The catalytic function of cytochrome P450 is entwined with its membrane-bound nature.
Cytochrome P450, a family of monooxygenase enzymes, is organized as a catalytic metabolon, which requires enzymatic partners as well as environmental factors that tune its complex dynamic. P450 and its reducing counterparts-cytochrome P450-reductase and cytochrome b 5 -are membrane-bound proteins located in the cytosolic side of the endoplasmic reticulum. They are believed to dynamically associate to form functional complexes. Increasing experimental evidence signifies the role(s) played by both protein-protein and protein-lipid interactions in P450 catalytic function and efficiency. However, the biophysical challenges posed by their membrane-bound nature have severely limited high-resolution understanding of the molecular interfaces of these interactions. In this article, we provide an overview of the current knowledge on cytochrome P450, highlighting the environmental factors that are entwined with its metabolic function. Recent advances in structural biophysics are also discussed, setting up the bases for a new paradigm in the study of this important class of membrane-bound enzymes.


Two-dimensional hybrid germanium zeotype formed by selective coordination of the trans-1,2-diaminocyclohexane isomer to the ge atom: heterogeneous acid-base bifunctional catalyst.
[C 6H 10(NH 2) 2Ge 3O 6] ICMM9 is a two-dimensional germanate in which the metallic atoms are covalently bonded to chelating diamines. Its layered structure having some similitude with that of the pyroxene mineral, presents a totally new topology with two 4-c nodes. The solvothermal synthesis reaction allows the separation in situ of the two 1,2-diaminocyclohexane isomers by selective coordination of the trans isomer to octahedral Ge atoms of the ICMM9 framework. This material behaves as an active and selective heterogeneous acid-base bifunctional catalyst.


Infundibulopelvic stenosis--evaluation of diagnostic imaging.
Infundibulopelvic stenosis is a very rare kidney disease. This congenital disorder must be differentiated from multicystic dysplastic kidney, polycystic kidney disease, simple renal cysts and mega-(poly)-calicosis. Associated abnormalities of the ureter are rare. Ureteric obstruction was associated in our two patients, and in one case agenesis of the bladder and a duplicated genital tract were also present.


Bactericidal Activity of Lactic Acid against Clinical, Carbapenem-Hydrolyzing, Multi-Drug-Resistant Klebsiella pneumoniae Planktonic and Biofilm-Forming Cells.
: Carbapenem resistant Klebsiella pneumoniae has been highlighted to be a critical pathogen by the World Health Organization. The objectives of this study were to assess the efficacy of lactic acid (LA) against planktonic cells and biofilms formed by carbapenem-hydrolyzing K. pneumoniae isolates obtained from the nares of preterm neonates. Time-kill assays with graded percentages of (v/v) LA in water were initially carried out against planktonic cells of a meropenem (MRP)-resistant K. pneumoniae isolate, JNM11.C4. The efficacy parameters such as optimal incubation time and minimum inhibitory concentration were determined by comparing colony-forming unit counts (log(10)CFU). Scanning electron microscopy was used to visualize cell damage. Likewise, JNM11.C4 biofilms were treated with graded series of (v/v) LA. Six carbapenem-hydrolyzing isolates were next used to validate the results. A reduction of 3.6 ± 0.6 log(10) CFU/mL in JNM11.C4 planktonic cells and >3 ± 0.03log(10) CFU/mL in biofilm-forming cells were observed using 0.225% and 2% LA, respectively, after three hours. Similar decreases in viable cell-counts were observed both in the case of planktonic (˃3.6 ± 0.3log(10) CFU/mL) and biofilm-forming cells (3.8 ± 0.3log(10) CFU/mL) across all the six clinical isolates. These results indicate that LA is an effective antimicrobial against planktonic carbapenem-hydrolyzing K. pneumoniae cells and biofilms.


Disposition of penicillin G after administration of benzathine penicillin G, or a combination of benzathine penicillin G and procaine penicillin G in cattle.
Plasma concentration of penicillin G was evaluated in beef steers after administration of either a combination of benzathine penicillin G and procaine penicillin G in a 1:1 mixture at a dosage of 9,000 U/kg of body weight, IM (n = 5), 24,000 U/kg, IM (n = 5), or 8,800 U/kg, SC (n = 5), or benzathine penicillin G alone at a dosage of 12,000 U/kg, IM (n = 7). Plasma concentration of penicillin G was measured by use of a high-performance liquid chromatography assay that had a limit of determination of 0.005 microgram/ml. At a dosage for this combination of 9,000 U/kg IM, and 8,800 U/kg, SC, which are approved label recommendations in Canada, and the United States, respectively, mean (+/- SEM) peak plasma concentration was 0.58 (+/- 0.15) and 0.44 (+/- 0.02) microgram/ml, respectively. Although plasma penicillin concentration was quantifiable for 7 days in the steers that received 9,000 U/kg, IM, and for 4 days in the steers that received 8,800 U/kg, SC, the concentration was < 0.1 microgram/ml in both groups after the first 12 hours. After administration of the combination at dosage of 24,000 U/kg, IM, there was an initial peak plasma concentration at approximately 2 hours; thereafter, plasma concentration decreased slowly, with half-life of 58 hours. Although plasma penicillin G concentration was quantifiable for 12 days at this dosage, concentration was < 0.1 microgram/ml after the first 48 hours. After the initial 48 hours, plasma concentration of penicillin was of similar magnitude and decreased at similar rate for the combination at dosage of 24,000 U/kg and for 12,000 U/kg of benzathine penicillin G alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of the left lateral recumbent position compared with the supine and upright positions on placental blood flow in normal late pregnancy.
The placental blood flow was assessed by the 99mTc accumulation method in 10 normal pregnancies in the left lateral recumbent position accomplished by a 15 degree wedge and in the supine position. The postural change caused a 17% decrease in the mean placental accumulation rate, which was not statistically significant. Ten patients were moved from the left lateral recumbent position to the upright position, which caused a statistically significant 23% decrease in the mean accumulation rate. Other haemodynamic variables studied were the maternal heart rate and the systolic and diastolic blood pressures. The clinical significance of the haemodynamic changes produced by alterations in posture are briefly discussed.


Hematologic effects of cis-platinum-bleomycin therapy.
A prospective study of the hematologic findings in 19 patients receiving cis-platinum (C-P) bleomycin (B) for squamous cell carcinoma of the head and neck was performed. CP 3 mg/kg was given on day 1, B 15 mg/m2 on day 3 and then by continuous infusison from day 3 to 10. Hematocrits declined in all patients from a mean of 41.6 +/- 3.9 to 36.6 +/- 4.9 (p less than 0.001) with the nadir seen by 10 days, reticulocyte count was unchanged. In 1 patient marked hemolysis occurred over 10-day period associated with the appearance of irregular spherocytes on smear, a situation similar to the index case which initiated this study. 5 other patients had spherocytes. A significant lymphopenia in the absence of neutropenia and thrombocytopenia was also observed.


An easy and fast ultrasonic selective S-alkylation of hetaryl thiols at room temperature.
A series of 2-alkylthio derivatives of hetaryl thiols were synthesized by selective S-alkylation with alkyl halides (bromides and iodides) with ultrasonic irradiation at room temperature. The reaction was found to be generally applicable to hetaryl thiol derivatives with different substituents in the aromatic nucleus and various alkyl halides. The reaction gives high to excellent yields of products with high purity.


A variant of LEAFY reveals its capacity to stimulate meristem development by inducing RAX1.
In indeterminate inflorescences, floral meristems develop on the flanks of the shoot apical meristem, at positions determined by auxin maxima. The floral identity of these meristems is conferred by a handful of genes called floral meristem identity genes, among which the LEAFY (LFY) transcription factor plays a prominent role. However, the molecular mechanism controlling the early emergence of floral meristems remains unknown. A body of evidence indicates that LFY may contribute to this developmental shift, but a direct effect of LFY on meristem emergence has not been demonstrated. We have generated a LFY allele with reduced floral function and revealed its ability to stimulate axillary meristem growth. This role is barely detectable in the lfy single mutant but becomes obvious in several double mutant backgrounds and plants ectopically expressing LFY. We show that this role requires the ability of LFY to bind DNA, and is mediated by direct induction of REGULATOR OF AXILLARY MERISTEMS1 (RAX1) by LFY. We propose that this function unifies the diverse roles described for LFY in multiple angiosperm species, ranging from monocot inflorescence identity to legume leaf development, and that it probably pre-dates the origin of angiosperms.


Moringa oleifera Leaf Extract: Beneficial Effects on Cadmium Induced Toxicities - A Review.
Environment has been contaminated by heavy metals ever since the original magma of earth has solidified. One such toxin is cadmium. Cadmium that has been around since the industrial age, is considered hazardous both to us and to the environment. From time immemorial man is dependent on plants available in nature for several health benefits. Moringa oleifera, has nutritional, pharmacological and antioxidant properties, thus having several medicinal applications. In the present article, we discuss the dose and time dependent damage due to exposure to cadmium on kidneys, liver, testis, lipid profile and haematological parameters in adult Wistar rats and the protective effects of Moringa oleifera (pre-treatment) on cadmium induced damage.


Structural Transitions of the Metal-Organic Framework DUT-49(Cu) upon Physi- and Chemisorption Studied by in Situ Electron Paramagnetic Resonance Spectroscopy.
Flexible metal-organic frameworks (MOFs) exhibit a variety of phenomena attractive for basic and applied science. DUT-49(Cu) is one of the remarkable representatives of such MOFs, where phase transitions are coupled to pressure amplification and "negative gas adsorption". In this work we report important insights into structural transitions of DUT-49(Cu) upon physi- and chemisorption of gases and volatile liquids obtained by in situ electron paramagnetic resonance (EPR) spectroscopy. In this method, phase transitions are detected via the zero-field splitting in dimeric copper(II) units. First, a new approach was validated upon physisorption of n-butane. Then, using diethyl ether, we for the first time demonstrated that chemisorption can also trigger phase transition in DUT-49(Cu). On the basis of the EPR results, the transition appears completely reversible. The developed EPR-based approach can also be extended to other flexible MOFs containing paramagnetic metal paddlewheels, where high sensitivity and spectral resolution allow in situ studies of stimuli-induced structural variability.


