Intraobserver and interobserver reproducibility in linear measurements on axial images obtained by cone-beam computed tomography.
This study was performed to investigate the intra- and inter-observer variability in linear measurements with axial images obtained by PreXion (PreXion Inc., San Mateo, USA) and i-CAT (Imaging Sciences International, Xoran Technologies Inc., Hatfield, USA) CBCT scanners, with different voxel sizes. A cylindrical object made from nylon with radiopaque markers (phantom) was scanned by i-CAT and PreXion 3D devices. For each axial image, measurements were taken twice in the horizontal (distance A-B) and vertical (distance C-D) directions, randomly, with a one-week interval between measurements, by four oral radiologists with five years or more experience in the use of these measuring tools. All of the obtained linear measurements had lower values than those of the phantom. The statistical analysis showed high intra- and inter-observer reliability (p=0.297). Compared to the real measurements, the measurements obtained using the i-CAT device and PreXion tomography, on average, revealed absolute errors ranging from 0.22 to 0.59 mm and from 0.23 to 0.63 mm, respectively. It can be concluded that both scanners are accurate, although the linear measurements are underestimations, with no significant differences between the evaluators.


Disseminated Fusarium solani infection with cutaneous nodules in a bone marrow transplant patient.
Fusarium is a ubiquitous fungus that commonly colonizes ulcerated, burned, or traumatized skin and may cause keratitis and onychomycosis in healthy hosts. Serious disseminated infection due to Fusarium has been reported with increasing frequency in immunocompromised patients. We describe a bone marrow transplant patient who developed fungal septicemia and disseminated skin nodules due to Fusarium solani. Fusarium should be recognized as a potential cause of deep fungal infection in immunocompromised patients.


Significance and interpretation of molecular diagnostics for insecticide resistance management of agricultural pests.
Insecticide resistant pests become increasingly difficult to control in current day agriculture. Because of environmental and health concerns, the insecticide portfolio to combat agricultural pests is gradually decreasing. It is therefore crucial to make rational decisions on insecticide use to assure effective resistance management. However, resistance monitoring programs that inform on pest susceptibility and resistance are not yet common practice in agriculture. Molecular markers of resistance that are turned into convenient diagnostic tools are urgently needed and will only increase in importance. This review investigates which factors determine the strength, diagnostic value, and success of a diagnostic marker, and in which cases recent technical advances might provide new opportunities for decision making in an operational meaningful way.


Endoscopic diagnosis and treatment of neuroendocrine tumors of the digestive system.
The authors evaluated the role of endoscopic techniques in the diagnosis and in the potential treatment of neuroendocrine tumors (NET) localized in the gastro-entero-pancreatic system, on the basis of their experience and of the international literature. NET are rare tumors that arise from neuroendocrine cells of the gastrointestinal tract and pancreas. It is a possibility that both the digestive endoscopy and EUS play an important role in the diagnosis, staging and surveillance of this disease. In some cases, especially in the early stages, surgical endoscopy allows the treatment of such tumors.


Microscopic theory of current-driven domain wall motion.
The dynamics of a domain wall in ferromagnetic nanowires under electric current is theoretically studied. The driving mechanism is shown to depend on wall thickness. Thick walls, as in metallic wires, are propelled by the spin torque arising from spin polarization of current, while thin walls, as in nanocontacts and magnetic semiconductors, are driven by the pressure from charge current. The condition for small-current operation, which is a key issue when integrated into devices, is discussed.


Pt/Fe₃O₄ Core/Shell Triangular Nanoprisms by Heteroepitaxy: Facet Selectivity at the Pt-Fe₃O₄ Interface and the Fe₃O₄ Outer Surface.
Pt/Fe3O4 core/shell triangular nanoprisms were synthesized using seed-mediated heteroepitaxy. Their well-defined shape, facets, and ordered-assembly allowed detailed analysis of mechanism of the heteroepitaxy. At the Pt-Fe3O4 interface, existence of both lattice and chemical mismatch resulted in facet-selective epitaxy along ⟨111⟩ directions of two lattices. X-ray absorption fine structure measurements demonstrated that the Pt seed nanocrystals were composed of an iron-rich Pt-Fe metallic thin layer sandwiched between the Pt core and a Fe-O outer-surface. The Fe-O outer-surface of the seed nanocrystals presumably offered epitaxial sites for the following deposition of the Fe3O4 shell. Each tip and side of a triangular nanoprism respectively possessed a groove and a ridge, and a (111) plane parallel to the basal planes linked all grooves and ridges. This interesting (111) plane approximately bisected the triangle nanoprisms and located near the Pt-seed. The outer surface of the hybrid nanocrystals was also found to be facet-selective, that is, solely {111} facets of Fe3O4 lattice. These polar {111} facets allowed the surface to be only occupied with high-density iron ions, and thus offered best surface coordination for the electron donating ligands in the solution.


Three-dimensional model on thermal response of skin subject to laser heating.
A three-dimensional (3D) multilayer model based on the skin physical structure is developed to investigate the transient thermal response of human skin subject to laser heating. The temperature distribution of the skin is modeled by the bioheat transfer equation, and the influence of laser heating is expressed as a source term where the strength of the source is a product of a Gaussian shaped incident irradiance, an exponentially shaped axial attenuation, and a time function. The water evaporation and diffusion is included in the model by adding two terms regarding the heat loss due to the evaporation and diffusion, where the rate of water evaporation is determined based on the theory of laminar boundary layer. Cryogen spray cooling (CSC) in laser therapy is studied, as well as its effect on the skin thermal response. The time-dependent equation is discretized using the finite difference method with the Crank-Nicholson scheme and the stability of the numerical method is analyzed. The large sparse linear system resulted from discretizing the governing partial differential equation is solved by a GMRES solver and the expected simulation results are obtained.


Poissons, grenouilles, femmes et hommes: the appropriation and retention of archetypal systems for reproduction.
In contradistinction to other biological systems, the reproductive mechanisms in sexually reproducing species are unique in that their success relies upon a synchronous interaction between two separate individuals. Reproduction has become increasingly more efficient as higher forms have developed internal fertilization and gestation. Although our anthropomorphic perspective has dominated the understanding of reproductive processes, 'recent discoveries' make it clear that this reproductive efficiency has been gained by retention of previously present biological mechanisms whose origins are in the vestigial excretory tracts and ducts which are the precursors of the reproductive tract. We refer to these as 'archetypal systems'. They include the interaction between sex steroid sensitive tissues and sex steroids, the renin-angiotensin system and the macrophage/monokine response to infection. Through these mechanisms the reproductive tracts have maintained control over the microenvironment in which the reproductive processes occur. Thus, gamete development in male and female, and fertilization and early embryonic existence in the female tract prior to implantation still occur in compartments which are extracorporeal, i.e., separated from blood or subendothelial spaces, and are controlled by cellular mechanisms found in ancient excretory tracts. Since the majority of the changes between lower forms and contemporary mammals are anatomical modifications which have favoured the success of these extracorporeal events within the developing, generally land-based mammals, we should take special note of lower animals, understanding the evolutionary appropriation of mechanisms designed to furnish the suitable microenvironment from the surrounding tissues.(ABSTRACT TRUNCATED AT 250 WORDS)


Binding of [3H]-dopamine to human lymphocytes: possible relationship to neurotransmitter uptake sites.
Freshly isolated human lymphocytes from 11 healthy subjects had specific binding sites for dopamine which were dependent on time, temperature and sodium, and appeared to follow Michaelis-Menten kinetics. The apparent affinity constant (KD) of human lymphocytes for dopamine and the maximal number of binding sites (Bmax) were 109 +/- 21 nM and 2.66 +/- 1.75 pmol/10(7) cells, respectively. Dopamine binding was markedly affected by cocaine (IC50 = 150 nM) and other inhibitors of biogenic amine uptake. The relatively high potency of cocaine in competing for dopamine binding suggested that human lymphocytes may serve as a readily accessible model to detect changes in the neuronal uptake of dopamine and perhaps other monoamine neurotransmitters.


A subchronic intravenous toxicity study of magnesium fructose-1,6-diphosphate in beagle dogs.
Magnesium fructose-1,6-diphosphate is a novel agent of antimyocardial ischaemia. In the present study, the subchronic toxicity of magnesium fructose-1,6-diphosphate was investigated after 13-week repeated intravenous administration in beagle dogs. The animals received doses of 0, 75, 150 and 300 mg/kg/day (three males and three females for each dose). During the study period, clinical signs, mortality, body weights, food consumption, electrocardiogram, urinalysis, haematology, clinical biochemistry, macroscopic findings, organ weights and histopathology were examined. The administration of magnesium fructose-1,6-diphosphate resulted in increased incidence of clinical signs, including salivation and emesis. These effects were transient and were noted in almost all dogs given 300 mg/kg/day and occasionally noted in the 150 mg/kg/day dose-treated animals. Serum magnesium in the 150 mg/kg/day and 300 mg/kg/day dose-treated animals was significantly increased after 6- and 13-week administration, but recovered at the end of a 2-week recovery period. At 6 weeks, a statistically significant decrease in serum electrolytes, including sodium and potassium, was observed in the treatment groups. There were no other treatment-related findings. Under the conditions of the present study, magnesium fructose-1,6-diphosphate did not show any evidence of target organ toxicity. The no-observed-adverse-effect level for 13-week intravenous administration of magnesium fructose-1,6-diphosphate to beagle dogs was considered 75 mg/kg/day based on observations of clinical signs and serum electrolytes.


Postpartum anxiety and breast feeding.
To evaluate the relationship between postpartum anxiety and lactation experience, knowledge, confidence and performance. State anxiety was measured among breast-feeding women by the State Trait Anxiety Inventory before hospital discharge and at 1 month postpartum. Breast-feeding experience and knowledge were assessed by focused questions and confidence by the Breastfeeding Confidence Scale. Breast-feeding performance measures included breast-feeding immediately after delivery; formula supplementation in the hospital; full, exclusive breast-feeding; and breast-feeding termination at 1 month postpartum. Predischarge anxiety correlated inversely with breast-feeding confidence (r [339] = -0.27, p = 0.000) but not with experience or knowledge. As compared to low-anxiety mothers, those with high anxiety were less likely to breast-feed after delivery (53.0% vs. 65.1%, p = 0.049) and more likely to give their infants formula (43.9% vs. 29.1%, p = 0.022). In logistic regression models adjusting for demographic and social factors, high-anxiety mothers were less likely to practice full, exclusive breast-feeding (AOR = 0.39; 95% CI 0.20, 0.74; p < 0.005) and more likely to have terminated breastfeeding at 1 month (AOR = 4.40; 95% CI 1.70, 11.33; p < 0.005). Postpartum anxiety may be associated with reduced breast-feeding confidence and lactation performance. Awareness of this association may be helpful in identifying women at risk for lactation failure and targeting efforts to promote breast-feeding.


