Synthesis of single crystalline spinel LiMn2O4 nanowires for a lithium ion battery with high power density.
How to improve the specific power density of the rechargeable lithium ion battery has recently become one of the most attractive topics of both scientific and industrial interests. The spinel LiMn2O4 is the most promising candidate as a cathode material because of its low cost and nontoxicity compared with commercial LiCoO2. Moreover, nanostructured electrodes have been widely investigated to satisfy such industrial needs. However, the high-temperature sintering process, which is necessary for high-performance cathode materials based on high-quality crystals, leads the large grain size and aggregation of the nanoparticles which gives poor lithium ion battery performance. So there is still a challenge to synthesize a high-quality single-crystal nanostructured electrode. Among all of the nanostructures, a single crystalline nanowire is the most attractive morphology because the nonwoven fabric morphology constructed by the single crystalline nanowire suppresses the aggregation and grain growth at high temperature, and the potential barrier among the nanosize grains can be ignored. However, the reported single crystalline nanowire is almost the metal oxide with an anisotropic crystal structure because the cubic crystal structure such as LiMn2O4 cannot easily grow in the one-dimentional direction. Here we synthesized high-quality single crystalline cubic spinel LiMn2O4 nanowires based on a novel reaction method using Na0.44MnO2 nanowires as a self-template. These single crystalline spinel LiMn2O4 nanowires show high thermal stability because the nanowire structure is maintained after heating to 800 degrees C for 12 h and excellent performance at high rate charge-discharge, such as 20 A/g, with both a relative flat charge-discharge plateau and excellent cycle stability.


Splinting After Ear Reconstruction: A Stepwise and Inexpensive Workflow Protocol.
Long-term postoperative splinting plays a role in the prevention of contracture of the grafted skin after a second-stage ear reconstruction. The scar retraction could lead to an unfavorable aesthetic outcome. Splinting could play a role to overcome or prevent the loss of projection and the obliteration of the sulcus. We have defined the characteristics of an ideal long-term splint and present a stepwise clinical protocol for the fabrication of an ethylene-vinyl acetate splint. The splint was applied to all patients included in a prospective study on the postoperative splinting regime. Ethylene-vinyl acetate has proved its safety and longevity in dental prosthetics. Patient compliance was optimal, and no allergic reactions, pressure sores, or skin necrosis were reported. The splint is self-retaining and light weight. Because of its transparent color, it can be easily camouflaged. A stepwise clinical protocol for the fabrication of a low-cost patient-specific ear splint is presented.


Evaluation of high-resolution microarray platforms for genomic profiling of bone tumours.
Several high-density oligonucleotide microarray platforms are available for genome-wide single nucleotide polymorphism (SNP) detection and microarray-based comparative genomic hybridisation (array CGH), which may be used to detect copy number aberrations in human tumours. As part of the EuroBoNeT network of excellence for research on bone tumours (eurobonet.eu), we have evaluated four different commercial high-resolution microarray platforms in order to identify the most appropriate technology for mapping DNA copy number aberrations in such tumours. DNA from two different cytogenetically well-characterized bone sarcoma cell lines, representing a simple and a complex karyotype, respectively, was tested in duplicate on four high-resolution microarray platforms; Affymetrix Genome-Wide Human SNP Array 6.0, Agilent Human Genome CGH 244A, Illumina HumanExon510s-duo and Nimblegen HG18 CGH 385 k WG tiling v1.0. The data was analysed using the platform-specific analysis software, as well as a platform-independent analysis algorithm. DNA copy number was measured at six specific chromosomes or chromosomal regions, and compared with the expected ratio based on available cytogenetic information. All platforms performed well in terms of reproducibility and were able to delimit and score small amplifications and deletions at similar resolution, but Agilent microarrays showed better linearity and dynamic range. The platform-specific analysis software provided with each platform identified in general correct copy numbers, whereas using a platform-independent analysis algorithm, correct copy numbers were determined mainly for Agilent and Affymetrix microarrays. All platforms performed reasonably well, but Agilent microarrays showed better dynamic range, and like Affymetrix microarrays performed well with the platform-independent analysis software, implying more robust data. Bone tumours like osteosarcomas are heterogeneous tumours with complex karyotypes that may be difficult to interpret, and it is of importance to be able to well separate the copy number levels and detect copy number changes in subpopulations. Taking all this into consideration, the Agilent and Affymetrix microarray platforms were found to be a better choice for mapping DNA copy numbers in bone tumours, the latter having the advantage of also providing heterozygosity information.


[Computer-based assessment of visual acuity--technical realization].
Testing of visual acuity for distant vision can be computerized by using monitor screens to present optotypes. Because of the limited spatial resolution of conventional monitors, measurement of visual acuity for near vision is not possible. This paper describes a new computer-aided method for the measurement of both near and distant visual acuity. Our approach to the assessment of visual acuity for near vision is based on a recently developed liquid crystal display (a screen, LCD) measuring 10.5 mm x 15 mm. The LCD permits the presentation of optotypes for the measurement of visual acuity between 0.063 and 1.25 at a viewing distance of 40 cm (near/distant). The presentation of optotypes for the assessment of the acuity of distant vision uses a standard 17" monitor that permits visual acuity figures of between 0.032 and 1.6 to be assessed.


Platelet function in pre-eclampsia.
Pronounced hemostatic changes occur during pregnancy, and the balance shifts markedly in favor of hypercoagulability. Although primarily a result of a marked rise in the levels of several procoagulants and a fall in some natural anticoagulants, platelet activation also contributes to this prothrombotic tendency. Several studies have confirmed the accentuation of platelet activation in pre-eclampsia (P-EC), which remains an important obstetric complication affecting ~2 to 4% of pregnancies. Although there is still a long way to go, significant inroads have been made in the understanding of this enigmatic condition. Whereas the pathogenesis of P-EC is protean and involves a complex interplay of placental and maternal tissues, platelet activation is likely to contribute to several clinical features. Several techniques have been used to assess platelet activation in P-EC. Detection of aberrations of platelet function and activation appear to have predictive value for its diagnosis. The findings also lend support to the use of antiplatelet agents as prophylaxis in those women with a high risk of developing the condition.


Disentangling precopulatory and postcopulatory sexual selection in polyandrous species.
Sexual selection operates on a sequence of events, from mating to offspring production. Which stages in this sequence undergo stronger selection, especially the relative importance of pre- versus postcopulatory processes, are intensely debated issues. Unequal siring success among mates of polyandrous females is classically taken as evidence for a large contribution of postcopulatory processes to the variance in male reproductive success (var(RSm )). However, paternity skews also depend on the timing and number of copulations, a source of variation that should be considered precopulatory rather than postcopulatory. We develop a method for decomposing var(RSm ) accounting for copulatory activity and apply it to experimental mating groups of the snail Physa acuta. In our experiment, 40% of var(RSm ) emerges at the precopulatory stage, only half of which depends on variation in mating success (number of partners). Ignoring copulation characteristics can therefore lead to severe underestimation of precopulatory sexual selection. Moreover, although only 36% of var(RSm ) arises at the postcopulatory stage, this is when sexual selection on body weight mostly occurs. Finally, trade-offs were detected between different components of precopulatory success, whereas pre- and postcopulatory success appear independent. Our study opens the way to a detailed quantitative understanding of sexual selection in polyandrous species.


Prevention of neointimal formation by a serine protease inhibitor, FUT-175, after carotid balloon injury in rats.
In vivo and vitro studies revealed the activation of thrombin and the complement system in vascular lesion formation during the process of atherosclerosis, along with pathological proliferation of smooth muscle cells. We examined the effect of the synthetic serine protease inhibitor FUT-175 (developed as a potent inhibitor of thrombin and the complement system) on vascular lesions using balloon dilatation-induced neointimal formation in the carotid artery of rats. Sprague-Dawley (SD) rats underwent balloon dilatation injury of the left carotid artery to induce neointimal formation. Three groups of these rats (n=8, each) were treated with daily intraperitoneal injections of 1 of the following doses of FUT-175: 0.5, 1.0, or 2.0 mg/d in 1 mL of saline for 7 consecutive days. The control group (n=8) was similarly treated with 1 mL of saline for 7 days. The injections were started immediately after balloon injury. Two weeks after the injury, the left carotid arteries were perfusion-fixed, and the areas of the neointimal and medial layer were analyzed under a microscope. A morphometric analysis revealed that there were significant differences in the intima-media ratio between the 4 groups treated with vehicle (saline) or a low, medium, or high dose of FUT-175 (1.45+/-0.11, 1.08+/-0.06, 0.71+/-0.04, or 0.32+/-0.04, respectively). This suppression was achieved in a dose-dependent manner by the administration of FUT-175 after balloon injury. In the histological study, it was demonstrated that FUT-175 suppresses the production of platelet-derived growth factor (PDGF)-BB in the neointima and the medial smooth muscle cell layer. After balloon injury activated proteases that were inhibited by FUT-175 were demonstrated to have an essential role in the development of the pathological thickening of the arterial wall.


Whisker vibration information carried by rat barrel cortex neurons.
Rats can make extremely fine texture discriminations by "whisking" their vibrissa across the surface of an object. We have investigated one hypothesis for the neuronal basis of texture representation by measuring how clusters of neurons in the barrel cortex of anesthetized rats encode the kinetic features of sinusoidal whisker vibrations. Mutual information analyses of spike counts led to a number of findings. Information about vibration kinetics became available as early as 6 msec after stimulus onset and reached a peak at approximately 20-30 msec. Vibration speed, proportional to the product of vibration amplitude (A) and frequency (f), was the kinetic property most reliably reported by cortical neurons. Indeed, by measuring information when the complete stimulus set was collapsed into feature-defined groups, we found that neurons reduced the dimensionality of the stimulus from two features (A, f) to a single feature, the product Af. Moreover, because different neurons encode stimuli in the same manner, information loss was negligible even when the activity of separate neuronal clusters was pooled. This suggests a decoding scheme whereby target neurons could capture all available information simply by summating the signals from separate barrel cortex neurons. These results indicate that neuronal population activity provides sufficient information to allow nearly perfect discrimination of two vibrations, based on their deflection speeds, within a time scale comparable with that of a single whisking motion across a surface.