Incidence and regional distribution of lung overinflation during mechanical ventilation with positive end-expiratory pressure.
In patients with acute lung injury, alveolar recruitment resulting from positive end-expiratory pressure (PEEP) may be associated with overinflation of previously aerated lung regions. The aim of this study was to assess the incidence and regional distribution of lung overinflation resulting from mechanical ventilation with PEEP. Reanalysis with a specific software including a color-coding system of quantitative lung computed tomography data obtained in four previous prospective studies. A 20-bed surgical intensive care unit of a Parisian university hospital. Thirty-two patients with acute lung injury in whom computed tomography of the whole lung was obtained at zero end-expiratory pressure (ZEEP) and PEEP 15 cm H2O. None. Total lung recruitment was measured as the reaeration of poorly aerated (computed tomography attenuations ranging between -500 and -100 Hounsfield units) and nonaerated (computed tomography attenuations > or = -100 Hounsfield units) lung areas, and overinflation was measured as the lung volume characterized by computed tomography attenuations < or = -900 Hounsfield units. PEEP was associated with a significant alveolar recruitment (423 +/- 178 mL). Concomitantly, a lung overinflation of 123 +/- 138 mL was found in 14 patients (44%). In eight patients without chronic obstructive pulmonary disease, lung overinflation was predominantly found in nondependent lung regions located beneath the dome of diaphragm. In six patients with a past history of chronic obstructive pulmonary disease, PEEP increased the volume of emphysematous areas present in apical lung regions and produced an overinflation of nondependent lung regions located beneath the dome of diaphragm. Lung overinflation resulting from mechanical ventilation with PEEP is observed in more than one third of patients with acute lung injury lying supine and predominates in caudal and nondependent lung regions. Furthermore, in patients with a history of chronic obstructive pulmonary disease, PEEP markedly increases the volume of emphysematous lung regions.


A Novel Derivative of (-)mycousnine Produced by the Endophytic Fungus Mycosphaerella nawae, Exhibits High and Selective Immunosuppressive Activity on T Cells.
An endophytic fungus, Mycosphaerella nawae ZJLQ129, was isolated from the leaves of the traditional Chinese medicine Smilax china. From the fermentation broth and mycelium, a dibenzofurane compound (-)mycousnine (1) was isolated. Chemical modification of it to the amide derivative (-)mycousnine enamine (2), which is new to science, was found to have high and selective immunosuppressive activity: similar to cyclosporin A, (-)mycousnine enamine (2) selectively inhibited T cell proliferation, suppressed the expression of the surface activation antigens CD25 and CD69 and the formation and expression of the cytokines interleukin-2 as well as interferon γ in activated T cells, but did not show any effect on the proliferation of B cells and cancer cells (PANC-1 and A549) and the activation of macrophages. Furthermore, the cytotoxicity of (-)mycousnine enamine was lower than that of cyclosporin A, and its therapeutic index (TC50/EC50) was 4,463.5, which is five-fold higher than that of cyclosporin A. We conclude that (-)mycousnine enamine (2), the semi-synthestic product prepared from the native product (-)mycousnine (1) of the endophyte M. nawae is a novel effective immunosuppressant showing low toxicity and high selectivity.


The modified cone reconstruction in the treatment of Ebstein's anomaly: Case reports.
To investigate the early and mid-term clinical outcomes of the modified cone reconstruction in the treatment of Ebstein's anomaly (EA) which provide appropriate surgical treatment for clinical and reduce the incidence of re-operation and valve replacement. Clinical data of 18 consecutive patients with EA in our hospital between May 2008 and August 2015 were analyzed retrospectively. All patients were diagnosed by echocardiography. Among these patients, according to New York Heart Association functional grade, there were 12 patients with grade II cardiac function and 6 patients with grade III. All patients had severe tricuspid regurgitation grade. All patients were diagnosed EA. One case was with acute arterial embolism and amputation of left lower extremity caused by paradoxical embolism of combined secundum atrial septal defect. The modified cone reconstruction in the treatment of EA of the tricuspid valve uses its own tissues to form not only central bloodstream, but also the coaption between 2 leaflets. For those patients whose anterior leaflet developed poor and smaller, the valve leaflet was widened by using autologous pericardial. For all patients, tricuspid annulus were reinforced by autologous pericardial. One case was combined with double-orifice technique due to postoperative poor closure of the tricuspid valve. There were 2 cases with arrhythmia, and they returned to normal after medication. The rest patients recovered smoothly with no death. Review of echocardiography: 1 patient with moderate regurgitation, the rest of patients' leaflets coapted well and had no tricuspid stenosis. All cases were followed up postoperatively for 9 to 38 months, and there were 14 patients with grade I cardiac function and 4 patients with grade II. The early and mid-term clinical outcomes of the modified cone reconstruction in the treatment of EA were which can make leaflets coapt and had a strong antiregurgitation ability, reducing the incidence of re-operation, valve replacement, and postoperative mortality.


Contrast-induced acute kidney injury in cirrhotic patients. A retrospective analysis.
The nephrotoxic potential of intravenous iodinated contrast (IC) is controversial. Cirrhotic patients are often submitted to imaging procedures involving IC and small changes in renal function may have detrimental effects. Retrospective analysis of hospitalized patients with elective imaging by either contrast-enhanced CT or MRI. Contrast induced acute kidney injury (CI-AKI) was diagnosed if there was either an increase of SCr by 25% or by 44 μmol/L or a decrease of estimated glomerular filtration rate by 25% by day 3. Between 2004 and 2012 152 patients (female: 30.3%, age: 60 ± 10.8 years, MELD 13 ± 6) were included in this study of which 84 (55.3%) had received IC and 68 (44,7%), who served as controls, MRI with gadolinium based contrast (non-IC). Baseline parameters were well matched except for age (61.7 vs. 56.9) years in the IC vs. non-IC groups, p = 0.005). 15 patients (17.9%) receiving IC and 4 patients (5.9%) not receiving IC (p = 0.026) reached the composite end-point for CI-AKI. In multivariable regression analysis INR [B = 0.252 (95% CI: 0.108-0.397), p = 0.001]; IC [B = 0.136 (95% CI: 0.023-0.248), p = 0.019] and serum sodium [B = 0.011 (95% CI: 0.001-0.023); p = 0.080] were independently associated with changes of SCr. In conclusion IC may cause renal dysfunction in cirrhotic patients. Patients subjected to imaging using IC should be closely monitored.


Differential gene expression during desiccation stress in the insect-killing nematode Steinernema feltiae IS-6.
The developmentally arrested life stage of the entomopathogenic nematode Steinernema feltiae is exposed to threats of survival, including desiccation. We adopted a comprehensive approach to the study of the molecular mechanisms of desiccation stress tolerance in S. feltiae IS-6. We identified, expressed sequence tags (ESTs) that are differentially expressed during desiccation stress in S. feltiae IS-6 infective juveniles using DNA subtractive hybridization. These ESTs included genes that are known to be stress related, genes that are homologous to hypothetical Caenorhabditis elegans proteins, and novel genes that may be involved in traits specific to S. feltiae. Expression pattern characterization revealed that all analyzed ESTs were induced during 8 and 24 hr of dehydration of S. feltiae IS-6. Our results unveiled some of the components of the genetic networks that are activated in S. feltiae IS-6 during dehydration and suggested a differing pattern of temporal regulation during nematode dehydration.


On design of free-form refractive beam shapers, sensitivity to figure error, and convexity of lenses.
The problem of design of a two-lens optical system for reshaping the irradiance distribution of a laser beam in a prescribed manner is considered in the geometrical optics approximation. The presented design equations are derived in a rigorous manner and are applicable to free-form two-lens optical systems without any a priori symmetry assumptions on radiance profiles and beam cross sections. The obtained equations are applied to derive an equation defining sensitivity of the output radiation intensity to figure errors. This equation is applied to analyze sensitivity in several cases, including rotationally symmetric reshapers with nonrotationally symmetric figure error. The presented approach shows also that even in the general case two different designs are available for the same data. In one of these designs one lens is always concave or convex and the second is convex or concave, while in the second design the lenses may be neither convex nor concave. Since, in general, the surface lenses are aspherical, the availability of a design with convex/concave lenses is particularly important for fabrication.


Molecular profiling of endometrial malignancies.
Molecular profiling of endometrial neoplasms reveals genetic changes in endometrial carcinomas that support the dualistic model, in which type I carcinomas are estrogen-dependent, low grade lesions and type II carcinomas are nonestrogen dependent and high grade. The molecular changes in type I endometrial carcinomas include mutations in PTEN, PIK3CA, KRAS, and beta-catenin, along with microsatellite instability, whereas type II endometrial carcinomas are characterized by genetic alterations in p53, HER2/neu, p16, and E-cadherin. For endometrial neoplasms with a malignant mesenchymal component, C-MYC mutations and loss of heterozygosity are frequently seen in carcinosarcomas, and a fusion gene, JAZF1/JJAZ1, is distinctive for endometrial stromal sarcoma. In addition, p53 mutations may play an important role in tumorigenesis of undifferentiated endometrial sarcoma. These molecular changes can help in the diagnosis of endometrial neoplasms, as well as form the basis of molecular targeted therapy.


Diaryldimethylpiperazine ligands with mu- and delta-opioid receptor affinity: Synthesis of (+)-4-[(alphaR)-alpha-(4-allyl-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide and (-)-4-[(alphaR)-alpha-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide.
We have explored the synthesis of compounds that have good affinity for both mu- and delta-opioid receptors from the (alphaR,2S,5S) class of diaryldimethylpiperazines. These non-selective compounds were related to opioids that have been found to interact selectively with mu- or delta-opioid receptors as agonists or antagonists. In our initial survey, we found two compounds, (+)-4-[(alphaR)-alpha-(4-allyl-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide (14) and its N-H relative, (-)-4-[(alphaR)-alpha-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide (15), that interacted with delta-receptors with good affinity, and, as we hoped, with much higher affinity at mu-receptors than SNC80. The relative configuration of the benzylic position in (+)-4-[(alphaR)-alpha-(4-allyl-(2S,5S)-dimethyl-1-piperazinyl)-(3-methoxyphenyl)methyl]-benzyl alcohol (10) was determined by X-ray crystallographic analysis of a crystal that was an unresolved twin. The absolute stereochemistry of that benzylic stereogenic center was unequivocally derived by the X-ray crystallographic analysis from the two other centers of asymmetry in the molecule that were known. Those were established from the synthesis via a dipeptide cyclo-L-Ala-L-Ala in which the absolute stereochemistry was established.


