could have different functions and fates when exocytosed into the parasite-containing vacuole.


Generation of robust bispecific antibodies through fusion of single-domain antibodies on IgG scaffolds: a comprehensive comparison of formats.
Bispecific antibodies (bsAbs) enable dual binding of different antigens with potential synergistic targeting effects and innovative therapeutic possibilities. The formation of bsAbs is, however, often dependent on complex engineering strategies with a high risk of antibody chain mispairing leading to contamination of the final product with incorrectly assembled antibody species. This study demonstrates formation of bsAbs in a generic and conceptually easy manner through fusion of single-domain antibodies (sdAbs) onto IgG scaffolds through flexible 10 amino acid linkers to form high-quality bsAbs with both binding functionalities intact and minimal product-related impurities. SdAbs are attractive fusion partners due to their small and monomeric nature combined with antigen-binding capabilities comparable to conventional human antibodies. By systematically comparing a comprehensive panel of symmetric αPD-L1×αHER2 antibodies, including reversely mirrored antigen specificities, we investigate how the molecular geometry affects production, stability, antigen binding and CD16a binding. SdAb fusion of the heavy chain was generally preferred over light chain fusion for promoting good expression and high biophysical stability as well as maintaining efficient binding to both antigens. We find that N-terminal sdAb fusion might sterically hinder antigen-binding to the Fv region of the IgG scaffold, whereas C-terminal fusion might disturb antigen-binding to the fused sdAb. Our work demonstrates a toolbox of complementary methods for in-depth analysis of key features, such as in-solution dual antigen binding, thermal stability, and aggregation propensity, to ensure high bsAb quality. These techniques can be executed at high-throughput and/or with very low material consumption and thus represent valuable tools for bsAb screening and development.


Epitaxial Growth of SrTiO3 Films on Cube-Textured Cu-Clad Substrates by PLD at Low Temperature Under Reducing Atmosphere.
The growth of epitaxial {001}<100> SrTiO3 (STO) on low-cost cube-textured Cu-based clad substrate at low temperature was carried out by means of pulsed laser deposition (PLD). STO film was deposited in one step under a reducing atmosphere (5% H2 and 95% Ar mixture) to prevent the oxidation of the metal surface. The optimization of PLD parameters leads to a sharpest biaxial texture at a temperature as low as 500 °C and a thickness of 500 nm with a (100) STO layer. The upper limit of highly textured STO thickness was also investigated. The maximum thickness which retains the best quality {001}<100> texture is 800 nm, since the texture is preserved not only through the layer but also on the surface. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) measurements showed that STO films are continuous, dense, and smooth with very low roughness (between 5 and 7 nm). This paper describes the development of STO layer by means of PLD in absence of oxygen throughout the process, suggesting an alternative and effective method for growing highly {001}<100> textured STO layer on low-cost metal substrates.


Shape control of II-VI semiconductor nanomaterials.
Anisotropic II-VI semiconductor nanocrystals and nanoparticles have become important building blocks for (potential) nanotechnological applications. Even though a wide variety of differently shaped nanoparticles of this class can be prepared, the underlying mechanisms are mostly not fully understood. This Review article provides a brief overview of the currently studied shape-evolution mechanisms and the most prominent synthesis methods for such particles, with an aim to provide a fundamental understanding on how different morphologies evolve, and to function as a tool to aid in the preparation of specific nanocrystals.


Collection of circulating stem cells and their use for autograft in adults with acute lymphoblastic leukaemia.
The level of peripheral blood granulocyte-monocytic precursors (PB CFU-GM) was studied serially in 10 adult patients with acute lymphoblastic leukaemia (ALL) in early complete remission after induction chemotherapy. The patients were distributed into 2 main groups according to the morphological French-American-British classification: ALL2 and ALL3. Collection of circulating stem cells (CSC) by cytapheresis was performed in 7 of these 10 patients with satisfactory results, except in 2 ALL2 patients, both of whom had chromosome translocation, which could have been a contributing factor. It appears, moreover, that even with 2 or 3 inductions courses, the more intensive the chemotherapy regimen in previously non-treated patients, the higher the peak of PB CFU-GM and the better the collection of CSC. The measurement of CFU-GM is certainly a less effective indicator of pluripotent stem cells in blood than in bone marrow, and it is probably necessary, but sufficient, to inject 5 times more CFU-GM than normally injected in marrow transplants to allow prompt and stable engraftment. The feasibility of this new graft technique seems for the moment undeniable, the main problem in ALL is the risk of relapse.