Serotonin dimers: application of the bivalent ligand approach to the design of new potent and selective 5-HT(1B/1D) agonists.
A series of serotonin dimers of formula 4 in which two serotonin moeities are linked together through their 5-hydroxyl residue has been prepared and evaluated as 5-HT(1B/1D) receptor agonists. Binding experiments at cloned human 5-HT(1B), 5-HT(1D), and 5-HT(1A) receptors show that all of these dimers are very potent ligands at 5-HT(1B/1D) receptors with increased binding selectivity vs the 5-HT(1A) receptor when compared to serotonin. Studies of inhibition of the forskolin-stimulated c-AMP formation mediated by the human 5-HT(1B) receptor (formerly the 5-HT(1Dbeta) receptor) demonstrate that all of these serotonin dimers behave as full agonists. Among them, the piperazide derivatives of bis-serotonin, 4g,j, were also identified as very potent agonists in contracting the New Zealand white rabbit saphenous vein (pD2 = 7.6 in each case compared to 5.8 for sumatriptan). Results analysis supports the hypothesis that the important increase in potency of the serotonin dimers can be attributed to the presence of two serotonin pharmacophores in the same molecule, while the enhanced selectivity for 5-HT(1B/1D) receptor subtypes may be due to the position of the spacer attachment to serotonin.


COVID-19 and HIV: Clinical Outcomes among Hospitalized Patients in the United States.
The concurrence of HIV and COVID-19 yields unique challenges and considerations for healthcare providers, patients living with HIV, and healthcare systems at-large. Persons living with HIV may face a higher risk of acquiring SARS-CoV-2 infection and experiencing worse clinical outcomes compared to those without. Notably, COVID-19 may have a disproportionate impact on historically disadvantaged populations, including African Americans and those stratified in a lower socio-economic status. Using the National Inpatient Sample (NIS) database, we compared patients with a diagnosis of both HIV and COVID-19 and those who exclusively had a diagnosis of COVID-19. The primary outcome was in-hospital mortality. Secondary outcomes were intubation rate and vasopressor use; acute MI, acute kidney injury (AKI); AKI requiring hemodialysis (HD); venous thromboembolism (VTE); septic shock and cardiac arrest; length of stay; financial burden on healthcare; and resource utilization. A total of 1,572,815 patients were included in this study; a COVID-19-positive sample that did not have HIV (n = 1,564,875, 99.4%) and another sample with HIV and COVID-19 (n = 7940, 0.56%). Patients with COVID-19 and HIV did not have a significant difference in mortality compared to COVID-19 alone (10.2% vs. 11.3%, respectively, p = 0.35); however, that patient cohort did have a significantly higher rate of AKI (33.6% vs. 28.6%, aOR: 1.26 [95% CI 1.13-1.41], p < 0.001). Given the complex interplay between HIV and COVID-19, more prospective studies investigating the factors such as the contribution of viral burden, CD4 cell count, and the details of patients' anti-retroviral therapeutic regimens should be pursued.


[Determination of cytomegalo-, herpes simplex- and rubellavirus-antibodies resp. during perinatal period by Elisa-technique (author's transl)].
Cytomegalovirus (CMV)-infections attract increased attention among viral infections in the pre- und perinatal period resp. The decreasing cell mediated immunity by the end of pregnancy may favour conditions for primary infections or reactivations with CMV. With the Elisa-technique we looked for CMV-specific antibody status in the perinatal period with special respect to striking titers. The same serum samples were screened for antibody status to Herpes simplex virus (HSV) type 1 specific IgG and rubellavirus specific IgG resp. 67% were positive for CMV-IgG, 90% for HSV-type 1-IgG and 93.5% for rubellavirus IgG. CMV-specific IgM antibodies were found in 3.6% but only 1.5% were suspicious for recent CMV-infections according to higher CMV specific IgM titers.


Induction of fibronectin matrix assembly in human fibrosarcoma cells by dexamethasone.
Previous studies have suggested that the assembly of fibronectin into the extracellular matrix of cultured fibroblasts is mediated by specific matrix assembly receptors that recognize a binding site in the amino terminus of the fibronectin molecule (McKeown-Longo, P.J., and D.F. Mosher, 1985, J. Cell Biol., 100:364-374). In the presence of dexamethasone, human fibrosarcoma cells (HT-1080) acquired the ability to specifically bind exogenous plasma fibronectin and incorporate it into a detergent-insoluble extracellular matrix. Dexamethasone-induced fibronectin binding to HT-1080 cells was time dependent, dose dependent, and inhibited by cycloheximide. Saturation binding curves indicated that dexamethasone induced the appearance of 7.7 X 10(4) matrix assembly receptors per cell. The induced receptors exhibited a dissociation constant (KD) for soluble fibronectin of 5.0 X 10(-8) M. In parallel experiments, normal fibroblasts exhibited 4.1 X 10(5) receptors (KD = 5.3 X 10(-8) M) per cell. In the presence of cycloheximide, the induced fibronectin-binding activity on HT-1080 cells returned to uninduced levels within 12 h. In contrast, fibronectin-binding activity on normal fibroblasts was stable in the presence of cycloheximide for up to 54 h. The first-order rate constant (Kt = 2.07 X 10(-4) min-1) for the transfer of receptor-bound fibronectin to extracellular matrix was four- to fivefold less than that for normal fibroblasts (Kt = 1.32 X 10(-3) min-1). Lactoperoxidase-catalyzed iodination of HT-1080 monolayers indicated that a 48,000-mol-wt cell surface protein was enhanced with dexamethasone. The results from these experiments suggest that dexamethasone induces functional matrix assembly receptors on the surface of HT-1080 cells; however, the rate of incorporation of fibronectin into the matrix is much slower than that of normal fibroblasts.


Stool specimen for diagnosis of pulmonary tuberculosis in adults: protocol for a systematic review and meta-analysis.
Tuberculosis (TB) continues to be a significant health burden, most commonly affecting the lungs and referred to as pulmonary TB (PTB). Diagnostic techniques of PTB primarily rely on expectorated sputum samples. However, the diagnostic yields are often hindered due to insufficient volume and quality of the sputum specimens. Moreover, some individuals are unable to provide sputum samples due to scanty sputum production or difficulty in coughing up and require an invasive procedure to obtain a respiratory sample, such as bronchoscopic or gastric aspiration. Thus, challenges in the acquisition of respiratory specimens warrant an alternate specimen. Therefore, this systematic review aims to evaluate the diagnostic accuracy of a stool specimen for the diagnosis of PTB in adults. We will search MEDLINE (Ovid), Embase (Ovid), Web of Science and Cochrane database from inception to April 2021 using a comprehensive search strategy. Two reviewers will independently perform screening, data extraction and quality assessment. The risk of bias assessment and applicability of results of eligible studies will be performed using the Quality of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects models will be performed to calculate pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio and diagnostic odds ratio along with 95% CI of stool specimen for each reported diagnostic method against any of the reference standard test (ie, mycobacterial culture or smear microscopy or Xpert assay using respiratory specimens). Heterogeneity between studies will be assessed by I2 statistics and Q statistic of the χ2 test. The results will be disseminated through publishing in a peer-reviewed medical journal and public presentations in relevant national and international conferences. As this is a systematic review of publicly available data, ethics approval is not required. CRD42021245203.


[Lack of benefit from the intermittent administration of insulin in treatment using subcutaneous perfusion pump in type 1 diabetes].
Our study is based on two constatations: 1) Hyperinsulinaemia, a possible atherogenic factor, is frequent under continuous subcutaneous insulin infusion. 2) Pulsatile intravenous insulin delivery improve the insulin's hypoglycaemic activity. To test if equivalent metabolic control can be obtained with a reduced intermittent subcutaneous infused insulin dose, we compared nocturnal metabolic control of 8 c-peptide negative type 1 diabetic patients under three experimental conditions: Continuous usual dose test (1.0 +/- 0.1 u/h); Intermittent half dose test (1.0 +/- 0.1 u/h, 30 min/h); Continuous half dose test (0.5 +/- 0.05 u/h) Five parameters were monitored: blood glucose, plasma free insulin and beta-hydroxy-butyrate, free fatty acid and glycerol plasma level. No significant differences were found between intermittent and continuous half-dose tests. We conclude that, in our experimental conditions, intermittent subcutaneous insulin infusion does not reduce the metabolic degradation induced by insulin dose reduction.