Endogenous Plasmids and Chromosomal Genome Reduction in the Cardinium Endosymbiont of Dermatophagoides farinae.
Cardinium bacteria are well known as endosymbionts that infect a wide range of arthropods and can manipulate host reproduction to promote their vertical transmission. As intracellular bacteria, Cardinium species undergo dramatic genome evolution, especially their chromosomal genome reduction. Although Cardinium plasmids have been reported to harbor important genes, the role of these plasmids in the genome evolution is yet to be fully understood. In this study, 2 genomes of Cardinium endosymbiont bacteria in astigmatic mites were de novo assembled, including the complete circular chromosomal genome of Cardinium sp. DF that was constructed in high quality using high-coverage long-read sequencing data. Intriguingly, 2 circular plasmids were assembled in Cardinium sp. DF and were identified to be endogenous for over 10 homologous genes shared with the chromosomal genome. Comparative genomics analysis illustrated an outline of the genome evolution of Cardinium bacteria, and the in-depth analysis of Cardinium sp. DF shed light on the multiple roles of endogenous plasmids in the molecular process of the chromosomal genome reduction. The endogenous plasmids of Cardinium sp. DF not only harbor massive homologous sequences that enable homologous recombination with the chromosome, but also can provide necessary functional proteins when the coding genes decayed in the chromosomal genome. IMPORTANCE As bacterial endosymbionts, Cardinium typically undergoes genome reduction, but the molecular process is still unclear, such as how plasmids get involved in chromosome reduction. Here, we de novo assembled 2 genomes of Cardinium in astigmatic mites, especially the chromosome of Cardinium sp. DF was assembled in a complete circular DNA using high-coverage long-read sequencing data. In the genome assembly of Cardinium sp. DF, 2 circular endogenous plasmids were identified to share at least 10 homologous genes with the chromosomal genome. In the comparative analysis, we identified a range of genes decayed in the chromosomal genome of Cardinium sp. DF but preserved in the 2 plasmids. Taken together with in-depth analyses, our results unveil that the endogenous plasmids harbor homologous sequences of chromosomal genome and can provide a structural basis of homologous recombination. Overall, this study reveals that endogenous plasmids participate in the ongoing chromosomal genome reduction of Cardinium sp. DF.


Conjugation of active iron superoxide dismutase to nanopatterned surfaces.
Superoxide dismutase enzymes (SODs) are an essential part of the first line of cellular defense system against free radicals species. They catalyze the dismutation of superoxide radicals into oxygen and hydrogen peroxide. Although several studies have examined the attachment of superoxide dismutases to nanoparticles and nanostructures, never has been used a member of the Fe/MnSOD family. In this study, the behavior of plant origin FeSOD enzyme on three different nanopatterned surfaces was investigated as a function of covalent and electrostatic binding. Fluorescence microscopy was used to demonstrate that the protein is attached only to the gold layer. We also examined the activity of SOD by a colorimetric assay, and we have shown that the enzyme remains active after attachment to the three different surfaces under both kind of binding (electrostatic and covalent). This methodology could be useful for those who want to functionalize nanostructures with a SOD enzyme and test the activity. This process could be of great interest for the development of peroxynitrite and superoxide biosensors.


The use of heterologous promoters for adeno-associated virus (AAV) protein expression in AAV vector production.
Although adeno-associated virus (AAV) vectors are potentially useful gene transfer vehicles for gene therapy, the vector production system is currently at the developmental stage. We constructed AAV helper plasmids (Rep and Cap expression plasmids) by replacing a native AAV promoter, p5, with various heterologous promoters to examine whether the efficiency of AAV vector production was influenced by modulating the AAV protein expression pattern. The helper plasmids containing heterologous promoters (EF, CMV, SV40, B19p6, and CAG promoters, respectively) expressed Rep78/68 more efficiently than a conventional helper plasmid (pIM45), but the expression of Rep52/40 and Cap decreased, resulting in a significant reduction in AAV vector production. Furthermore, the efficiency of vector production never fully recovered even if the Cap proteins were supplied by an additional expression plasmid. A large amount of Rep78/68 and/or a reduced level of Rep52/40 may have deleterious effects on AAV vector production. The present findings will aid in the development of a more efficient AAV vector production system.


Clinical Predictors of Engagement in Inpatient Rehabilitation Among Stroke Survivors With Cognitive Deficits: An Exploratory Study.
The purpose of this exploratory study was to identify clinical predictors that could distinguish clients' level of engagement in inpatient rehabilitation following stroke. This is a secondary analysis of pooled data from three randomized controlled trials that examined the effects of a behavioral intervention. The sample (n=208) consisted of clients with stroke who had cognitive deficits (Quick-EXIT≥3) and were admitted to inpatient rehabilitation facilities associated with a university medical center. Individuals with pre-morbid dementia, aphasia and mood disorders were excluded. The Pittsburgh Rehabilitation Participation Scale was used to measure engagement. Clinical predictors were measured using the Functional Independence Measure, National Institutes of Health Stroke Scale, Repeatable Battery for the Assessment of Neuropsychological Status, selected subtests of the Delis-Kaplan Executive Function System, Patient Health Questionnaire-9, and Chedoke McMaster Stroke Assessment. Simple logistic regression identified individual clinical predictors associated with engagement. Hierarchical logistic regression identified the strongest predictors of engagement. Impairments in executive functions [mean D-KEFS, odds ratio (OR)=4.062; 95% confidence interval (CI)=.866, 19.051], impairments in visuospatial skills (RBANS Visuospatial Index Score, OR=3.940; 95% CI=1.317, 11.785), impairments in mood (Patient Health Questionnaire-9, OR=2.059, 95% CI=.953, 4.449), and male gender (OR=2.474; 95% CI=1.145, 5.374) predicted levels of engagement in inpatient rehabilitation after controlling for study intervention group, baseline stroke severity, and baseline disability. Executive functions, visuospatial skills, mood, and gender distinguished individuals with high or low engagement in inpatient rehabilitation following stroke. Further studies should examine additional factors that may influence engagement (therapist-client relationship, treatment expectancy). (JINS, 2018, 24, 572-583).


Predictors of door-to-balloon delay in primary angioplasty.
In the treatment of acute myocardial infarction, delayed reperfusion therapy is associated with increased mortality. Predictors of delay have been described for fibrinolysis but not for primary percutaneous transluminal coronary angioplasty (pPTCA). Therefore, we studied 40,017 consecutive patients with acute myocardial infarction who underwent pPTCA in the National Registry of Myocardial Infarction between June 1994 and April 2000. Median door-to-balloon times were calculated, and factors independently associated with a delay of >120 minutes were determined by logistic regression. The median door-to-balloon time among all patients was 111 minutes (interquartile range 84 to 152). The proportion of patients with a delay of >2 hours was greater among those aged > or = 65 years (49% vs 41%), women (50% vs 42%), patients with contraindications to fibrinolysis (60% vs 41%), and those without chest pain on admission (61% vs 43%, all p <0.0001). Delay was also more common with transfer from another hospital (87% vs 38%), with presentation outside the hours of 8 A.M. to 4 P.M. (51% vs 38%), and in hospitals performing <49 pPTCAs/year (47% vs 41%, all p <0.0001). The strongest independent predictor of delay was hospital transfer, along with non-daytime presentation and low-volume centers. Older age, female sex, and non-white race were weaker predictors. Both patient and hospital factors are associated with delay in pPTCA after presentation. These findings may help design treatment algorithms to minimize delay, thus improving the survival benefit of pPTCA. These results may also help design trials of combination reperfusion strategies.


Natural and induced T regulatory cells in cancer.
CD4+Foxp3+ T regulatory (Treg) cells control many facets of immune responses ranging from autoimmune diseases, to inflammatory conditions, and cancer in an attempt to maintain immune homeostasis. Natural Treg (nTreg) cells develop in the thymus and constitute a critical arm of active mechanisms of peripheral tolerance particularly to self antigens. A growing body of knowledge now supports the existence of induced Treg (iTreg) cells which may derive from a population of conventional CD4+ T cells. The fork-head transcription factor (Foxp3) typically is expressed by natural CD4+ Treg cells, and thus serves as a marker to definitively identify these cells. On the contrary, there is less consensus on what constitutes iTreg cells as their precise definition has been somewhat elusive. This is in part due to their distinct phenotypes which are shaped by exposure to certain inflammatory or "assault" signals stemming from the underlying immune disorder. The "policing" activity of Treg cells tends to be uni-directional in several pathological conditions. On one end of the spectrum, Treg cell suppressive activity is beneficial by curtailing T cell response against self-antigens and allergens thus preventing autoimmune diseases and allergies. On the other end however, their inhibitory roles in limiting immune response against pseudo-self antigens as in tumors often culminates into negative outcomes. In this review, we focus on this latter aspect of Treg cell immunobiology by highlighting the involvement of nTreg cells in various animal models and human tumors. We further discuss iTreg cells, relationship with their natural counterpart, and potential co-operation between the two in modulating immune response against tumors. Lastly, we discuss studies focusing on these cells as targets for improving anti-tumor immunity.


Prospective evaluation of the Ottawa Ankle Rules in a university sports medicine center. With a modification to increase specificity for identifying malleolar fractures.
In a sports medicine center, we prospectively evaluated the Ottawa Ankle Rules over 1 year for their ability to identify clinically significant ankle and midfoot fractures and to reduce the need for radiography. We also developed a modification to improve specificity for malleolar fracture identification. Patients with acute ankle injuries (< or = 10 days old) had the rules applied and then had radiographs taken. Sensitivity, specificity, and the potential reduction in the use of radiography were calculated for the Ottawa Ankle Rules in 132 patients and for the new "Buffalo" rule in 78 of these patients. There were 11 clinically significant fractures (fracture rate, 8.3% per year). In these 132 patients, the Ottawa Ankle Rules would have reduced the need for radiography by 34%, without any fractures being missed (sensitivity 100%, specificity 37%). In 78 patients, the specificity for malleolar fracture for the new rule was significantly greater than that of the Ottawa Ankle Rules malleolar rule (59% versus 42%), sensitivity remained 100%, and the potential reduction in the need for radiography (54%) was significantly greater. The Ottawa Ankle Rules could significantly reduce the need for radiography in patients with acute ankle and midfoot injuries in this setting without missing clinically significant fractures. The Buffalo modification could improve specificity for malleolar fractures without sacrificing sensitivity and could significantly reduce the need for radiography.