Does learning to read shape verbal working memory?
Many experimental studies have investigated the relationship between the acquisition of reading and working memory in a unidirectional way, attempting to determine to what extent individual differences in working memory can predict reading achievement. In contrast, very little attention has been dedicated to the converse possibility that learning to read shapes the development of verbal memory processes. In this paper, we present available evidence that advocates a more prominent role for reading acquisition on verbal working memory and then discuss the potential mechanisms of such literacy effects. First, the early decoding activities might bolster the development of subvocal rehearsal, which, in turn, would enhance serial order performance in immediate memory tasks. In addition, learning to read and write in an alphabetical system allows the emergence of phonemic awareness and finely tuned phonological representations, as well as of orthographic representations. This could improve the quality, strength, and precision of lexical representations, and hence offer better support for the temporary encoding of memory items and/or for their retrieval.


Intrauterine infusion of high doses of pig trophoblast interferons has no antiluteolytic effect in cyclic gilts.
In the pig species, the preimplanting trophoblast is known to synthesize and secrete high amounts of interferon during early development. Previous experiments in cyclic gilts using total conceptus secretory proteins suggested that porcine trophoblastic interferons, unlike those of ruminants, exert no effect on the luteal cycle. In the present experiment, cyclic Meishan gilts were divided into two groups, cannulated on both uterine horns, and given daily injections of either a placebo or increasing doses of a mixture of recombinant interferon-gamma and interferon-delta, on Days 11-14 of the estrous cycle. In treated gilts, the injected doses were much higher than those previously found in uterine perfusates from pregnant gilts. However, no significant differences could be found between the control (n = 4) and the treated (n = 5) group concerning the days of the estrous cycle for mid-decrease of progesterone (control: Day 14.5+/-0.57 [mean+/-SD]; treated: Day 15+/-1.25), the day of estrus (control: Day 19+/-0.96; treated: Day 19.6+/-0.55), and the subsequent ovulation rate (control: 14+/-2.2 corpora lutea; treated: 13.1+/-1.1 corpora lutea). These data confirm that pig trophoblastic interferons, unlike those of ruminants, do not themselves exert an antiluteolytic effect. A possible synergistic effect of embryonic estrogens on the luteal functions of nonpregnant sows remains to be determined.


Cultural diversity in central America and Panama: its relationship to conservation and planning.
The most frequently overlooked aspect of conservation of natural resources and economic development is human cultural diversity. However, conservation and development of natural resources are basically human-oriented endeavors and all conservation and developmental efforts ought to start with a clear understanding of the varied needs of the people. In addition, cultural diversity is a natural resource that ought to be protected along with all the more commonly recognized resources of the ecosystems of which humans form an integral part. Cultural diversity in a large measure is an ecological phenomenon because such diversity includes variations in the ways different people perceive and utilize the environments in which they live. Thus, cultural diversity, in large measure, equates with ecological diversity. It has been well established that a high degree of ecological diversity (including taxonomic, niche, biogeochemical and other measures of diversity) is a necessary attribute of humid tropical ecosystems if such ecosystems are to remain viable over long periods of time. The current land-use trends in Central America and Panama are leading toward ever larger areas being devoted to monocultural use with sharply reduced ecological diversity that poses great dangers for the near and long terms. In addition, the resultant removal of people from rural areas results in growing social, economic and political problems, that are not being successfully met by developing nations. Not only is there a growing wastage of human resources, a weakening of the social structures, and an increasing and dangerous dependence upon monocultures oriented toward export markets, but the ecological diversity of the previous existing land-use systems are being lost. This kind of diversity is probably no less valuable to the ecological health of a nation's agriculture, forestry, and general resource utilization than is the genetic diversity of "primitive" crop plant varieties which biologists now recognize and increasingly seek to preserve as "modern" crop plant varieties become ever more simple genetically and hence ever more vulnerable to disease and other perturbations.


[Clostridium novyi type A bacteriophages (author's transl)].
In the culture fluids and on the cells of two toxigenic strains of Clostridium novyi type A, bacteriophages were detected and confirmed by electron microscopy (Fig. 1 and 2). The heads of the bacteriophages are hexagonal and 500 A in diameter. The tails have a length of 1400 A and a diameter of 60 A. Reproduction of the bacteriophages was not yet possible owing to the lack of sensitive indicator strains.


