Extraskeletal Ewing's sarcoma. A clinicopathologic and electron microscopic. Analysis of 8 cases.
This clinicopathologic study concerns 8 cases of extraskeletal Ewing's sarcoma, including electron-microscopic examination of one case. In three patients, autopsy was done. The age of the patients ranged from 12 to 31 years with a median of 16 years. The tumors mainly arose in the soft tissues of the trunk (4 cases) and the lower extremity (3 cases). Histologically, they were made up of closely packed uniform, small cells, arranged in sheets separated by strands of fibrovascular stroma. The tumor cells had round to oval nuclei with finely dispersed chromatin and scanty ill-defined cytoplasm almost invariably containing a fair amount of diastase-digested PAS-positive material. Ultrastructurally, the tumor cells were composed principally of undifferentiated mesenchymal cells, and contained prominent pools of glycogen in the cytoplasm. Aggregates of intermediate filaments were seen in a perinuclear location. These light- and electron-microscopic findings are indistinguishable from those of Ewing's sarcoma of the bone. Differential points from other soft-tissue small round cell sarcomas such as malignant neuroepithelioma (peripheral neuroblastoma), embryonal or alveolar rhabdomyosarcoma were briefly discussed.


Characterization of stretch-activated cation current in coronary smooth muscle cells.
Stretch-activated ion currents were recorded from vascular smooth muscle (VSM) after enzymatic isolation of single cells from porcine coronary arterioles. Patch pipettes were used to record whole cell current and control cell length. Under voltage clamp in physiological saline solution, an inward cation current (I(CAT)) was activated by 105--135% longitudinal stretch. I(CAT) coincided with an increase in intracellular Ca(2+) concentration. Under current clamp, membrane depolarization was induced by stretch. The magnitude of I(CAT) varied from -0.8 to -6.9 pA/pF at a holding potential of -60 mV. I(CAT) was graded with stretch, inactivated on release, and could be repeatedly induced. A potassium current (I(K)) activated in unstretched cells by depolarization was also enhanced by stretch. In Ca(2+)-free bath solution, stretch-induced enhancement of I(K) was blocked, but I(CAT) was still present. Hexamethyleneamiloride (50 microM), a reputed inhibitor of mechanosensitive channels, blocked I(CAT) and the stretch-induced increase in I(K) but not basal I(K). Grammostolla spatulata venom (1:100,000) blocked basal I(K), blocked stretch-induced increases in I(K), and blocked I(CAT). Iberiotoxin, a specific Ca(2+)-activated K(+) channel blocker, did not alter I(CAT) but blocked the stretch-induced increase in I(K) and increased the magnitude of stretch-induced depolarization. We concluded that longitudinal stretch directly activates a cation current and secondarily activates a Ca(2+)-activated K(+) current in isolated coronary myocytes. Although these two currents would partially counteract each other, the predominance of I(CAT) at physiological potentials is likely to explain the depolarization and contraction observed in intact coronary VSM during pressure elevation.


PEIMAN 1.0: Post-translational modification Enrichment, Integration and Matching ANalysis.
Conventional proteomics has discovered a wide gap between protein sequences and biological functions. The third generation of proteomics was provoked to bridge this gap. Targeted and untargeted post-translational modification (PTM) studies are the most important parts of today's proteomics. Considering the expensive and time-consuming nature of experimental methods, computational methods are developed to study, analyze, predict, count and compute the PTM annotations on proteins. The enrichment analysis softwares are among the common computational biology and bioinformatic software packages. The focus of such softwares is to find the probability of occurrence of the desired biological features in any arbitrary list of genes/proteins. We introduce Post-translational modification Enrichment Integration and Matching Analysis (PEIMAN) software to explore more probable and enriched PTMs on proteins. Here, we also represent the statistics of detected PTM terms used in enrichment analysis in PEIMAN software based on the latest released version of UniProtKB/Swiss-Prot. These results, in addition to giving insight to any given list of proteins, could be useful to design targeted PTM studies for identification and characterization of special chemical groups. Database URL: http://bs.ipm.ir/softwares/PEIMAN/


Prelamin A and ZMPSTE24 in premature and physiological aging.
As human longevity increases, understanding the molecular mechanisms that drive aging becomes ever more critical to promote health and prevent age-related disorders. Premature aging disorders or progeroid syndromes can provide critical insights into aspects of physiological aging. A major cause of progeroid syndromes which result from mutations in the genes LMNA and ZMPSTE24 is disruption of the final posttranslational processing step in the production of the nuclear scaffold protein lamin A. LMNA encodes the lamin A precursor, prelamin A and ZMPSTE24 encodes the prelamin A processing enzyme, the zinc metalloprotease ZMPSTE24. Progeroid syndromes resulting from mutations in these genes include the clinically related disorders Hutchinson-Gilford progeria syndrome (HGPS), mandibuloacral dysplasia-type B, and restrictive dermopathy. These diseases have features that overlap with one another and with some aspects of physiological aging, including bone defects resembling osteoporosis and atherosclerosis (the latter primarily in HGPS). The progeroid syndromes have ignited keen interest in the relationship between defective prelamin A processing and its accumulation in normal physiological aging. In this review, we examine the hypothesis that diminished processing of prelamin A by ZMPSTE24 is a driver of physiological aging. We review features a new mouse (LmnaL648R/L648R) that produces solely unprocessed prelamin A and provides an ideal model for examining the effects of its accumulation during aging. We also discuss existing data on the accumulation of prelamin A or its variants in human physiological aging, which call out for further validation and more rigorous experimental approaches to determine if prelamin A contributes to normal aging.


Atypical hemangioma of the breast: a diagnostic pitfall in breast fine-needle aspiration.
We report on the fine-needle aspiration (FNA) cytology of atypical hemangioma of the breast in a 52-yr-old female. The patient presented with a 2-cm palpable left breast mass. An FNA of the mass was performed following a mammogram, corresponding to the palpable breast mass. The FNA demonstrated the presence of numerous atypical single spindle cells scattered throughout a hemorrhagic background. An unequivocal diagnosis of malignancy was not rendered in this case. However, the degree of cytologic atypia suggested a malignant process, and a recommendation for an excisional biopsy was made. Atypical hemangioma should therefore be included in the differential diagnosis of angiosarcoma and other benign and malignant spindle-cell lesions of the breast encountered on cytologic samples.


Predicting breeding habitat for amphibians: a spatiotemporal analysis across Yellowstone National Park.
The ability to predict amphibian breeding across landscapes is important for informing land management decisions and helping biologists better understand and remediate factors contributing to declines in amphibian populations. We built geospatial models of likely breeding habitats for each of four amphibian species that breed in Yellowstone National Park (YNP). We used field data collected in 2000-2002 from 497 sites among 16 basins and predictor variables from geospatial models produced from remotely sensed data (e.g., digital elevation model, complex topographic index, landform data, wetland probability, and vegetative cover). Except for 31 sites in one basin that were surveyed in both 2000 and 2002, all sites were surveyed once. We used polytomous regression to build statistical models for each species of amphibian from (1) field survey site data only, (2) field data combined with data from geospatial models, and (3) data from geospatial models only. Based on measures of receiver operating characteristic (ROC) scores, models of the second type best explained likely breeding habitat because they contained the most information (ROC values ranged from 0.70 to 0.88). However, models of the third type could be applied to the entire YNP landscape and produced maps that could be verified with reserve field data. Accuracy rates for models built for single years were highly variable, ranging from 0.30 to 0.78. Accuracy rates for models built with data combined from multiple years were higher and less variable, ranging from 0.60 to 0.80. Combining results from the geospatial multiyear models yielded maps of "core" breeding areas (areas with high probability values for all three years) surrounded by areas that scored high for only one or two years, providing an estimate of variability among years. Such information can highlight landscape options for amphibian conservation. For example, our models identify alternative areas that could be protected for each species, including 6828-10 764 ha for tiger salamanders, 971-3017 ha for western toads, 4732-16 696 ha for boreal chorus frogs, and 4940-19 690 ha for Columbia spotted frogs.


Structural alignment of proteins by a novel TOPOFIT method, as a superimposition of common volumes at a topomax point.
Similarity of protein structures has been analyzed using three-dimensional Delaunay triangulation patterns derived from the backbone representation. It has been found that structurally related proteins have a common spatial invariant part, a set of tetrahedrons, mathematically described as a common spatial subgraph volume of the three-dimensional contact graph derived from Delaunay tessellation (DT). Based on this property of protein structures, we present a novel common volume superimposition (TOPOFIT) method to produce structural alignments. Structural alignments usually evaluated by a number of equivalent (aligned) positions (N(e)) with corresponding root mean square deviation (RMSD). The superimposition of the DT patterns allows one to uniquely identify a maximal common number of equivalent residues in the structural alignment. In other words, TOPOFIT identifies a feature point on the RMSD N(e) curve, a topomax point, until which the topologies of two structures correspond to each other, including backbone and interresidue contacts, whereas the growing number of mismatches between the DT patterns occurs at larger RMSD (N(e)) after the topomax point. It has been found that the topomax point is present in all alignments from different protein structural classes; therefore, the TOPOFIT method identifies common, invariant structural parts between proteins. The alignments produced by the TOPOFIT method have a good correlation with alignments produced by other current methods. This novel method opens new opportunities for the comparative analysis of protein structures and for more detailed studies on understanding the molecular principles of tertiary structure organization and functionality. The TOPOFIT method also helps to detect conformational changes, topological differences in variable parts, which are particularly important for studies of variations in active/ binding sites and protein classification.