[Effect of NGX6 on gene expression profile of colon carcinoma cell line HT-29].
Colon cancer is one of the most common malignant tumors, but the mechanism involved in its pathogenesis is not fully understood. Under the foundation of early study, we intended to explore the effects of NGX6 on the gene expression profile of colon carcinoma cell line HT-29. pcDNA3.1-NGX6-transfected HT-29 cells were used as the test, and empty vector-transfected HT-29 cells were used as the control. Differentially expressed genes were screened with high-throughout BiostarH-80sx1 DNA microarray; part of the results of DNA microarray was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). NGX6 transfection induced wide changes of the gene expression profile of HT-29 cells. A total of 377 genes were up-regulated or down-regulated by more than 3 folds, which were involved in cell signal transduction, cell cycle controlling, cell apoptosis, cytokinetics, gene transcription and translation, DNA damage and repairing, protein synthesis, metabolism, and so on. Some of them belonged to some important signal pathways related with cell proliferation and metastasis, such as DDK1, ILK, MMP-1 and COL11A1 in Wnt/beta-catenin signal pathway, ILK in ILK signal pathway, EpHB2 in Eph-Ephrins signal pathway, ROCK2 in RhoA signal pathway, RANBP1 in RanGTPase signal pathway, and RBBP1 in RB/RBBP1 signal pathway. NGX6 transfection leads to molecular changes of some important signal pathways, and may suppress cell proliferation and metastasis of tumor by regulating these signal pathways.


Representation of Nursing Scientists from German-speaking countries in High Impact Journals. A bibliometric publication analysis
Background: The frequency of publications by nursing scientists from the German-speaking area in journals with a high impact factor is an indicator for participation of the discipline in the international discourse. Previous publication analyses focused on nursing science journals only and regularly found an underrepresentation of experimental studies and clinical topics. Aim: To identify and analyse the number of publications by nursing scientists from Germany, Austria and German-speaking Switzerland in international high impact journals. Method: The Journal Citation Reports were used to identify nursing relevant categories of journals in which the highest 10 % of the years 2010 to 2014 were selected according to the 5-year Impact Factor. Inclusion of publications and data extraction were carried out by two independent persons. Results: 106939 publications from 126 journals were screened; 100 publications were identified with 229 contributions by 114 nursing scientists. 42 % of studies are observational and 11 % are experimental. The majority of studies are clinically oriented (55 %). More than 50 % have been published in the past two years. Conclusions: The number of publications by nursing scientists from the German-speaking countries in High Impact Journals is low. There is an increase throughout the observation period. In opposite to former analyses a higher proportion of clinical research has been found.


Bestiality: An introduction for legal and mental health professionals.
Bestiality, or human-animal intercourse, has been a concern of the legal and mental health communities for many years. Ancient legal codes delineated punishments for those who engaged in the behavior, denoting a moral and general societal concern surrounding bestiality dating to ancient times. Despite this longstanding interest in and legal efforts to punish humans for having sex with animals, there has been little research on the behavior. Current available research has largely been siloed based on the populations studied, making it difficult to render any firm conclusions about bestiality's prevalence, frequency, and the risk posed by those who have sex with animals. It is important for clinicians to know the legal status of the behavior in their jurisdictions, to understand possible medical and psychiatric complications and comorbidities, and to know how to evaluate and treat individuals who engage in bestiality or have the related diagnosis of zoophilic disorder. This article provides an overview of the terminology and research pertaining to bestiality, summarizes legal and ethical considerations, and describes clinically relevant information for the evaluation and management of individuals engaged in sex with animals.


Bone regeneration using titanium nonwoven fabrics combined with fgf-2 release from gelatin hydrogel microspheres in rabbit skull defects.
The objective of this study was to modify titanium nonwoven fabrics (Ti) with a hydroxyapatite (HA)-like coating and fibroblast growth factor (FGF)-2 combination, and evaluate the bone regeneration potential of the modified Ti. Biodegradable gelatin hydrogel microspheres (GM) were prepared as a carrier matrix for the controlled release of FGF-2. Ti, HA-coated Ti (Ti-HA), and Ti-HA incorporating GM (Ti-HA-GM) infused FGF-2 were applied to skull defects of rabbits. Then osteointegration in the Ti was evaluated by alkaline phosphatase activity, Ca(2+) content, and histological observation, and the hemoglobin content was assessed for angiogenic measurement. Ti-HA-GM promoted bone regeneration to a significantly greater extent than Ti, Ti-HA, or mixed Ti-HA and free FGF-2 6 weeks after application, and it also enhanced the hemoglobin content. It is concluded that the combination of HA-like coating and FGF-2 release promotes Ti induction of bone regeneration.


State-of-the-art and challenges in the analysis of renewable gases.
The development of renewable and low-carbon gases for injection into the gas grid obtained by different processes such as anaerobic digestion, pyrogasification, hydrothermal gasification, and methanation, followed by upgrading steps, increases the demand for analysis and characterization in order to fully manage their integration into the gas value chain. If the analysis of the main compounds (methane, carbon dioxide, hydrogen, and carbon monoxide) is well described, the analysis of impurities in renewable gases remains more challenging due to their various natures and quantities. After a brief description of renewable and low-carbon methane production processes, the review focuses on the methods used for the analysis of the different compounds in renewable gases, from the main ones to impurities at ppbv levels. Gas chromatography (GC), coupled with different detectors, is the preferred technique, enabling the analysis and quantification of siloxanes, terpenes, oxygenates, and sulfur compounds. Recently, comprehensive two-dimensional GC has been applied to renewable gases, increasing the number of compounds detected. Non-chromatographic techniques are also reviewed. As sampling is of major importance in the search for reliable analyses, a whole section is devoted to this aspect. Among the available methods, pre-concentration on adsorbent tubes emerges as the most relevant solution.


Engineering the substrate specificity of D-amino-acid oxidase.
The high resolution crystal structure of D-amino-acid oxidase (DAAO) from the yeast Rhodotorula gracilis provided us with the tool to engineer the substrate specificity of this flavo-oxidase. DAAO catalyzes the oxidative deamination of D-amino acids, with the exception of D-aspartate and D-glutamate (which are oxidized by D-aspartate oxidase, DASPO). Following sequence homology, molecular modeling, and simulated annealing docking analyses, the active site residue Met-213 was mutated to arginine. The mutant enzyme showed properties close to those of DASPO (e.g. the oxidation of D-aspartate and the binding of l-tartrate), and it was still active on D-alanine. The presence of an additional guanidinium group in the active site of the DAAO mutant allowed the binding (and thus the oxidation) of D-aspartate, but it was also responsible for a lower catalytic activity on D-alanine. Similar results were also obtained when two additional arginines were simultaneously introduced in the active site of DAAO (M213R/Y238R mutant, yielding an architecture of the active site more similar to that obtained for the DASPO model), but the double mutant showed very low stability in solution. The decrease in maximal activity observed with these DAAO mutants could be due to alterations in the precise orbital alignment required for efficient catalysis, although even the change in the redox properties (more evident in the DAAO-benzoate complex) could play a role. The rational design approach was successful in producing an enzymatic activity with a new, broader substrate specificity, and this approach could also be used to develop DAAO variants suitable for use in biotechnological applications.


Evaluation of cellular effects of silicon dioxide nanoparticles.
Silica nanoparticles (nSiO2s) are an important type of manufactured nanoparticles. Although there are some reports about the cytotoxicity of nSiO2, the association between physical and chemical properties of nSiO2s and their cellular effects is still unclear. In this study, we examined the correlation between the physiochemical properties and cellular effects of three kinds of amorphous nSiO2s; sub-micro-scale amorphous SiO2, and micro-scale amorphous and crystalline SiO2 particles. The SiO2 particles were dispersed in culture medium and applied to HaCaT human keratinocytes and A549 human lung carcinoma cells. nSiO2s showed stronger protein adsorption than larger SiO2 particles. Moreover, the cellular effects of SiO2 particles were independent of the particle size and crystalline phase. The extent of cell membrane damage and intracellular ROS levels were different among nSiO2s. Upon exposure to nSiO2s, some cells released lactate dehydrogenase (LDH), whereas another nSiO2 did not induce LDH release. nSiO2s caused a slight increase in intracellular ROS levels. These cellular effects were independent of the specific surface area and primary particle size of the nSiO2s. Additionally, association of solubility and protein adsorption ability of nSiO2 to its cellular effects seemed to be small. Taken together, our data suggest that nSiO2s do not exert potent cytotoxic effects on cells in culture, especially compared to the effects of micro-scale SiO2 particles. Further studies are needed to address the role of surface properties of nSiO2s on cellular processes and cytotoxicity.


Synthesis of stable aminoacyl-tRNA analogues containing triazole as a bioisoster of esters.
Aminoacyl-tRNAs have important roles in a variety of biological processes, including protein synthesis by ribosomes, targeting of proteins for degradation by the proteasome, and bacterial cell wall synthesis. Here we describe the synthesis of stable aminoacyl-tRNA analogues containing 1,4- and 1,5-substituted 1,2,3-triazole rings. The procedure involves i) Cu- and Ru-catalysed cycloadditions of 3'-azidoadenosine and alkynes, which produced the 1,4 and 1,5 regioisomers of the triazoles, respectively, ii) coupling between the resulting triazole-deoxyadenosine derivatives and a deoxycytidine phosphoramidite, and iii) the enzymatic ligation of the substituted dinucleotides with a 22 nt RNA microhelix that mimics the acceptor arm of tRNA. Nucleoside and nucleotide compounds were characterized by MS spectrometry and (1)H, (31)P and (13)C NMR spectroscopy and were assayed for inhibition of FemX(Wv), an alanyltransferase essential for the formation of the peptidoglycan network of gram-positive bacterial pathogens. The low IC(50) values obtained (2 to 4 microM) indicate that the five-membered triazole rings acted as bioisosters of esters and can be used for the design of stable aminoacyl-tRNA analogues.