Closed reduction and internal fixation of displaced unstable lateral condylar fractures of the humerus in children.
Open reduction and internal fixation of a displaced unstable fracture of the lateral condyle of the humerus in a child usually produces a good result. Only a few reports have focused on closed reduction and internal fixation of these fractures. We prospectively studied closed reduction and internal fixation to determine its usefulness as the initial treatment for displaced unstable fractures of the lateral condyle of the humerus. We classified lateral condylar humeral fractures into five groups according to the degree of displacement and the fracture pattern as determined on four radiographic views and created an algorithm for the treatment of these fractures on the basis of this classification system. We prospectively treated sixty-three unstable fractures (in forty-two boys and twenty-one girls) and assessed the quality of closed reduction. Thirteen of seventeen stage-3 fractures were reduced to < or =1 mm of residual displacement. Thirty of forty stage-4 fractures and three of six stage-5 fractures were reduced to < or =2 mm of displacement. In ten of forty stage-4 fractures and three of six stage-5 fractures, closed reduction to within 2 mm failed and open reduction and internal fixation was performed. There were no major complications such as osteonecrosis of the trochlea or capitellum, nonunion, malunion, or early physeal arrest. Closed reduction and internal fixation is an effective treatment for unstable displaced lateral condylar fractures of the humerus in many children. If fracture displacement after closed reduction exceeds 2 mm, open reduction and internal fixation is recommended.


Acoustic settings combination as a sensory crispness indicator of dry crispy food.
Crispness is a critical attribute of quality for crispy products, which can be evaluated through both instrumental and sensory analyses. The aim of the study was to identify the best combination of settings of a device coupled to a texture analyzer for acoustic analysis in order to find strong correlations with the sensory texture. For that, nine commercial food products were submitted to force and acoustic (acoustic envelope detector) analyses, using two settings for acoustic data acquisition (gain 1 and gain 4), and two settings for acoustic data management (threshold 0.5 and 2.5). The products were also evaluated using texture descriptive sensory analysis. The gain changing from 1 to 4 (enhancing the test sensitivity) increased the number of acoustic peaks and reduced the sound pressure level. Changing the threshold from 0.5 to 2.5 (reducing the interference of background noise on the acquired data) reduced the number of acoustic peaks. The correlation between the instrumental and the sensory analysis showed gain 1 as the most adequate acoustic setting to obtain the acoustic parameters of products with different crispness intensities. Moreover, threshold 2.5 is the most appropriate for acoustic data collection. Therefore, sensory attributes and instrumental properties strong correlations indicate that texture analyzer in combination with the acoustic envelope detector is a good instrument to mimic human mastication and texture perception, through both force and sound stimuli. This study about dry crisp food may contribute to the literature and food industry, as well to future studies about wet crispy and crunchy foods.


Sense-aware lexical sophistication indices and their relationship to second language writing quality.
The relationship of lexical sophistication to second language (L2) production quality has received much attention in the past few decades. Viewed as a multidimensional construct, lexical sophistication has been measured using indices that tap into various distributional, formal, semantic, acquisitional, and psycholinguistic properties of words and certain n-gram properties (e.g., Kyle et al., 2018). However, existing indices have not systematically accounted for the fact that polysemous words are used with distinct senses in different contexts and that those senses may not be equally sophisticated for L2 learners. The current study addresses this gap by proposing three frequency-based lexical sophistication indices that take into account the reference-corpus frequency of the senses with which polysemous words are used in learner texts and assessing their predictive power for L2 English writing quality both in comparison to and in combination with existing lexical sophistication indices. Results from the analysis of a corpus of exam scripts produced by L2 learners sitting for the Cambridge First Certificate in English (Yannakoudakis et al., 2011) show that two sense-aware indices proposed correlated more strongly with holistic scores of L2 English writing quality than existing indices. Integrating the new sense-aware indices with existing ones in a regression model resulted in higher predictive power for L2 English writing quality than models built with either set of indices alone. The implications of our findings for future L2 lexical sophistication research are discussed.


Amphojeloma: antacid impaction in a critically ill patient.
Patients in the intensive care unit seldom have mechanical small-bowel obstruction, and obstruction due to medication bezoars is even less common. A 65-year-old woman, in the intensive care unit because of septic shock and acute renal failure, had a small-bowel obstruction due to Amphojel concretions. Obstruction from such a cause may be prevented by including non-constipating antacids, stool softeners or sorbitol. Aggressive use of H2-antagonists to prevent gastrointestinal bleeding in septic patients will reduce the need for orally administered antacids. When obstruction occurs due to antacid concretions, it may be relieved by passing a long intestinal tube, by giving enemas for colonic obstruction or by operation.


A mapping study of ensemble classification methods in lung cancer decision support systems.
Achieving a high level of classification accuracy in medical datasets is a capital need for researchers to provide effective decision systems to assist doctors in work. In many domains of artificial intelligence, ensemble classification methods are able to improve the performance of single classifiers. This paper reports the state of the art of ensemble classification methods in lung cancer detection. We have performed a systematic mapping study to identify the most interesting papers concerning this topic. A total of 65 papers published between 2000 and 2018 were selected after an automatic search in four digital libraries and a careful selection process. As a result, it was observed that diagnosis was the task most commonly studied; homogeneous ensembles and decision trees were the most frequently adopted for constructing ensembles; and the majority voting rule was the predominant combination rule. Few studies considered the parameter tuning of the techniques used. These findings open several perspectives for researchers to enhance lung cancer research by addressing the identified gaps, such as investigating different classification methods, proposing other heterogeneous ensemble methods, and using new combination rules. Graphical abstract Main features of the mapping study performed in ensemble classification methods applied on lung cancer decision support systems.


Training innate immunity: the changing concept of immunological memory in innate host defence.
The inability of innate immunity to build an immunological memory is considered a main difference with adaptive immunity. This concept has been challenged by studies in plants, invertebrates and mammals. Recently, a paradigm shift in our understanding host defence has been triggered by the mounting evidence for innate immune memory, leading to increased responses to secondary infections. Important differences between the cell populations and the molecular mechanisms exist between the adaptive traits of innate host defence on the one hand and immunological memory of adaptive immunity on the other hand. The lasting state of enhanced innate immunity termed 'trained immunity' is mediated by prototypical innate immune cells such as natural killer cells and monocytes/macrophages. It provides protection against reinfection in a T/B-cell-independent manner, with both specific mechanisms and nonspecific epigenetic reprogramming mediating these effects. This concept represents a paradigm change in immunity, and its putative role in resistance to reinfection may represent the next step in the design of future vaccines.


[Assessment of temporary hearing changes related to work as a bartender].
Noise in entertainment industry often reaches high sound pressure levels. Nevertheless, the risk of hearing loss in this sector is insufficiently recognized. The aim of this study was the assessment of the relationship between noise exposure and temporary threshold shifts (TTS) for people working as bartenders at a variety of entertainment venues. The study comprised a total of 18 bartenders (mean age was 25±7 years old) employed at a music club (N = 8), pub (N = 5) and discotheque (N = 5). Personal dosimeters were used for determining noise levels and frequency characteristics. Hearing was evaluated by pre- (before work) and post-exposure (up to 15 min after the end of work) pure tone audiometry. Hearing tests were carried out for bartenders during 2 or 3 sessions while working on weekends. The mean personal noise exposure level normalized to a nominal 8-hour working day was 95 dBA, above 4 times higher than the accepted legal limit. The TTS values (10 dB HL or more) were significant at 4 kHz for both ears for 77% of bartenders. People working as bartenders represent a professional group with an increased risk of hearing loss. Raising awareness of this fact and implementing hearing protection programs in this group of workers is urgently needed, in line with the European Commission Directive (EU Directive 2003/10/EC). Med Pr. 2019;70(1):17-25.


Population structure and linkage disequilibrium in elite barley breeding germplasm from the United States.
Cultivated barley is known to have a complex population structure and extensive linkage disequilibrium (LD). To conduct robust association mapping (AM) studies of economically important traits in US barley breeding germplasm, population structure and LD decay were examined in a complete panel of US barley breeding germplasm (3840 lines) genotyped with 3072 single nucleotide polymorphisms (SNPs). Nine subpopulations (sp1‒sp9) were identified by the program STRUCTURE and subsequently confirmed by principle component analysis (PCA). Out of the nine subpopulations, seven were very similar to the respective subpopulations identified by Hamblin et al. (2010) which were based on half of the germplasm and half of the SNP markers, but two subpopulations were found to be new. One subpopulation was dominated by six-rowed spring lines from Utah State University (UT) and the other was composed of six-rowed spring lines from multiple breeding programs (USDA-ARS Aberdeen (AB), Busch Agricultural Resources Inc. (BA), UT, and Washington State University (WA)). LD was found to decay across a range from 4.0 to 19.8 cM. This result indicates that the germplasm genotyped with 3072 SNPs would be robust for mapping and possibly identifying the causal polymorphisms contributing to disease resistance and perhaps other traits.


Synthesis and Optical Properties of [Cu6E6(SnPh)2(PPh2Et)6] (E = S, Se, Te) Cluster Molecules.
A homologous series of three copper-tin-chalcogenide cluster molecules [Cu6E6(SnPh)2(PPh2Et)6] (E = S, Se, Te) was synthesized by reactions of CuO(O)CCH3 and PhSnCl3 with E(SiMe3)2 in the presence of PPh2Et. The cluster cage structures are similar, with slight differences in the bridging modes of the respective chalcogenide ligands E. The onset of the optical absorption displays a significant decrease of ca. 1.1 eV on going from sulfur to tellurium. The differences in bonding and electronic excitations can be rationalized by DFT and TDDFT calculations. All complexes display near-infrared phosphorescence at cryogenic temperatures. In parallel with the absorption, the emission maximum shifts to lower energies in a series of sulfur, selenium, and tellurium compounds. In particular, the copper-tin-tellurium complex emits at an energy as low as ca. 0.97 eV (1280 nm).