Bottom-up growth of carbon nanotube multilayers: unprecedented growth.
An unusual growth phenomenon, with no precedent in vapor-phase thin film growth, is described here, for the case of the growth of stacked multiple layers of vertically aligned carbon nanotubes(1-6) on solid substrates. As multiple layers of ordered nanotubes are sequentially deposited from the vapor onto the substrate, each layer nucleates and grows from the original substrate surface at the bottom of the existing multiple stacks of nanotubes. In contrast to conventional understanding of thin film deposition,(7) the mechanism here has similarities to porous oxide film formation on surfaces.(8) The stacked layers of aligned nanotubes act as fully permeable membranes for the downward diffusion of growth precursor vapors, allowing growth to occur at the buried solid interface. The preexisting multiple nanotube stacks lift up to accommodate the vertical growth of fresh layers, allowing the formation of nanotube towers extending in millimeter lengths. Our results provide evidence for a new growth phenomenon, characterized by selective, interface-driven, bottom-up growth of self-assembled nanowires at buried interfaces, covered with weakly adhering thick porous membranes.


Should anthropology be part of cognitive science?
Anthropology and the other cognitive science (CS) subdisciplines currently maintain a troubled relationship. With a debate in topiCS we aim at exploring the prospects for improving this relationship, and our introduction is intended as a catalyst for this debate. In order to encourage a frank sharing of perspectives, our comments will be deliberately provocative. Several challenges for a successful rapprochement are identified, encompassing the diverging paths that CS and anthropology have taken in the past, the degree of compatibility between (1) CS and (2) anthropology with regard to methodology and (3) research strategies, (4) the importance of anthropology for CS, and (5) the need for disciplinary diversity. Given this set of challenges, a reconciliation seems unlikely to follow on the heels of good intentions alone.


Ferromagnetic Quantum Critical Point Avoided by the Appearance of Another Magnetic Phase in LaCrGe_{3} under Pressure.
The temperature-pressure phase diagram of the ferromagnet LaCrGe_{3} is determined for the first time from a combination of magnetization, muon-spin-rotation, and electrical resistivity measurements. The ferromagnetic phase is suppressed near 2.1 GPa, but quantum criticality is avoided by the appearance of a magnetic phase, likely modulated, AFM_{Q}. Our density functional theory total energy calculations suggest a near degeneracy of antiferromagnetic states with small magnetic wave vectors Q allowing for the potential of an ordering wave vector evolving from Q=0 to finite Q, as expected from the most recent theories on ferromagnetic quantum criticality. Our findings show that LaCrGe_{3} is a very simple example to study this scenario of avoided ferromagnetic quantum criticality and will inspire further study on this material and other itinerant ferromagnets.


Clinical implications of anti-HTLV antibody titer, abnormal lymphocytes in HTLV carriers and HTLV genome negative adult T-cell leukemia-lymphoma.
Abnormally large lymphocytes with Pelger-like nuclear lobulation have been found in peripheral blood of smoldering adult T-cell leukemia-lymphoma (ATL) patients. They are also found in quite low percentage in peripheral blood of healthy HTLV carriers. Therefore, it has become difficult to discriminate smoldering ATL having only abnormal lymphocytes from a healthy human T-cell leukemia virus (HTLV) carrier only by morphology and serology. We found that patients with smoldering ATL with visceral organ involvement such as skin or lung lesions had much higher titer (about 1 : 1,000) of anti-HTLV antibodies than those with other subtypes of ATL (about 1 : 250); the difference was highly significant (p less than 0.001). In addition, the period of survival of patients with smoldering ATL having antibody with high titer was much longer than that of patients with other subtypes of ATL, suggesting the role of a host immune response. Four cases of HTLV-negative ATL were found to have the same chromosomal abnormality as that has been seen in HTLV-positive typical ATL; the situation was quite similar to Burkitt's lymphoma. Since it has been considered that HTLV does not include oncogenes, a common oncogenic mechanism, ATL specific cellular oncogenes, might exist: they might be activated by HTLV or a mechanism other than a virus.