Functionally conserved PPARG exonic circRNAs enhance intramuscular fat deposition by regulating PPARG and HSL.
Circular RNAs (circRNA) are a kind of endogenous biological macromolecules that play significant roles in many biological processes, including adipogenesis, a precisely orchestrated process that is mediated by a large number of factors. Among them, peroxisome proliferator-activated receptor gamma (PPARG), is undoubtedly the most important regulator of adipocyte development in all types of adipose tissue. The formation of intramuscular fat (IMF), is a key factor that influences the meat quality in livestock animals. PPARG has been demonstrated to show a positive correlation with IMF deposition although the regulatory mechanism involved is not known. This study demonstrates that PPARG mediates IMF deposition by producing multiple exonic circRNAs (circPPARGs). Three circPPARGs promote adipogenic differentiation and inhibit the proliferation of intramuscular preadipocytes and these effects are conserved across several species including buffaloes, cattle and mice. Notably, circPPARG1 interacts with PPARG protein to inhibit the transcription of hormone sensitive lipase (HSL) involved in lipolysis. In addition, the positive effects of circPPARG1 on IMF deposition were identified in mice in vivo. Thus, PPARG drives IMF deposition, not only through the common transcription factor pathway, but also by producing circRNAs. This study provides new insights into our understanding of the regulatory mechanisms of PPARG in IMF deposition.


G protein betagamma subunits modulate the number and nature of exocytotic fusion events in adrenal chromaffin cells independent of calcium entry.
G-protein-coupled receptors (GPCR) play important roles in controlling neurotransmitter and hormone release. Inhibition of voltage-gated Ca(2+) channels (Ca(2+) channels) by G protein betagamma subunits (Gbetagamma) is one prominent mechanism, but there is evidence for additional effects distinct from those on calcium entry. However, relatively few studies have investigated the Ca(2+)-channel-independent effects of Gbetagamma on transmitter release, so the impact of this mechanism remains unclear. We used carbon fiber amperometry to analyze catecholamine release from individual vesicles in bovine adrenal chromaffin cells, a widely used neurosecretory model. To bypass the effects of Gbetagamma on Ca(2+) entry, we stimulated secretion using ionomycin (a Ca(2+) ionophore) or direct intracellular application of Ca(2+) through a patch pipette. Activation of endogenous GPCR or transient transfection with exogenous Gbetagamma significantly reduced the number of amperometric spikes (the number of vesicular fusion events). The charge ("quantal size") and amplitude of the amperometric spikes were also significantly reduced by GPCR/Gbetagamma. We conclude that independent from effects on calcium entry, Gbetagamma can regulate both the number of vesicles that undergo exocytosis and the amount of catecholamine released per fusion event. We discuss possible mechanisms by which Gbetagamma might exert these novel effects including interaction with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex.


Virgin coconut oil supplementation in diet modulates immunity mediated through survival signaling pathways in rats.
Background Virgin coconut oil (VCO), a cold processed form of coconut oil, is traditionally consumed in Asian countries owing to its nutritional and medicinal properties. The aim of this study was to investigate whether the health benefits of VCO involve alterations in immune responses that are regulated by intracellular signaling molecules in the spleens of rats. Methods Young male Wistar rats were fed with three doses of VCO in diet for 30 days. At the end of the treatment period, spleens were isolated and in vitro effects on immune responses (Concanavalin A [Con A]-induced lymphoproliferation and cytokine production), and direct effects of VCO treatment on intracellular signaling molecules and antioxidant status were examined. Serum was collected to measure glucose, lipid levels, and leptin. Results VCO supplementation in diet enhanced Con A-induced splenocyte proliferation and Th1 cytokine production while it suppressed the proinflammatory cytokine production. VCO increased the expression of mechanistic target of rapamycin (p-mTOR), sirtuin1 (SIRT1), liver kinase B1 (p-LKB1) p-ERK, and p-CREB in spleen. Similarly, VCO increased the activities of antioxidant enzymes while it suppressed lipid peroxidation in the spleen. VCO diet had hypolipidemic effects on the rats: an increase in high density lipoprotein cholesterol (HDL-C) levels while lowering triacylglycerol (TAG) levels. Conclusion The health benefits of VCO may be mediated through enhanced Th1 immunity through the upregulation of survival signaling pathways and inhibition of free radical generation in the spleen besides its capacity to induce hypolipidemia.


Characterization of the effects of bupropion on the reinforcing properties of nicotine and food in rats.
Bupropion is an atypical antidepressant drug that is the only nonnicotine-based prescription medicine approved for smoking cessation by the Food and Drug Administration. The aim of the present experiments was to investigate the effects of bupropion (5-40 mg/kg) on the reinforcing properties of nicotine and food in rats. The effects of bupropion were studied under two schedules of reinforcement: a fixed ratio 5 time-out 20-sec (FR5 TO20 s) and a progressive ratio (PR). Rats were trained to respond for nicotine (0.01 or 0.03 mg/kg/infusion, free base) or food under the FR5 TO20 s schedule. Pretreatment with the highest dose of bupropion (40 mg/kg) resulted in a significant reduction (approximately 50%) of nicotine intake in rats self-administering 0.03 mg/kg/infusion of nicotine. The same dose of bupropion also decreased (approximately 40%) the self-administration of 0.01 mg/kg/infusion of nicotine, but this effect did not reach statistical significance. Pretreatment with bupropion slightly (approximately 15%) reduced responding for food under the FR5 TO20 s schedule. Finally, pretreatment with bupropion did not affect the self-administration of nicotine (0.03 mg/kg/infusion) under a PR schedule, but dose-dependently increased responding for food under the same PR schedule. These findings indicate that a high dose of bupropion decreases the reinforcing properties of nicotine as measured under an FR schedule, while having no apparent effects on breaking points for nicotine under a PR schedule that reflects both the reinforcing properties and the motivation to obtain nicotine.


Quantitative gallium scanning in pulmonary sarcoidosis.
Pulmonary parenchymal involvement in sarcoidosis is due to noncaseating granuloma, fibrosis or both. To assess the granulomatous activity in pulmonary sarcoidosis, we performed gallium-67 citrate scans in 41 patients with sarcoidosis and in 13 non-sarcoid patients, who were free of pulmonary disease and served as controls. Gallium score, a measure of gallium accumulation in lung parenchyma, was obtained from the sum of activity indices (ratio of accumulated gallium activity over a chest quadrant and soft tissues of the mid-thigh) from each of the quadrants over the anterior and posterior aspects of the chest. The gallium score in patients with sarcoidosis was significantly higher than the gallium score in controls. The gallium scores in patients with sarcoidosis, with radiographically apparent pulmonary infiltrate were significantly higher than the scores in the patients with no radiographic evidence of pulmonary parenchymal involvement. The gallium scores in patients not receiving corticosteroids were significantly higher compared to patients who were receiving corticosteroids, and furthermore, the gallium scores fell significantly when corticosteroids were initiated. There was a significant correlation between serum angiotensin-converting enzyme (SACE) activity and gallium score. In 11 patients, 27 sequential gallium scans were performed and changes in gallium score correlated well with the changes in SACE activity and clinical assessment. These findings suggest that quantitative evaluation of gallium scans may be useful in assessing granulomatous activity of pulmonary sarcoidosis and following its response to therapy.


High-Throughput Screening of Metal-Organic Frameworks for CO2 Capture in the Presence of Water.
Competitive coadsorption of water is a major problem in the deployment of adsorption-based CO2 capture. Water molecules may compete for adsorption sites, reducing the capacity of the material, and dehumidification prior to separating CO2 from N2 increases process complexity and cost. The development of adsorbent materials that can selectively adsorb CO2 in the presence of water would be a major step forward in the deployment of CO2 capture materials in practice. In this study, large-scale computational screening was carried out to search for metal-organic frameworks (MOFs) with high selectivity toward CO2 over H2O. Calculating framework charges for thousands of MOFs is a significant challenge, so initial screening used a fast, but approximate, charge calculation method. On the basis of the initial screening, 15 MOFs were selected, and Monte Carlo simulations were carried out to compute the adsorption isotherms for these MOFs using more accurate framework charges calculated by density functional theory. A detailed investigation was performed on the effect of using different methods for calculating partial charges, and it was found that electrostatic interactions contribute the majority of the adsorption energy of H2O in the selected MOFs.


Cervical cancer in the screening era: who fell victim in spite of successful screening programs?
To compare profiles of a prescreening and screening cohort of women with cervical cancer regarding histopathology and clinical variables in order to identify those remaining at risk despite successful screening programs. By analyzing these profiles we hope to improve future screening methods. The prescreening and screening cohorts consisted of 5,046 and 1,174 women, respectively, treated for cervical cancer at the Department of Gynecological Oncology at Radiumhemmet, Karolinska University Hospital, during the periods 1944-1957 and 1990-2004. Mean age increased from 48.9 years to 55.3 years in the cohorts treated 1944-1957 and 1990-2004, respectively. The percentage of patients older than 69 years was 5.4% and 27.3% in the prescreening and screening period, respectively. A shift towards earlier stages at diagnosis, a reduction of squamous cervical cancer and an increase of adenocarcinoma were observed in the screening cohort. The percentage of adenocarcinoma was about 6 times higher among younger patients. Cases of stump cancer and cervical cancer associated with pregnancy have declined. Eighty-seven women in the screening cohort had a history of treatment for in situ carcinoma by conization; 28% of these cases developed cervical cancer within one year after conization. The profile changed in the screening era indicating a need to refine screening for improved detection of in older women. This study, one of the largest clinical series of cervical cancer, provides an important baseline with which later studies can be compared to evaluate the effects of human papillomavirus vaccine and other important changes in this field.