Synthesis, characterization, and in vitro activity against Candida spp. of fluconazole encapsulated on cationic and conventional nanoparticles of poly(lactic-co-glycolic acid).
In this study, nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) loaded with fluconazole (FLZ) and FLZ-NPs coated with the cationic polymer polyethylenimine (PEI) (FLZ-NP-PEI) were synthetized in order to improve antimycotic activity against four strains of Candida spp. of clinical relevance. FLZ-NPs and FLZ-NP-PEI were synthesized by double emulsion solvent-diffusion (DES-D) and characterized. Minimum inhibitory concentration (MIC50) and minimum fungicide concentration (MFC) were determined in vitro by culturing Candida strains in the presence of these nanocompounds. FLZ-NPs were spherical in shape with hydrodynamic sizes of ~222 nm and surface charge of -11.6 mV. The surface charges of these NPs were successfully modified using PEI (FLZ-NP-PEI) with mean hydrodynamic sizes of 281 nm and surface charge of 23.5 mV. The efficiency of encapsulation (~53%) and a quick release of FLZ (≥90% after 3 h) were obtained. Cytotoxicity assay showed a good cell viability for FLZ-NPs (≥86%), and PEI-modified NPs presented a decrease in cell viability (~38%). FLZ-NPs showed an increasing antifungal activity of FLZ for sensitive (Candida parapsilosis ATCC22019 and Candida albicans ATCC10231, MIC50 =0.5 and 0.1 µg/mL, respectively) and resistant strains (Candida glabrata EMLM14 and Candida krusei ATCC6258, MIC50 =0.1 and 0.5 µg/mL, respectively). FLZ-NP-PEI showed fungicidal activity even against C. glabrata and C. krusei (MFC =4 and 8 µg/mL, respectively). MIC50 values showed best results for FLZ-NPs and FLZ-NP-PEI. Nevertheless, only FLZ-NP-PEI displayed fungicidal activity against the studied strains.


Developmental pluripotency of the nuclei of neurons in the cerebral cortex of juvenile mice.
Nuclei isolated from green fluorescent protein-marked neurons in the cerebral cortex of juvenile mice (14-21 d after birth) were injected into enucleated oocytes that were allowed to develop into blastocysts. Embryonic stem (ES) cell lines were established from the inner cell mass of 76 cloned blastocysts after injecting 2026 neuronal nuclei. Some ES cells were injected individually into enucleated oocytes (nuclear transfer). Other ES cells were transferred into the blastocoeles of tetraploid blastocysts (tetraploid complementation). Two-cell embryos after nuclear transfer were transferred to the oviducts of surrogate mothers. Four (1.5%) of 272 nuclear-transferred two-cell embryos developed to term, and two (0.7%) developed into fertile adults. Nineteen (1.9%) of 992 tetraploid blastocysts receiving ES cells reached term, and 10 (1.0%) developed into adults. These findings demonstrate that some of the nuclei of differentiated neurons in the cerebral cortex of juvenile mice maintain developmental pluripotency.


The area under the concentration-time curve of all-trans-retinoic acid is the most suitable pharmacokinetic correlate to the embryotoxicity of this retinoid in the rat.
Earlier studies with etretinate and its metabolite acitretin suggested that area under the concentration-time curve (AUC) is the most suitable pharmacokinetic correlate to etretinate-induced teratogenesis. In an attempt to test this hypothesis with respect to the embryotoxic effects of all-trans-retinoic acid (all-trans-RA), we determined the embryotoxicity and plasma pharmacokinetics of all-trans-RA and its metabolites following administration of all-trans-RA to Wistar rats on Gestational Day (GD) 9, either subcutaneously (sc; dose levels 1, 3, or 5 mg/kg body mass) or orally (po; 5 mg/kg body mass). The 5 mg/kg dose of all-trans-RA was not embryotoxic when administered orally but led to high rates of embryolethality and skeletal defects following sc treatment. Determination of retinoids by HPLC showed that all-trans-RA reached similar maximum plasma concentrations (C(max)) after both dosing regimens, but its plasma AUC was ca. threefold higher after sc injection than po administration due to the slower uptake rate of the drug and its limited detoxification via beta-glucuronidation following sc injection. Furthermore, retinoid analysis in rat tissues (liver, kidney, duodenum, and jejunum), collected 1 hr after sc or po administration of 5 mg all-trans-RA/kg body mass on GD 9, confirmed that formation of all-trans-retinoyl-beta-glucuronide was much more extensive after po than after sc administration. Finally, linear regression analysis of either C(max). or AUC values of all-trans-RA in rat plasma and fetal abnormality rates showed that AUC values are better correlated with the embryotoxic outcome than C(max) [AUC-based correlation coefficient (r) > 0.90; C(max)-based r < 0.43]. Our findings establish the relevance of the AUC of all-trans-RA, and not its C(max), as the most appropriate pharmacokinetic marker of embryonic exposure and embryotoxic potency of all-trans-RA and stress the importance of the duration of exposure as a major determinant of embryotoxic outcome for retinoids.


Nomogram for predicting 90-day mortality in patients with Acinetobacter baumannii-caused hospital-acquired and ventilator-associated pneumonia in the respiratory intensive care unit.
We built a prediction model of mortality risk in patients the with Acinetobacter baumannii (AB)-caused hospital-acquired (HAP) and ventilator-associated pneumonia (VAP). In this retrospective study, 164 patients with AB lower respiratory tract infection were admitted to the respiratory intensive care unit (RICU) from January 2019 to August 2021 (29 with HAP, 135 with VAP) and grouped randomly into a training cohort (n = 115) and a validation cohort (n = 49). Least absolute shrinkage and selection operator regression and multivariate Cox regression were used to identify risk factors of 90-day mortality. We built a nomogram prediction model and evaluated model discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curves, respectively. Four predictors (days in intensive care unit, infection with carbapenem-resistant AB, days of carbapenem use within 90 days of isolating AB, and septic shock) were used to build the nomogram. The AUC of the two groups was 0.922 and 0.823, respectively. The predictive model was well-calibrated; decision curve analysis showed the proposed nomogram would obtain a net benefit with threshold probability between 1% and 100%. The nomogram model showed good performance, making it useful in managing patients with AB-caused HAP and VAP.


Malnutrition, Depression, Poor Sleep Quality, and Difficulty Falling Asleep at Night Are Associated with a Higher Risk of Cognitive Frailty in Older Adults during the COVID-19 Restrictions.
The COVID-19 restrictions, such as social isolation and disruption of daily routines, can have detrimental effects, including increased stress, anxiety, sleep disturbance, and physical and cognitive decline among older adults. This study aimed to examine the association between nutritional status, depression, sleep quality, falling asleep at night, and cognitive frailty (CF) among older Thai adults during the COVID-19 pandemic. This cross-sectional study included 408 older adults with an average age of 70.54 (5.49) years. CF was determined using Fried's frailty phenotype and the Montreal Cognitive Assessment Basic. The Mini Nutritional Assessment-Short Form, Pittsburgh Sleep Quality Index, and geriatric depression assessment were used for assessment. Multiple logistic regression analysis demonstrated that participants who were malnourished (OR 3.786; 95%CI 1.719-8.335), depressed (OR 5.003; 95%CI 2.399-10.434), had poor sleep quality (OR 1.613; 95%CI 1.041-2.500), and engaged in difficulty falling asleep (OR 1.809; 95%CI 1.022-3.203) had a higher risk of CF compared to those who did not exhibit these factors. Therefore, malnutrition, depression, poor sleep quality, and difficulty falling asleep were identified as risk factors for CF among older adults in Thailand linked to the impact of the COVID-19 pandemic. It is crucial to develop interventions to prevent CF resulting from the mentioned variables.


Efficient manipulation of Förster resonance energy transfer through host-guest interaction enables tunable white-light emission and devices in heterotopic bisnanohoops.
In this study, we synthesized and reported the heterotopic bisnanohoops P5-[8,10]CPPs containing cycloparaphenylenes (CPPs) and a pillar[5]arene unit, which act not only as energy donors but also as a host for binding energy acceptors. We demonstrated that a series of elegant FRET systems could be constructed successfully through self-assembly between donors P5-[8,10]CPPs and acceptors with different emissions via host-guest interaction. These FRET systems further allow us to finely adjust the donors P5-[8,10]CPPs and acceptors (BODIPY-Br and Rh-Br) for achieving multiple color-tunable emissions, particularly white-light emission. More importantly, these host-guest complexes were successfully utilized in the fabrication of white-light fluorescent films and further integrated with a 365 nm LED lamp to create white LED devices. The findings highlight a new application of carbon nanorings in white-light emission materials, beyond the common recognition of π-conjugated molecules.


Analysis of the cytogenetic response in peripheral blood lymphocytes from breast cancer patients following chemotherapy.
The presence of chromosomal aberrations induced in circulating lymphocytes from breast cancer patients during chemotherapy was analyzed. Ten breast cancer patients undergoing neoadjuvant chemotherapy and ten healthy women (controls) were evaluated. Metaphases were obtained from cultures of peripheral lymphocytes stimulated with phytohemaglutinin and metaphase blockage was achieved with colchicine. One hundred metaphases were analyzed for chromosomal aberrations and 1,000 cells for the mitotic index. No significant differences were observed regarding the frequency of chromosomal aberrations, number of cells with chromosomal aberrations and mitotic index between the controls and patients before chemotherapy. However, after the first chemotherapy cycle, the numbers of chromosomal aberrations and cells with them was greater. After the third cycle, the mitotic index was lower, but the fifth cycle produced an increase in relation to the third and fourth cycles. The results suggest that chemotherapy raises the number of chromosomal aberrations and favors persistence of stable chromosomal abnormalities.