Pathogens in PICU before and during the SARS-CoV-2 pandemic in China: a multicenter retrospective study.
Nonpharmacological interventions for COVID-19 could reduce the incidence of children hospitalized in pediatric intensive care units (PICU) and the incidence of children with bacterial infections. This study aimed to evaluate changes in the bacterial profile of children in PICU before and during the COVID-19 pandemics. This is a retrospective study, involving clinical data of children with positive bacterial cultures admitted to the PICU respectively in 2019 and 2021. In total 652 children were included in this study. The total number of hospitalized patients and the incidence of bacteria-positive children in 2021 were lower than those in 2019. There were no significant differences in the ratio of Gram-positive bacterial infection, Gram-negative bacteria infection or fungi infection between the two years. The rate of Streptococcus pneumoniae in 2021 was higher than that in 2019(p = 0.127). The incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend(p = 0.002). The distribution of previous underlying diseases in children admitted to PICU with different outcomes of bacterial infection between the two years were homogeneous (p > 0.05). After the implementation of COVID-19 isolation, prevention and control measures, the number of hospitalizations and bacterial infections in PICU decreased, which may be due to changes in population's behavior patterns. Meanwhile, the incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend.


The size-dependent ferroelectric phase transition in BaTiO₃ nanocrystals probed by surface plasmons.
A new technique for probing the temperature dependence of the dielectric constant of ferroelectric nanocrystals (NCs) using shifts in the localized surface plasmon resonance (LSPR) wavelength of gold nanoparticles attached to the surface of the ferroelectric NCs is demonstrated. This technique can selectively probe the surface of the NCs and was used to study the ferroelectric-to-paraelectric phase transition of barium titanate (BTO) nanocubes in three size regimes of 16 ± 4, 47 ± 11, and 220 ± 140 nm. Temperature-dependent Raman spectroscopy was also applied to probe the whole volume of the NCs. The LSPR-based technique revealed that the ∼16 nm BTO NCs were dominated by surface effects, and as the NC size increased bulk BTO behavior governed. This supports recent propositions about the lack of intrinsic size dependence of the transition temperature. Therefore, the surface chemistry/structure probably affected the ferroelectric behavior rather than finite size effects. A distinct phase transition at the surface characterized by a very long relaxation time was detected by the LSPR-based technique.


Comparison and prognostic validation of multiple methods of quantification of myocardial blood flow with 82Rb PET.
The quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) using PET with (82)Rb in patients with known or suspected coronary artery disease has been demonstrated to have substantial prognostic and diagnostic value. However, multiple methods for estimation of an image-derived input function and several models for the nonlinear first-pass extraction of (82)Rb by myocardium have been used. We sought to compare the differences in these methods and models and their impact on prognostic assessment in a large clinical dataset. Consecutive patients (n = 2,783) underwent clinically indicated rest-stress myocardial perfusion PET with (82)Rb. The input function was derived using a region of interest (ROI) semiautomatically placed in the region of the mitral valve, factor analysis, and a hybrid method that creates an ROI from factor analysis. We used 5 commonly used extraction models for (82)Rb to estimate MBF and MFR. Pearson correlations, bias, and Cohen κ were computed for the various measures. The relationship between MFR/stress MBF and annual rate of cardiac mortality was estimated with spline fits using Poisson regression. Finally, incremental value was assessed with the net reclassification improvement using Cox proportional hazards regression. Correlations between MFR or stress MBF measures made with the same input function derivation method were generally high, regardless of extraction model used (Pearson r > 0.90). However, correlations between measures derived with the ROI method and other methods were only moderate (Pearson r = 0.42-0.62). Importantly, substantial biases were seen for most combinations. We saw that the relationship between cardiac mortality and stress MBF was variable depending on the input function method and extraction model, whereas the relationship between MFR and risk was highly consistent. Net reclassification improvement was comparable for most methods and models for MFR but was highly variable for stress MBF. Although both stress MBF and MFR can improve prognostic assessment, MFR is substantially more consistent, regardless of choice of input function derivation method and extraction model used.


Three chymotrypsin genes are members of the AdpA regulon in the A-factor regulatory cascade in Streptomyces griseus.
AdpA is a key transcriptional activator in the A-factor regulatory cascade in Streptomyces griseus, activating a number of genes required for secondary metabolism and morphological differentiation. Of the five chymotrypsin-type serine protease genes, sprA, sprB, and sprD were transcribed in response to AdpA, showing that these protease genes are members of the AdpA regulon. These proteases were predicted to play the same physiological role, since these protease genes were transcribed in a similar time course during growth and the matured enzymes showed high end-to-end similarity to one another. AdpA bound two sites upstream of the sprA promoter approximately at positions -375 and -50 with respect to the transcriptional start point of sprA. Mutational analysis of the AdpA-binding sites showed that both AdpA-binding sites were essential for transcriptional activation. AdpA bound a single site at position -50 in front of the sprB promoter and greatly enhanced the transcription of sprB. The AdpA-binding site at position -40 was essential for transcription of sprD, although there was an additional AdpA-binding site at position -180. Most chymotrypsin activity excreted by S. griseus was attributed to SprA and SprB, because mutant deltasprAB, having a deletion in both sprA and sprB, lost almost all chymotrypsin activity, as did mutant deltaadpA. Even the double mutant deltasprAB and triple mutant deltasprABD grew normally and developed aerial hyphae and spores over the same time course as the wild-type strain.