Carbohydrates - a scoping review for Nordic Nutrition Recommendations 2023.
Dietary carbohydrates are a major source of energy in the Nordic and Baltic countries. The health effects of different types of carbohydrates vary and there is a need to update the evidence regarding specific carbohydrates and their effects on health-related outcomes. The aim of this scoping review was to describe the evidence for the role of total carbohydrates (fiber excluded), glycemic index (GI) or glycemic load (GL) and added or free sugars for health-related outcomes as a basis for setting and updating dietary reference values for the Nordic Nutrition Recommendation (NNR) 2023. We included evidence from several qualified systematic reviews (the World Cancer Research Fund, the European Food Safety Authority, the World Health Organization, the United States Dietary Guidelines Advisory Committee, the United Kingdom Scientific Advisory Committee on Nutrition) identified by the NNR project in line with the protocol description. There is limited evidence that total carbohydrate intake (fiber excluded) outside of the current recommended range of 45-60% of energy is associated with health-related outcomes. There were no consistent benefits on clinical outcomes when changing the GI of a diet. High intake of dietary sugars is well known to be associated with dental caries. There was evidence from randomized control trials on surrogate disease endpoints, for a positive and causal relationship between the intake of added and free sugars and risk of some chronic metabolic diseases with moderate level of certainty for obesity and dyslipidaemia. The level of certainty was high for an association between high intake of sugar-sweetened beverages and risk of several chronic metabolic diseases. While there is limited evidence that total carbohydrates and GI and GL of the diet are related to health outcomes, the evidence suggests that high intakes of added and free sugars are related to detrimental health effects. In addition, with increasing intake of added and free sugars, there is less room for healthy foods and micronutrients, which is especially important for those with low energy intake, such as children.


The structure of graphene on graphene/C60/Cu interfaces: a molecular dynamics study.
Two experimental studies reported the spontaneous formation of amorphous and crystalline structures of C60 molecules intercalated between graphene and a surface. The findings observed included interesting phenomena ranging from reaction between fullerene C60s ('C60s' stands for plural of C60) under graphene to graphene sheets sagging between C60s and control of strain in these sheets. Motivated by this work, we performed fully atomistic reactive molecular dynamics simulations to investigate the formation and thermal stability of graphene sheet wrinkles as well as graphene attachment to and detachment from a surface when the sheet is laid over a previously distributed array of C60 molecules on a copper surface at different temperatures. As graphene compresses the C60s against the surface, and graphene attachment to the surface in between C60s depends on the height of the wrinkles in the graphene sheet, configurations with both frozen and non-frozen fullerenes were investigated in the simulations in order to examine the experimental result of stable, sagged graphene sheets when the distance between C60s is about 4 nm and the height of the wrinkles in the sheet is about 0.8 nm. Below a distance of 4 nm between fullerenes, the graphene is predicted to become locally suspended and less strained. The simulations predict that this happens when the fullerenes can deform under the compressive action of the graphene sheet. If the fullerenes are kept frozen, spontaneous 'blanketing' of graphene is predicted only when the distance between neighbouring C60s is equal to or great than about 7 nm. These predictions agree with a mechanical model relating the rigidity of a graphene sheet to the energy of graphene-surface adhesion. This work further reveals the structure of intercalated molecules and the role of stability and sheet wrinkling on the preferred configuration of graphene. This study thus might assist in the development of two-dimensional confined nanoreactors for chemical reactions.


Inhibitory effects of spirulina platensis on carcinogen-activating cytochrome P450 isozymes and potential for drug interactions.
Spirulina platensis (SP) has been considered as potential food source of 21st century due to its remarkable nutrient profile and therapeutic benefits. However, the cytochrome P450 (CYP)-mediated drug/chemical interaction potential of SP has not yet been pursued. We investigated the effects of SP on the expressions and enzymatic activities of main CYP isozymes. After the rats were orally administered with SP daily for 5 consecutive weeks, there were significant downregulations in hepatic expression levels and inhibition in enzymatic activities of CYP1A2 and CYP2E1 compared to controls. In addition, a significant decrease was observed in CYP2C6-associated enzyme activity with no remarkable changes in messenger RNA (mRNA)/protein levels. The SP application resulted in significant increases in mRNA/protein levels of both CYP2B1 and CYP3A1 without a significant change in enzyme activities. These findings partly explain the chemopreventive properties of SP toward various organ toxicities, mutagenesis, and carcinogenesis; however, its coadministration with some CYP substrates may lead to undesirable drug interactions.


Different associations of apolipoprotein E polymorphism with metabolic syndrome by sex in an elderly Chinese population.
The metabolic syndrome (MetS) is characterized by a cluster of metabolic disorders including abnormal lipid and lipoprotein metabolism. Apolipoprotein E (ApoE) is involved in the regulation of the metabolism of cholesterol, lipoproteins, and triglycerides. The common ApoE polymorphism has been found to be associated with cardiovascular disease and diabetes. This study evaluated the ApoE genetic polymorphism and its relation to MetS defined by the modified National Cholesterol Education Program and International Diabetes Federation criteria in a population-based cross-sectional survey of an elderly Chinese population in Beijing, China. Genotypes of 937 men and 1385 women were included in the study. All participants were measured for blood pressure, anthropometric measurements, and fasting concentrations of glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We applied a logistic regression model to derive adjusted odds ratios (ORs) and their 95% confidence intervals. In this Chinese population, the ɛ2, ɛ3, and ɛ4 allele frequencies were 8.3%, 83.4%, and 8.3% for men and 8.7%, 82.9%, and 8.4% for women, respectively. In men, concentrations of fasting triglycerides were higher among the APOE2 and E4 subjects; and a lower level of high-density lipoprotein cholesterol was observed in the APOE4 group. There were approximately linear associations of low-density lipoprotein cholesterol levels with APOE genotype groups in both men and women. We observed that the ɛ4 allele was associated with a significantly increased OR of MetS defined by the modified National Cholesterol Education Program criteria in men (OR, 1.75; 95% confidence interval, 1.17-2.63). In summary, our data show that common polymorphism of ApoE gene is associated with the presence of MetS in an elderly Chinese population.


Receptiveness and preferences of health-related smartphone applications among Vietnamese youth and young adults.
As smartphone becomes increasingly prevalent and affordable, more youths today can own a smartphone device and download applications in various application stores. Smartphone applications have been proven to be useful for youths in various aspects. However, there has been a paucity of data looking into the preferences of Vietnamese youths and adolescents with regards to health-related applications and their receptiveness towards smartphone apps. Therefore, this study aimed to determine the receptiveness and preferences of health-related smartphone applications (mHealth apps) among online Vietnamese youths and adolescents. An online cross-sectional study was conducted between the periods of August till October 2015 in Vietnam. Respondent-driven sampling technique (RDS) was utilized to recruit participants. Participants were asked questions about their history of downloading and using health-related smartphone applications and their receptiveness when using these applications. Moreover, socio-demographic characteristics and health status were also self-reported. Multivariate logistic regression was employed to determine associated factors. Among 1028 participants, 57.4% owned a smartphone and only 14.1% of smartphone users have used a health-related smartphone application, and most of these individuals downloaded the applications for disease prevention (66.3%). 66.4% of the participants who owned these applications reported that health applications were useful and 92.8% reported being satisfied with the functionalities of the applications which they owned. Among smartphone users, people who were employed (OR = 15.46; 95%CI = 4.93-48.47) were more likely to download mHealth apps. Meanwhile, youths with higher EQ-5D index had a lower likelihood of downloading healthcare-related smartphone applications (OR = 0.17; 95%CI = 0.04-0.81). This study highlighted a low rate of mHealth apps utilization among online Vietnamese youths and adolescents but a high acceptance of individuals who already used these apps. Developing mHealth apps or interventions towards the disease prevention and quality of life improvement could be feasible to proliferate the benefits of such applications in youths and adolescents in Vietnam. Further research should be conducted to optimize the contents and interfaces of mHealth apps that meet the needs of these populations.


Interpretation and Prediction of the CO2 Sequestration of Steel Slag by Machine Learning.
The utilization of steel slag for CO2 sequestration is an effective way to reduce carbon emissions. The reactivity of steel slag in CO2 sequestration depends mainly on material and process parameters. However, there are many puzzles in regard to practical applications due to the different evaluations of process parameters and the lack of investigation of material parameters. In this study, 318 samples were collected to investigate the interactive influence of 12 factors on the carbonation reactivity of steel slag by machine learning with SHapley Additive exPlanations (SHAP). Multilayer perceptron (MLP), random forest, and support vector regression models were built to predict the slurry-phase CO2 sequestration of steel slag. The MLP model performed well in terms of prediction ability and generalization with comprehensive interpretability. The SHAP results showed that the impact of the process parameters was greater than that of the material parameters. Interestingly, the iron ore phase of steel slag was revealed to have a positive effect on steel slag carbonation by SHAP analysis. Combined with previous literature, the carbonation mechanism of steel slag was proposed. Quantitative analysis based on SHAP indicated that steel slag had good carbonation reactivity when the mass fractions of "CaO + MgO", "SiO2 + Al2O3", "Fe2O3", and "MnO" varied from 50-55%, 10-15%, 30-35%, and <5%, respectively.


Royal Darwinian Demons: Enforced Changes in Reproductive Efforts Do Not Affect the Life Expectancy of Ant Queens.
One of the central tenets of life-history theory is that organisms cannot simultaneously maximize all fitness components. This results in the fundamental trade-off between reproduction and life span known from numerous animals, including humans. Social insects are a well-known exception to this rule: reproductive queens outlive nonreproductive workers. Here, we take a step forward and show that under identical social and environmental conditions the fecundity-longevity trade-off is absent also within the queen caste. A change in reproduction did not alter life expectancy, and even a strong enforced increase in reproductive efforts did not reduce residual life span. Generally, egg-laying rate and life span were positively correlated. Queens of perennial social insects thus seem to maximize at the same time two fitness parameters that are normally negatively correlated. Even though they are not immortal, they best approach a hypothetical "Darwinian demon" in the animal kingdom.


Point-of-care testing in haemostasis.
Point-of-care testing (POCT) in haematology has seen a significant increase in both the spectrum of tests available and the number of tests performed annually. POCT is frequently undertaken with the belief that this will reduce the turnaround time for results and so improve patient care. The most obvious example of POCT in haemostasis is the out-of-hospital monitoring of the International Normalized Ratio in patients receiving a vitamin K antagonist, such as warfarin. Other areas include the use of the Activated Clotting Time to monitor anticoagulation for patients on cardio-pulmonary bypass, platelet function testing to identify patients with apparent aspirin or clopidogrel resistance and thrombelastography to guide blood product replacement during cardiac and hepatic surgery. In contrast to laboratory testing, POCT is frequently undertaken by untrained or semi-trained individuals and in many cases is not subject to the same strict quality control programmes that exist in the central laboratory. Although external quality assessment programmes do exist for some POCT assays these are still relatively few. The use of POCT in haematology, particularly in the field of haemostasis, is likely to expand and it is important that systems are in place to ensure that the generated results are accurate and precise.