Ziryab and Us: Tradition and Collaboration in the Interpretation of an Arab-Andalusian Musical Myth.
The ninth-century poet and musician, Ziryab, is synonymous with the musical cultures of Muslim Spain (al-Andalus) and the idea of commonality between different genres across the Mediterranean. While some scholars have deconstructed the myth of Ziryab at a historiographical level, there has been less consideration of how the myth is interpreted in contemporary musical practice. This article examines how Ziryab is reinterpreted in the present through intercultural music making. Drawing on fieldwork in Madrid and Valencia (2016), I focus on the Ziryab and Us: A New Vision of the Arab-Andalusian Heritage project, in which French, Israeli, Moroccan and Spanish musicians sought to reinterpret the legend of Ziryab through the lens of their own musical traditions. I argue that Ziryab functioned as a discursive trope that engendered a series of micro-social relations between the musicians, framed by ideas of musical affinity, a shared cultural space (the Mediterranean) and cross-cultural exchange. But beyond the ideals of musical connection that Ziryab implies, the relational processes that characterised the project were not always unified. Therefore, I examine some of the points of tension that emerged when the musicians brought together distinct traditions under the rubric of a shared 'Andalusian' or Mediterranean heritage.


Effect of NOS3 gene polymorphism on response to Tricyclic antidepressants in migraine attacks.
Migraine is a chronic neurological disorder, characterized by recurrent moderate to severe headaches. Worldwide migraine affects nearly 15%. Studies suggest that genes involved in the production of nitric oxide (NO) may act as genetic factors for migraine. NO synthase 3 (NOS3) by expressing enzyme NOS regulates endothelial derived NO. One class of medications used as first-line treatment in migraine prophylaxis is tricyclic antidepressants (TCAs). The aim of this study was to determine effects of NOS3 gene Glu298Asp polymorphism in the production of NO and response of patients to TCAs in migraine attacks. A total of 80 migraine patients were invited to participate in the study. Patients recorded the characteristics of their migraine attacks such as frequency of attacks and intensity of headaches for the 1(st) month of the study. Then peripheral blood samples were taken from all subjects in order to determine patients' genotype distribution, mRNA expression level of NOS3 and NO content of plasma. Patients were then instructed to use 25 mg nortriptyline at night before bed for 3 months. At the end of 3(rd) month of the treatment patients again recorded the migraine characteristics for 1 month and blood sampling was performed in order to determine the level of plasma NO. The patients' genotype distribution for TT, GT, and GG was 9, 24, and 47 subjects, respectively. Mean NO level in patients with TT genotype was less in comparison to GT and GG genotypes before and after use of TCAs (P < 0.05). Mean intensity of headaches in patients with TT genotype was lower in comparison to GT and GG genotypes before and after use of TCAs (based on verbal numerical rating scale). Mean frequency of migraine attacks after use of TCAs was significantly decreased in all genotypes of NOS3 Glu298Asp polymorphism particularly in TT genotype (P < 0.05). Presence of T allele of the Glu298Asp polymorphism may be a factor for TT genotype patients to produce less NO and is a favorable factor for better response to TCAs in reducing migraine attacks in comparison to GT and GG genotypes.


Changes of Metabolomic Profile in Helianthus annuus under Exposure to Chromium(VI) Studied by capHPLC-ESI-QTOF-MS and MS/MS.
The application of capHPLC-ESI-QTOF-MS and MS/MS to study the impact of Cr(VI) on metabolites profile in Helianthus annuus is reported. Germinated seeds were grown hydroponically in the presence of Cr(VI) (25 mgCr/L) and root extracts of the exposed and control plants were analyzed by untargeted metabolomic approach. The main goal was to detect which metabolite groups were mostly affected by Cr(VI) stress; two data analysis tools (ProfileAnalysis, Bruker, and online XCMS) were used under criteria of intensity threshold 5 · 104 cps, fold change ≥ 5, and p ≤ 0.01, yielding precursor ions. Molecular formulas were assigned based on data processing with two computational tools (SIRIUS and MS-Finder); annotation of candidate structures was performed by database search using CSI:FingerID and MS-Finder. Even though ultimate identification has not been achieved, it was demonstrated that secondary metabolism became activated under Cr(VI) stress. Among 42 candidate compounds returned from database search for seven molecular formulas, ten structures corresponded to isocoumarin derivatives and eleven were sesquiterpenes or sesquiterpene lactones; three benzofurans and four glycoside or pyrane derivatives of phenolic compounds were also suggested. To gain further insight on the effect of Cr(VI) in sunflower, isocoumarins and sesquiterpenes were selected as the target compounds for future study.


Genome-wide association study for jumping performances in French sport horses.
A genome-wide association study was performed to identify single nucleotide polymorphisms (SNPs) associated with jumping performances of warmbloods in France. The 999 horses included in the study for jumping performances were sport horses [mostly Selle Français (68%), Anglo-Arabians (13%) and horses from the other European studbooks]. Horses were genotyped using the Illumina EquineSNP50 BeadChip. Of the 54,602 SNPs available on this chip, 44,424 were retained after quality testing. Phenotypes were obtained by deregressing official breeding values for jumping competitions to use all available information, that is, the performances of each horse as well as those of its relatives. Two models were used to test the effects of the genotypes on deregressed phenotypes: a single-marker mixed model and a haplotype-based mixed model (significant: P < 1E-05; suggestive: P < 1E-04). Both models included a polygenic effect to take into account familial structures. For jumping performances, one suggestive quantitative trait locus (QTL) located on chromosome 1 (BIEC2_31196 and BIEC2_31198) was detected with both models. This QTL explains 0.7% of the phenotypic variance. RYR2, a gene encoding a major calcium channel in cardiac muscle in humans and mice, is located 0.55 Mb from this potential QTL.


Quantifying Hand Strength and Isometric Pinch Individuation Using a Flexible Pressure Sensor Grid.
Modulating force between the thumb and another digit, or isometric pinch individuation, is critical for daily tasks and can be impaired due to central or peripheral nervous system injury. Because surgical and rehabilitative efforts often focus on regaining this dexterous ability, we need to be able to consistently quantify pinch individuation across time and facilities. Currently, a standardized metric for such an assessment does not exist. Therefore, we tested whether we could use a commercially available flexible pressure sensor grid (Tekscan F-Socket [Tekscan Inc., Norwood, MA, USA]) to repeatedly measure isometric pinch individuation and maximum voluntary contraction (MVC) in twenty right-handed healthy volunteers at two visits. We developed a novel equation informed by the prior literature to calculate isometric individuation scores that quantified percentage of force on the grid generated by the indicated digit. MVC intra-class correlation coefficients (ICCs) for the left and right hands were 0.86 (p < 0.0001) and 0.88 (p < 0.0001), respectively, suggesting MVC measurements were consistent over time. However, individuation score ICCs, were poorer (left index ICC 0.41, p = 0.28; right index ICC -0.02, p = 0.51), indicating that this protocol did not provide a sufficiently repeatable individuation assessment. These data support the need to develop novel platforms specifically for repeatable and objective isometric hand dexterity assessments.


[Reproduction and psyche].
Mental health and mental disorders can have a close connection to reproduction, especially for women but also for men. The most frequent disorders or problems are described, i.e., mental problems during pregnancy and after delivery, during the menstrual cycle and around menopause. Possible consequences of miscarriage, stillbirth and induced abortion are presented as well as the special problem of a wish for a child in mentally ill women and their treatment during pregnancy.


Calcium-sensing receptor-mediated mitogen-activated protein kinase pathway improves the status of transplanted mouse embryonic stem cells in rats with acute myocardial infarction.
Several studies have identified the critical role of calcium-sensing receptors (CaSRs) in cardiac ischaemia/reperfusion injury and cardiac hypertrophy and have demonstrated that CaSRs induce myocardial apoptosis by activating MAPKs. Using acute myocardial infarction rat models, we found that a combination therapy of CaSR inhibition and embryonic stem cell (ESC) transplantation after acute myocardial infarction (AMI) leads to a dramatic reduction in the infarct size; a significant increase in the maximum rising and falling rate (+dp/dtmax and -dp/dtmax, respectively) of left ventricular pressure; a significant decrease in left ventricular end-diastolic pressure; a significant decrease in the mRNA expression level of CaSR, Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ERK, p-JNK and p-P38 protein together with apoptosis indexes in the C and E groups; and a significant decrease in cTnT levels as well as LDH and CK activity. These findings indicate that cardiac function could be enhanced significantly by combination therapy with CaSR inhibition and ESC transplantation; the effect was better than ESC transplantation alone, and the mechanism might be associated with a reduction in cell apoptosis via the inhibition of the MAPK pathway. Apoptosis could be reduced through CaSR, which regulates the MAPK pathway and apoptosis-related protein. Our study indicated that CaSR inhibitors have a pivotal role in the treatment of AMI.


Thermal conductivity predictions of herringbone graphite nanofibers using molecular dynamics simulations.
Non-equilibrium molecular dynamics (NEMD) simulations are used to investigate the thermal conductivity of herringbone graphite nanofibers (GNFs) at room temperature by breaking down the axial and transverse conductivity values into intralayer and interlayer components. The optimized Tersoff potential is used to account for intralayer carbon-carbon interactions while the Lennard-Jones potential is used to model the interlayer carbon-carbon interactions. The intralayer thermal conductivity of the graphene layers near room temperature is calculated for different crease angles and number of layers using NEMD with a constant applied heat flux. The edge effect on a layer's thermal conductivity is investigated by computing the thermal conductivity values in both zigzag and armchair directions of the heat flow. The interlayer thermal conductivity is also predicted by imposing hot and cold Nosé-Hoover thermostats on two layers. The limiting case of a 90° crease angle is used to compare the results with those of single-layer graphene and few-layer graphene. The axial and transverse thermal conductivities are then calculated using standard trigonometric conversions of the calculated intralayer and interlayer thermal conductivities, along with calculations of few-layer graphene without a crease. The results show a large influence of the crease angle on the intralayer thermal conductivity, and the saturation of thermal conductivity occurs when number of layers is more than three. The axial thermal conductivity, transverse thermal conductivity in the crease direction, and transverse thermal conductivity normal to the crease for the case of a five-layer herringbone GNF with a 45° crease angle are calculated to be 27 W∕m K, 263 W∕m K, and 1500 W∕m K, respectively, where the axial thermal conductivity is in good agreement with experimental measurements.