Risk factors for urinary tract infection in children with urinary urgency.
To identify which independent variable would be strong predictor of febrile urinary tract infection (UTI) in children and adolescents with overactive bladder. A search was made of the institute's database for all patients diagnosed with overactive bladder over the preceding four years. Children and adolescents under 18 years of age with overactive bladder and no neurological or anatomical alterations of the lower urinary tract were included in the study. The independent variables were: sex, age, ethnicity (Brazilians of African descendence/others), the presence of urinary urgency, daytime incontinence, enuresis, frequent urination, infrequent voiding (≤3 voids/day), nocturia, holding maneuvers, straining to void, intermittent urinary flow, constipation and encopresis. An analysis was conducted to identify patients with febrile UTI and subsequently determine predictors of this condition. Univariate and multivariate analyses were performed. Overall, 326 patients (214 girls/112 boys) were evaluated. The mean age of the patients was 7.7±3.19 years (± standard deviation). The incidence of febrile UTI was 39.2%. Being female and infrequent voiding were factors significantly associated with febrile UTI, both in the univariate and multivariate analyses. These results show that being female and infrequent voiding constituted significant risk factors for a diagnosis of febrile UTI in these children.


Effects of naloxone on glucose and insulin regulation during endotoxicosis in fed and fasted rats.
This study examined the effects of naloxone on glucose and insulin dyshomeostasis during endotoxicosis in ad libitum fed and overnight-fasted rats. Plasma glucose levels were measured in vivo to assess the effects of naloxone on glucose regulation during endotoxicosis. Naloxone's effects on endotoxin-induced portal and systemic hyperinsulinemia were evaluated in vivo. In addition, the ability of naloxone to alter the insulin hypersecretory state of the endotoxic pancreas was evaluated using the in vitro perfused rat pancreas preparation. Naloxone did not alter endotoxin-induced glucose dyshomeostasis in fasted rats, but potentiated hypoglycemia in fed, endotoxic rats. Naloxone potentiated endotoxin-induced hyperinsulinemia and insulin hypersecretion from the endotoxic pancreas in fed, but not fasted, rats. Thus the results indicated that naloxone had no apparent beneficial effects on glucose and insulin dyshomeostasis during endotoxicosis in either fed or fasted rats, and potentiated glucose and insulin dyshomeostasis in fed, endotoxic rats. Since naloxone is a specific opiate antagonist, these results suggested that endogenous opiate systems do not play a significant deleterious role in the glucose and insulin dyshomeostasis of endotoxic shock. In addition, this study identified prior feeding history of rats (ad libitum feeding vs. overnight fasting) as an important variable relative to the study of naloxone's effects on glucose and insulin regulation during endotoxicosis.


Characterization of Plasmodium Lactate Dehydrogenase and Histidine-Rich Protein 2 Clearance Patterns via Rapid On-Bead Detection from a Single Dried Blood Spot.
A rapid, on-bead enzyme-linked immunosorbent assay for Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein 2 (HRP2) was adapted for use with dried blood spot (DBS) samples. This assay detected both biomarkers from a single DBS sample with only 45 minutes of total incubation time and detection limits of 600 ± 500 pM (pLDH) and 69 ± 30 pM (HRP2), corresponding to 150 and 24 parasites/μL, respectively. This sensitive and reproducible on-bead detection method was used to quantify pLDH and HRP2 in patient DBS samples from rural Zambia collected at multiple time points after treatment. Biomarker clearance patterns relative to parasite clearance were determined; pLDH clearance followed closely with parasite clearance, whereas most patients maintained detectable levels of HRP2 for 35-52 days after treatment. Furthermore, weak-to-moderate correlations between biomarker concentration and parasite densities were found for both biomarkers. This work demonstrates the utility of the developed assay for epidemiological study and surveillance of malaria.