[The institutional violence in day-care and pre-schools according to mothers' view].
The objective of this research is to know the institutional violence in the day-care centers and preschools by the mothers' view. It was elaborated with two approaches:quantitative and qualitative. The researcher through interview and observation made the collection of primary data, and the qualitative data werw collected by recorded interview, being made the content analysis. The results show that 23,9%of the mothers affirm that violence exists against the child; the proportion of children that didn't suffer violence in the day-care center can be considered statistically significant, when cmpared with those already suffered, independently of the time of frequency in the day-care center (p= 0,95);the mothers say they don't know the cause of the institutional violence; the physical violence appears with larger incidence; it is more frequent the mother to try to know the cause of theviolence, and the minus, to denounce to Guardian Council. It's compatible to the parents the child's protection and they need to know the ways of protecting them of the infantile violence.


Reappraisal of brain MRI features in patients with multiple sclerosis and neuromyelitis optica according to anti-aquaporin-4 antibody status.
Brain lesions are not uncommon in neuromyelitis optica (NMO) patients with anti-aquaporin-4 (AQP4) antibody; however, the appearance of these lesions is said to be different from that of those in Western patients with multiple sclerosis (MS). To clarify the similarities and dissimilarities of brain lesions in anti-AQP4 antibody-positive and -negative MS and NMO patients, we examined the presence of anti-AQP4 antibody in the sera of 148 consecutive patients fulfilling Poser's criteria for clinically definite MS, of whom 38 also met the revised NMO criteria, using an immunofluorescence method, and analyzed brain lesions by magnetic resonance imaging (MRI). Brain lesions fulfilling the Barkhof criteria were significantly more common in 121 patients without anti-AQP4 antibody than in 27 patients with anti-AQP4 antibody (57.0% vs. 33.3%, P=0.033), while the frequency of those that met the Paty criteria was not different between the two groups (74.4% vs. 73.5%). Ovoid lesions were detected more commonly in patients without anti-AQP4 antibody than in those with the antibody (72.3% vs. 48.2%, P=0.022). The anti-AQP4 antibody-positive patients had significantly more atypical brain lesions, such as extensive brain lesions, than the anti-AQP4 antibody-negative ones (18.5% vs. 1.7%, P=0.0023). Thus, although MS-like brain lesions are more common in anti-AQP4 antibody-negative patients than anti-AQP4 antibody-positive patients, approximately 30 to 50% of patients with anti-AQP4 antibody harbour brain MRI lesions indistinguishable from those present in typical MS patients, such as periventricular ovoid lesions, suggesting the existence of considerable overlap in brain MRI features between anti-AQP4 antibody-positive and -negative Asian patients. In the present study, NMO patients with brain lesions showed a significantly higher annualized relapse rate (P(corr)=0.017) and higher frequency of anti-AQP4 antibody (P(corr)<0.0001) than typical NMO patients without brain lesions, suggesting that development of brain lesions in NMO may reflect high disease activity and thus be a warning sign.


[Peritoneal dialysis in acute renal failure in children].
Data on the treatment of infants with acute renal failure are presented. Indications for renal substitute therapy are enumerated and hemodialysis and peritoneal dialysis are compared. Complications of peritoneal dialysis are discussed and methods for their treatment are presented. The authors demonstrate that peritoneal dialysis is an effective, safe, and available method for treating acute renal failure in infants.


The impact of inpatient rehabilitation on progressive multiple sclerosis.
One of the primary aims of rehabilitation for patients with multiple sclerosis (MS) is to reduce their levels of disability and handicap, yet little systematic research into the outcomes of this intervention has been undertaken. This stratified, randomized, wait-list controlled study evaluated the effectiveness of a short period of multidisciplinary inpatient rehabilitation in people with MS. Sixty-six patients in the progressive phase of the disease were assessed at 0 and 6 weeks with validated measures of impairment (Expanded Disability Status Scale and Functional Systems), disability (Functional Independence Measure), and handicap (London Handicap Scale). Both groups were comparable in terms of age, sex, disease duration and severity, disability, and handicap. At the end of 6 weeks, although the level of impairment in both groups remained the same, those who participated in a short period of inpatient rehabilitation (average of 25 days) significantly improved their level of disability and handicap compared with those in the wait-list control group. Despite unchanging impairment, inpatient rehabilitation resulted in reduced disability and handicap in patients with progressive MS.


The neuronal migration defect in mice with Zellweger syndrome (Pex5 knockout) is not caused by the inactivity of peroxisomal beta-oxidation.
The purpose of this study was to investigate whether deficient peroxisomal beta-oxidation is causally involved in the neuronal migration defect observed in Pex5 knockout mice. These mice are models for Zellweger syndrome, a peroxisome biogenesis disorder. Neocortical development was evaluated in mice carrying a partial or complete defect of peroxisomal beta-oxidation at the level of the second enzyme of the pathway, namely, the hydratase-dehydrogenase multifunctional/bifunctional enzymes MFP1/L-PBE and MFP2/D-PBE. In contrast to patients with multifunctional protein 2 deficiency who present with neocortical dysgenesis, impairment of neuronal migration was not observed in the single MFP2 or in the double MFP1/MFP2 knockout mice. At birth, the double knockout pups displayed variable growth retardation and about one half of them were severely hypotonic, whereas the single MFP2 knockout animals were all normal in the perinatal period. These results indicate that in the mouse, defective peroxisomal beta-oxidation does not cause neuronal migration defects by itself. This does not exclude that the inactivity of this metabolic pathway contributes to the brain pathology in mice and patients with complete absence of functional peroxisomes.


The cooperative activities of CSLD2, CSLD3, and CSLD5 are required for normal Arabidopsis development.
Glycosyltransferases of the Cellulose Synthase Like D (CSLD) subfamily have been reported to be involved in tip growth and stem development in Arabidopsis. The csld2 and csld3 mutants are root hair defective and the csld5 mutant has reduced stem growth. In this study, we produced double and triple knockout mutants of CSLD2, CSLD3, and CSLD5. Unlike the single mutants and the csld2/csld3 double mutant, the csld2/csld5, csld3/csld5, and csld2/ csld3/csld5 mutants were dwarfed and showed severely reduced viability. This demonstrates that the cooperative activities of CSLD2, CSLD3, and CSLD5 are required for normal Arabidopsis development, and that they are involved in important processes besides the specialized role in tip growth. The mutant phenotypes indicate that CSLD2 and CSLD3 have overlapping functions with CSLD5 in early plant development, whereas the CSLD2 and CSLD3 proteins are non-redundant. To determine the biochemical function of CSLD proteins, we used transient expression in tobacco leaves. Microsomes containing heterologously expressed CSLD5 transferred mannose from GDP-mannose onto endogenous acceptors. The same activity was detected when CSLD2 and CSLD3 were co-expressed but not when they were expressed separately. With monosaccharides as exogenous acceptors, microsomal preparations from CSLD5-expressing plants mediated the transfer of mannose from GDP-mannose onto mannose. These results were supported by immunodetection studies that showed reduced levels of a mannan epitope in the cell walls of stem interfascicular fibers and xylem vessels of the csld2/csld3/csld5 mutant.


Intermittent straining accelerates the development of tissue properties in engineered heart valve tissue.
Tissue-engineered heart valves lack sufficient amounts of functionally organized structures and consequently do not meet in vivo mechanical demands. To optimize tissue architecture and hence improve mechanical properties, various in vitro mechanical conditioning protocols have been proposed, of which intermittent straining is most promising in terms of tissue properties. We hypothesize that this is due to an improved collagen matrix synthesis, maturation, and organization, triggered by periodic straining of cells. To test this hypothesis, we studied the effect of intermittent versus constrained conditioning with time (2-4 weeks), using a novel model system of human heart valve tissue. Temporal variations in collagen production, cross-link density, and mechanical properties were quantified in engineered heart valve tissue, cyclically strained for 3-h periods, alternated with 3-h periods rest. In addition, an innovative method for vital collagen imaging was used to monitor collagen organization. Intermittent straining resulted in increased collagen production, cross-link densities, collagen organization, and mechanical properties at faster rates, as compared to constrained controls, leading to stronger tissues in shorter culture periods. This is of utmost importance for heart valve tissue engineering, where insufficient mechanical properties are currently the main limiting factor.


Genetic assay for small fragments of bacteriophage phi X174 deoxyribonucleic acid.
The double-stranded replicative form deoxyribonucleic acid (RF-DNA) of bacteriophage phiX174 was fragmented by pancreatic deoxyribonuclease, and the complementary strand fragments were then annealed to intact viral single strands. When such complexes infected Escherichia coli spheroplasts, some of the progeny virus bore genetic markers derived from the RF-DNA fragments. In this way, genetic markers have been salvaged from DNA fragments less than 50 nucleotides in length. This method is potentially useful as a specific assay to aid in the purification of genetically defined DNA fragments and also as a mechanism for the incorporation of small chemically synthesized DNA sequences into viral genomes.


Substantial DNA damage from submicromolar intracellular hydrogen peroxide detected in Hpx- mutants of Escherichia coli.
Since the discovery of catalase, it has been postulated that aerobic organisms generate enough oxidants to threaten their own fitness and, in particular, their genetic stability. An alternative is that these enzymes exist to defend the cell against more-abundant oxidants imposed by external sources. These hypotheses were tested directly through study of Hpx- (katG katE ahpCF) mutants of Escherichia coli, which lack enzymes to scavenge hydrogen peroxide (H2O2). These strains grew well in anaerobic medium but poorly when they were aerated. The Hpx- bacteria formed filaments and exhibited high rates of mutagenesis, both indicators of DNA damage. An additional recA mutation caused Hpx- cells to die rapidly upon aeration, even though the intracellular H2O2 was <1 microM. Spin-trap experiments detected substantial hydroxyl radicals, and cell-permeable iron chelators eliminated both the phenotypic defects and hydroxyl-radical formation, confirming that the Fenton reaction was responsible. An Hpx- oxyR strain exhibited even more DNA lesions than did the Hpx- mutant, indicating that the OxyR stress response induced protein(s) that suppressed DNA damage. One critical protein was Dps, an iron-sequestration protein, because Hpx- dps mutants exhibited sensitivity similar to that of the Hpx- oxyR mutant. These results reveal that aerobic E. coli generates sufficient H2O2 to create toxic levels of DNA damage. Scavenging enzymes and controls on free iron are required to avoid that fate. The rate constant of the Fenton reaction measured at physiological pH was much higher than under the acidic conditions that were used to determine the commonly cited value.


Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility.
Appropriate gastrointestinal motility is essential to properly control the body energy level. Intracellular Ca2+ ([Ca2+]i) oscillations in interstitial cells of Cajal (ICCs; identified with c-Kit immunoreactivity) are considered to be the primary mechanism for the pacemaker activity in gastrointestinal motility. In the present study, RT-PCR examinations revealed predominant expression of the type 1 isoform of sulphonylurea receptors (SUR1) in ICCs of the mouse ileum, but expression of SUR2 was predominant in smooth muscle. In cell clusters prepared from the same tissue, smooth muscle contractility and pacemaker [Ca2+]i activity in ICCs were found to be differentially modulated by K(ATP) channel openers and sulphonylurea compounds, in accordance with the expression of SUR isoforms. 1 microM cromakalim nearly fully suppressed the mechanical activity in smooth muscle, whereas ICC pacemaker [Ca2+]i oscillations persisted. Greater concentrations (approximately 10 microM) of cromakalim attenuated pacemaker [Ca2+]i oscillations. This effect was not reversed by changing the reversal potential of K+, but was prevented by glibenclamide. Diazoxide at 30 muM terminated ICC pacemaker [Ca2+]i oscillations, but again treatment with high extracellular K+ did not restore them. These results suggest that SUR can modulate pacemaker [Ca2+]i oscillations via voltage-independent mechanism(s), and also that intestinal pacemaking and glucose control are closely associated with SUR.


Static Stretch Increases the Pro-Inflammatory Response of Rat Type 2 Alveolar Epithelial Cells to Dynamic Stretch.
Background: Mechanical ventilation (MV) inflicts stress on the lungs, initiating or increasing lung inflammation, so-called ventilator-induced lung injury (VILI). Besides overdistention, cyclic opening-and-closing of alveoli (atelectrauma) is recognized as a potential mechanism of VILI. The dynamic stretch may be reduced by positive end-expiratory pressure (PEEP), which in turn increases the static stretch. We investigated whether static stretch modulates the inflammatory response of rat type 2 alveolar epithelial cells (AECs) at different levels of dynamic stretch and hypothesized that static stretch increases pro-inflammatory response of AECs at given dynamic stretch. Methods: AECs, stimulated and not stimulated with lipopolysaccharide (LPS), were subjected to combinations of static (10, 20, and 30%) and dynamic stretch (15, 20, and 30%), for 1 and 4 h. Non-stretched AECs served as control. The gene expression and secreted protein levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein 2 (MIP-2) were studied by real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The effects of static and dynamic stretch were assessed by two-factorial ANOVA with planned effects post-hoc comparison according to Šidák. Statistical significance was considered for p < 0.05. Results: In LPS-stimulated, but not in non-stimulated rat type 2 AECs, compared to non-stretched cells: 1) dynamic stretch increased the expression of amphiregulin (AREG) (p < 0.05), MCP-1 (p < 0.001), and MIP-2 (<0.05), respectively, as well as the protein secretion of IL-6 (p < 0.001) and MCP-1 (p < 0.05); 2) static stretch increased the gene expression of MCP-1 (p < 0.001) and MIP-2, but not AREG, and resulted in higher secretion of IL-6 (p < 0.001), but not MCP-1, while MIP-2 was not detectable in the medium. Conclusion: In rat type 2 AECs stimulated with LPS, static stretch increased the pro-inflammatory response to dynamic stretch, suggesting a potential pro-inflammatory effect of PEEP during mechanical ventilation at the cellular level.


[From gene to disease; hypophosphataemic rickets and the PHEX gene].
X-linked hypophosphataemic rickets is associated with mutations in the PHEX gene on the short arm of the X chromosome, encoding a membrane-bound endoprotease which is predominantly expressed in osteoblasts. Defective PHEX function leaves phosphaturic peptides such as FGF23 uncleaved, enabling these peptides, known as phosphatonins, to fully exert their phosphaturic potential in the proximal tubule of the kidney. An autosomally inherited form of hypophosphataemic rickets is caused by mutations in the proteolytic processing site of FGF23 itself, while in tumour-induced osteomalacia overproduction of FGF23 and possibly other phosphatonins causes the processing capacity to be exceeded, resulting in phosphaturic hypophosphataemia and osteomalacia.


Synthetic aperture interference light (SAIL) microscopy for high-throughput label-free imaging.
Quantitative phase imaging (QPI) is a valuable label-free modality that has gained significant interest due to its wide potentials, from basic biology to clinical applications. Most existing QPI systems measure microscopic objects via interferometry or nonlinear iterative phase reconstructions from intensity measurements. However, all imaging systems compromise spatial resolution for the field of view and vice versa, i.e., suffer from a limited space bandwidth product. Current solutions to this problem involve computational phase retrieval algorithms, which are time-consuming and often suffer from convergence problems. In this article, we presented synthetic aperture interference light (SAIL) microscopy as a solution for high-resolution, wide field of view QPI. The proposed approach employs low-coherence interferometry to directly measure the optical phase delay under different illumination angles and produces large space-bandwidth product label-free imaging. We validate the performance of SAIL on standard samples and illustrate the biomedical applications on various specimens: pathology slides, entire insects, and dynamic live cells in large cultures. The reconstructed images have a synthetic numeric aperture of 0.45 and a field of view of 2.6 × 2.6 mm2. Due to its direct measurement of the phase information, SAIL microscopy does not require long computational time, eliminates data redundancy, and always converges.


Differential pulse polarographic investigation of the antifungal drugs itraconazole, ketoconazole, fluconazole and voriconazole using a dropping mercury electrode.
The electrochemical reactions of the antifungal drugs itraconazole, ketoconazole, fluconazole and voriconazole have been investigated by differential pulse polarography (DPP) using a dropping mercury electrode (DME). All investigations were carried out in Britton-Robinson buffer solutions and methanol with varying pH values. Ketoconazole and itraconazole both showed a reduction peak with a potential between -1.5V and -1.6 V. Stable and reproducible conditions for the determination of itraconazole (c = 1 x 10(-7) M) were found within the pH range of 6.0 to 8.0 and for the determination of ketoconazole (c = 5 x 10(-8) M) within pH 6.0 to 7.0. Voriconazole showed a reduction peak with a peak potential of -1.7 V (c = 1 x 10(-5) M) within the pH range of 8.0 to 10.0. In the case of fluconazole no electrochemical activity was found.


Young Child Nutrition: Knowledge and Surveillance Gaps across the Spectrum of Feeding.
The first 1000 days is a critical window to optimize nutrition. Young children, particularly 12-24 month-olds, are an understudied population. Young children have unique nutrient needs and reach important developmental milestones when those needs are met. Intriguingly, there are differences in the dietary patterns and recommendations for young children in the US vs. globally, notably for breastfeeding practices, nutrient and food guidelines, and young child formulas (YCFs)/toddler drinks. This perspective paper compares these differences in young child nutrition and identifies both knowledge gaps and surveillance gaps to be filled. Parental perceptions, feeding challenges, and nutrition challenges are also discussed. Ultimately, collaboration among academia and clinicians, the private sector, and the government will help close young child nutrition gaps in both the US and globally.


Characterization of the apical membrane ionic permeability of the rabbit proximal convoluted tubule.
Basolateral membrane potential (psi BL), transepithelial potential (psi T), and the ratio of apical to basolateral membrane resistance (RA/RBL) were measured in rabbit proximal convoluted tubules (PCT) perfused in vitro. Analysis of RA/RBL changes using several luminal perfusates indicates that the cotransport of Na with glucose and alanine would represent 19% of the apical conductance in normal conditions; the cotransport of Na with acetate, citrate, sulfate, and phosphate would represent 7%, whereas Na, K, and Cl diffusion would represent 10, 4, and 0% of this apical conductance, respectively. On the other hand, psi BL values can also be analyzed using the equivalent circuit of the epithelium to obtain the apical membrane equivalent electromotive force (EA) in the presence of each perfusate. These values, as well as the preceding values obtained from RA/RBL measurements, indicate that in the absence of cotransported solutes the transference number for Na diffusion is several times larger than for K diffusion. Among the conductance pathways studied, the transference number sequence would be as follows: Na cotransport with alanine and glucose greater than Na cotransport with anions greater than Na diffusion greater than K diffusion greater than Cl diffusion. This study also suggests the presence of another important but unidentified apical ionic permeation pathway, since the total of the transference numbers obtained from RA/RBL analysis represents only 40% of the total apical membrane conductance and the absolute values of EA are difficult to account for using only the tested apical membrane permeation pathways.


Doppler ophthalmic blood pressure measurement in the hemodynamic evaluation of occlusive carotid artery disease.
In 102 patients with angiographically proven occlusive carotid artery disease of 60-100% diameter reduction, Doppler ophthalmic artery pressure and blood flow direction were recorded by the recently developed ophthalmomanometry-Doppler technique. Among these 102 patients, 50 presented with complete carotid artery occlusions and 52 with carotid artery diameter stenoses of greater than or equal to 60%. Mean +/- SD Doppler ophthalmic artery pressure was 69 +/- 15 mm Hg ipsilateral to the occlusion and 86 +/- 18 mm Hg ipsilateral to a stenosis of the carotid artery (p less than 0.001). The mean +/- SD Doppler ophthalmic pressure index (ratio of the ophthalmic artery to systemic blood pressure) was lower ipsilateral to the occlusion (0.46 +/- 0.08) than ipsilateral to a carotid artery stenosis (0.54 +/- 0.08; p less than 0.001); in both, the index was clearly diminished compared with normal values (0.68 +/- 0.04; p less than 0.001). It is concluded that the intracranial hemodynamic consequences in the patients with occlusion are on average more profound than in the patients with stenosis. In carotid artery occlusions, the mean +/- SD ipsilateral ophthalmic pressure index was 0.46 +/- 0.06 for antegrade and 0.46 +/- 0.09 for retrograde ophthalmic artery blood flow. In carotid artery stenoses, the mean +/- SD ipsilateral ophthalmic pressure index was 0.55 +/- 0.07 for antegrade and 0.48 +/- 0.06 for retrograde ophthalmic artery blood flow (p less than 0.01). These results indicate that in carotid stenoses the collateral capacity of the ophthalmic artery is insufficient compared with intracranial collaterals, while in carotid occlusions the blood flow direction in the ophthalmic artery does not predict intracranial hemodynamic compensation.