Hypertrophic non-obstructive cardiomyopathy with aortic and mitral regurgitation: an unusual presentation for surgical option.
The case is described of a pediatric patient with hypertrophic non-obstructive cardiomyopathy (HNCM) presenting with aortic and mitral regurgitation. This 17-year-old boy had been followed for HNCM since he was aged 4 years. Serial echocardiography had been showing the emergence and progression of aortic regurgitation and mitral regurgitation since the patient was aged 6 years. He started to have syncope attacks at 16 years of age and fell into congestive heart failure at 17 years. He underwent successful mitral valve repair by means of double-orifice technique, and aortic valve repair with raphe triangular resection, cusp plication and subvalvular annuloplasty.


Factors related to low birth rate among married women in Korea.
The purpose of this study was to explore the factors influencing low birth rate among married women using the National Survey data in Korea. We compared the different influences on women's first and subsequent childbirths. This study was a secondary analysis using the "National Survey on Fertility and Family Health and Welfare", which was a nationally representative survey conducted by the Korea Institute for Health and Social Affairs. We analyzed the data of 3,482 married women (aged between 19 and 39 years) using SPSS 20.0 program for descriptive statistics, t-test, one-way ANOVA, and binary and ordinal logistic regression models. The factors influencing women's first childbirth included perceptions about the value of marriage and children and their education level. The factors influencing their subsequent childbirths included multifaceted variables of maternal age during the first childbirth, residential area, religion, monthly household income, perceptions about the value of marriage and children, and social media. It is necessary to improve women's awareness and positive perceptions about marriage and children in order to increase the birth rate in Korea. Moreover, consistently providing financial and political support for maternal and childcare concerns and using social media to foster more positive attitudes toward having children may enhance birth rates in the future.


Thermoelasticity of Injection-Molded Parts.
In the realm of injection-molded parts, small length scale deformation defects such as sink marks often pose a major challenge to the aesthetics or functionality of the parts. To address this problem, we present a comprehensive thermoelastomechanical approach that calculates the deformation of injection molded plastic by solving the elastic problem at each time step. In our methodology, two treatments of the molten core are considered: one as a liquid and the other as a rubbery state. Our results suggest that the rubbery state treatment provides higher accuracy in predicting the deformation results, as it maintains the displacement of the localized thermal shrinkage in its vicinity. The validity of our method is supported by empirical measurements on produced parts from the existing literature as well as on samples that we molded independently.


Expression of SOX9 and CDX2 in nongoblet columnar-lined esophagus predicts the detection of Barrett's esophagus during follow-up.
The diagnosis of Barrett's esophagus in the United States requires both endoscopically evident columnar-lined esophagus and the presence of goblet cells by histology. Currently, there is no consensus on how patients with nongoblet columnar-lined esophagus should be followed. In this study, we investigated whether biomarkers can be used to predict the detection of goblet cells in follow-up biopsies. Patients with nongoblet columnar-lined esophagus were identified. In 13 of these cases, goblet cells were detected in subsequent follow-up endoscopic biopsies (Barrett's group). Additionally, 26 cases that remained negative for goblet cells in follow-up biopsies served as controls. Immunohistochemistry for CDX2, SOX9, BMP4, SHH, and MUC2 was performed on the initial biopsies and graded independently by at least two pathologists in a masked manner. CDX2 was positive in the nongoblet columnar epithelium of 7/13 cases in the Barrett's group and in 4/26 controls (sensitivity 54%, specificity of 85%, odds ratio (OR) 6.4). Strong and diffuse immunoreactivity for SOX9 was detected in 10/13 cases in the Barrett's group and in 1/26 controls (sensitivity 77%, specificity 96%, OR 83.3). Combining CDX2 and SOX9 as a panel increased sensitivity to 85%, although the specificity decreased to 85% (OR 30.3). SHH, BMP4, and MUC2 expression showed no significant difference between the Barrett's and control groups. In patients with nongoblet columnar-lined esophagus, SOX9 and CDX2 may be useful in identifying a subset of patients who have a higher risk of being diagnosed for Barrett's esophagus (developing goblet cells) and need closer follow-up.


Aggregation behavior of latex particles in shear flow confined between two parallel plates.
In this study, the aggregation and breakup behaviors of latex particles in shear flow confined between two parallel plates were investigated using an in situ observation apparatus with a laser scanning confocal microscope. To investigate the effects of shear rate and the gap width between two parallel plates on the size and structure of the aggregates in the steady state, the distributions of the projected cross-sectional area and perimeter-based fractal dimension of the aggregates were measured. As a result, the average size of the aggregates decreases as shear rate increases and the gap width decreases due to the hydrodynamic effect acting on the aggregates. The size distributions of the aggregates become narrow as the gap width decreases. In addition, the fractal dimension, that is, the structure of the aggregates, was almost independent of shear rate and the gap width and approximately 1.2, which suggests that the aggregates are relatively compact.


Skin Necrosis with Oculomotor Nerve Palsy Due to a Hyaluronic Acid Filler Injection.
Performing rhinoplasty using filler injections, which improve facial wrinkles or soft tissues, is relatively inexpensive. However, intravascular filler injections can cause severe complications, such as skin necrosis and visual loss. We describe a case of blepharoptosis and skin necrosis caused by augmentation rhinoplasty and we discuss the patient's clinical progress. We describe the case of a 25-year-old female patient who experienced severe pain, blepharoptosis, and decreased visual acuity immediately after receiving a filler injection. Our case suggests that surgeons should be aware of nasal vascularity before performing an operation, and that they should avoid injecting fillers at a high pressure and/or in excessive amounts. Additionally, filler injections should be stopped if the patient complains of severe pain, and appropriate measures should be taken to prevent complications caused by intravascular filler injections.


[Comparative treatment of acute leukemia in adults].
13 full remissions and 8 partial remissions were achieved in 32 first treatments of acute leukaemia. The average duration of full remissions amounted to 225 days, that of partial remissions was 140 days. The average survival time of responders amounted to 410 days, that of non-responders was 52 days. The results of 18 recidive treatments were distinctly worse. Allowing for alexane permanent infusion, the findings and complications of different therapeutical schemes were compared. Improvements of the results seem to be only possible, if cytostatic treatment is supplemented by taking initial and progress evaluating, prognostic relevant parameters into consideration (e.g. stem cell cultures), and by escalating supportive measures including histocompatible blood cell substitution and reverse isolation as well as transplantation of human bone-marrow.


PCR Identification and Phylogenetic Analysis of Trichomonas gallinae from Domestic Pigeons in Guangzhou, China.
Avian trichomoniasis caused by Trichomonas gallinae is a serious protozoan disease worldwide. The domestic pigeon (Columba livia domestica) is the main host for T. gallinae and plays an important role in the spread of the disease. Based on the internal transcribed spacers of nuclear ribosomal DNA of this parasite, a pair of primers (TgF2/TgR2) was designed and used to develop a PCR assay for the diagnosis of T. gallinae infection in domestic pigeons. This approach allowed the identification of T. gallinae, and no amplicons were produced when using DNA from other common avian pathogens. The minimum amount of DNA detectable by the specific PCR assay developed in this study was 15 pg. Clinical samples from Guangzhou, China, were examined using this PCR assay and a standard microscopy method, and their molecular characteristics were determined by phylogenetic analysis. All of the T. gallinae-positive samples detected by microscopic examination were also detected as positive by the PCR assay. Most of the samples identified as negative by microscopic examination were detected as T. gallinae positive by the PCR assay and were confirmed by sequencing. The positive samples of T. gallinae collected from Guangzhou, China, were identified as T. gallinae genotype B by sequencing and phylogenetic analyses, providing relevant data for studying the ecology and population genetic structures of trichomonads and for the prevention and control of the diseases they cause.


Lung Nodule Segmentation and Recognition Algorithm Based on Multiposition U-Net.
Lung nodules are the main lesions of the lung, and conditions of the lung can be directly displayed through CT images. Due to the limited pixel number of lung nodules in the lung, doctors have the risk of missed detection and false detection in the detection process. In order to reduce doctors' work intensity and assist doctors to make accurate diagnosis, a lung nodule segmentation and recognition algorithm is proposed by simulating doctors' diagnosis process with computer intelligent methods. Firstly, the attention mechanism model is established to focus on the region of lung parenchyma. Then, a pyramid network of bidirectional enhancement features is established from multiple body positions to extract lung nodules. Finally, the morphological and imaging features of lung nodules are calculated, and then, the signs of lung nodules can be identified. The experiments show that the algorithm conforms to the doctor's diagnosis process, focuses the region of interest step by step, and achieves good results in lung nodule segmentation and recognition.


Inhibition of aceclidine-stimulated outflow facility, accommodation and miosis in rhesus monkeys by muscarinic receptor subtype antagonists.
Aceclidine can dissociate accommodative and outflow facility responses in monkeys and humans. We sought to determine if different muscarinic receptor subtypes control outflow facility, accommodative and pupillary responses to aceclidine in the living rhesus monkey eye, as a possible basis for this separation. Each eye was cannulated with one branched and one unbranched needle. Baseline measurements (of outflow facility by two-level constant pressure perfusion; refraction by Hartinger coincidence refractometry and pupil diameter by vernier calipers) were recorded after anterior chamber exchange with (one eye) or without (opposite eye), muscarinic receptor subtype antagonist (pirenzepine, AF-DX 116 or 4-DAMP). The eyes were then exchanged a second time with these solutions plus added aceclidine. The response to aceclidine (the differences from baseline) in the presence or absence of antagonist were compared. The M3 muscarinic receptor subtype antagonist 4-DAMP was the most potent inhibitor of all three responses to aceclidine. The dissociation of accommodative, outflow facility and miotic responses to aceclidine in rhesus monkeys does not appear to be due to differences in the muscarinic receptor subtypes that can currently be distinguished pharmacologically.


Nanocluster formation in electron-irradiated Li2O crystals observed by elastic diffuse neutron scattering.
Previous work performed on electron-irradiated Li2O crystals has demonstrated the simultaneous formation of two populations of colloids of metallic lithium, one is associated with oxygen bubbles and a typical size of >10 microm, while the other one consists of nanoclusters in the range of <10 nm. In the present neutron scattering investigation these small colloids are characterized in detail based on a thorough analysis of distortion scattering around Bragg peaks. It is shown that the small lithium colloids are slightly elongated precipitates with typical dimensions of around approximately 5 nm. For the large lithium colloids a well-defined orientation relation with respect to the Li2O matrix has been determined.