Retracted: Worst Pattern Of Invasion and occult cervical metastases for oral squamous carcinoma.
The above article, published online in Wiley Online Library as the Version of Record on March 28, 2017 (doi 10.1002/hed.24754), has been retracted by agreement between the Editor-in-Chief, Ehab Y. Hanna, and Wiley Periodicals, Inc. The retraction has been agreed owing to a dispute as to authorship and inclusion of some data in the analysis. Velosa, C., Shi, Q., Stevens, T. M., Chiosea, S. I., Purgina, B., Carroll, W., Rosenthal, E., Morlandt, A., Loree, T. and Brandwein-Weber, M. S. (2017), Worst pattern of invasion and occult cervical metastases for oral squamous carcinoma. Head Neck. doi:10.1002/hed.24754.


Seedling Albinism Induced by an Extract of Alternaria tenuis.
The chlorophyll deficiency in citrus seedlings known as albinism was induced by inoculating seed with certain clones of Alternaria tenuis, or by germination of the seed in contact with extracts from the fungus. The active material in the extracts apparently has a rather specific inhibiting effect on chlorophyll formation in seedlings of various species.


The resolution of a transsexual wish in a five-year-old boy.
The brief truncated psychoanalytic treatment of a transsexual boy described in this paper demonstrates the development of transference reactions and their subsequent resolution. The analytic situation allowed this young patient to live out again his relationship with his parents in his relationship with the analyst, to recover from wishing to be a member of the female sex, and to work through his conflicted symbiosis with his mother. Carlos became able to individuate and disidentify from her into a separate male child, in order to be able to identify with, and accept, his own biological and psychological maleness. It is to be hoped that our success with this patient will encourage others to treat and study children suffering from gender identity problems via the psychoanalytic approach.


Ionic Strength Differentially Affects the Bioavailability of Neutral and Negatively Charged Inorganic Hg Complexes.
Mercury (Hg) bioavailability to bacteria in marine systems is the first step toward its bioamplification in food webs. These systems exhibit high salinity and ionic strength that will both alter Hg speciation and properties of the bacteria cell walls. The role of Hg speciation on Hg bioavailability in marine systems has not been teased apart from that of ionic strength on cell wall properties, however. We developed and optimized a whole-cell Hg bioreporter capable of functioning under aerobic and anaerobic conditions and exhibiting no physiological limitations of signal production to changes in ionic strength. We show that ionic strength controls the bioavailability of Hg species, regardless of their charge, possibly by altering properties of the bacterial cell wall. The unexpected anaerobic bioavailability of negatively charged halocomplexes may help explain Hg methylation in marine systems such as the oxygen-deficient zone in the oceanic water column, sea ice or polar snow.


Analysis of disease-dependent sedative profiles of H(1)-antihistamines by large-scale surveillance using the visual analog scale.
Sedation is the most frequent side effect of H(1)-antihistamines, and, sometimes, it may be life-threatening for patients. Evaluation of the sedative properties of H(1)-antihistamines is important to improve the patients' quality of life (QOL). Therefore, we carried out a large-scale surveillance quantified through a questionnaire using visual analog scale (VAS) from 1,742 patients. The results showed that the degree of sleepiness caused by some nonsedative second-generation antihistamines, including fexofenadine, olopatadine and cetirizine, was disease dependent. In atopic dermatitis, an unexpectedly low VAS score of sleepiness was obtained for the first-generation antihistamine d-chlorpheniramine, which is similar to those obtained for bepotastine and epinastine. d-Chlorpheniramine also showed a high VAS score in efficacy. Meanwhile, fexofenadine showed a higher VAS score of sleepiness in atopic dermatitis than those obtained in the other allergic diseases including allergic rhinitis, urticaria and asthma. In asthma, a higher VAS score of sleepiness was found for olopatadine, ebastine and cetirizine, when compared with d-chlorpheniramine. On the other hand, bepotastine showed the lowest VAS score for sleepiness. Our findings suggest the existence of unknown factors influencing the sedative properties of H(1)-antihistamines. Therefore, appropriate H(1)-antihistamines may need to be selected, depending on allergic diseases, to improve patients' QOL.