Animal production and soil characteristics from integrated crop-livestock systems: toward sustainable intensification.
Sustainable intensification of land-use practices has never been more important to ensure food security for a growing world population. When combined under thoughtful management, cover cropping and crop-livestock integration under no-till systems can benefit from unexpected synergies due to their unique features of plant-animal diversification and complex agroecosystem functions. Mimicking the nutrient coupling/decoupling processes of natural ecosystems by diversifying plant and animal components of no-till integrated crop-livestock operations is an essential feature of the design of agroecological systems that support self-regulating feedbacks and lend resilience while increasing productivity and ecosystem service provision. Focusing on grazing animals as drivers of agroecosystem change, we highlight the benefits of grazed cover crops in rotation with cash crops for primary and secondary production and for soil physical, chemical, and biological parameters. However, careful management of grazing intensity is imperative; overgrazing drives soil deterioration, while light to moderate grazing enhances overall system functioning and allows for the generation of emergent properties.


Gastric hyalinization as a possible consequence of corrosive injury.
We report a case of gastric obstruction due to hyalinization of the antrum. The endoscopic appearance of the lesion was suggestive of Crohn's disease or gastric neoplasm. Biopsy showed pseudopolypous gastritis with ulceration and fibroid granulation. Surgery was carried out to relieve the obstruction. Examination of the resected specimen showed massive hyalinization of all layers of the antral wall with circular collagenous infiltration and a normal duodenal bulb. The question of hyaloid gastritis as a unique entity is raised. Subsequently, information from the patient revealed the cause: voluntary acid ingestion causing corrosive injury.


Statistical Analysis on Rate Parameters of the H2-O2 Reaction System.
Quantitative rate determination of elementary reactions is a major task in the study of chemical kinetics. To ensure the fidelity of their determination, progressively tightened constraints need to be placed on their measurement, especially with the development of various notable experimental techniques. However, the evaluation of reaction rates and their uncertainties is frequently conducted with substantial subjectivity due to data source, thermodynamic conditions, sampling range, and sparsity. To reduce the extent of biased rate evaluation, we propose herein an approach of uncertainty-weighted statistical analysis, utilizing weighted average, and weighted least-square regression in statistical inference. Based on the backbone H2/O2 chemistry, rate data for each elementary reaction are collected from the time-history profile in shock tube experiments and high-level theoretical calculations, with their assigned weight inversely depending on uncertainty, which would overall avoid subjective assessments and provide more accurate rate evaluation. Aided by sensitivity analysis, the rates of a few key reactions are further constrained in the less investigated low- to intermediate-temperature conditions using high-fidelity flow reactor data. Good performance of the constructed mechanism is confirmed with validation against the target of the high-fidelity flow reactor data. This study demonstrates a systematic approach for reaction rate evaluation and uncertainty quantification.


Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain-free female cats.
To assess the potential of a thermal carbon dioxide (CO2) laser to explore antinociception in pain-free cats. Experimental, prospective, blinded, randomized study. Sixty healthy adult female cats with a (mean±standard deviation) weight of 3.3±0.6 kg. Cats were systematically allocated to one of six treatments: saline 0.2 mL per cat; morphine 0.5 mg kg(-1); buprenorphine 20 μg kg(-1); medetomidine 2 μg kg(-1); tramadol 2 mg kg(-1), and ketoprofen 2 mg kg(-1). Latency to respond to thermal stimulation was assessed at baseline and at intervals of 15-30, 30-45, 45-60, 60-75, 90-105 and 120-135 minutes. Thermal thresholds were assessed using time to respond behaviourally to stimulation with a 500 mW CO2 laser. Within-treatment differences in response latency were assessed using Friedman's test. Differences amongst treatments were assessed using independent Kruskal-Wallis tests. Where significant effects were identified, pairwise comparisons were conducted to elucidate the direction of the effect. Cats treated with morphine (χ2=12.90, df=6, p=0.045) and tramadol (χ2=20.28, df=6, p=0.002) showed significant increases in latency to respond. However, subsequent pairwise comparisons indicated that differences in latencies at specific time-points were significant (p<0.05) only for tramadol at 60-75 and 90-105 minutes after administration (21.9 and 43.6 seconds, respectively) in comparison with baseline (11.0 seconds). No significant pairwise comparisons were found within the morphine treatment. Injections of saline, ketoprofen, medetomidine or buprenorphine showed no significant effect on latency to respond. The CO2 laser technique may have utility in the assessment of thermal nociceptive thresholds in pain-free cats after analgesic administration and may provide a simpler alternative to existing systems. Further exploration is required to examine its sensitivity and comparative utility.


Risk-benefit assessment of therapies for Mycobacterium avium complex infections.
Mycobacterium avium complex (MAC) is an important pathogen that can cause chronic lung disease in immunocompetent patients and disseminated disease in patients with the acquired immunodeficiency syndrome (AIDS). Treatment of MAC with antituberculosis drugs was unsatisfactory, but the introduction of the newer macrolides, clarithromycin and azithromycin, and of rifabutin has greatly improved the outcome of treatment regimens for MAC. However, these agents are also associated with many new treatment-related adverse effects and potential drug-drug interactions. Rifamycins [rifampicin (rifampin) more than rifabutin] induce cytochrome P450 enzymes and accelerate the metabolism of clarithromycin and HIV protease inhibitors. Conversely, clarithromycin inhibits these enzymes, resulting in increased rifabutin toxicity. The net results are treatment regimens that may be extremely difficult to tolerate, especially for elderly or debilitated patients. Clarithromycin and azithromycin must be administered in combination with other agents such as ethambutol to prevent the emergence of macrolide resistance. Unfortunately, not all patients respond to the combination of a macrolide, rifabutin and ethambutol, and many have significant adverse effects (mostly gastrointestinal) with this regimen. For some patients the treatment is worse than the disease. The same 3-drug regimen is also effective therapy for disseminated MAC in AIDS patients, in whom the additional problem of a rifamycin/protease inhibitor interaction may be present. Fortunately, as opposed to pulmonary MAC disease in immunocompetent patients, disseminated MAC disease is a diminishing problem because of effective prophylactic regimens for MAC and improved antiretroviral therapy for HIV. Significant progress has been made in the treatment of MAC disease with the introduction of the newer macrolides. It is to be hoped that even better drugs that are more active against MAC and are associated with less toxicity and drug-drug interactions will be introduced in the future.


Primary cytomegalovirus infection in pediatric nurses: a meta-analysis.
A meta-analysis of six controlled studies was performed to evaluate the risk of cytomegalovirus (CMV) infection among pediatric nurses. The pooled risk ratio for CMV infection in pediatric nurses using cumulative incidence data was statistically significant (risk ratio [RR] 2.7; 95% confidence interval [CI] 1.33 - 5.52), but person-year analysis taking account of follow-up periods demonstrated a trend toward increased risk that failed to reach statistical significance (RR 1.8; 95% CI 0.88 - 3.55). Despite pooling, there was low statistical power for comparing person-year rates. The studies included in this analysis failed to provide data on several potential confounding variables. We conclude that studies published prior to the widespread adoption of universal precautions suggest that pediatric nurses may have been at increased risk for CMV infection due to occupational exposure, but inadequate design and sample size of the studies prevent a definitive conclusion. Well-designed, controlled studies are still needed to define the occupational risk of CMV infection.


Role of Proximal Optimization Technique Guided by Intravascular Ultrasound on Stent Expansion, Stent Symmetry Index, and Side-Branch Hemodynamics in Patients With Coronary Bifurcation Lesions.
Bench models of coronary bifurcation lesions demonstrated that the proximal optimization technique (POT) expanded the stent and opened the side branch (SB). We investigated the role of POT guided by intravascular ultrasound on the main vessel (MV) stent expansion and SB fractional flow reserve (FFR) in patients with coronary bifurcation lesion. In 40 patients with coronary bifurcation lesion, 120 intravascular ultrasound examinations of the MV were performed at baseline, after MV stenting, and POT followed by 95 FFR measurements of the SB. In the proximal stent segment, stent volume index and minimum stent area were larger after POT versus MV stenting (9.2±3.4 versus 7.40±2.0 mm3/mm and 7.65±1.8 versus 6.38±1.7 mm2, respectively; P<0.01). In the bifurcation segment, minimum stent area was larger after POT versus MV stenting (6.45±2.1 versus 5.9±2.0 mm2, respectively; P<0.05). POT expanded the stent symmetrically. After POT, SB FFR was <0.75 in 12 patients (30%), which improved to >0.75 after SB dilation or SB stenting+final POT. SB FFR was significantly higher after POT+SB dilation or SB stenting+final POT versus after MV stenting and POT. This is the first study of POT guided by intravascular ultrasound in patients with coronary bifurcation lesion, demonstrating that POT symmetrically expanded the proximal and bifurcation segments of the stent. After POT, SB FFR was <0.75 in a third of patients, which improved to >0.75 after SB dilation or SB stenting+final POT.