"The child can remember your voice": parent-child communication about sexuality in the South African context.
There is a wealth of research on parent-child communication about sexual and reproductive health and rights (SRHR) and its influence on young people's sexual behaviours. However, most of it is from the global North. The aim of this study was to explore parent-child communication in three South African provinces: Eastern Cape, KwaZulu-Natal (KZN) and Mpumalanga. Nine, peer, focus group discussions (FGDs) were conducted with young and adult black African men and women in their spoken languages. Data were analysed thematically. Findings revealed that cultural and religious constructions of taboo silenced direct communication and restricted the discussed topics. Parents' older age, low educational level, lack of knowledge, and discomfort in talking about sexuality matters were reported to restrict conversations with children about sex and sexuality. The influence of these factors differed for parents residing in an urban setting who were more liberal than their counterparts residing in more rural areas. The child's age and gender were also reported to be a consideration in approaching these conversations. There is a need for interventions to assist parents on how to communicate with their children about SRHR topics beyond pregnancy and HIV/AIDS. These interventions should take into account and address factors that seem to influence parent-child communication.


Large enhancement of nonlinear optical response in a hybrid nanobiomaterial consisting of bacteriorhodopsin and cadmium telluride quantum dots.
We report wavelength-dependent enormous enhancement of the nonlinear refractive index of wild-type bacteriorhodopsin in the presence of semiconductor quantum dots. The effect is strongest in the region just below the absorption edge of both constituents of this hybrid material and in samples that show strong Förster resonance energy transfer. We show that enhancements of up to 4000% can be achieved by controlled engineering of the hybrid structure involving variations of the molar ratio of the constituents. This new hybrid material with exceptional nonlinear properties will have numerous photonic and optoelectronic applications employing its photochromic, energy transfer, and conversion properties.


Interaction of safranal and picrocrocin with ctDNA and their preferential mechanisms of binding to GC- and AT-rich oligonucleotides.
Saffron (Crocus sativus L.) shows different biological properties, some of which relate to its special components including safranal (deglycosylated picrocrocin). In our previous study on the mechanism of saffron functions, interaction of saffron carotenoids with DNA and oligonucleotides was reported. The present study aimed to investigate the interaction of safranal with calf thymus DNA (ctDNA), oligo(GC)15, and oligo(AT)15 in comparison with picrocrocin. Circular dichroism (CD) and fluorometric results show the nonintercalative/minor groove binding of the mentioned ligands to ctDNA. The CD plots indicate that picrocrocin interacts with DNA and oligonucleotides at lower concentrations than safranal does, which is accompanied by B- to C-DNA transition. At higher concentrations, it induces more conformational changes, that is, unstacking of DNA and oligonucleotides bases, the same as saffron carotenoids. However, similar results are obtained for safranal interaction with ctDNA (56% AT) and oligo(AT)15, but after adding safranal (with a free aldehyde group) to oligo(GC)15, the CD spectra show some changes (two positive and a displaced negative peaks) that are characteristics of triple-helix DNA. Thus, the mechanism for B- to H-DNA transition, due to the interaction of safranal with GC-rich sequences, is presented here.


Multiple retinol and retinal dehydrogenases catalyze all-trans-retinoic acid biosynthesis in astrocytes.
All-trans-retinoic acid (atRA) stimulates neurogenesis, dendritic growth of hippocampal neurons, and higher cognitive functions, such as spatial learning and memory formation. Although astrocyte-derived atRA has been considered a key factor in neurogenesis, little direct evidence identifies hippocampus cell types and the enzymes that biosynthesize atRA. Here we show that primary rat astrocytes, but not neurons, biosynthesize atRA using multiple retinol dehydrogenases (Rdh) of the short chain dehydrogenase/reductase gene family and retinaldehyde dehydrogenases (Raldh). Astrocytes secrete atRA into their medium; neurons sequester atRA. The first step, conversion of retinol into retinal, is rate-limiting. Neurons and astrocytes both synthesize retinyl esters and reduce retinal into retinol. siRNA knockdown indicates that Rdh10, Rdh2 (mRdh1), and Raldh1, -2, and -3 contribute to atRA production. Knockdown of the Rdh Dhrs9 increased atRA synthesis ∼40% by increasing Raldh1 expression. Immunocytochemistry revealed cytosolic and nuclear expression of Raldh1 and cytosol and perinuclear expression of Raldh2. atRA autoregulated its concentrations by inducing retinyl ester synthesis via lecithin:retinol acyltransferase and stimulating its catabolism via inducing Cyp26B1. These data show that adult hippocampus astrocytes rely on multiple Rdh and Raldh to provide a paracrine source of atRA to neurons, and atRA regulates its own biosynthesis in astrocytes by directing flux of retinol. Observation of cross-talk between Dhrs9 and Raldh1 provides a novel mechanism of regulating atRA biosynthesis.


Direct interaction between fd phage pilot protein pIII and the TolQ-TolR proton-dependent motor provides new insights into the import of filamentous phages.
Filamentous phages are one of the simplest examples of viruses with a protein capsid that protects a circular single-stranded DNA genome. The infection is very specific, nonlytic, and can strongly affect the physiology or provide new pathogenic factors to its bacterial host. The infection process is proposed to rely on a pore-forming mechanism similar to that of certain nonenveloped eukaryotic viruses. The Ff coliphages (including M13, fd, and f1) have been intensively studied and were used to establish the sequence of events taking place for efficient crossing of the host envelope structure. However, the mechanism involved in the penetration of the cell inner membrane is not well understood. Here, we identify new host players involved in the phage translocation mechanism. Interaction studies by a combination of in vivo biochemical methods demonstrate that the adhesion protein pIII located at the tip of the phage binds to TolQ and TolR, two proteins that form a conserved proton-dependent molecular motor in the inner membrane of the host cell. Moreover, in vivo cysteine cross-linking studies reveal that the interactions between the pIII and TolQ or TolR occur between their transmembrane helix domains and may be responding to the proton motive force status of the cell. These results allow us to propose a model for the late stage of filamentous phage translocation mediated by multiple interactions with each individual component of the host TolQRA complex.


Unexplained Gait and Balance Changes: A Case Report of Myxoma Mitigation in a Breast Reduction Patient.
In Fall 2020, a female physical therapist (PT) developed mild changes in gait, infrapatellar tendon pain, and lateral patellar tracking. As a PT in good physical condition, she did not access her employer's occupational health clinic but instead she self-treated. Two months after symptom onset and self-treatment, she was diagnosed with an intramuscular myxoma within her left vastus lateralis, the largest muscle within the quadricep. The employee was at risk of slips, trips, and falls as the mass grew. Due to the location and increasing size of the mass, the employee required surgical treatment. Healthcare workers, particularly those who provide treatment, are likely to self-treat rather than seek assistance from the occupational health professional. The employee was seen by a plastic surgeon for an unrelated medical condition which is when the myxoma was diagnosed. Further delay may have led to occupational injury associated with the balance and gait disturbances. Opportunity exists for the occupational health professional to provide a review of services, including screening for musculoskeletal changes associated with occupational injury such as those described herein. This is especially important among those healthcare workers who tend to self-treat.


The complete chloroplast genome sequence of Tussilago farfara (Asteraceae).
Tussilago farfara is a member of the family Asteraceae. In this paper, we reported the complete chloroplast (cp) genome sequence of T. farfara. The results showed that T. farfara complete chloroplast genome comprises 151,325 bp, containing a largen single copy (LSC) region of 83,370 bp, a small single copy (SSC) region of 18,273 bp, and a pair of inverted repeats (IRs) region of 24,841 bp. The genome has a GC content of 37.4%. The LSC, SSC, and IR regions represent 35.5%, 30.6%, and 43.0% of the T. farfara chloroplast genome length. We annotated 132 genes, comprising 87 protein-coding genes (PCGs), eight rRNA genes, and 36 tRNA genes. A phylogenetic analysis based on 31 cpDNA genomes suggested that the T. farfara is closely related to Farfugium japonicum.


Pre-hospital trauma care: a proposal for more efficient evaluation.
Although mortality is an important outcome parameter for pre-hospital trauma care, it is influenced by many factors other than pre-hospital trauma care alone. We therefore studied an alternative method to evaluate pre-hospital trauma care by calculating the change in probability of survival (Ps) according to the TRISS methodology, before and directly after the pre-hospital trauma care. Correlations between patient characteristics and a change in Ps were assessed. Further, required sample sizes were calculated for an 80% power to detect a hypothetical 3% reduction in mortality and the corresponding change in Ps. In 140 of 191 patients with an Injury Severity Score > or =16, the Ps did not change. In 36, the Ps increased and in 15 patients, the Ps decreased. Between these three groups, significant differences were found in Revised Trauma Score and age, but no clear differences in Injury Severity Score or mortality. A 3% difference in mortality would require 6800 patients, in contrast to 3500 when the change in Ps was the primary outcome parameter. A change in Ps is a promising outcome parameter for a more efficient evaluation of pre-hospital trauma care. A good collaboration is, however, required between ambulance services and the trauma center for reliable registration.


Treating older adults as ends rather than means only.
The treatment of older adults by nurses requires professional knowledge, skills, and attitudes which are carefully thought out and put into practice in organizations and societies that do not always respect the perspectives and priorities of older adults. McCormack's person-centered nursing with older adults approach seeks to help nurses deal with this bind. His approach, as critiqued by Landers and McCarthy, is discussed here.


BAF200 is required for heart morphogenesis and coronary artery development.
ATP-dependent SWI/SNF chromatin remodeling complexes utilize ATP hydrolysis to non-covalently change nucleosome-DNA interactions and are essential in stem cell development, organogenesis, and tumorigenesis. Biochemical studies show that SWI/SNF in mammalian cells can be divided into two subcomplexes BAF and PBAF based on the subunit composition. ARID2 or BAF200 has been defined as an intrinsic subunit of PBAF complex. However, the function of BAF200 in vivo is not clear. To dissect the possible role of BAF200 in regulating embryogenesis and organ development, we generated BAF200 mutant mice and found they were embryonic lethal. BAF200 mutant embryos exhibited multiple cardiac defects including thin myocardium, ventricular septum defect, common atrioventricular valve, and double outlet right ventricle around E14.5. Moreover, we also detected reduced intramyocardial coronary arteries in BAF200 mutants, suggesting that BAF200 is required for proper migration and differentiation of subepicardial venous cells into arterial endothelial cells. Our work revealed that PBAF complex plays a critical role in heart morphogenesis and coronary artery angiogenesis.