Smartphone-Based Self-Testing of COVID-19 Using Breathing Sounds.
Telemedicine could be a key to control the world-wide disruptive and spreading novel coronavirus disease (COVID-19) pandemic. The COVID-19 virus directly targets the lungs, leading to pneumonia-like symptoms and shortness of breath with life-threatening consequences. Despite the fact that self-quarantine and social distancing are indispensable during the pandemic, the procedure for testing COVID-19 contraction is conventionally available through nasal swabs, saliva test kits, and blood work at healthcare settings. Therefore, devising personalized self-testing kits for COVID-19 virus and other similar viruses is heavily admired. Many e-health initiatives have been made possible by the advent of smartphones with embedded software, hardware, high-performance computing, and connectivity capabilities. A careful review of breathing sounds and their implications in identifying breathing complications suggests that the breathing sounds of COVID-19 contracted users may reveal certain acoustic signal patterns, which is worth investigating. To this end, acquiring respiratory data solely from breathing sounds fed to the smartphone's microphone strikes as a very appealing resolution. The acquired breathing sounds can be analyzed using advanced signal processing and analysis in tandem with new deep/machine learning and pattern recognition techniques to separate the breathing phases, estimate the lung volume, oxygenation, and to further classify the breathing data input into healthy or unhealthy cases. The ideas presented have the potential to be deployed as self-test breathing monitoring apps for the ongoing global COVID-19 pandemic, where users can check their breathing sound pattern frequently through the app.


Protocol of a feasibility randomised controlled trial of Empowered Conversations: training family carers to enhance their relationships and communication with people living with dementia.
Communication difficulties can cause frustration, low mood, and stress for people living with dementia and their carer. Carers should be offered training on adapting their communication skills. However, it is not common for skills-based education to examine emotional aspects of care and the effect of dementia on relationships. The Empowered Conversations (EC) training course was developed in response to a gap in service provision and has been adapted to a virtual format (Zoom). It addresses the specific psychological, relationship, and communication needs of informal and family dementia carers. The primary aim of the study is to investigate the feasibility of conducting a multi-centre randomised controlled evaluation trial of EC. Secondary aims include exploring the acceptability of delivering the intervention online and examining the optimum way of establishing cost-effectiveness. The feasibility trial uses a pragmatic data-collector blind parallel two-group RCT design with two arms (EC intervention plus treatment as usual, and treatment as usual waitlist control). There will be a 2:1 allocation in favour of the EC-training intervention arm. 75 participants will complete baseline outcome measures exploring their role as a carer, including their physical and mental health, attitudes to caring, quality of life, and use of health and social care services. These will be repeated after six-months. Participants allocated to the treatment group who complete the course will be invited to participate in a qualitative interview discussing their experience of EC. The study will investigate recruitment pathways (including facilitators and barriers to recruitment), estimate retention levels and response rates to questionnaires, obtain additional evidence regarding proof of concept, and consider the most appropriate primary outcome measures and methods for evaluating cost-effectiveness. The results of the feasibility study will be used to inform the development of a multicentre randomised controlled trial in the United Kingdom. ISRCTN15261686 (02/03/2022).


Design and synthesis of (+)-discodermolide-paclitaxel hybrids leading to enhanced biological activity.
Potential binding modes of (+)-discodermolide at the paclitaxel binding site of tubulin have been identified by computational studies based on earlier structural and SAR data. Examination of the prospective binding modes reveal that the aromatic pocket occupied by the paclitaxel side chain is unoccupied by (+)-discodermolide. Based on these findings, a small library of (+)-discodermolide-paclitaxel hybrids have been designed and synthesized. Biological evaluation reveals a two- to eight-fold increase in antiproliferative activity compared to the parent molecule using the A549 and MCF-7 cancer cell lines.


[Experiences with digital luminescence radiography (DLR) in pediatric radiology].
X-ray examinations represent a variety of indications with different demands on exposure latitude, spatial and contrast resolution of screen-film-system combinations in paediatric radiography. The value of digital luminescent radiography (DLR) was compared to conventional x-ray examinations carried out with screen-film-systems, speed class 200, by analysing matched digital and conventional exposures in 200 abdominal, 600 skeletal and 300 chest examinations. The exposure of DLR was reduced to 50% of conventional exposure. Analysing the results in abdominal and skeletal radiography, DLR proved to be diagnostically equivalent to conventional radiography despite the reduction in exposure dose. DLR of the newborn chest compared to conventional x-ray studies was not always sufficient due to lower digital spatial resolution.


Estimating Metastatic Risk of Pancreatic Ductal Adenocarcinoma at Single-Cell Resolution.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by intra-tumoral heterogeneity, and patients are always diagnosed after metastasis. Thus, finding out how to effectively estimate metastatic risk underlying PDAC is necessary. In this study, we proposed scMetR to evaluate the metastatic risk of tumor cells based on single-cell RNA sequencing (scRNA-seq) data. First, we identified diverse cell types, including tumor cells and other cell types. Next, we grouped tumor cells into three sub-populations according to scMetR score, including metastasis-featuring tumor cells (MFTC), transitional metastatic tumor cells (TransMTC), and conventional tumor cells (ConvTC). We identified metastatic signature genes (MSGs) through comparing MFTC and ConvTC. Functional enrichment analysis showed that up-regulated MSGs were enriched in multiple metastasis-associated pathways. We also found that patients with high expression of up-regulated MSGs had worse prognosis. Spatial mapping of MFTC showed that they are preferentially located in the cancer and duct epithelium region, which was enriched with the ductal cells' associated inflammation. Further, we inferred cell-cell interactions, and observed that interactions of the ADGRE5 signaling pathway, which is associated with metastasis, were increased in MFTC compared to other tumor sub-populations. Finally, we predicted 12 candidate drugs that had the potential to reverse expression of MSGs. Taken together, we have proposed scMetR to estimate metastatic risk in PDAC patients at single-cell resolution which might facilitate the dissection of tumor heterogeneity.


Novel classification of knee osteoarthritis severity based on spatiotemporal gait analysis.
To describe a novel classification method for knee osteoarthritis (OA) based on spatiotemporal gait analysis. Gait analysis was initially performed on 2911 knee OA patients. Females and males were analyzed separately because of the influence of body height on spatiotemporal parameters. The analysis included the three stages of clustering, classification and clinical validation. Clustering of gait analysis to four groups was applied using the kmeans method. Two-thirds of the patients were used to create a simplified classification tree algorithm, and the model's accuracy was validated by the remaining one-third. Clinical validation of the classification method was done by the short form 36 Health Survey (SF-36) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires. The clustering algorithm divided the data into four groups according to severity of gait difficulties. The classification tree algorithm used stride length and cadence as predicting variables for classification. The correct classification accuracy was 89.5%, and 90.8% for females and males, respectively. Clinical data and number of total joint replacements correlated well with severity group assignment. For example, the percentages of total knee replacement (TKR) within 1 year after gait analysis for females were 1.4%, 2.8%, 4.1% and 8.2% for knee OA gait grades 1-4, respectively. Radiographic grading by Kellgren and Lawrence was found to be associated with the gait analysis grading system. Spatiotemporal gait analysis objectively classifies patients with knee OA according to disease severity. That method correlates with radiographic evaluation, the level of pain, function, number of TKR.


The synergistic effect of Au-COF nanosheets and artificial peroxidase Au@ZIF-8(NiPd) rhombic dodecahedra for signal amplification for biomarker detection.
Here, a new type of signal amplification strategy is proposed employing Au nanoparticle (AuNP)-functionalized covalent organic framework (Au-COF) nanosheets and AuNP functionalized ZIF-8(NiPd) (Au@ZIF-8(NiPd)) rhombic dodecahedra nanocomposites for sandwich electrochemical sensor construction. The peroxidase mimics Au@ZIF-8(NiPd) took the place of natural enzymes in enzyme-assisted amplification strategies, both acting as catalysts for H2O2 reduction for signal amplification, and serving as ideal nanocarriers for signal probe anchoring. The cancer biomarker thrombin (TB) was selected as the target. Thrombin binding aptamers (TBA 2) were fixed on Au@ZIF-8(NiPd), and the obtained TBA 2-Au@ZIF-8(NiPd) bioconjugates were employed as tracer labels, and TB was sandwiched between the tracer labels and capture probe TBA 1 which were immobilized on the Au-COF nanosheet modified electrode. Au-COFs with a high specific area, super electroconductivity, and uniformly distributed AuNPs were utilized as the electrode substrate to fix TBA 1. Exploiting the sandwich method, the proposed TB aptasensor exhibited a wide linear range of 0.1 pM to 20 nM with a low detection limit of 15 fM (S/N = 3). The ingenious sensing strategy enriched the application diversity of the artificial enzyme and showed promise in research and development of point-of-care diagnostics.


Anti-HLA antibodies in regenerative medicine stem cell therapy.
Research on stem cell therapies for regenerative medicine is progressing rapidly. Although the use of autologous stem cells is a tempting choice, there are several instances in which they are either defective or not available in due time. Allogenic stem cells derived from healthy donors presents a promising alternative. Whether autologous or allogenic, recent advances have proven that stem cells are not as immune privileged as they were thought. Therefore understanding the interactions of these cells with the recipient immune system is paramount to their clinical application. Transplantation of stem cells induces humoral as well as cellular immune response. This review focuses on the humoral response elicited by stem cells upon their administration and consequences on the survival and maintenance of the graft. Current transplantation identifies pre- and post-transplantation anti-HLA antibodies as immune rejection and cell signaling effectors. These two mechanisms are likely to operate similarly in the context of SC therapeutics. Ultimately this knowledge will help to propose novel strategies to mitigate the allogenic barriers. Immunogenetics selection of the donor cell and immunomonitoring are key factors to allow the implementation of regenerative stem cell in the clinics.