Genetic studies relating to the production of transformed clones diploid in the tryptophan region of the Bacillus subtilis genome.
Transformation experiments with Bacillus subtilis strains carrying trpE26 (the marker responsible for the detection of merodiploid clones after transformation or transduction) have established the precise position of this marker on the "aromatic region" of the chromosome, at the distal end of the anthranilate synthetase locus. Integration efficiency of the mutant allele (trpE26) seems to be very low. Co-transfer of markers situated on either side of it is almost nil when both donor and recipient carry this mutation. The "exclusion" of trpE26 does not, however, affect recombination frequencies for nearby markers. To explain these facts we considered the hypothesis of a preferential breakage of the deoxyribonucleic acid (DNA) at the trpE26 site or that of an insertion mutation. These studies have also demonstrated the establishment of physical linkage of a marker from the exogenote (hisH2) to a resident marker (tyrA1) in stable and unstable merodiploid clones, thus confirming integration of the donor DNA segment into a genetic structure of the recipient. Furthermore, duplication was shown in merodiploid clones (through reversion and transformation) for a locus of the recipient (tyrA) which was not involved in the initial transformation. This suggests that the diploid condition in this region extends beyond the transformed area. Interpretation of the genetic constitution of these partial diploids calls for postulation of the existence of long duplications, a second (incomplete) chromosome, or an episome-like element.


Brief measure of expressed emotion: internal consistency and stability over time.
The study examined three methodological aspects of expressed emotion (EE) as assessed in the course of PACE (Psychosocial Assessment of Childhood Experiences) interviews with a parent. In a sample of 87 children, aged 6 13 years, enrolled in a prospective study examining the role of stress on the course of asthma, EE was assessed at three time points, 9 months apart. A high degree of agreement was found among the three concurrent measures of negative and positive EE (kappas from 0.74 to 0.97, and from 0.45 to 0.88, respectively; p < or = 0.0001 in all instances). The temporal stability of all measures was lower, although statistically significant in all but 2 instances (kappas from 0.19 to 0.59, and from 0.11 to 0.39, respectively). The temporal stability across measures, as well as across interviewers and over time, was broadly similar (kappas from 0.21 to 0.56 for negative EE, and from 0.09 to 0.38 for positive EE, with all but three of the 36 statistically significant). The findings provide support for the underlying assumptions of the PACE-EE and show the utility of measures based on just very brief periods of non-directive interviewing, making them practical in a wide range of studies with EE just one of a larger set of measures.


Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice.
We undertook a quantitative trait locus (QTL) analysis in mice to identify modifier genes that might influence the severity of human iron disorders. We identified a strong QTL on mouse chromosome 9 that differentially affected macrophage iron burden in C57BL/10J and SWR/J mice. A C57BL/10J missense allele of an evolutionarily conserved gene, Mon1a, cosegregated with the QTL in congenic mouse lines. We present evidence that Mon1a is involved in trafficking of ferroportin, the major mammalian iron exporter, to the surface of iron-recycling macrophages. Differences in amounts of surface ferroportin correlate with differences in cellular iron content. Mon1a is also important for trafficking of cell-surface and secreted molecules unrelated to iron metabolism, suggesting that it has a fundamental role in the mammalian secretory apparatus.


[Transcervical myomectomy and uterine fibroids: report of ten cases].
Uterine fibroids are the most common tumors of the uterus, their distribution in anatomical layers and segments of it are very varied clinical manifestations are usually abnormal bleeding and known treatments, the surgery is the most accomplished, either myomectomy or hysterectomy by both endoscopy and laparotomy, transvaginal approach is less common, but consider it a right way and solving the problem in selected cases. To present a well-defined study protocol in patients with abnormal uterine bleeding, and myomectomy as a surgical transcervical simple, safe and effective in patients with intracavitary myoma protruded through the cervical canal. ten patients are presented with abnormal uterine bleeding and anemia of various degrees, studied over a period of two years, following a research protocol for clinical methods, cabinet and laboratory diagnosis was submucosal fibroids with single fibroid, pedunculated protruding a vagina, treatment was performed transcervical myomectomy. The surgical procedure was obtained by solving the problem, having found the ten patients in the subsequent revisions in the outpatient, asymptomatic and without tumor lesions in the uterus. This study shows that performing a notarization in patients with abnormal uterine bleeding and making appropriate surgical treatment, achieves the desired objectives.


Ionization of short polymethacrylic acid: titration, DLS, and model calculations.
In this work the charging of polymethacrylic acid in excess electrolyte solution is investigated experimentally by titration and dynamic light scattering. The results are analyzed by a penetrable sphere model, which employs the Poisson-Boltzmann equation for the description of electrostatic interactions and takes into account specific binding of H+ and Na+. The evaluation of the DLS data yields two relaxation modes. The slow mode is present only at finite degrees of charging and is therefore caused by collective diffusion. The fast mode, which corresponds to diffusion coefficients in the range from (1.1 to 1.5) x 10(-10) m2 s(-1), is present over the whole pH range. This reflects the diffusional dynamics of the polyion itself and allows the calculation of hydrodynamic radii for equivalent spheres (RH). These increase from 1.5 nm at pH 2.14 up to 1.8 nm for a degree of deprotonation alpha=0.47 at pH 5.86. With a further increase of pH the radii slightly decrease to 1.6 nm. Setting the radius of the penetrable sphere equal to RH, we can successfully model the overall charging curve with logK0H=4.85 and logK0Na=-0.6. This means that weak complexes of the type COO---Na are formed, which reduce the effective charge inside the polyelectrolyte coil.


Syndecan receptors: pericellular regulators in development and inflammatory disease.
The syndecans are the major family of transmembrane proteoglycans, usually bearing multiple heparan sulfate chains. They are present on virtually all nucleated cells of vertebrates and are also present in invertebrates, indicative of a long evolutionary history. Genetic models in both vertebrates and invertebrates have shown that syndecans link to the actin cytoskeleton and can fine-tune cell adhesion, migration, junction formation, polarity and differentiation. Although often associated as co-receptors with other classes of receptors (e.g. integrins, growth factor and morphogen receptors), syndecans can nonetheless signal to the cytoplasm in discrete ways. Syndecan expression levels are upregulated in development, tissue repair and an array of human diseases, which has led to the increased appreciation that they may be important in pathogenesis not only as diagnostic or prognostic agents, but also as potential targets. Here, their functions in development and inflammatory diseases are summarized, including their potential roles as conduits for viral pathogen entry into cells.


HIV risk behavior among psychiatric outpatients: association with psychiatric disorder, substance use disorder, and gender.
People living with a mental illness are disproportionately vulnerable to human immunodeficiency virus. The current study sought to examine the influence of psychiatric disorder, substance use disorder, and gender on risky sexual behavior in this vulnerable population. Participants were 228 female and 202 male outpatients (66% mood disorder, 34% schizophrenia), each of whom took part in a Structured Clinical Interview for the DSM-IV and a comprehensive assessment of sexual risk behavior. Univariate and multivariate analyses tested a priori hypotheses. The results indicated that risk behavior was more frequent among patients diagnosed with a mood disorder (compared with those diagnosed with schizophrenia) or a substance use disorder (compared with those without a comorbid disorder) or both. We recommend routine human immunodeficiency virus risk screening and risk reduction programs for this vulnerable population.


Genetic and antigenic variation of capsid protein VP7 of serotype G1 human rotavirus isolates.
The deduced amino acid sequences of the outer capsid protein, VP7, of serotype G1 rotavirus clinical isolates collected over a 6 year period (1990-1995) in Melbourne, Australia, were examined. Phylogenetic analysis characterized the sequences into two discrete clusters representing two of the four global lineages of human G1 VP7 proteins. Antigenic characterization using a panel of serotype G1-specific neutralizing monoclonal antibodies classified lineage II isolates (1990-1993) as monotype G1a while lineage I isolates were classified as monotype G1b (1993-1995). Examination of the sequences of the neutralization epitope regions of VP7 revealed a particular amino acid substitution at residue 94 in region A (Asp --> Ser/Thr) that correlated with lineage and monotype designation. Our results indicated that temporal genetic variation of the VP7 of serotype G1 rotaviruses was associated with changes in the antigenicity of these isolates.


Effectiveness of overhead lifting devices in reducing the risk of injury to care staff in extended care facilities.
Patient and/or resident handling is a major cause of injury to healthcare workers. The effectiveness of an overhead ceiling lift programme at mitigating the risk of injury from resident handling was evaluated by comparing injury data and staff perceptions before and after implementation of the programme, and by comparison with a similar unit that did not implement an overhead ceiling lift programme. A questionnaire was used to assess perceived risk of injury and discomfort, preferred resident handling methods, frequency of performing designated resident handling tasks, perceived physical demands, work organization, and staff satisfaction. Staff preferred overhead ceiling lifts to other methods of transfer (manual or floor lifts) when lifting or transferring residents. A significant reduction was observed in the perceived risk of injury and discomfort to the neck, shoulders, back, hands, and arms of care staff. Compensation costs due to lifting and transferring tasks were reduced by 68% for the intervention unit and increased by 68% for the comparison unit. Overhead ceiling lifts were not beneficial in reducing the perceived risk of injury, pain or discomfort, or compensation costs when used to reposition residents. The study demonstrated an overall cost-savings associated with the installation of the overhead lifts, and highlighted areas for further improvement.


Longing for home: displacement, memory and identity.
This article focuses on the relationship between the country of birth and the ability of the individual from that country to create a sense of home, identity and belonging in other countries and cultures. What is home? Is home the place where you were born and raised, where your parents live or where they are buried? Is home the place from where you were dislocated or where you live now? What does longing for home mean? The author draws on theory to address these questions but her personal story plays a prominent part.


Association of HeartMate II left ventricular assist device flow estimate with thermodilution cardiac output.
Cardiac output (CO) assessment is important in treating patients with heart failure. Durable left ventricular assist devices (LVADs) provide essentially all CO. In currently used LVADs, estimated device flow is generated by a computerized algorithm. However, LVAD flow estimate may be inaccurate in tracking true CO. We correlated LVAD (HeartMate II) flow with thermodilution CO during postoperative care (day 2-10 after implant) in 81 patients (5,616 paired measurements). Left ventricular assist device flow and CO correlated with a low correlation coefficient (r = 0.42). Left ventricular assist device readings were lower than CO measurements by approximately 0.36 L/min, trending for larger difference with higher values. Left ventricular assist device flow measurements showed less temporal variability compared with CO. Grouping for simultaneous measured blood pressure (BP < 60, 60-70, 70-80, 80-90, and ≥90), the correlation of CO with LVAD flow differed (R = 0.42, 0.67, 0.48, 0.32, 0.32, respectively). Indicating better correlation when mean blood pressure is 60 to 70 mm Hg. Left ventricular assist device flow generally trends with measured CO, but large variability exists, hence flow measures should not be assumed to equal with CO. Clinicians should take into account variables such as high CO, BP, and opening of the aortic valve when interpreting LVAD flow readout. Direct flow sensors incorporated in the LVAD system may allow for better estimation.