Obesity increases mortality in liver transplantation--the Danish experience.
Obesity is increasing in the western world at an epidemic rate. The USA results in obese patients undergoing orthotopic liver transplantation (OLT) are divergent, and so far no European experience has been reported. This study was designed to determine if obesity is a risk factor for mortality and morbidity in OLT in a medium-size European center. In a retrospective study of the records of 365 consecutive patients who had undergone OLT from 1990 to 2003, 20 obese patients [body mass index (BMI) > 30 kg/m2] were identified. Their data were compared with those of the nonobese (BMI < 30 kg/m2) patients operated immediately before. There were no differences in demographic data, diagnosis leading to OLT, United Network of Organ Sharing (UNOS) classification, Child-Pugh score, or preoperative morbidity. The groups were also comparable concerning donor data, duration of operation, use of blood products, intensive care unit (ICU), or hospital admission. Mortality was, however, significantly increased in the obese group (P = 0.01). Our study clearly demonstrates an increased mortality in obese patients undergoing OLT and the relative scarcity of organs taken into account, it seems reasonable to consider obesity as a relative contraindication to OLT.


A comparative study of cholecalciferol, dihydrotachysterol and alfacalcidol in the treatment of elderly patients with hypocalcaemia.
Fifty elderly patients with hypocalcaemia were randomly treated for 8 weeks with either oral dihydrotachysterol, parenteral cholecalciferol or oral alfacalcidol. All three treatments were successful in normalizing the serum calcium levels in most patients within 2 weeks. Hypercalcaemia was seen only with alfacalcidol but was rapidly reversed once treatment was discontinued. Hypercalcaemia was not observed with either dihydrotachysterol or cholecalciferol. These therefore, require less frequent biochemical monitoring. A single cholecalciferol injection eliminates the problems of compliance.


[Pharma-Clinics. The drug of the month. Venlafaxine (Efexor)].
Venlafaxine (Efexor) is the first representative of a new class of antidepressants: serotonin noradrenaline reuptake inhibitors. Its usual dose is 75 mg/d in two intakes but can be progressively increased until a maximal daily dose of 375 mg/d in severe or resistant depression, particularly among inpatients. The efficacy of venlafaxine is at least equivalent to reference antidepressants. At high doses, venlafaxine could even exhibit a better efficacy and a shorter latency than current compounds. Its profile of side-effects is quite similar to selective serotonin reuptake inhibitors with mainly nausea, with the exception if an increase in blood pressure which can appear at high doses. In total, venlafaxine represents an interesting innovation in the pharmacological treatment of depression.


Lost in summation: depression among African American female caregivers and noncaregivers.
Ethnic differences in mental health have been established using large between-group research designs. Across ethnicity, studies have found that caregivers are at increased risk for depression, but little is known about within-group variability in depressive symptomatology. African American caregivers and noncaregivers were compared on different factors of depressive symptoms as measured by the Center for Epidemiologic Studies Depression subscales. Caregivers reported significantly less positive affect than noncaregivers. Rates were similar for negative affect, somatic complaints, and interpersonal relations. Depression may present itself in different ways among African Americans in the caregiving context, and results suggest information may be lost when global measures of depression are used.


Protective effect of losartan and ramipril against stress induced insulin resistance and related complications: Anti-inflammatory mechanisms.
Chronic restraint stress (CRS) is known to cause various behavioural and biochemical alterations, leading to several negative health outcomes. The present study was designed to explore the impact of inhibiting Renin angiotensin aldosterone system (RAAS) and inflammatory pathways in stress pathophysiology. In the present study, male LACA mice were subjected to restraint stress daily for 30 days. Losartan, nimesulide, ramipril, minocycline and their combinations were administered 45min prior to restraint stress daily and their effects were observed. Restraint stressed mice depicted depression like behavior along with increased oxidative stress markers in their brains. CRS induced insulin resistance depicted by hyperglycemia, hyperinsulinemia, hypercholesteremia, increased glycosylated hemoglobin and HOMA-IR. Besides, treatment with losartan, nimesulide, ramipril and minocycline significantly restored the behavioural and biochemical alterations and improved insulin sensitivity in stressed mice. Combination treatments synergistically reversed depression like behavior and decreased plasma glucose levels. Moreover they restored insulin levels, glycosylated hemoglobin levels and HOMA-IR values to the normal. This study signifies the synergistic effect of simultaneously blocking RAS and inflammatory pathways in stress pathophysiology.


The meaning of natural childbirth.
The term "natural childbirth" encompasses a variety of methods, including the Lamaze, Bradley, and home-birth approaches, which place more or less reliance on medical technology. Aristotle's analysis of three levels of human activity--digestion and reproduction, perception and locomotion, and abstract thinking--and Pellegrino and Thomasma's classification of the "living body," "lived body," and "lived self," provide a principled framework in which each of these childbirth practices can be considered natural.


Comparison of expert and job-exposure matrix-based retrospective exposure assessment of occupational carcinogens in The Netherlands Cohort Study.
Reliable retrospective exposure assessment continues to be a challenge in most population-based studies. Several methodologies exist for estimating exposures retrospectively, of which case-by-case expert assessment and job-exposure matrices (JEMs) are commonly used. This study evaluated the reliability of exposure estimates for selected carcinogens obtained through three JEMs by comparing the estimates with case-by-case expert assessment within the Netherlands Cohort Study (NLCS). The NLCS includes 58,279 men aged 55-69 years at enrolment in 1986. For a subcohort of these men (n=1630), expert assessment is available for exposure to asbestos, polycyclic aromatic hydrocarbons (PAHs) and welding fumes. Reliability of the different JEMs (DOMJEM (asbestos, PAHs), FINJEM (asbestos, PAHs and welding fumes) and Asbestos JEM (asbestos) was determined by assessing the agreement between these JEMs and the expert assessment. Expert assessment revealed the lowest prevalence of exposure for all three exposures (asbestos 9.3%; PAHs 5.3%; welding fumes 11.7%). The DOMJEM showed the highest level of agreement with the expert assessment for asbestos and PAHs (κs=0.29 and 0.42, respectively), closely followed by the FINJEM. For welding fumes, concordance between the expert assessment and FINJEM was high (κ=0.70). The Asbestos JEM showed poor agreement with the expert asbestos assessment (κ=0.10). This study shows case-by-case expert assessment to result in the lowest prevalence of occupational exposure in the NLCS. Furthermore, the DOMJEM and FINJEM proved to be rather similar in agreement when compared with the expert assessment. The Asbestos JEM appeared to be less appropriate for use in the NLCS.


Automated assistance for human factors analysis in complex systems.
A tool and a method for scenario-based workload assessment and performance validation in complex socio-technical systems design, such as command and control rooms of military vessels, are described. We assess workload in terms of communication and the task load that each agent is able to handle. The method employs subjective task and communication estimates used to calculate the workload of human operators, using static and scenario-based analyses. This enables the identification of bottlenecks to be addressed by the designer with the appropriate allocation of function between humans and smart technology. This task is supported by the functional allocation adviser tool. A case study demonstrating the use of the tool for the design of the command and control room of a military vessel is presented.


Emotional descriptors of words as predictors of recall in a paired-associate task.
An extended replication of Contini and Whissell's 1992 experiment (N = 64 subjects) confirmed that there is a recall disadvantage for emotional words, especially active words, whether these serve as the cue or as the associate in a paired-associate task. A regression formula with trials, two gender variables, and seven emotional predictors (R2 = .77) was successful in predicting recall for 160 trials. Words or their CVC associates were better recalled if the words were emotionally neutral and least well recalled if the words were active or both unpleasant and passive.


[SARS-CoV-2 infection and solid organ transplantation].
Transplantation has become a valid therapeutic option for an increasing number of patients with end-stage organ disease. The emergence of SARS-CoV-2 coronavirus infection and associated disease (COVID-19) has alarmed the transplant community, since recommendations for adequate follow-up of organ transplant recipients during the acute phase of a pandemic are limited. Furthermore, treatment options against COVID-19 disease and adequate adjustment of immunosuppression in at risk patients remain a concern. This review summarizes current knowledge on the incidence and clinical course of SARS-CoV-2 infection in patients with solid organ transplantation. It also discusses therapeutic strategies and provides general recommendations on how to proceed with transplantation programs in a time when health care resources may become scarce.


Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome.
Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from maternal alcohol use. We used a non a priori approach to prioritize candidate pathways during alcohol-induced teratogenicity in early mouse embryos. Two C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams with alcohol (2x 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter-exposure to PK11195 (4 mg/kg) significantly protected B6J embryos but slightly promoted FASD in B6N embryos. Microarray transcript profiling was performed on the embryonic headfold 3 hr after the first maternal alcohol injection (GEO data series accession GSE1074). This analysis revealed metabolic and cellular reprogramming that was substrain-specific and/or PK11195-dependent. Mapping ethanol-responsive KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed down-regulation of ribosomal proteins and proteasome, and up-regulation of glycolysis and pentose phosphate pathway in B6N embryos; and significant up-regulation of tight junction, focal adhesion, adherens junction, and regulation of the actin cytoskeleton (and near-significant up-regulation of Wnt signaling and apoptosis) pathways in both substrains. Expression networks constructed computationally from these altered genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14, PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are consistent with the growing view that developmental exposure to alcohol alters common signaling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195.


[The liver-cell specific drug delivery system].
There have been a growing interest in the area of liver-cell specific drug delivery in recent years. This may be because of the failure of pharmacological approaches to cure the liver diseases due to the nonspecific delivery towards other organs and several side effects. Currently it has been demonstrated that liver-cell specific drug delivery can be achieved by coupling drugs to various ligands containing carrier systems such as polymers, liposomes and proteins. Saccharide, LDL and bile acids were employed as cell specific ligands. These carriers can be used as shuttles for targeting drugs specifically towards liver cells such as hepatocytes and non-parenchymal cells.