Swedish farmers attitudes, expectations and fears in relation to growing genetically modified crops.
This study evaluates a survey about Swedish farmers' attitude towards genetically modified (GM) crops, and their perception concerning potential benefits and drawbacks that cropping of an insect resistant (IR) GM variety would involve. The questions were "tick a box" choices, included in a yearly omnibus survey sent to 1000 Swedish farmers (68% response rate). The results showed that a majority of the farmers were negative, although almost one third claimed to be neutral to GM crops. The farmers recognized several benefits both in terms of agricultural production and for the environment, but they were also highly concerned about the consumers' unwillingness to buy GM products. Farmers perceived an increase in yield, but nearly as many farmers thought that there would be no benefits with growing an IR GM crop. Several differences in hopes and concerns of the farmers surveyed were revealed when they were divided in positive, neutral and negative groups. Farmers negative to GM were more concerned than positive farmers about IR GM crops being dangerous for humans, livestock or other organisms to consume. GM-positive farmers seemed to be most concerned about potential problems with growing a marketable crop and expensive seeds, but saw a reduced health risk to the grower, due to less use of pesticides, as a possible benefit. The results among the GM-neutral farmers were in most cases closely related to the positive farmers' choices, implying that they believe that there are advantages with growing an IR GM crop, but also fear potential drawbacks. This general uncertainty about GM IR crops may prevent them from accepting the new technology.


Drug Recognition Expert (DRE) examination characteristics of cannabis impairment.
The Drug Evaluation and Classification Program (DECP) is commonly utilized in driving under the influence (DUI) cases to help determine category(ies) of impairing drug(s) present in drivers. Cannabis, one of the categories, is associated with approximately doubled crash risk. Our objective was to determine the most reliable DECP metrics for identifying cannabis-driving impairment. We evaluated 302 toxicologically-confirmed (blood Δ(9)-tetrahydrocannabinol [THC] ≥1μg/L) cannabis-only DECP cases, wherein examiners successfully identified cannabis, compared to normative data (302 non-impaired individuals). Physiological measures, pupil size/light reaction, and performance on psychophysical tests (one leg stand [OLS], walk and turn [WAT], finger to nose [FTN], Modified Romberg Balance [MRB]) were included. Cases significantly differed from controls (p<0.05) in pulse (increased), systolic blood pressure (elevated), and pupil size (dilated). Blood collection time after arrest significantly decreased THC concentrations; no significant differences were detected between cases with blood THC <5μg/L versus ≥5μg/L. The FTN best predicted cannabis impairment (sensitivity, specificity, positive/negative predictive value, and efficiency ≥87.1%) utilizing ≥3 misses as the deciding criterion; MRB eyelid tremors produced ≥86.1% for all diagnostic characteristics. Other strong indicators included OLS sway, ≥2 WAT clues, and pupil rebound dilation. Requiring ≥2/4 of: ≥3 FTN misses, MRB eyelid tremors, ≥2 OLS clues, and/or ≥2 WAT clues produced the best results (all characteristics ≥96.7%). Blood specimens should be collected as early as possible. The frequently-debated 5μg/L blood THC per se cutoff showed limited relevance. Combined observations on psychophysical and eye exams produced the best cannabis-impairment indicators.


Reirradiation of glioblastoma through the use of a reduced dose rate on a tomotherapy unit.
Pulsed Reduced Dose Rate (PRDR) is a method of irradiation designed to minimize radiation-related toxicities in patients undergoing reirradiation for loco-regional reoccurrence of glioblastoma. PRDR delivers a standard 2 Gy fraction delivered on a conventional medical linear accelerator using conventional 3D conformal beam arrangements. To reduce the likelihood of normal tissue complications, radiation is delivered over ten 0.2 Gy sub-fractions with a 3 minute time interval between subfractions to give a maximal time averaged dose rate of 4 Gy/hr. However, a TomoTherapy unit has a fixed output rate of 8 Gy/min. If the dose per fraction is conventionally planned at less than 0.6 Gy/fraction, the result is a clinically unacceptable treatment plan. The method described in this paper involves a virtual grid style blocking scheme, where half of the beam angles are directionally blocked using 15 equally spaced segments surrounding the center of the image set. Ten patients treated using conventional PRDR with an average PTV volume of 353.3 ml were retrospectively re-planned using five techniques (standard 2 Gy fraction, 2 Gy in ten 0.2 Gy fractions without grid blocking, two grid patterns, and a combination plan incorporating both grids) and analyzed with conformation numbers (CN), homogeneity indexes (HI), and dose volumes to normal tissues. Plans were optimized using equal constraints and machine parameters. The grid method allowed for clinically acceptable treatment plans at 0.2 Gy with a treatment time < or = 3 min per subfraction. The average HI was slightly poorer for the combination plan versus the standard 2 Gy fraction plan (0.064 versus 0.027) and the CN was similar over all techniques (0.72 - 0.73) employed. Normal tissue dose volumes for each patient were also similar for each technique. Initial ion chamber measurements agree with predicted values for a 0.2 Gy subfraction. PRDR is deliverable on a TomoTherapy system using our virtual directional blocking method. Results can be slightly improved through the use of two grids alternated on a daily basis. The dose to normal structures for individual patients was similar for all methods.


Selectivity of terrestrial gastropod extinctions on an oceanic archipelago and insights into the anthropogenic extinction process.
Anthropogenic impacts have led to widespread extinctions of species on oceanic islands but the nature of many of these extinctions remains poorly known. Here we investigate extinction selectivities of terrestrial gastropods from the Ogasawara archipelago in the northwest Pacific, where anthropogenic threats have changed over time, shifting primarily from the effects of habitat loss to predation by a variety of different predators. Across all of the islands, extinct species had significantly smaller geographic ranges compared with species that are still alive, but among the surviving species, ranges of those that are currently declining due to human impacts do not differ significantly from those that are not threatened. Extinctions were selective with respect to spire index (SI) of shells, a trait of potential functional importance, but the relationship between body size and extinction vulnerability varied among extinction agents, some of which were strongly size selective, whereas others were not. Overall, whereas anthropogenic impacts have resulted in nonrandom losses of phenotypic diversity, the patterns of selectivity are complex, vary among islands, and with the type of threat. As extinction agents have changed historically, so has the pattern of loss. Because of the changing nature of anthropogenic impacts, resiliency to one type of threat does not guarantee long-term survival of species and future patterns of biodiversity loss on these islands are likely to be different from those in the past.


Phycomycosis caused by Basidiobolus haptosporus in two horses.
Basidiobolus haptosporus was isolated from a horse with a rapidly progressive ulcerative lesion of the ventral midline. The pathologic findings of an irregular line of yellow material composed of hyphae, eosinophils, and granulomatous inflammation between the superficial edematous tissue and the underlying muscle, and hyphae in tissue sections intimately surrounded by granular eosinophilic cuffs were considered diagnostic for this and one other case diagnosed retrospectively. Both horses were successfully treated by surgery and potassium iodide.


Measurement of support surface efficacy: pressure.
Two methods can be used to assess the relative pressure-relieving/pressure-reducing effects of clinical support surfaces. The interaction occurring at the interface between the human body and the support surface--known as the interface pressure--can be measured with an interface pressure system. Reactive hyperemia, the physiologic response to pressure, can be measured with thermography and laser Doppler flowmetry. Using mannequins and human subjects that represent typical body types in the older population, a protocol was developed for collecting data on the effects of support surfaces on interface pressure and reactive hyperemia.


Improved measurements of intracellular nitric oxide in intact microvessels using 4,5-diaminofluorescein diacetate.
4,5-Diaminofluorescein diacetate (DAF-2 DA) has been widely used for the measurement of nitric oxide (NO) in living cells and tissues. We previously established a method that demonstrated platelet activating factor (PAF)-induced endothelial NO production in intact venules using DAF-2 DA. In previous applications, the loading dye was removed from the extracellular space before NO measurements. However, in high permeability vessels, endothelial cells quickly released the accumulated intracellular DAF-2 after the washout, which compromises the NO measurement. The objective of this study was to investigate if the presence of DAF-2 DA during NO measurements could overcome the dye retention problem and enhance the sensitivity of NO detection. Experiments were conducted in individually perfused rat venules, and endothelial NO was measured using fluorescence imaging under basal and stimulated conditions with continuous perfusion of DAF-2 DA. Continuous dye perfusion was found to promote a relatively constant endothelial dye concentration in both normal and high permeability vessels throughout the experiment. With the use of this method, the basal and stimulated NO was quantified after endothelial DAF-2 concentrations reached a steady state. Our results showed enhanced sensitivity of detecting PAF-stimulated NO compared with a previous method. We also found that the hydrolyzed intracellular DAF-2, the precursor of DAF-2 triazole, contributed significantly to the measured fluorescence and that an appropriate subtraction of non-NO-dependent intracellular DAF-2 fluorescence is critical for the assessment of NO in living tissues. This method overcame the dye leakage problem, enhanced the sensitivity of NO detection, and improved NO quantification, demonstrating significant advantages over existing methodologies using DAF-2.


Single Percutaneous Tract Combined with Flexible Nephroscopy in the Management of Kidney Stones 2-4 cm: Better Options of Treatment Protocols.
To investigate the safety and efficacy of single percutaneous tract combined with flexible nephroscopy in the Management of 2-4 cm renal calculi. We retrospectively analysed the treatment data of patients with 2-4 cm renal calculi from June 2010 to June 2017. The data included 217 cases of percutaneous nephrolithotomy (PNL), 441 cases of retrograde intrarenal surgery (RIRS) and 217 cases of single-access percutaneous nephrolithotomy combined with flexible nephroscopy (PNCFN). The collected data were analyzed. A total of 875 cases were studied, with an average age of 42.35 ± 10.29 years. Group PNCFN showed the highest stone-free rates (SFRs)(73.7 vs 66.7 vs 80.2, P = .00), best patient satisfaction (89.84 vs 87.23 vs 92.29, P = .00). The length of stay was shorter in the RIRS group relative to the other two groups (5.22 vs 5.65 vs 3.72, P = .00). Haemoglobin decrease (> 10 g/L) was higher in group PNL than that in group RIRS and group PNCFN (P = .012). Hospitalization fees (RMB) were Increased in group PNCFN compared with that in group PNL and group RIRS (34563.45 vs 21334.69 vs 33343.16, P = .000). Treatment protocols of PNL decreased from 17.51% to 9.22%, those for RIRS from 5.22% to 17.69%, peaking at 2012, PNCFN from 8.29% to 15.67% showed a rapid growth trend. The percutaneous nephrolithotomy combined with flexible nephroscopy treatment on renal calculi of 2-4 cm was associated with higher stone-free rates and better patient satisfaction than RIRS and PNL.