Soft X-ray photochemistry beamline at SPring-8.
Design and construction of a soft X-ray beamline at SPring-8 is reported. The beamline utilizes high-quality linearly polarized soft X-rays obtainable from a figure-8 undulator for the study of photophysical and photochemical processes of atoms, molecules and surfaces in the inner-shell excitation region. It consists of two experimental stations, a photochemistry station and a chemical vapour deposition (CVD) station. A high-resolution grating monochromator is installed at the photochemistry station, while the intense undispersed undulator radiation is used at the CVD station. Unique features of the experimental chambers and of the analysis and characterization systems are described along with those of the monochromator.


The treatment of medically handicapped children.
There are a number of chronic medical conditions in which dental care for the child is of vital importance as their general health may be put at serious risk if they develop dental disease or require dental treatment. The more common medical conditions which cause these problems are summarized and the associated risks discussed. The need for the dentist providing care to have sufficient knowledge of the medical conditions and forms of treatment which put the child at risk is stressed. Some of the other problems which occur during dental care of chronically sick children are considered, and these include paediatric medication and certain types of diet therapy which have an adverse effect on dental health, provision of dental treatment and the emotional and social problems which occur in families in which there is a seriously ill child. Finally, the aims of dental care for this group of patients is discussed.


A pig model of the preterm neonate: anthropometric and physiological characteristics.
Large animal models are an essential tool in the development of rationally-based new clinical therapies for preterm infants. We provide a description of the newborn pig as a model of the preterm neonate in terms of growth parameters, physiology and the requirement for intensive care over a range of gestational ages. Twenty-nine litters of piglets (n = 298) were delivered by caesarean section at six timepoints during gestation from 91d to 113d (term = 115d). Two groups, at 91 and 97d gestation, also received maternal glucocorticoid treatment. At four of these timepoints, piglets (n = 79) were ventilated, sedated and monitored using standard neonatal intensive care techniques for up to 8 h in various experimental protocols. Body weight increased from mean 697 g (SD 193) at 91d gestation to 1331 g (SD 368) at 113d gestation. Piglets delivered at 97d gestation were able to be resuscitated and kept alive for at least 8 h on respiratory support after surfactant administration. Maternal glucocorticoid treatment 48 h and 24 h hours prior to delivery reduced the requirement for ventilator support and improved cardiovascular stability. The pig provides a relevant model for the study of human preterm physiology and for investigation of novel therapies to improve outcomes.


Demographic, clinical and biochemical correlates of the length of stay for different polarities in Chinese inpatients with bipolar disorder: A real-world study.
Introduction: Many patients with bipolar disorder (BD) need hospitalization, while the number of hospital beds for these patients is limited. Managing the length of stay (LOS) is an effective solution to this issue. Research on LOS and its influencing factors in BD is limited in China. This study aimed to identify the factors relevant to LOS in different polarities in Chinese patients with BD. Method: This was a real-world, cross-sectional study. Data were obtained from the electronic medical record system. Patients admitted to Beijing Anding Hospital between Jan 2014 and Dec 2017 and diagnosed with BD were included. Demographic information, clinical characteristics, and biochemical variables were collected. Patients were classified into short and long LOS groups based on a cutoff value. A univariate study and a multivariate logistic regression analysis were performed to identify variables related to LOS in various BD polarities. The receiver operating characteristic (ROC) analysis was utilized to evaluate the discrimination accuracy of the regression model. Result: Four thousand six hundred and seventy-five visits from 4,451 individuals were included in the analysis. For the whole sample, unmarried status, psychotic features, and family history of mental disorders were positively associated with long LOS (all p < 0.05). There was an additive interaction between a family history of mental disorders and polarities (p < 0.05). For manic episodes, unmarried status, psychotic features, and family history of mental disorders were positively associated with long LOS (all p < 0.05). For depressive episodes, psychotic features and high-density lipoprotein cholesterol (HDLC) levels were positively associated with long LOS (all p < 0.05). For mixed states, unmarried status was positively associated with long LOS, while low-density lipoprotein cholesterol (LDLC) levels were negatively associated with LOS (all p < 0.05). The area under the curve (AUC) values for depressive episodes, manic episodes, and mixed states in the combined model were 0.587, 0.553, and 0.619, respectively (all p < 0.05). Discussion: The findings suggested that LOS correlates differed by polarity, with marital status, psychotic features, a family history of mental disorders, and lipid levels strongly linked with LOS in patients with BD.


The effect of ketorolac on posterior thoracolumbar spinal fusions: a prospective double-blinded randomised placebo-controlled trial protocol.
Ketorolac has been shown to provide quality postoperative pain control and decrease opioid requirement with minimal side effects following spinal surgery. However, the literature addressing its use in spinal fusions is highly variable in both its effectiveness and complications, such as pseudarthrosis. Recent literature postulates that ketorolac may not affect fusion rates and large randomised controlled trials are needed to demonstrate ketorolac as a safe and effective adjuvant treatment to opioids for postoperative pain control. This is a multihospital, prospective, double-blinded, randomised placebo-controlled trial. Data concerning fusion rates, postoperative opioid use, pain scores, length of stay will be recorded with the aim of demonstrating that the use of ketorolac does not decrease thoracolumbar spinal fusion rates while identifying possible adverse events related to short-term minimal effective dose compared with placebo. Additionally, this investigation aims to demonstrate a decrease in postoperative opioid use demonstrated by a decrease in morphine equivalence while showing equivalent postoperative pain control and decrease the average length of stay. Ethical approval was obtained at all participating hospitals by the institutional review board. The results of this study will be submitted for publication in peer-reviewed journals. NCT03278691.


Renal tubular acidosis--underrated problem?
Renal tubular acidosis (RTA) is a hyperchloremic metabolic acidosis characterized by a normal anion gap and normal (or near normal) glomerular filtration rate in the absence of diarrhoea. Inherited isolated forms of renal tubular acidosis are not common. However, they can also be a part of a more generalized tubule defect, like in Fanconi syndrome. In recent years more and more gene mutations have been found which are associated with RTA (mutations in the gene SLC4A4, encoding a Na(+)-HCO(3)(-) cotransporter (NBC-1); in the gene SLC4A1, encoding Cl(-)/HCO3(-) exchanger (AE1); in the gene ATP6B1, encoding B1 subunit of H(+)-ATPase; in the gene CA2 encoding carbonic anhydrase II; and others) and allow better understanding of underlying processes of bicarbonate and H(+) transport. Isolated renal tubular acidosis can be frequently acquired due to use of certain drug groups, autoimmune disease or kidney transplantation. As the prevalence of acquired forms of RTA is common, new therapeutic options for the currently used supplementation of oral alkali, are awaited.


Effect of pindolol and nifedipine alone and in combination on haemodynamic parameters/variables in essential hypertension.
Thirteen patients with essential hypertension were started on pindolol 10-20 mg daily and twelve on nifedipine 20-60 mg daily. At the end of 6 weeks inadequate responders (B.P. greater than 140/90) were put onto combined treatment with both drugs, ten of the pindolol and six of the nifedipine patients being affected. Combined therapy then continued for a further 6-week period, while adequate responders (B.P. less than 140/90) continued with their initial drug. In addition to blood pressure, heart rate and cardiac index were also measured, and total peripheral resistance index was calculated. Where blood pressure decreased below 140/90 at the end of 12 weeks in patients on combined treatment, the original drug was withdrawn, leaving the patient on a single-drug regimen again, this time with the 'second compound'. This manoeuvre was followed by a rise in blood pressure in five out of eight patients in whom pindolol was withdrawn and in two out of six after nifedipine withdrawal. No definite conclusions can be drawn from these findings, and it may be that a better approach to the problem of poor responders would be to try each drug on its own before combining them, rather than combining first and then withdrawing the initial treatment. The increased peripheral resistance typical of essential hypertension was not adversely affected by either drug, while combined treatment had a beneficial effect on this parameter.


Bioactive Bafilomycins and a New N-Arylpyrazinone Derivative from Marine-derived Streptomyces sp. HZP-2216E.
A MeOH extract prepared from culture of an actinomycete Streptomyces sp. HZP-2216E isolated from marine green algae Ulva pertusa was found to significantly inhibit proliferation of human glioma cells. Two different media were applied to culture this marine actinomycete, which produced two new compounds of 23-O-butyrylbafilomycin D and streptoarylpyrazinone A, together with known bafilomycin D, 9-hydroxybafilomycin D, and bafilomycin A1. Structures of new compounds were determined by extensive NMR spectroscopic analyses and HRESIMS data. Bioactive assay indicated that all isolated bafilomycins significantly inhibited the proliferation of different glioma cell lines and the growth of methicillin-resistant Staphylococcus aureus with 23-O-butyrylbafilomycin D as the most active compound. Streptoarylpyrazinone A is a new N-arylpyrazinone derivative existing as a zwitterion, and this type of compounds was rarely found from natural resources.


Complications of humeral head replacement for proximal humeral fractures.
The indications for humeral head replacement in acute fractures and in chronic fracture problems have been studied over many decades and are reasonably well defined. Complications have probably been understudied. Many different complications occur, and their frequency and the need for reoperation is quite high. Because of the variety of complications that occur, familiarity with preventive measures and treatment options is important, not only to deal with complications arising from endoprostheses, but also to treat musculoskeletal infections, nerve injuries, fractures, instability, nonunion of tuberosities, malunion, and rotator cuff or capsule contracture or tearing. Physicians also must be able to integrate reparative/reconstructive surgery with a program of postoperative rehabilitation. The challenges are many. Treatment often provides considerable improvement for the patient, but often the extent of the improvement is somewhat less than optimal.


Unsuccessful suicide by carbon monoxide: a secondary benefit of emissions control.
Emission systems and devices are required on automobile engines to reduce air pollution problems. Catalytic converters have been used on most 1975 and newer automobiles to reduce hydrocarbon and carbon monoxide (CO) emissions to a value that meets the Environmental Protection Agency requirements established for 1975 and 1976. The 1980-1981 Boise, Idaho, study shows that with a functioning catalytic converter either unmeasurable or sublethal quantities of CO appear in automobile exhaust. Thus, emissions control has produced a secondary benefit in reducing the number of suicides by CO poisoning from automobile exhaust fumes.