VEGF and MVD expression in sinus augmentation with autologous bone and several graft materials.
The aim of this study was to assess vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in maxillary sinus augmentation with autogenous bone and different graft materials for evaluating their angiogenic potential. Biopsies were harvested 10 months after sinus augmentation with a combination of autogenous bone and different graft materials: hydroxyapatite (HA, n = 6 patients), demineralized freeze-dried bone allograft (DFDBA, n = 5 patients), calcium phosphate (CP, n = 5 patients), Ricinus communis polymer (n = 5 patients) and control group--autogenous bone only (n = 13 patients). In all the samples, higher intensities of VEGF expression were prevalent in the newly formed bone, while lower intensities of VEGF expression were predominant in the areas of mature bone. The highest intensity of VEGF expression in the newly formed bone was expressed by HA (P < 0.001) and CP in relation to control (P < 0.01) groups. The lowest intensities of VEGF expression in newly formed bone were shown by DFDBA and polymer groups (P < 0.05). When comparing the different grafting materials, higher MVD were found in the newly formed bone around control, HA and CP (P < 0.001). Various graft materials could be successfully used for sinus floor augmentation; however, the interactions between bone formation and angiogenesis remain to be fully characterized.


Walkaround: mobile balance support for therapy of walking.
We describe here the Walkaround, a new rehabilitation device that allows walking without hand support of individuals with limited ability to control posture. The design of this device was motivated by the recent development of functional electrical therapy of walking in individuals with hemiplegia, who in many cases need postural and body weight assistance while walking. The Walkaround assists humans with a compromised posture, inability to fully support the body weight on one leg, and prevents their falls. These three features are accomplished by an ergonomic lumbar belt being attached to a rigid wheeled frame by a suspensor system. The height of the frame which interfaces the ground by three telescopic bars, the size of the belt, and the pretension of the suspension system, can all be adjusted to complement the size and the needs of the potential user. The amount of body weight support can be adjusted by setting the lengths of telescopic bars and the pretension of the springs in the suspensors. The prototype device was tested on five individuals with hemiplegia. The walking assisted by the Walkaround was significantly faster (Deltav = 0.13 m/s p 0.05) in comparison to walking assisted by a therapist. The symmetry index between paretic and non affected leg was decreased (Delta R(stance) = -7.4% p 0.05, Delta R (swing) =-9.2%, p 0.05, symmetry improved) when walking assisted by the Walkaround. The users and therapists were positive about the performance of the Walkaround. The users felt safer and the therapists were relieved from the physical effort allowing them to concentrate more on assisting - a nearly normal walking pattern.


Pleiotropy of ABO gene: correlation of rs644234 with E-selectin and lipid levels.
The ABO gene has been widely studied and associated with many different diseases such as myocardial infarction and diabetes. Pleiotropic effects of the ABO locus have been demonstrated. Indeed it affects different phenotypes such as E- and P-selectins, triglycerides and total cholesterol. The goal of this work was to study the SNP rs644234 located in the ABO gene with different phenotypes related with diseases where the ABO gene has been involved. We analyzed the SNP rs644234 located in the ABO gene, by performing association studies with different lipid phenotypes as well as with the soluble E-selectin levels in 348 adults from the STANISLAS Family Study. The major rs644234*T allele was associated with increased levels of soluble E-selectin (p=8.7×10-12). According to the lipid phenotypes, the major rs644234*T allele was associated with decreased levels of apolipoproteins E (ApoE) (p=0.001) and low-density lipoprotein cholesterol (LDL-C) (p=0.032) but was associated with increased levels of high-density lipoprotein cholesterol (HDL-C) (p=0.013). The association of the HDL-C was especially significant in the male individuals (p=0.001). We confirmed that ABO is a major locus for serum soluble E-selectin levels variability, and we also correlated this gene with different lipid phenotypes. Furthermore, we demonstrated that this pleiotropic effect is independent. This is the first time that a correlation has been made between the ABO gene and the ApoE levels. According to these results, the major allele of this polymorphism may have a protective effect when it comes to cardiovascular related diseases, and more specifically when it comes to the lipid phenotypes.


Crystal structure of human otubain 2.
Ubiquitylation, the modification of cellular proteins by the covalent attachment of ubiquitin, is critical for diverse biological processes including cell cycle progression, signal transduction and stress response. This process can be reversed and regulated by a group of proteases called deubiquitylating enzymes (DUBs). Otubains are a recently identified family of DUBs that belong to the ovarian tumour (OTU) superfamily of proteins. Here, we report the first crystal structure of an OTU superfamily protein, otubain 2, at 2.1 A resolution and propose a model for otubain-ubiquitin binding on the basis of other DUB structures. Although otubain 2 is a member of the cysteine protease superfamily of folds, its crystal structure shows a novel fold for DUBs. Moreover, the active-site cleft is sterically occluded by a novel loop conformation resulting in an oxyanion hole, which consists uniquely of backbone amides, rather than the composite backbone/side-chain substructures seen in other DUBs and cysteine proteases. Furthermore, the residues that orient and stabilize the active-site histidine of otubain 2 are different from other cysteine proteases. This reorganization of the active-site topology provides a possible explanation for the low turnover and substrate specificity of the otubains.


[Quality assessment of different forms of Cervi Cornu Pantotrichum based on content of free amino acids].
In this study, we analyzed the composition and content of 25 free amino acids in 32 batches of different forms of Cervi Cornu Pantotrichum(CCP; one-branched, two-branched, and three-branched) from 15 producing areas. The clustering analysis and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed based on the content of 25 free amino acids. Potential differential metabolites were identified based on VIP value. The results showed that there were 25 free amino acids in CCP, and the average content of essential, non-essential, and total amino acids was 6.13, 32.99, and 39.12 mg·g~(-1), respectively. The clustering analysis and OPLS-DA demonstrated that 25 free amino acids had different content among the three forms of CCP, of which two-branched CCP samples were separately gathered into a group. Five differential components, including glutamic acid, tryptophan, ornithine, γ-aminobutyric acid, and hydroxylysine, were screened out as potential quality markers for the identification of different forms of CCP. This study provides a theoretical basis for the quality evaluation, processing, and utilization of different forms of CCP.


[Cardioprotection of mitoSlo1 channel activation involves mitochondrial permeability transition in ischemia and reperfusion of rat hearts].
To investigate whether the cardioprotection of mitochondrial Slo channel (mitoSlo(1) channel) is associated with mitochondrial permeability transition in isolated rat hearts subjected to ischemia and reperfusion. Isolated perfused rat hearts were subjected to 30 min regional ischemia (occlusion of left anterior descending artery) and 120 min reperfusion. The infarct size, lactate dehydrogenase (LDH) release during reperfusion and ventricular hemodynamic parameters were measured. Pretreatment with mitoSlo(1) channel opener, NS1619 10 micromol/L for 10 min reduced the infarct size and LDH release, and improved the recovery of left ventricular developed pressure, left ventricular end-diastolic pressure, maximal rise/fall rate of left ventricular pressure and coronary flow during reperfusion. Administration of atractyloside (20 micromol/L), an opener of mitochondrial permeability transition pore, for 20 min (last 5 min of ischemia and first 15 min of reperfusion) attenuated the reduction of infarct size and LDH release and improvement of left ventricular performance induced by NS1619. In the isolated mitochondria, a significant inhibition of Ca(2+)-induced swelling was observed when mitochondria were incubated with NS1619. MitoSlo(1) channel activation by NS1619 protects the myocardium against ischemia and reperfusion injury by inhibiting mitochondrial permeability transition pore opening.


Nursing informatics year in review.
Nurses' role in patient care has evolved and so has their role in the use of technology to improve health care delivery. Nursing informatics research seeks to study the science of nursing, computer technology, and information science to enhance the quality of nursing practice. In an effort to increase patient safety and reduce health care-associated costs, nursing administrators have been challenged to incorporate technology and nursing practice. Unfortunately, health care institutions may not benefit from this body of work, as nursing informatics research associated with increased patient safety and cost containment may not be readily accessible for nursing administrators. The purpose of this study was to present the findings of a nursing informatics literature review and highlight those publications seen as most influential in the last year. In addition, we seek identify common topics and emerging themes in nursing informatics published research.


Super-High Magnification Dermoscopy in 190 Clinically Atypical Pigmented Lesions.
Super-high (×400) magnification dermoscopy (D400) is a new non-invasive imaging technique that has been shown to add information for the differential diagnosis of melanocytic lesions in a pilot study. Our study aimed to confirm if D400 can add details for the discrimination of clinically atypical nevus and melanoma. This is a retrospective observational, multicentric study enrolling patients who received ×20 (D20) and ×400 (D400) magnification dermoscopic examinations of pigmented skin lesions. Dermoscopic images were retrospectively evaluated by three observers for the presence/absence of nine D20 and twenty D400 dermoscopic features defined in the previous pilot study. Univariate and multivariate analyses were carried out to find predictors of benign and malignant behaviors. At D20, an atypical pigment network, blue-whitish veil, atypical vascular pattern, regression, and homogenous pattern were more frequent in melanoma than in nevi (p < 0.001). At D400, melanoma showed more frequently than benign lesions, melanocytes with an irregular arrangement and irregular in shape and size (p < 0.001). A network with edged papillae was more frequent in benign lesions than melanomas (p < 0.001). Our study confirms that D400 can identify melanocytes with an irregular arrangement, and irregularities in shape and size in melanomas, adding information to the conventional D20 examination.


[Treatment of hypertension emergencies].
Hypertensive emergencies are defined as situations where a seriously elevated blood pressure threatens the patients life or vital organ functions. Since treatment of hypertensive emergencies by a rapid reduction of blood pressure can be complicated by serious unwanted effects, the treatment indications should be defined cautiously. In addition the principles of autoregulation of blood flow and vascular resistance in hypertensive patients should be considered as well as the widely differing effects of the drugs used in hypertensive emergencies like alpha- and beta-adrenergic blocking substances, central sympatholytics and vasodilating agents. A reduction of cardiac output as a consequence of betablockade or central sympatholytics may be beneficial in patients with aneurysms, but may result in severe central hypoperfusion in others which can also be induced by vasodilators by local and systemic steal effects. Therefore we propose a treatment scheme for hypertensive emergencies based on pathophysiological considerations with special regard to cerebral perfusion. In many instances calcium-antagonists can be considered as drugs of first choice since they lower blood pressure in relation to pretreatment blood pressure and have only a weak negative inotropic effect. In addition they exert their vasodilating action predominantly in vessels with a high vasoconstrictor tone and do not reduce cerebral perfusion despite a marked reduction of blood pressure within a short time. In every case the initial emergency treatment should be followed by a careful long term management of hypertension.