"Low Testosterone Levels in Body Fluids Are Associated With Chronic Periodontitis".
There is a debate over the association between low testosterone levels in body fluids and the occurrence of chronic periodontitis (CP). The aim of the present systematic review was to assess whether low testosterone levels in body fluids reflect CP. In order to identify studies relevant to the focus question: "Is there a relationship between low testosterone levels in body fluids and CP?" an electronic search without time or language restrictions was conducted up to June 2016 in indexed databases using different keywords: periodontitis, chronic periodontitis, periodontal diseases, testosterone, and gonadal steroid hormones. A total of eight studies were included in the present systematic review. The number of study participants ranged from 24 to 1,838 male individuals with ages ranging from 15 to 95 years. Seven studies measured testosterone levels in serum, two studies in saliva, and one study in gingiva. Four studies reported a negative association between serum testosterone levels and CP. Two studies reported a positive association between decreased testosterone levels in serum and CP. Increased levels of salivary testosterone among patients with CP were reported in one study; whereas one study reported no significant difference in the concentration of salivary testosterone between patients with and without CP. One study identified significant increase in the metabolism of testosterone in the gingiva of patients with CP. Within the limits of the evidence available, the relationship between low testosterone levels and CP remains debatable and further longitudinal studies and control trials are needed.


Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow.
Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis. Here, we identified mechanosensitive genes in vivo through a genome-wide microarray study using mouse endothelial RNAs isolated from the flow-disturbed left and the undisturbed right common carotid artery. We found 62 and 523 genes that changed significantly by 12 hours and 48 hours after ligation, respectively. The results were validated by quantitative polymerase chain reaction for 44 of 46 tested genes. This array study discovered numerous novel mechanosensitive genes, including Lmo4, klk10, and dhh, while confirming well-known ones, such as Klf2, eNOS, and BMP4. Four genes were further validated for protein, including LMO4, which showed higher expression in mouse aortic arch and in human coronary endothelium in an asymmetric pattern. Comparison of in vivo, ex vivo, and in vitro endothelial gene expression profiles indicates that numerous in vivo mechanosensitive genes appear to be lost or dysregulated during culture. Gene ontology analyses show that disturbed flow regulates genes involved in cell proliferation and morphology by 12 hours, followed by inflammatory and immune responses by 48 hours. Determining the functional importance of these novel mechanosensitive genes may provide important insights into understanding vascular biology and atherosclerosis.


Liquid embolization material reduces the delivered radiation dose: clinical myth or reality?
To be radiopaque, BAVM embolization products must contain high-atomic-number materials, which may also attenuate photon beams delivered with radiosurgery. This "shielding effect" has been invoked to explain why radiation therapy may be less effective for previously embolized BAVMs. To evaluate the impact of embolization material on radiation dose, we measured and compared the dose delivered to the center of an AVM model, before and following embolization with various materials in a LINAC. Two in vitro AVM models were constructed by drilling interconnected tubular perforations in plastic water phantoms to simulate nidal vessels. Phantoms were designed to allow the positioning of a radiation detector at their center. One model was embolized with Onyx 18 and a second model, with a combination of Indermil, Lipiodol, tungsten powder, and Onyx 18. The radiation delivered was compared between embolized and nonembolized controls following irradiation with a standard 250-cGy dose. The mean dose of radiation delivered to the model embolized with Onyx alone was 244 ± 5 cGy before and 246 ± 5 cGy following embolization. The mean dose of radiation delivered to the model embolized with various agents was 242 ± 5 cGy before, and 254 ± 5 cGy after embolization. Embolic material did not reduce the radiation dose delivered by a LINAC to the center of our experimental BAVM models. The shielding effect may be compensated by scattered and reflected radiation.


Aortic stenosis: diagnosis and treatment.
Aortic stenosis is the most important cardiac valve disease in developed countries, affecting 3 percent of persons older than 65 years. Although the survival rate in asymptomatic patients with aortic stenosis is comparable to that in age- and sex-matched control patients, the average overall survival rate in symptomatic persons without aortic valve replacement is two to three years. During the asymptomatic latent period, left ventricular hypertrophy and atrial augmentation of preload compensate for the increase in afterload caused by aortic stenosis. As the disease worsens, these compensatory mechanisms become inadequate, leading to symptoms of heart failure, angina, or syncope. Aortic valve replacement should be recommended in most patients with any of these symptoms accompanied by evidence of significant aortic stenosis on echocardiography. Watchful waiting is recommended for most asymptomatic patients, including those with hemodynamically significant aortic stenosis. Patients should be educated about symptoms and the importance of promptly reporting them to their physicians. Serial Doppler echocardiography is recommended annually for severe aortic stenosis, every one or two years for moderate disease, and every three to five years for mild disease. Cardiology referral is recommended for all patients with symptomatic aortic stenosis, those with severe aortic stenosis without apparent symptoms, and those with left ventricular dysfunction. Many patients with asymptomatic aortic stenosis have concurrent cardiac conditions, such as hypertension, atrial fibrillation, and coronary artery disease, which should also be carefully managed.


Radiation therapy for melanoma brain metastases: a systematic review.
Radiation therapy (RT) for melanoma brain metastases, delivered either as whole brain radiation therapy (WBRT) or as stereotactic radiosurgery (SRS), is an established component of treatment for this condition. However, evidence allowing comparison of the outcomes, advantages and disadvantages of the two RT modalities is scant, with very few randomised controlled trials having been conducted. This has led to considerable uncertainty and inconsistent guideline recommendations. The present systematic review identified 112 studies reporting outcomes for patients with melanoma brain metastases treated with RT. Three were randomised controlled trials but only one was of sufficient size to be considered informative. Most of the evidence was from non-randomised studies, either specific treatment series or disease cohorts. Criteria for determining treatment choice were reported in only 32 studies and the quality of these studies was variable. From the time of diagnosis of brain metastasis, the median survival after WBRT alone was 3.5 months (IQR 2.4-4.0 months) and for SRS alone it was 7.5 months (IQR 6.7-9.0 months). Overall patient survival increased over time (pre-1989 to 2015) but this was not apparent within specific treatment groups. These survival estimates provide a baseline for determining the incremental benefits of recently introduced systemic treatments using targeted therapy or immunotherapy for melanoma brain metastases.


An e-health intervention for increasing diabetes knowledge in African Americans.
An evidence-based e-health program, eCare We Care, was developed to disseminate information on diabetes management through web-based interactive tutorials. This study examined the effect of the eCare We Care program on diabetes knowledge development in African American adults with low diabetes literacy. Forty-six African American adults with type 1 or type 2 diabetes and low diabetes literacy were recruited from two health-care centres in eastern Winston Salem, North Carolina. The eCare We Care program included four weekly sessions: introduction to diabetes; eye complications; foot care; and meal planning. Significant differences in scores on the diabetes knowledge survey were demonstrated between the eCare We Care program participants and the comparison group. Study findings indicate the eCare We Care program is more effective in improving diabetes knowledge of African American adults with low diabetes literacy than paper-based, text-only tutorials. The eCare We Care program can be an effective educational strategy for improving diabetes knowledge and decreasing diabetes disparities among African American adults.


Laser therapy in cataract surgery.
Since the development of ultrasound phacoemulsification more than 25 years ago, cataract surgery has changed dramatically. One of the major changes in cataract surgery has been the research into the use of laser for the removal of cataracts. To date, both ultraviolet and infrared wavelengths have been studied, with the infrared showing more promise. The ultraviolet end of the spectrum has shown promise, but concerns with safety have hindered its progress. An infrared laser device developed by Dodick has been used successfully for the removal of cataracts under an Investigational Device Exemption from the Food and Drug Administration and a second infrared laser developed by Colvard should be approved soon. These developments have brought us a step closer to realizing the dream of laser cataract surgery.


Preclinical Alzheimer disease and risk of falls.
We determined the rate of falls among cognitively normal, community-dwelling older adults, some of whom had presumptive preclinical Alzheimer disease (AD) as detected by in vivo imaging of fibrillar amyloid plaques using Pittsburgh compound B (PiB) and PET and/or by assays of CSF to identify Aβ₄₂, tau, and phosphorylated tau. We conducted a 12-month prospective cohort study to examine the cumulative incidence of falls. Participants were evaluated clinically and underwent PiB PET imaging and lumbar puncture. Falls were reported monthly using an individualized calendar journal returned by mail. A Cox proportional hazards model was used to test whether time to first fall was associated with each biomarker and the ratio of CSF tau/Aβ₄₂ and CSF phosphorylated tau/Aβ₄₂, after adjustment for common fall risk factors. The sample (n = 125) was predominately female (62.4%) and white (96%) with a mean age of 74.4 years. When controlled for ability to perform activities of daily living, higher levels of PiB retention (hazard ratio = 2.95 [95% confidence interval 1.01-6.45], p = 0.05) and of CSF biomarker ratios (p < 0.001) were associated with a faster time to first fall. Presumptive preclinical AD is a risk factor for falls in older adults. This study suggests that subtle noncognitive changes that predispose older adults to falls are associated with AD and may precede detectable cognitive changes.