Increased mitochondrial glycerol-3-phosphate acyltransferase protein and enzyme activity in rat epididymal fat upon cessation of wheel running.
Triacylglycerol synthesis in rat epididymal fat overshoots sedentary levels at 10, 29, and 53 h of physical inactivity after 21 days of wheel running. The purposes of the present study were to determine 1) whether this effect is also observed after an acute bout of physical activity and 2) what enzymatic changes might contribute to this effect. We show that more than one bout of physical activity, such as that which occurs with 21 days of wheel running, is necessary for palmitic acid incorporation into triacylglyceride (triglyceride synthesis) to overshoot sedentary values, which suggests that pretranslational mechanisms may be responsible for this overshoot effect. Ten hours after 21 days of wheel running, activity of the mitochondrial glycerol-3-phosphate acyltransferase-1 (mtGPAT1) isoform, a key regulator of triacylglycerol synthesis, overshot sedentary values by 48% and remained higher than sedentary values at 29 and 53 h of reduced physical activity. The overshoot in mtGPAT1 activity was accompanied by an increase in mtGPAT protein level. Cyclic AMP response element-binding protein-binding protein level was higher in sedentary 29 h after 21 days of wheel running. AMP kinase-alpha Thr(172) phosphorylation was increased immediately after treadmill running, but decreased to sedentary values by 5 h after activity. Casein kinase-2alpha protein level and activity were unchanged. We conclude that an increase in mtGPAT protein might contribute to the overshoot in triacylglycerol synthesis.


Free radical production by azomethine H: effects on pancreatic and hepatic tissues.
The antimalarial properties of azomethine H represent the basis for its use as a chemotherapeutic agent. This work was carried out in order to verify the biological side effects of azomethine H and to clarify the contribution of reactive oxygen species (ROS) in this process. It was shown that azomethine H increased serum activities of amylase, alanine transaminase (ALT) and the TBARS concentrations, in rats. No changes were observed in glutathione peroxidase and catalase activities. The drug-induced tissue damage might be due to superoxide radicals (O2.-), since Cu-Zn superoxide dismutase activities were increased by azomethine H treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in azomethine H activity. We concluded that (O2.-) maybe produced as a mediator of azomethine H action.


Regulation of cyclic electron flow by chloroplast NADPH-dependent thioredoxin system.
Linear electron transport in the thylakoid membrane drives photosynthetic NADPH and ATP production, while cyclic electron flow (CEF) around photosystem I only promotes the translocation of protons from stroma to thylakoid lumen. The chloroplast NADH dehydrogenase-like complex (NDH) participates in one CEF route transferring electrons from ferredoxin back to the plastoquinone pool with concomitant proton pumping to the lumen. CEF has been proposed to balance the ratio of ATP/NADPH production and to control the redox poise particularly in fluctuating light conditions, but the mechanisms regulating the NDH complex remain unknown. We have investigated potential regulation of the CEF pathways by the chloroplast NADPH-thioredoxin reductase (NTRC) in vivo by using an Arabidopsis knockout line of NTRC as well as lines overexpressing NTRC. Here, we present biochemical and biophysical evidence showing that NTRC stimulates the activity of NDH-dependent CEF and is involved in the regulation of generation of proton motive force, thylakoid conductivity to protons, and redox balance between the thylakoid electron transfer chain and the stroma during changes in light conditions. Furthermore, protein-protein interaction assays suggest a putative thioredoxin-target site in close proximity to the ferredoxin-binding domain of NDH, thus providing a plausible mechanism for redox regulation of the NDH ferredoxin:plastoquinone oxidoreductase activity.


[Effect of the intravenous administration of homologous albumin on the lipolytic enzyme activity of rabbit blood plasma].
Activity of main lipolytic enzymes of rabbit blood plasma, lipoprotein lipase (LPL) and liver tissue triglyceride lipase (L-TGL) as well as intensity of lipoprotein lipolysis in vivo, which was estimated by an increase of unesterified fatty acids in blood plasma, studied after intravenous administration of homologous albumin at a dose of 200 mg/kg of body mass. The data obtained suggest that albumin is involved in regulation of lipoprotein lipolysis due to activation of LPL, caused by asseption of unesterified fatty acids, which are liberated after hydrolysis of triglycerides. This effect was exhibited by albumin only under conditions of active stimulation of lipolytic reactions, it occurs after intravenous administration of heparin (100 IU/kg of body mass). Albumin did not activate lipoprotein lipolysis and lipolytic enzymes in intact animals. Activity of L-TGL in blood plasma was less distinctly subjected to the regulatory effect of albumin.