High-performance liquid chromatography/electrospray mass spectrometry for the analysis of modified bases in DNA: 7-(2-hydroxyethyl)guanine, the major ethylene oxide-DNA adduct.
A method was developed for the analysis of 7-(2-hydroxyethyl)guanine (7HEG), the major DNA adduct formed after exposure to ethylene oxide (EO). The method is based on DNA neutral thermal hydrolysis, adduct micro-concentration, and final characterization and quantification by HPLC coupled to single-ion monitoring electrospray mass spectrometry (HPLC/SIR-ESMS). The method was found to be selective, sensitive, and easy to handle with no need for enzymatic digestion or previous sample derivatization. Detection limit was found to be close to 1 fmol of adduct injected (10(-10) M), thus allowing the detection of approximately three modified bases on 10(8) intact nucleotides in blood sample analysis. Quantification results are shown for 7HEG after calf thymus DNA and blood exposure to various doses of EO, in both cases obtaining clear dose-response relationships.


Use of rifampicin and ciprofloxacin combination therapy after surgical debridement in the treatment of early manifestation prosthetic joint infections.
Prosthetic joint infections are difficult to eradicate, and antibiotic and surgical treatment strategies lack standardisation. The present study followed 29 patients (median age 72 years, median American Society of Anesthesia score of two) with early prosthetic joint infections. Treatment consisted of device retention, surgical debridement and therapy with rifampicin and ciprofloxacin for 3 months. This treatment regimen failed in five patients during the study, with a median observation period of 674 days. The results of this study confirm the findings of the only previous study on device retention with antibiotic treatment.


Possible role of the CNS in regulating insulin secretion via humoral factors.
Among the several possible mechanisms responsible for hyperinsulinemia of obese rodents, an abnormal CNS-endocrine pancreas axis has been postulated. This axis appears to involve neural (parasympathetic, sympathetic) relationships. A humoral link between the CNS and the pancreas could also exist, as based on data from these and other laboratories. Indeed, CNS sites such as the ventrolateral, the ventromedial hypothalamus or the neurointermediate lobe of the pituitary, have been shown to contain substances possessing insulin secretion modulating activity. The precise nature of these substances has yet to be determined, as well as their ability to actually be released into the systemic circulation.


Toward Accountable Discrimination-Aware Data Mining: The Importance of Keeping the Human in the Loop-and Under the Looking Glass.
"Big Data" and data-mined inferences are affecting more and more of our lives, and concerns about their possible discriminatory effects are growing. Methods for discrimination-aware data mining and fairness-aware data mining aim at keeping decision processes supported by information technology free from unjust grounds. However, these formal approaches alone are not sufficient to solve the problem. In the present article, we describe reasons why discrimination with data can and typically does arise through the combined effects of human and machine-based reasoning, and argue that this requires a deeper understanding of the human side of decision-making with data mining. We describe results from a large-scale human-subjects experiment that investigated such decision-making, analyzing the reasoning that participants reported during their task to assess whether a loan request should or would be granted. We derive data protection by design strategies for making decision-making discrimination-aware in an accountable way, grounding these requirements in the accountability principle of the European Union General Data Protection Regulation, and outline how their implementations can integrate algorithmic, behavioral, and user interface factors.


Effects of polyadenylic acids on functions of murine RNA tumor viruses.
Single-stranded polyribonucleotides, which competitively inhibit murine RNA tumor virus reverse transcriptase in vitro, were tested as inhibitors of various virus functions in cell culture. The compounds had two concentration-dependent effects. At high concentrations (100 mug/ml), both poly(adenylic acid) [poly(A)] and poly(2'-O-methyladenylic acid) [poly(Am)] inhibited the uptake of radioactively labeled leukemia virus by Swiss mouse embryo cells, but neither had a similar effect on Sindbis virus adsorption. At low concentrations (10 mug/ml), poly(Am) did not inhibit the uptake of leukemia virus but did inhibit virus replication by 85%; in contrast, the replication of Sendai virus and Sindbis virus was not inhibited significantly at this concentration. Both compounds were effective only when added prior to or early during virus infection. Poly(Am) was a much more effective inhibitor than poly(A), probably due to the nuclease resistance of the former compound. Poly(Am) at 5 mug/ml also inhibited transformation of 3T3 cells by Moloney sarcoma virus. However, neither poly(A) nor poly(Am) at high concentrations inhibited the activation of endogenous leukemia virus by iododeoxyuridine in AKR mouse embryo cells. These results suggest that virus reverse transcriptase plays an essential role in both the replication of exogenous murine leukemia viruses and the transformation of cells by murine sarcoma viruses but probably has no role in the activation of endogenous leukemia virus.


Changing concepts in the management of differentiated thyroid cancer.
The management of patients with differentiated thyroid cancer has changed significantly over the last few decades. Mortality has decreased as the result of earlier detection, refined surgical approaches, subsequent radioiodine ablation, and the development of more sensitive methods for detecting and monitoring disease recurrence. The latter has been facilitated by serum thyroglobulin measurements, the use of recombinant human thyrotropin, and the use of 18F-deoxyglucose/positron emission tomography in selected instances where radioiodine imaging fails to locate known or suspected recurrent or metastatic disease.


Phenolics from Castanea sativa leaves and their effects on UVB-induced damage.
The phytochemical investigation of the methanol extract of the leaves of Castanea sativa Mill., source of the Italian PGI (Protected Geographical Indication) product 'Marrone di Roccadaspide' (Campania region) afforded as main compounds crenatin (1), chestanin (2), gallic acid (3), cretanin (4), 5-O-p-coumaroylquinic acid (5), p-methylgallic acid (6) and quercetin-3-O-glucoside (7). To quantify the isolated compounds a LC-ESI(QqQ)MS method working with a very sensitive and selective mass tandem experiment called Multiple Reaction Monitoring (MRM) has been developed. Moreover the antioxidant capacity by TEAC assay and the ability of compounds 1-7 to protect HaCaT human keratinocytes from UVB-induced damage has been investigated.


Post-translational modulation of pluripotency.
The maintenance of pluripotency relies on an intricate transcriptional network hinged on a key set of transcription factors. Pluripotent stem cells have been shown to be sensitive to modulations of the cellular abundance and transcriptional activity of these key pluripotency factors. Recent evidence highlights the important role of post-translational modifications, including ubiquitination, sumoylation, phosphorylation, methylation, and acetylation, in regulating the levels and activity of pluripotency factors to achieve a balance between pluripotency and differentiation.


Visual Examination Standard for Forklift and Crane Operators: A Report for 66 Operators of a Factory in Mumbai.
Forklift and crane industry in India is progressing at a rapid pace and the visual integrity of the operators is crucial for occupational safety. Hence, we performed a vision screening at a factory based in Mumbai. To evaluate the current visual status of forklift and crane operators working at a factory in Mumbai. Prospective observational cross-sectional. All forklift and crane operators were invited to undertake visual examination that included visual acuity (VA) assessment, refraction, slit-lamp examination, color vision assessment, visual field assessment, and stereopsis. Referrals were made for participants who needed further assessment. Mean and standard deviation were calculated and presented. A total of 66 forklift operators with an average age of 48 years that ranged from 26-60 years completed the study. The average distance VA in LogMAR with current spectacles was 0.1 ± 0.14. The near VA with usual spectacles averaged at 0.63 M ± 0.2 M. The best-corrected VA (BCVA) of 0 LogMAR was not achieved by 12% subjects; however, all participants except one met the 0.3 LogMAR visual acuity criteria. The average stereopsis was 55.8 ± 47.8 with 8% operators had lower than acceptable levels of stereopsis while 7% could not meet the set criteria. One operator had 400 s of an arc and 4 had 100 s of arc stereopsis. The study demonstrates an urgent need to set up standards for vision assessment at the time of employment and frequency of eye examination for forklift and other powered industrial vehicles.


Do people know how others view them? An empirical and theoretical account.
Meta-accuracy is the extent to which people know how others see them. Following D.A. Kenny and L. Albright (1987), we show how the social relations model (SRM) can be used to investigate meta-accuracy. The results from 8 SRM studies involving 569 subjects are reviewed. We argue that people determine how others view them not from the feedback that they receive from others but from their own self-perceptions. Consistent with this argument are the findings that (a) people overestimate the degree of consistency in the ways that different targets view them and (b) people are better at understanding how others generally view them than how they are uniquely viewed by specific individuals.


Relationship Between Mental Health, Resilience, and Physical Activity in Older Adults: A 2-Year Longitudinal Study.
The aim of this study was to longitudinally investigate the association between resilience and mental health in older adults and to determine the influence of physical activity on this relationship. A total of 291 older adults were included in a 2-year follow-up study. Adjusted linear regression models evaluated the association between resilience at baseline and mental health after 2 years in sufficiently and insufficiently physically active older adults. A negative correlation was found between resilience at baseline and depression, anxiety, and stress after 2 years for the overall sample. This association changed after stratifying the group. Sufficiently physically active individuals made greater use of the resilience components "Self-Sufficiency" and "Perseverance," whereas insufficiently physically active individuals made greater use of "Meaning of Life" and "Existential Singularity." Physical activity can influence the relationship between resilience and mental health. These results can help guide the devising of more effective interventions for this age group.


Clinical impact and management of fluconazole discontinuation on sirolimus levels in bone marrow transplant patients.
Sirolimus, an immunosuppressant, is indicated post-allogeneic stem cell transplant to reduce the risk of graft-versus-host-disease. Sirolimus is metabolized by cytochrome P450 3A4 and is a substrate of the P-glycoprotein (P-gp) drug efflux pump. Interactions with known inhibitors of the CYP3A4 enzyme and P-glycoprotein, such as fluconazole, are anticipated. Co-administration of fluconazole leads to an increase in sirolimus blood concentrations due to an inhibition of metabolism. The discontinuation of fluconazole will likely result in a decline in sirolimus blood concentrations, leaving patients at risk of graft-versus-host-disease. We report on three patients managed by the Hematology, Oncology Blood and Marrow Transplant Program at the Alberta Children's Hospital. The discontinuation of fluconazole showed a marked reduction in sirolimus trough levels, requiring >200% increase in sirolimus dose to achieve therapeutic levels.