Computer vision vs. spectrofluorometer-assisted detection of common nitro-explosive components with bola-type PAH-based chemosensors.
Computer vision (CV) algorithms are widely utilized in imaging processing for medical and personal electronics applications. In sensorics CV can provide a great potential to quantitate chemosensors' signals. Here we wish to describe a method for the CV-assisted spectrofluorometer-free detection of common nitro-explosive components, e.g. 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT), by using polyaromatic hydrocarbon (PAH, PAH = 1-pyrenyl or 9-anthracenyl) - based bola-type chemosensors. The PAH components of these chemical bolas are able to form stable, bright emissive in a visual wavelength region excimers, which allows their use as extended matrices of the RGB colors after imaging and digital processing. In non-polar solvents, the excimers have poor chemosensing properties, while in aqueous solutions, due to the possible micellar formation, these excimers provide "turn-off" fluorescence detection of DNT and TNT in the sub-nanomolar concentrations. A combination of these PAH-based fluorescent chemosensors with the proposed CV-assisted algorithm offers a fast and convenient approach for on-site, real-time, multi-thread analyte detection without the use of fluorometers. Although we focus on the analysis of nitro-explosives, the presented method is a conceptual work describing a general use of CV for quantitative fluorescence detection of various analytes as a simpler alternative to spectrofluorometer-assisted methods.


The sources of extracellular potassium accumulation in the CA1 region of hippocampal slices.
To estimate the relative contributions of pre- and postsynaptic elements, and of synaptic and action potential-related currents, to the elevation of interstitial potassium ([K+]o) that occurs during neural activation, we measured [K+]o and focal electrical potential (Vec) during ortho- and antidromic stimulation, before and after blocking synaptic transmission, in the CA1 region of hippocampal tissue slices in vitro. Single stimulus pulses could cause delta [K+]o as large as 0.25 mM in stratum (st.) pyramidale and 0.27 mM in st. radiatum; stimulus trains could cause delta [K+]o as large as 10.5 mM in st. pyramidale and 6.25 mM in st. radiatum. Stimulus trains also caused negative Vec shifts; these shifts were related in a linear fashion to delta [K+]o. For a given increase in [K+]o, the change in Vec was greater in st. radiatum than in st. pyramidale. In st. pyramidale, the delta [K+]o evoked by antidromic stimulation was 65% of the delta [K+]o evoked by orthodromic stimulation (with equal population spike amplitudes). Blockade of synaptic transmission by removal of Ca2+ reduced orthodromically evoked delta [K+]o in st. radiatum by 52%; delta [K+]o in st. pyramidale was abolished. Removal of Ca2+ caused an 11% decrease in the delta [K+]o evoked in st. pyramidale by antidromic stimulation. We conclude that in the layer of dendritic trees (st. radiatum), approximately half of the K+ ions released into the interstitial space during orthodromic stimulation come from presynaptic terminals, with the remainder probably resulting from the ion currents of postsynaptic potentials. Among the pyramidal cell bodies (st. pyramidale), almost all of the excess K+ is released by action potential currents.


Misdiagnosis of Rheumatoid Arthritis in a Long-Term Cohort of Early Arthritis Based on the ACR-1987 Classification Criteria.
Correct diagnosis of early rheumatoid arthritis (RA) is essential for optimal treatment choices. No pathognomonic test is available, and diagnosis is based on classification criteria, which can result in misdiagnosis. Here, we examined the differences between actual and misdiagnosed RA cases in a long-term cohort of patients included based on the ACR-1987 classification criteria. Patients in the BARFOT (Better Anti-Rheumatic PharmacOTherapy) cohort (n=2543) with at least four follow-up visits during the initial 5 years from enrolment were assessed, and a change in diagnosis was reported by the treating rheumatologist. The groups were analysed with respect to the individual classification criteria, antibodies to citrullinated proteins (ACPA), disease activity (DAS28) and radiographic changes from inclusion up to 2 years. Forty-five patients (1.8%) were misdiagnosed (RA-change group). When compared to those in the RA-change group, the patients who kept their diagnosis (RA-keep) were more often RF positive (64% vs 21%, p<0.001) or ACPA positive (59% vs 8%, p<0.001). They were also more likely to fulfil more than four ACR-1987 criteria (64% vs 33%, p<0.001) and to have radiographic changes at inclusion (RA-keep 27% vs RA-change 12%, p=0.04). The groups had a similar evolution of DAS28 and its components as well as of radiological joint destruction. Diagnosis of RA according to the ACR-1987 criteria had a high precision in this long-term cohort. A diagnosis of RA should be re-evaluated in patients who do not fulfil more than four ACR-1987 criteria especially in patients negative for RF.


Compromised trigemino-coerulean coupling in migraine sensitization can be prevented by blocking beta-receptors in the locus coeruleus.
Migraine is a disabling neurological disorder, characterized by recurrent headaches. During migraine attacks, individuals often experience sensory symptoms such as cutaneous allodynia which indicates the presence of central sensitization. This sensitization is prevented by oral administration of propranolol, a common first-line medication for migraine prophylaxis, that also normalized the activation of the locus coeruleus (LC), considered as the main origin of descending noradrenergic pain controls. We hypothesized that the basal modulation of trigeminal sensory processing by the locus coeruleus is shifted towards more facilitation in migraineurs and that prophylactic action of propranolol may be attributed to a direct action in LC through beta-adrenergic receptors. We used simultaneous in vivo extracellular recordings from the trigeminocervical complex (TCC) and LC of male Sprague-Dawley rats to characterize the relationship between these two areas following repeated meningeal inflammatory soup infusions. Von Frey Hairs and air-puff were used to test periorbital mechanical allodynia. RNAscope and patch-clamp recordings allowed us to examine the action mechanism of propranolol. We found a strong synchronization between TCC and LC spontaneous activities, with a precession of the LC, suggesting the LC drives TCC excitability. Following repeated dural-evoked trigeminal activations, we observed a disruption in coupling of activity within LC and TCC. This suggested an involvement of the two regions' interactions in the development of sensitization. Furthermore, we showed the co-expression of alpha-2A and beta-2 adrenergic receptors within LC neurons. Finally propranolol microinjections into the LC prevented trigeminal sensitization by desynchronizing and decreasing LC neuronal activity. Altogether these results suggest that trigemino-coerulean coupling plays a pivotal role in migraine progression, and that propranolol's prophylactic effects involve, to some extent, the modulation of LC activity through beta-2 adrenergic receptors. This insight reveals new mechanistic aspects of LC control over sensory processing.


Prenatal cocaine exposure and child development: what do we know and what do we do?
The literature remains unclear about the effects of prenatal cocaine exposure on child development. Meanwhile, the implications for public policy and treatment and for our scientific understanding of the toxicity of cocaine are substantial. In this article we describe; (1) our current understanding of the effects of prenatal cocaine use and child outcome, (2) the issues that need to be investigated, and (3) implications for treatment of cocaine exposed children. Findings from our database of the published literature shows that our knowledge is still limited, scattered, and compromised by methodological problems that mitigate any conclusions about whether or not or how prenatal cocaine exposure affects child outcome. The cocaine problem is more complicated than first envisioned--it is a multifactorial problem including the use of other drugs, parenting, and environmental lifestyle issues. However, we also show that, even though the effects may be more subtle than initially anticipated, prenatal cocaine exposure will substantially increase in the number of school age children who will need special education services. Clinicians working with these children and families need to be prepared to address psychosocial and environmental issues, as well as developmental performance, in order to optimize their assessment and intervention.


Skull metastasis from thyroid follicular carcinoma with difficult diagnosis of the primary lesion.
A 57-year-old male patient presented with an immobile ellipsoid mass of 6-cm diameter in the right occipitoparietal region. Cranial computed tomography showed the mass with dense contrast enhancement causing bone destruction. After embolization of the mass, total resection was performed. Histological examination showed the mass had a capsule, with no invasion of the dura mater or dermis, and the follicles of various sizes covered with mono-lined thyrocytes were full of colloid. Immunohistochemical examination showed positive staining for thyroglobulin. Postoperatively, levels of thyroid hormones were normal, and thyroid ultrasonography and technetium-99m scintigraphy showed no abnormalities. Fine needle aspiration biopsy performed at various locations of the thyroid gland revealed no atypical thyroid cells. Whole body technetium-99m scintigraphy found no abnormal bone involvement. The histological evidence was suggestive of follicular carcinoma metastasis. Surgical treatment was planned for the thyroid gland, but the patient did not consent. Two years later, the patient presented with the pain and sensitivity in the sacrum, the right iliac wing, and the right caput femoris. Computed tomography revealed lytic lesions in these areas. Bone metastases were identified. Whole body scintigraphy showed increased activity in these regions, but the cranium and all other tissues were normal. The patient underwent total thyroidectomy under a diagnosis of follicular carcinoma. The present case of a lytic skull lesion associated with normal thyroid tissue on admission but finally treated as follicular thyroid cancer emphasizes the difficulty in histological discrimination of follicular carcinoma from normal thyroid tissue.