Evaluation of separate urine collection and treatment to augment existing wastewater treatment works.
Simultaneous increases in wastewater loads and effluent quality demand improved nutrient removal techniques. A simple technique for nitrogen removal is post-denitrification with methanol. The tradeoff between better effluent vs. methanol consumption is debatable. Methanol dosing is not only un-sustainable in the long term, but the cost of methanol is also becoming increasingly important. Urine contains 80% of the total nitrogen (N) and 50% of the phosphate in wastewater. Separate collection and treatment of urine could improve existing treatment works and diminish the need for post-denitrification. In this paper, a nitritation-denitrification process is proposed where 20-30% of the N in urine is removed with the COD available in urine. The treated urine consists of ammonium-nitrite, which is to be introduced to the anoxic zone of a conventional treatment plant. Optimal denitrification via nitrite is possible with COD from other wastewater sources. The case study presented here shows that 40-50% urine separation and improvement of the flow scheme would improve effluent quality from 19 to 10 g N/m3, which would eliminate the need for post-denitrification.


[Quick radioimmunoassay method for the determination of estrogens].
The aim of this report is to describe a quick method for measuring plasma estrogens by radio immunoassay in one day. Briefly, 1000 cpm of estradiol-3-H were added to 0.1 to 1.5 ml of plasma or serum to calculate losses during the procedure. After ether extraction and without any purification step, aliquots for tracer recoveries and the radioimmunoassay were taken. The antiserum working dilution was 1:100,000. The incubation of the antiserum at 37degreesC with the tritiated and cold estradiol lasts one hour. The free and bound fractions were separated with charcoal/dextran. With this method, 95% of estradiol, 16% of estrone and 6% of estriol are quantified. Other steroids normally present in plasma produce no interference. The minimal detectable level is 10 pg. Pasma and water blanks are indistinguishable of zero (C.V. 1%). Intra-analysis coefficient of variation is 6.1%. Mass recovery of estradiol (5 ng), estrone (5 ng) and estriol (5ng) are 4.75, 0.83 and 0.31 ng, respectively. Tracer recoveries are 92.6%. When plasma levels of estradiol are determined during menstrual cycle, normal and/or pathological pregnancy, by either the method described herein or measured selectively, the results show no significant differences. Finally, practical usefulness of this method is stressed, inasmuch results are obtained in six hours and one person can easily perform 200 samples in one week.


Territorial behavior of a green hairstreak Chrysozephyrus smaragdinus (Lepidoptera: Lycaenidae): site tenacity and wars of attrition.
Males of Chrysozephyrus smaragdinus were active from late morning to late afternoon, during which they showed territorial behavior, perhaps for mating. The territorial male stayed in a particular area and occasionally flew around it, referred to hereafter as the inspection area. When other male intruded into this area, the territorial male rushed to him. Then, they engaged in a circling flight regarded as a "war of attrition". During this flight, the two males sometimes strayed far away from the territory. After the circling flight, the resident returned to his territory in almost all cases (98%). Despite such intrusions, many residents defended their territory for several successive days. This suggests strongly the "effect of prior residence". We recorded the circling flights with a high-speed video camera, and confirmed that the male that ceased the circling flight first was the loser. This finding gave some validity to consider circling flight as wars of attrition. In a few cases, the territorial male mated with a female that came to the territory. These once mated males held the territory no longer, suggesting that mating experience should restrict the next mating opportunity in this species.


STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1.
The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for subgroups of CD4(+) cells can be explained, at least partly, by the selective use of G protein-coupled receptors (GPCRs). We have identified a novel human gene, STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to chemokine receptors and to chemokine receptor-like orphan receptors. STRL33 is expressed in lymphoid tissues and activated T cells, and is induced in activated peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest, STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for fusion mediated by Envs from both T cell line-tropic and macrophage-tropic HIV-1 strains. STRL33-transfected Jurkat cell lines also supported enhanced productive infection with HIV-1 compared with control Jurkat cells. Despite the sequence similarities between STRL33 and chemokine receptors, STRL33-transfected cell lines did not respond to any in a panel of chemokines. Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection.


Low-dimensional compounds containing bioactive ligands. Part XIV: High selective antiproliferative activity of tris(5-chloro-8-quinolinolato)gallium(III) complex against human cancer cell lines.
Four gallium(III) complexes, [Ga(ClQ)3]⋅MeOH (1 - MeOH), [Ga(ClQ)3] (1), [Ga(BrQ)3] (2), [Ga(dIQ)3] (3) and [Ga(CQ)3] (4), were prepared (H-ClQ = 5-chloro-8-quinolinol, H-BrQ = 7-bromo-8-quinolinol, H-dIQ = 5,7-diiodo-8-quinolinol, H-CQ = 5-chloro-7-iodo-8-quinolinol) and characterised by elemental analysis, IR and NMR spectroscopy. Single crystal structure analysis of 1 - MeOH confirmed that the complex has a molecular structure with gallium(III) metal ion coordinated in mer-fashion by N- and O-donor atoms of three ClQ ligands. Stability of all complexes in DMSO was proved by 1H NMR spectroscopy. The in vitro antiproliferative activity of 1 was evaluated against the A2780, MBA-MB-231 and HCT116 cell lines. Complex 1 displays higher antiproliferative activity (IC50 values in the range 2.1-6 μm) compared to the ClQ ligand and cisplatin; and a significant selective antiproliferative potency (IC50 = 136 μm, for normal MRC5pd30 cell line). Radical scavenging experiments revealed that complex 1 exhibits the highest antioxidant activity of the prepared complexes as well as the ligands.


Chiral Decomposition of Twisted Graphene Multilayers with Arbitrary Stacking.
We formulate the chiral decomposition rules that govern the electronic structure of a broad family of twisted N + M multilayer graphene configurations that combine arbitrary stacking order and a mutual twist. We show that at the magic angle in the chiral limit the low-energy bands of such systems are composed of chiral pseudospin doublets that are energetically entangled with two flat bands per valley induced by the moiré superlattice potential. The analytic construction is supported by explicit numerical calculations based on realistic parametrization. We further show that vertical displacement fields can open energy gaps between the pseudospin doublets and the two flat bands, such that the flat bands may carry nonzero valley Chern numbers. These results provide guidelines for the rational design of topological and correlated states in generic twisted graphene multilayers.


Metabolic effects of pulmonary obstruction on myocardial functioning: a pilot study using multiple time-point 18F-FDG-PET imaging.
The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the right ventricle (RV) of patients with chronic obstructive pulmonary disease (COPD) and to characterize the variability of 18F-FDG uptake in the RV at different time points following radiotracer administration using PET/computerized tomography (CT). Impaired RV systolic function, RV hypertrophy, and RV dilation are associated with increases in mean pulmonary arterial pressure in patients with COPD. Metabolic changes in the RV using 18F-FDG-PET images 2 and 3 h after tracer injection have not yet been investigated. Twenty-five patients with clinical suspicion of lung cancer underwent 18F-FDG-PET/CT imaging at 1, 2, and 3 h after tracer injection. Standardized uptake values (SUVs) and volumes of RV were recorded from transaxial sections to quantify the metabolic activity. The SUV of RV was higher in patients with COPD stages 1-3 as compared with that in patients with COPD stage 0. RV SUV was inversely correlated with FEV1/FVC pack-years of smoking at 1 h after 18F-FDG injection. In the majority of patients, 18F-FDG activity in RV decreased over time. There was no significant difference in the RV myocardial free wall and chamber volume on the basis of COPD status. The severity of lung obstruction and pack-years of smoking correlate with the level of 18F-FDG uptake in the RV myocardium, suggesting that there may be metabolic changes in the RV associated with lung obstruction that can be detected noninvasively using 18F-FDG-PET/CT. Multiple time-point images of the RV did not yield any additional value in this study.


Direct Effects of Toxic Divalent Cations on Contractile Proteins with Implications for the Heart: Unraveling Mechanisms of Dysfunction.
The binding of calcium and magnesium ions to proteins is crucial for regulating heart contraction. However, other divalent cations, including xenobiotics, can accumulate in the myocardium and enter cardiomyocytes, where they can bind to proteins. In this article, we summarized the impact of these cations on myosin ATPase activity and EF-hand proteins, with special attention given to toxic cations. Optimal binding to EF-hand proteins occurs at an ionic radius close to that of Mg2+ and Ca2+. In skeletal Troponin C, Cd2+, Sr2+, Pb2+, Mn2+, Co2+, Ni2+, Ba2+, Mg2+, Zn2+, and trivalent lanthanides can substitute for Ca2+. As myosin ATPase is not a specific MgATPase, Ca2+, Fe2+, Mn2+, Ni2+, and Sr2+ could support myosin ATPase activity. On the other hand, Zn2+ and Cu2 significantly inhibit ATPase activity. The affinity to various divalent cations depends on certain proteins or their isoforms and can alter with amino acid substitution and post-translational modification. Cardiac EF-hand proteins and the myosin ATP-binding pocket are potential molecular targets for toxic cations, which could significantly alter the mechanical characteristics of the heart muscle at the molecular level.


Stroke prevention strategies in Africa: a scoping review protocol.
The objective of this scoping review is to map the existing strategies on methods and interventions for primary and secondary stroke prevention in Africa. Stroke is among the leading causes of disability globally. African nations have higher stroke mortality and case fatality rates than the industrialized world, leading to significant social and financial costs, which necessitates efficient preventative methods. Despite the high prevalence of stroke in Africa, the scope of stroke-prevention strategies in Africa is unknown. Consequently, mapping diverse approaches to preventing stroke in Africa could provide direction for future research into stroke prevention in Africa. This review will incorporate studies that report methods or strategies used for stroke prevention in Africa. All primary and gray literature will be considered for inclusion. No language or date restrictions will be applied. The JBI methodological framework for scoping reviews will be adopted for this scoping review. A 3-step search strategy consisting of an initial limited search, a full search, and a screening of the reference lists of all included articles will be undertaken. Databases such as CINAHL, Scopus, PubMed, PEDRo, DORIS, Global Health, Web of Science, and Open Access Thesis and Dissertations will be searched. All search results will be screened, and relevant data extracted by 2 independent reviewers. The findings will be presented in the final scoping review and illustrated in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Figshare https://figshare.com/articles/journal_contribution/Stroke_prevention_strategies_in_Africa_a_scoping_review_protocol/21679904.