Levamisole potentiation of fluorouracil antiproliferative activity mimicked by orthovanadate, an inhibitor of tyrosine phosphatase.
Levamisole is an effective antihelminthic drug with immunomodulatory and anticancer activities in model systems. Combined with fluorouracil (5-FU) as adjuvant treatment following resection of Dukes' stage C colon carcinomas, levamisole significantly reduces mortality. However, neither 5-FU nor levamisole alone has a significant effect on survival in this patient group. Previously, we noted that in vitro levamisole potentiated the antiproliferative activity of 5-FU. Because levamisole is known to inhibit alkaline phosphatases and has been reported to inhibit dephosphorylation of some membrane phosphoproteins, we studied the effects of levamisole analogues and of chemically unrelated inhibitors of phosphatases for their ability to potentiate 5-FU inhibition of tumor cell line proliferation in vitro. Human cancer cell lines were exposed to drugs alone or in combination with 5-FU. Antiproliferative activity was measured by determining the extent of reduction of colony formation by the cell lines in test plates compared with control plates. We found that potentiation of 5-FU cytotoxicity by levamisole and by p-hydroxytetramisole, a metabolite of levamisole, is mimicked by orthovanadate, an inhibitor of tyrosine phosphatases, but not by okadaic acid, an inhibitor of serine and threonine phosphatases, Furthermore, l-p-bromotetramisole, a synthetic analogue of levamisole that is 10-fold more potent in inhibition of alkaline phosphatase than levamisole, potentiates the antiproliferative activity of 5-FU to a greater extent than d-p-bromotetramisole, a stereoisomer of l-p-bromotetramisole with little antiphosphatase activity. Inhibition of tyrosine phosphatases may be responsible for the potentiation by levamisole of the inhibitory activity of 5-FU in vitro. Inhibition of dephosphorylation of regulatory phosphoproteins may be related to the therapeutic efficacy of the combination of levamisole and 5-FU in the adjuvant treatment of colon carcinoma and may underlie at least some of the multiple effects of levamisole on immune parameters.


Female-to-male sex reversal in mice caused by transgenic overexpression of Dmrt1.
Genes related to Dmrt1, which encodes a DNA-binding DM domain transcription factor, act as triggers for primary sex determination in a broad range of metazoan species. However, this role is fulfilled in mammals by Sry, a newly evolved gene on the Y chromosome, such that Dmrt1 has become dispensable for primary sex determination and instead maintains Sertoli cell phenotype in postnatal testes. Here, we report that enforced expression of Dmrt1 in XX mouse fetal gonads using a Wt1-BAC transgene system is sufficient to drive testicular differentiation and male secondary sex development. XX transgenic fetal gonads showed typical testicular size and vasculature. Key ovarian markers, including Wnt4 and Foxl2, were repressed. Sertoli cells expressing the hallmark testis-determining gene Sox9 were formed, although they did not assemble into normal testis cords. Other bipotential lineages differentiated into testicular cell types, including steroidogenic fetal Leydig cells and non-meiotic germ cells. As a consequence, male internal and external reproductive organs developed postnatally, with an absence of female reproductive tissues. These results reveal that Dmrt1 has retained its ability to act as the primary testis-determining trigger in mammals, even though this function is no longer normally required. Thus, Dmrt1 provides a common thread in the evolution of sex determination mechanisms in metazoans.


Thyroid hormone-sensitive brown adipose tissue respiration in the newborn rabbit.
The effects of thyroid hormone treatment on brown adipose tissue (BAT) and liver metabolism were assessed by measuring oxygen consumption, sodium-potassium adenosine triphosphatase (Na-K-ATPase), and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) activities in tissues from triiodothyronine- (T3) and vehicle-injected (for 3 days) newborn and adult rabbits. In the newborns, basal BAT cellular respiration was increased [mean (%/- SE) = 119 +/- 18 vs. 65 +/- 4 microliter O2/10(6) cells-1 . h in controls (P less than 0.005)], whereas hepatic respiration was unchanged. Ouabain had no effect on basal BAT cellular respiration, but suppressed hepatic respiration by 30% in both newborn groups. T3 treatment had no effect on NE- (10(-6) M) stimulated BAT respiration, whereas adult hepatic respiration was increased almost twofold. alpha-GPD activities were increased in both newborn BAT and adult liver but not in newborn liver. Na-K-ATPase activity was significantly increased only in newborn liver. In conclusion, 1) both BAT and liver are thyroid-hormone sensitive in the newborn rabbit, but the responses to T3 treatment are different in the two tissues; 2) the failure to stimulate both hepatic alpha-GPD and respiration in the newborn appears to be a developmental phenomenon characteristic of the rabbit; 3) thyroid hormones have little effect on sodium transport-dependent respiration in either BAT of liver in the newborn rabbit.


A dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis.
Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In some HS patients, mutations in the ankyrin promoter have been hypothesized to lead to decreased ankyrin mRNA synthesis. The ankyrin erythroid promoter is a member of the most common class of mammalian promoters which lack conserved TATA, initiator or other promoter cis elements and have high G+C content, functional Sp1 binding sites and multiple transcription initiation sites. We identified a novel ankyrin gene promoter mutation, a TG deletion adjacent to a transcription initiation site, in a patient with ankyrin-linked HS and analyzed its effects on ankyrin expression. In vitro, the mutant promoter directed decreased levels of gene expression, altered transcription initiation site utilization and exhibited defective binding of TATA-binding protein (TBP) and TFIID complex formation. In a transgenic mouse model, the mutant ankyrin promoter led to abnormalities in gene expression, including decreased expression of a reporter gene and altered transcription initiation site utilization. These data indicate that the mutation alters ankyrin gene transcription and contributes to the HS phenotype by decreasing ankyrin gene synthesis via disruption of TFIID complex interactions with the ankyrin core promoter. These studies support the model that in promoters that lack conserved cis elements, the TFIID complex directs preinitiation complex formation at specific sites in core promoter DNA and provide the first evidence that disruption of TBP binding and TFIID complex formation in this type of promoter leads to alterations in start site utilization, decreased gene expression and a disease phenotype in vivo.


Interaction of platelet factor 4 with fibroblast growth factor 2 is stabilised by heparan sulphate.
The CXC chemokine platelet factor 4 (PF4) appears to inhibit tumour growth through its modulation of the activity of angiogenic growth factors. We investigated the heparan sulphate-dependent mechanism of PF4 inhibition of fibroblast growth factor 2 (FGF-2). The ability of PF4 to bind simultaneously to both FGF-2 and HS was assessed using affinity gel chromatography. Thirty-three to forty-two percent more HS bound to the FGF-2 affinity gel in the presence of PF4 than with HS alone. Protection assays showed that PF4 and FGF-2 bound to adjacent or overlapping sites together covering a 12 kDa stretch of HS. This study suggests that the three components may form a ternary complex. PF4 released at sites of angiogenesis may bind to angiogenic growth factors attached to endothelial cell surface HS to disrupt or prevent them from interacting with their signalling receptors. Manipulation of this mechanism may prove useful for clinical intervention of angiogenesis.


The Effect of Individual Factors, Socioeconomic and Social Participation on Individual Happiness: A Cross-Sectional Study.
Happiness and exhilaration are the most essential demands of human innate psychological needs that affect both physical and mental health. The present study aimed to investigate the effect of individual factors, socioeconomic and social participation on individual happiness. In this study, we evaluated 15 to 54-year-old individuals to find the effects of individual factors, socioeconomic and social partnership (formal or informal) on human happiness. A random sampling method was used in the present study. The Oxford Happiness Questionnaire (OHQ) was used. Data analysis was performed using descriptive statistics including; frequency, percentage, Mean±SD. Correlation coefficient, one way ANOVA and logistic regression were also used as analytical statistics. There was a significant relationship between gender (p=0.001, r=0.144), marital status (p=0.001, r=0.174), happy parents (p=0.001, r=0.194), educational grade (p=0.001, r=0.189), employment status (p=0.001, r=0.180), income (p=0.001, r=0.264), car ownership (p=0.001, r=0.173), informal social participation (p=0.001, r=0.3) and formal social participation (p=0.001, r=0.231) with happiness. However, the relationship between home ownership (p=0.346, r=-0.015), and happiness was not significant. It seems that good and cordial relations with others, including family, relatives and friends (informal social participation) are the main sources and the most important factors of life satisfaction and human happiness. Higher income can increase happiness by enhancing the possibility to access the needs, desires, problems solving, enhancing the social support and self esteem and opportunities to perform one's favourite activities.


Reproduction Ability and Growth Effect of Pin Nematode, Paratylenchus nanus, With Selected Field Pea Cultivars.
Greenhouse experiments were conducted to determine the reproductive ability and effect of the pin nematode Paratylenchus nanus from North Dakota on field pea cultivars. Reproduction of P. nanus was determined on seven field pea cultivars using naturally infested field soils at low (1,500/kg of soil) and high (4,500/kg soil) initial pin nematode densities. Nematode effect on plant growth and seed yield was evaluated at 4,500 P. nanus per 1 kg of soil by artificially inoculating P. nanus on six field pea cultivars. Reproductive factor (RF) of P. nanus was observed to be greater at the low density than the high density of the nematode. At the low population density, RF values ranged from 1.10 to 11.20, whereas at the high density, RF ranged from 1.20 to 2.50. In experiments evaluating P. nanus effects on cultivar growth, the nematode (4,500 P. nanus per 1 kg soil) caused reduction (P < 0.05) of plant height in most cultivars tested, and it also significantly impacted dry shoot weight and dry seed weight in some experiments. Plant height and shoot weight reductions were the highest in the cultivar Arcadia (up to 37 and 53%, respectively), with a dry seed weight reduction up to 32%. This research demonstrated for the first time the negative impact of P. nanus on field peas in controlled greenhouse conditions, which is an important step toward developing effective management strategies to improve the productivity of this leguminous crop.