Duplex Stable Isotope Labeling (DuSIL) for Simultaneous Quantitation and Distinction of Sialylated and Neutral N-Glycans by MALDI-MS.
Quantitative N-glycomics provides an effective tool for detecting glycosylation changes in cancer and other diseases. However, the lability of sialic acid and its lower ionization efficiency compared with that of neutral glycans make their analysis by mass spectrometry complicated and prevents the simultaneous quantitation and distinction of sialylated and neutral N-glycans by MS. To address this problem, we developed a novel approach duplex stable isotope labeling (DuSIL), to relatively quantify neutral and sialylated glycans concurrently by MALDI-MS. The duplex labeling strategy includes isotopic methylamidation labeling on the sialic acids and amino acid reductive amination on the reducing ends of N-glycans. Using this method, the labeled N-glycans showed doublet peaks with (6 + 3* N) Da mass difference for relative quantitation and discrimination of the number of sialic acids ( N). The DuSIL strategy is of high labeling efficiency, high reproducibility (CV < 20%), and good linearity ( R2 > 0.99) within 2 orders of magnitude of dynamic range. The strategy is successfully applied to measure N-glycan changes of IgG from human serum with colorectal cancer, demonstrating its potential in relative quantitation of the N-glycome in clinical samples.


High-speed system to generate congenic strains in medaka.
The congenic strain, an inbred strain containing a small genomic region from another strain, is a powerful tool to assess the phenotypic effect of polymorphisms and/or mutations in the substituted genomic region. Recent substantial progress in the genetic studies of complex traits increases the necessity of congenic strains and, therefore, a quick breeding system for congenic strains has become increasingly important in model organisms such as mouse and medaka. Traditionally, more than ten generations are necessary to produce a congenic strain. In contrast, a quick method has been reported previously for the mouse, in which the use of genetic markers reduces the required number of backcross generations to about a half that of the traditional method, so that it would take around six generations to obtain a congenic strain. Here, we present an even quicker congenic production system, which takes only about four generations. The system can produce medaka congenic strains having part of the HNI-II (an inbred medaka strain derived from the northern Japanese population, Oryzias sakaizumii) genome in the HdrR-II1 (another inbred strain from the southern Japanese population, O. latipes) background. In this system, the availability of frozen sperm and genotype data of the BC1 male population makes it possible to start marker-assisted congenic production after obtaining the BC2 population. Our evaluation revealed that the system could work well to increase the percentage of recipient genome as expected, so that a congenic strain may be obtained in about one year.


Degradation of airway neuropeptides by human lung tryptase.
Several lines of evidence suggest a possible role for mast cell proteases in modulating the biologic effects of neuropeptides. To explore the potential of such interactions in human airway, we examined the activity of human tryptase, the major secretory protease of human lung mast cells, against several neuropeptides with proposed regulatory functions in human airway. Using highly purified tryptase obtained from extracts of human lung, we determined the sites and rats of hydrolysis of vasoactive intestinal peptide (VIP), peptide histidine-methionine (PHM), calcitonin gene-related peptide (CGRP), and the tachykinins substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Tryptase hydrolyzes VIP rapidly at several sites (Arg12, Arg14, Lys20, and Lys21) with an overall kcat/Km of 1.5 x 10(5) M-1 s-1 and hydrolyzes PHM primarily at a single site (Lys20) with a kcat/Km of 1.9 x 10(4) M-1 s-1. Tryptase also rapidly hydrolyzes CGRP at two sites (Arg18 and Lys24) with a kcat/Km of 2.7 x 10(5) M-1 s-1. The tachykinins are not hydrolyzed by tryptase. These observations raise the possibility that tryptase-mediated degradation of the bronchodilators VIP and PHM combined with exaggerated mast cell release of tryptase may contribute to the increase in bronchial responsiveness and the decrease in immunoreactive VIP in airway nerves associated with asthma. The favorable rates of hydrolysis of CGRP suggest that tryptase may also terminate the effects of CGRP on bronchial and vascular smooth muscle tone and permeability.


Cobalt(II) Pentaaza-Macrocyclic Schiff Base Complex as Catalyst for Light-Driven Hydrogen Evolution in Water: Electrochemical Generation and Theoretical Investigation of the One-Electron Reduced Species.
We previously reported that the tetraazamacrocyclic Schiff base complex [CoIII(CR14)(X)2]n+ (CR14 = 2,12-dimethyl-3,7,11,17-tetraazabicyclo[11.3.1]heptadeca-1(17),2,11,13,15-pentaene, X = Cl (n = 1) (1-Cl2) or H2O (n = 3) (1-(H2O)2)) is a very efficient H2-evolving catalyst (HEC) in fully aqueous solutions at pH 4.0-4.5 when used in a photocatalytic system including a photosensitizer and ascorbate as sacrificial electron donor. The excellent H2-evolving activity of this complex, compared to other cobalt and rhodium catalysts studied in the same photocatalytic conditions, can be related to the high stability of its two-electron reduced form, the putative "Co(I)" state. These very interesting results led us to investigate the H2-evolving performances of a series of compounds from a close-related family, the pentaaza-macrocyclic cobalt [CoII(CR15)(H2O)2]Cl2 complex (2, CR15 = 2,13-dimethyl-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene), which comprises a larger macrocycle with five nitrogen atoms instead of four. Electrochemical as well as spectroscopic investigations in CH3CN coupled to density functional theory (DFT) calculations point to decoordination of one of the amine upon reduction of Co(II) to the low-valent "Co(I)" form. The resulting unchelated amine could potentially act as a proton relay promoting the H2 formation via proton-coupled-electron transfer (PCET) reactions. Besides, the iron, manganese, and zinc analogues, [FeII(CR15)(X)2]n+ (X = Cl (n = 0) or H2O (n = 2)) (3), [MnII(CR15)(CH3CN)2](PF6)2 (4), and {[ZnII(CR15)Cl](PF6)}n (5) were also synthesized and investigated. The photocatalytic activity of 2-5 toward proton reduction was then evaluated in a tricomponent system containing the [RuII(bpy)3]Cl2 photosensitizer and ascorbate, in fully aqueous solution. The photocatalytic activity of 2 was also compared with that of 1 in the same experimental conditions. It was found that the number of catalytic cycles versus catalyst for 2 are slightly lower than that for 1, suggesting that if the amine released upon reduction of 2 plays a role in promoting the H2-evolving catalytic activity, other factors balance this effect. Finally, photophysical and nanosecond transient absorption spectroscopies were used to investigate the photocatalytic system.


Passive adaptation to stress in adulthood after short-term social instability stress during adolescence in mice.
This study reports that short-term social instability stress (SIS) in adolescence increases passive-coping in adulthood in male mice. Short-term SIS decreased the latency of immobility and increased the frequency and time of immobility in tail suspension test. These findings support the hypothesis that adolescent stress can induce a passive adaptation to stress in adulthood, even if it is a short period of stress.


An additional reference axis for determining rotational alignment of the femoral component in total knee arthroplasty.
No studies have examined the trochlear line connecting the most anterior projections of the lateral and medial femoral condyles in relation to the surgical epicondylar axis. To determine if the trochlear line is more consistent relative to the transepicondylar axis than the posterior condylar axis and the Whiteside's line, the angles between the surgical epicondylar axis and each of the 3 axes in 50 knees of cadavers were measured using computed tomography scans. The results showed that the variability in the trochlear line for referencing the transepicondylar axis was comparable to those of the Whiteside line and the posterior condylar axis. The trochlear line may be considered as an additional reference axis for determining the rotational alignment of the femoral component in total knee arthroplasty.


Factors affecting the longevity of a short-term velocity store for predictive oculomotor tracking.
Fast (up to 30 degrees /s) anticipatory smooth pursuit eye movements can be built up with repeated transient motion stimuli. It is thought that such stimuli charge a putative internal store of velocity information that can then drive anticipatory movements in the absence of a target. The aim of this study was to investigate the longevity of this store. Previous experiments with single ramp stimuli (Wells and Barnes 1998) suggested that the store lasts for only a few seconds before decaying to a baseline level. In the current study we investigate the possibility that the store was not maximally charged by single stimuli, precipitating its decay. The magnitude of the anticipatory response was indexed by smooth eye velocity 100 ms after target onset ( V(100)). In experiment 1 the build-up of the anticipatory response was examined by presenting sets of stimuli (comprising from one to five ramps) within a tracking phase and leaving a dark period (the 'gap') of 9.6 s between successive tracking phases. Each ramp was preceded by an audio warning cue and was accompanied throughout its 480 ms duration by an audio tone. Audio cues continued during the gap to reinforce timing information. V(100) for the first and last ramps of each set increased as the number of ramps was increased from one to three but reached an asymptotic level thereafter, suggesting that the velocity store is maximally charged after three presentations. In experiment 2 the store was maximally charged by presenting five ramps in each tracking phase and its decay was examined by leaving gaps of either 7.2 s or 14.4 s between successive tracking phases. V(100) was not diminished after either gap interval. In experiment 3 the velocity store was less well consolidated during tracking phases comprising two ramps. V(100) for the first response after the gap was unaffected by the 7.2 s gap interval but was significantly reduced when the gap interval was 14.4 s. The interval between the warning cue and ramp onset strongly influenced the magnitude of the anticipatory response, the optimum level being elicited by a cue time of 600 ms. In conclusion, this study has shown that the internal velocity store can be sustained for periods as long as 14.4 s provided that it is initially charged to a sufficiently high level and that accurate external timing cues are provided. Furthermore, we provide evidence to suggest that this process may be controlled by a two-part sample and hold mechanism.


Cognitive design in action: developing assistive technology for situational awareness for persons who are blind.
Cognitive design constitutes a cognitively-informed engineering method for developing assistive technologies. The approach is challenging in that it involves matching key cognitive principles for a given problem domain to engineering principles, and that an independent validation procedure is required for the cognitive component. In addition, we argue for a broad set of evaluation criteria and adapt a participatory design framework, one that involves the client population throughout the design process. After laying out the main precepts of the approach, we illustrate these via a particular design process, seeking to provide situational awareness and navigational assistance to persons who are blind. The problem domain is described in some detail. A solution is then presented that involves matching the need for configural knowledge about the person's surroundings with a hierarchical organisation in the spatial database so that information may be presented to the user at different levels of detail. The process involved to implement this solution is then outlined, and appropriate validation experiments described. It is noted that the cognitive design process as presented here is in use now in a number of initiatives, and that it involves a high degree of collaboration between experts from different disciplines.