Regulation of eukaryotic messenger RNA turnover.
We have demonstrated the existence of multiple mRNA binding proteins that interact specifically with defined regions in posttranscriptionally regulated mRNAs. These domains appear to be destabilizers whose function can be attenuated by the interaction with the specific binding proteins. Thus, the ability to alter mRNA decay rates on demand, given different environmental or intracellular conditions, appears to be mediated by controlling the localization, activity, and overall function of the cognate binding protein. Based on our limited experience, we predict that most, if not all, of similarly regulated mRNAs will ultimately be found to interact with regulatory mRNA binding proteins. Under conditions whereby the mRNA binding proteins are constitutively active (e.g., tumor cell lines), abnormal mRNA decay will result, with accumulation and overtranslation. Such appears to be the case for cytokines and possibly amyloid protein precursor mRNAs in cancer and Alzheimer's disease, respectively. Conversely, mutagenesis of these critical 3' untranslated region elements will likely have comparable deleterious effects on the regulation of gene expression. To the extent that such derangements exist in human disease, attention to understanding the mechanistic detail at this level may provide insights into the development of appropriate therapeutics or treatment strategies.


Peer group image enhancement.
Peer group image processing identifies a "peer group" for each pixel and then replaces the pixel intensity with the average over the peer group. Two parameters provide direct control over which image features are selectively enhanced: area (number of pixels in the feature) and window diameter (window size needed to enclose the feature). A discussion is given of how these parameters determine which features in the image are smoothed or preserved. We show that the Fisher discriminant can be used to automatically adjust the peer group averaging (PGA) parameters at each point in the image. This local parameter selection allows smoothing over uniform regions while preserving features like corners and edges. This adaptive procedure extends to multilevel and color forms of PGA. Comparisons are made with a variety of standard filtering techniques and an analysis is given of computational complexity and convergence issues.


Acute and critically ill peripartum cardiomyopathy and 'bridge to' therapeutic options: a single center experience with intra-aortic balloon pump, extra corporeal membrane oxygenation and continuous-flow left ventricular assist devices.
Peripartum cardiomyopathy (PPCM) patients refractory to medical therapy and intra-aortic balloon pump (IABP) counterpulsation or in whom weaning from these therapies is impossible, are candidates for a left ventricular assist device (LVAD) as a bridge to recovery or transplant. Continuous-flow LVADs are smaller, have a better long-term durability and are associated with better outcomes. Extra corporeal membrane oxygenation (ECMO) can be used as a temporary support in patients with refractory cardiogenic shock. The aim of this study was to evaluate the efficacy and safety of mechanical support in acute and critically ill PPCM patients. This was a retrospective search of the patient database of the Ghent University hospital (2000 to 2010). Six PPCM-patients were treated with mechanical support. Three patients presented in the postpartum period and three patients at the end of pregnancy. All were treated with IABP, the duration of IABP support ranged from 1 to 13 days. An ECMO was inserted in one patient who presented with cardiogenic shock, multiple organ dysfunction syndrome and a stillborn baby. Two patients showed partial recovery and could be weaned off the IABP. Four patients were implanted with a continuous-flow LVAD (HeartMate II, Thoratec Inc.), including the ECMO-patient. Three LVAD patients were successfully transplanted 78, 126 and 360 days after LVAD implant; one patient is still on the transplant waiting list. We observed one peripheral thrombotic complication due to IABP and five early bleeding complications in three LVAD patients. One patient died suddenly two years after transplantation. In PPCM with refractory heart failure IABP was safe and efficient as a bridge to recovery or as a bridge to LVAD. ECMO provided temporary support as a bridge to LVAD, while the newer continuous-flow LVADs offered a safe bridge to transplant.


Mycorrhizal fungal establishment in agricultural soils: factors determining inoculation success.
Soil biota provide a number of key ecological services to natural and agricultural ecosystems. Increasingly, inoculation of soils with beneficial soil biota is being considered as a tool to enhance plant productivity and sustainability of agricultural ecosystems. However, one important bottleneck is the establishment of viable microbial populations that can persist over multiple seasons. Here, we explore the factors responsible for establishment of the beneficial soil fungi, arbuscular mycorrhizal fungi (AMF), which can enhance the yield of a wide range of agricultural crops. We evaluate field application potential and discuss ecological and evolutionary factors responsible for application success. We identify three factors that determine inoculation success and AM fungal persistence in soils: species compatibility (can the introduced species thrive under the imposed circumstances?); field carrying capacity (the habitat niche available to AMF); and priority effects (the influence of timing and competition on the establishment of alternative stable communities). We explore how these factors can be employed for establishment and persistence of AMF. We address the importance of inoculum choice, plant choice, management practices and timing of inoculation for the successful manipulation of the resulting AMF community.


Is there recent progress in the estimation of the postmortem interval by means of thanatochemistry?
Numerous methods have been proposed in the last 60 years for the determination of the time since death by chemical means. Many of them were reviewed by Schleyer in his monograph on the determination of the time since death by means of thanatochemistry about 40 years ago and none of these early methods has gained any practical value since they do not meet the demands in practice (being precise, reliable, giving an immediate result). While the earlier studies were mainly carried out on blood and cerebrospinal fluid (CSF) since the late 60s most investigations have been performed on vitreous humor (VH). This is mainly due to the fact that vitreous humor is topographically isolated and well protected, and thus, autolytic changes proceed slower compared to blood and CSF. The most studied parameter in VH is potassium and even nowadays reports on the postmortem rise of vitreous potassium are published, proposing new analytical methods or statistical evaluations. Chemical parameters studied for the determination of the time since death have to be differentiated according to the underlying process (catabolism, metabolic processes, pure autolysis and diffusion, putrefactive changes). In the present paper, recent studies on thanatochemistry are discussed regarding the underlying process, the analytical methods (for instance H magnetic resonance spectroscopy (1H MR spectroscopy), immunohistochemistry), the studied fluid compartment, the statistical evaluation and the precision of death time estimation. The value of chemical methods for the determination of the time since death is up to now very limited. This is supported by the fact that field studies on the reliability and precision of death time estimation by chemical means are still scarce in the literature.


Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands.
4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells.


Quantitative oculomotor findings in migrainous patients.
Neurotologic signs and symptoms, especially vestibular symptoms are common in migrainous patients. Involvement of the visual system in migrainures has received a great deal of attention in recent years, but the oculomotor part of the visual system has been largely ignored. The goal of this study was to investigate some parts of the central vestibular system using the oculomotor part of videonystagmographic evaluation, including spontaneous nystagmus, gaze-evoked nystagmus, smooth pursuit, saccade and optokinetic ystagmus interictally in migrainous patients. In this case-control study, 30 patients with migraine and 38 healthy volunteers within the age range of 18-48 years old were included spontaneous nystagmus; gaze-evoked nystagmus in right, left and up sides, smooth pursuit, optokinetic nystagmus using three different velocities and saccade test performed in both groups. The data were analyzed using SPSS for Windows 18.0. Some parameters of gain and phase and also morphology of the smooth pursuit, velocity of the saccade and slow phase velocity of optokinetic were significantly different in migrainures, although the statistical differences of these parameters were not clinically important as they were in the normal range of a defined device. These results may suggest the presence of subtle otoneurologic abnormalities in migrainous patients that is probably due to the efficiency of oculomotor function with vestibulocerebellar origin.


Accelerating artificial intelligence: How federated learning can protect privacy, facilitate collaboration, and improve outcomes.
Cross-institution collaborations are constrained by data-sharing challenges. These challenges hamper innovation, particularly in artificial intelligence, where models require diverse data to ensure strong performance. Federated learning (FL) solves data-sharing challenges. In typical collaborations, data is sent to a central repository where models are trained. With FL, models are sent to participating sites, trained locally, and model weights aggregated to create a master model with improved performance. At the 2021 Radiology Society of North America's (RSNA) conference, a panel was conducted titled "Accelerating AI: How Federated Learning Can Protect Privacy, Facilitate Collaboration and Improve Outcomes." Two groups shared insights: researchers from the EXAM study (EMC CXR AI Model) and members of the National Cancer Institute's Early Detection Research Network's (EDRN) pancreatic cancer working group. EXAM brought together 20 institutions to create a model to predict oxygen requirements of patients seen in the emergency department with COVID-19 symptoms. The EDRN collaboration is focused on improving outcomes for pancreatic cancer patients through earlier detection. This paper describes major insights from the panel, including direct quotes. The panelists described the impetus for FL, the long-term potential vision of FL, challenges faced in FL, and the immediate path forward for FL.


Ablation of Oxytocin Neurons Causes a Deficit in Cold Stress Response.
The paraventricular nucleus (PVN) is a critical locus of energy balance control. Three sets of neurons in the PVN are involved in regulating energy balance: oxytocin-expressing neurons (OXT-neurons), thyrotropin-releasing hormone-expressing neurons, and corticotrophin-releasing hormone-expressing neurons. To examine the role of OXT-neurons in energy balance, we ablated these neurons in mice by injecting diphtheria toxin into mice possessing both the oxytocin promoter driving cre expression and a cre-inducible diphtheria toxin receptor. Immunohistochemistry and real-time reverse transcriptase polymerase chain reaction confirmed that this injection caused a significant decrease in PVN OXT-neurons and OXT-mRNA abundance. OXT-neuron ablation did not alter food intake, weight, or energy expenditure at room temperature on either chow or a high-fat diet. To further characterize OXT-neuron-ablated mice, we examined their response to 1) intraperitoneal cholecystokinin (CCK) injection and 2) thermogenic stress. OXT-neuron-ablated mice had a blunted decrease in feeding response to CCK. When exposed to the extreme cold (4°C) for 3 hours, OXT-neuron-ablated mice had significant decreases in both rectal and brown adipose tissue temperature relative to controls, which was rescued by OXT treatment. Thermographic imaging revealed that OXT-neuron-ablated mice had increased body surface temperature. Thus, we report that OXT-neuron ablation shows no role for OXT-neurons in energy homeostasis at neutral temperature but reveals a heretofore unappreciated role for OXT-neurons and oxytocin specifically in regulating the thermogenic stress response.