Postnatal development of the amygdala: A stereological study in macaque monkeys.
Abnormal development of the amygdala has been linked to several neurodevelopmental disorders, including schizophrenia and autism. However, the postnatal development of the amygdala is not easily explored at the cellular level in humans. Here we performed a stereological analysis of the macaque monkey amygdala in order to characterize the cellular changes underlying its normal structural development in primates. The lateral, basal, and accessory basal nuclei exhibited the same developmental pattern, with a large increase in volume between birth and 3 months of age, followed by slower growth continuing beyond 1 year of age. In contrast, the medial nucleus was near adult size at birth. At birth, the volume of the central nucleus was half of the adult value; this nucleus exhibited significant growth even after 1 year of age. Neither neuronal soma size, nor neuron or astrocyte numbers changed during postnatal development. In contrast, oligodendrocyte numbers increased substantially, in parallel with an increase in amygdala volume, after 3 months of age. At birth, the paralaminar nucleus contained a large pool of immature neurons that gradually developed into mature neurons, leading to a late increase in the volume of this nucleus. Our findings revealed that distinct amygdala nuclei exhibit different developmental profiles and that the amygdala is not fully mature for some time postnatally. We identified different periods during which pathogenic factors might lead to the abnormal development of distinct amygdala circuits, which may contribute to different human neurodevelopmental disorders associated with alterations of amygdala structure and functions.


170 degrees wide-angle colonoscope: effect on efficiency and miss rates.
Small polyps are routinely missed during colonoscopy even with careful examination. To determine and compare endoscopic efficiency and polyp miss rate between a prototype 170 degrees wide-angle (WA) colonoscope and a standard (S) colonoscope. Two consecutive same-day colonoscopies were performed in 50 patients with intact colons. The patients were randomized to undergo the first colonoscopy with either the prototype WA 170 degrees angle of view colonoscope or an S adult 140 degrees angle of view colonoscope. The mean time for insertion was 2.09 (1.09) min versus 2.53 (1.47) min (p= 0.002) for the WA colonoscope and the S colonoscope, respectively. Similarly, the mean time for examination during withdrawal was shorter with the WA colonoscope (4.98 (0.94) vs 5.74 (1.12) min; p < 0.0001). The mean insertion time for the second examination was shorter than the insertion time for the first examination, irrespective of the colonoscope (p= 0.006). However, the withdrawal times were not significantly different between the first and second examinations (p= 0.11). The miss rate for all polyps with the WA colonoscope (19%) was similar to the miss rate with the S colonoscope (27%; p= 0.19). The miss rates for adenomas with the WA (10/33; 30.3%) and the S scope (15/50; 30%) were similar (p= 0.98). The use of the WA colonoscope was associated with a reduction in insertion time to the cecum, as well as examination time during withdrawal. No evidence was found that the accuracy of the two colonoscopes differs.


Mesh overlap for ventral hernia repair in current practice.
Sufficient overlap of mesh beyond the borders of a ventral hernia helps prevent hernia recurrence. Guidelines from the European Hernia Society and American Hernia Society recommend ≥ 2 cm overlap for open repair of < 1-cm hernias, ≥ 3-cm overlap for open repair of 1-4-cm hernias, ≥ 5-cm overlap for open repair of > 4-cm hernias, and ≥ 5-cm overlap for all laparoscopic ventral hernia repairs. We evaluated whether current practice reflects this guidance. We used the Michigan Surgical Quality Collaborative Hernia Registry to evaluate patients who underwent elective ventral and umbilical hernia repair between 2020 and 2022. Mesh overlap was calculated as [(width of mesh - width of hernia)/2]. The main outcome was "sufficient overlap," defined based on published EHS and AHS guidelines. Explanatory variables included patient, operative, and hernia characteristics. The main analysis was a multivariable logistic regression to evaluate the association between explanatory variables and sufficient mesh overlap. 4178 patients underwent ventral hernia repair with a mean age of 55.2 (13.9) years, 1739 (41.6%) females, mean body mass index (BMI) of 33.1 (7.2) kg/m2, and mean hernia width of 3.7 (3.4) cm. Mean mesh overlap was 3.7 (2.5) cm and ranged from - 5.5 to 21.4 cm. Only 1074 (25.7%) ventral hernia repairs had sufficient mesh overlap according to published guidelines. Operative factors associated with increased odds of sufficient overlap included myofascial release (adjusted odds ratio [aOR] 5.35 [95% CI 4.07-7.03]), minimally invasive approach (aOR 1.86 [95% CI 1.60-2.17]), and onlay mesh location (aOR 1.31 [95% CI 1.07-1.59]). Patient factors associated with increased odds of sufficient overlap included prior hernia repair (aOR 1.59 [95% CI 1.32-1.92]). Although sufficient mesh overlap is recommended to prevent ventral hernia recurrence, only a quarter of ventral hernia repairs in a state-wide cohort of patients had sufficient overlap according to evidence-based guidelines. Factors strongly associated with sufficient overlap included myofascial release, mesh type, and laparoscopic repair.


Nucleolar cycle and its correlation with chromatoid bodies in the Tilapia rendalli (Teleostei, Cichlidae) spermatogenesis.
The aim of this study was: (1) to monitor the nucleolar material distribution using cytological and cytochemical techniques and ultrastructural analysis; and (2) to compare the nucleolar material distribution with the formation of the chromatoid body (CB) in the germ epithelium of Tilapia rendalli. Nucleolar fragmentation occurred during the leptotene of prophase I and nucleolus reorganization occurred in the early spermatid nucleus. The area of the early spermatid nucleolus was significantly smaller than that of the spermatogonia nucleolus. Ultrastructural analysis showed an accumulation of nuages, which form the CB, before nucleolar fragmentation in the spermatogonia cytoplasm. The CB was observed in association with mitochondrial clusters in the cytoplasm of primary spermatocytes, as well as in those of initial and later spermatids. In conclusion, the nucleolus seems to be related to CB formation during spermatogenesis of T. rendalli, because at the moment of nucleolus fragmentation in the primary spermatocytes, the CB reaches its largest area and it is able to complete important functions during spermatogenesis. The reorganized nucleolus of the initial spermatids has a lower area due several factors, one of which is the probable migration of nucleolar fragments from the nucleus to the cytoplasm, therefore playing a role in CB formation.


Observation of the presuperfluid regime in a two-dimensional Bose gas.
In complementary images of coordinate-space and momentum-space density in a trapped 2D Bose gas, we observe the emergence of presuperfluid behavior. As phase-space density ρ increases toward degenerate values, we observe a gradual divergence of the compressibility κ from the value predicted by a bare-atom model, κ(ba). κ/κ(ba) grows to 1.7 before ρ reaches the value for which we observe the sudden emergence of a spike at p = 0 in momentum space. Momentum-space images are acquired by means of a 2D focusing technique. Our data represent the first observation of non-mean-field physics in the presuperfluid but degenerate 2D Bose gas.


5-HT(3) receptors, alcohol and aggressive behavior in mice.
Alcohol is a positive modulator at the 5-HT(3) receptor, which has been implicated in alcohol drinking, anxiety and aggression. The reported experiments explored the role of the 5-HT(3) receptor in aggressive behavior and alcohol-heightened aggression. Male, CFW mice were trained to self-administer 1.0 g/kg of alcohol, after which they confronted an intruder. Half of the CFW mice exhibited consistently increased aggressive behavior after alcohol and were designated as showing alcohol-heightened aggression, the others showed no increase and were designated as showing alcohol non-heightened aggression. The 5-HT(3) antagonist, ondansetron (0.01-1.0 mg/kg), significantly reduced aggression in both groups of CFW mice without affecting non-aggressive behaviors. Zacopride also reduced aggression effectively in both groups of mice, but at high doses began to affect walking. Male B6SJL/F2 transgenic 5-HT(3) over-expressing mice (TG) and wild-type mice (WT) were tested for aggressive behavior in their home cage. In those individuals that fought in tests of resident-intruder aggression, no differences were found in aggression after alcohol intake. In tests of aggression without alcohol intake, zacopride reduced aggression in both TG and WT mice at a dose of 56 mg/kg. Antagonism of 5-HT(3) receptors shows promising anti-aggressive effects, although these effects depend on the genetic background of the mice.


Grid based evaluation of a liver segmentation method for contrast enhanced abdominal MRI.
Recent developments in MRI contrast agents give new perspectives in radiological diagnosis and therapy planning, but require specific image analysis methods. By employment of an academic research grid, we are currently validating and optimizing a recently developed fully automatic method for liver segmentation in Gd-EOB enhanced MRI. The grid enables extensive parameter scans and evaluation against expert's reference segmentation. The implementation layout and so far reached results are presented. Furthermore, experiences made in the production phase and consequences resulting for the exploitation of publicly funded research grids for Healthgrid applications are given.


Increased dependence of leucine in posttraumatic sepsis: leucine/tyrosine clearance ratio as an indicator of hepatic impairment in septic multiple organ failure syndrome.
The body clearance of 10 plasma amino acids (AA) was determined from the rate of compared muscle-released AA and AA administered by infusion of total parenteral nutrition (TPN) compared to their estimated extracellular (ECW) pool in patients with multiple trauma with (n = 10) or without (n = 16) sepsis at 8-hour intervals. In both nonseptic and septic trauma, increasing TPN increased the mean clearance rate of all infused AA. When the individual AA clearance rates were normalized by the total AA infusion rate, regression-covariance analysis revealed that patients with sepsis had relatively impaired clearances of alanine (p less than 0.01) and methionine, proline, phenylalanine, and tyrosine p less than 0.05 for all). In contrast, the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p less than 0.05) in trauma patients with sepsis than in those without. At any AA infusion rate, compared with surviving patients with sepsis (p less than 0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine. The clearance ratio of leucine/tyrosine was increased in MOFS at any AA infusion rate (p less than 0.0001), was an indicator of severity, and, if persistent, was a manifestation of a fatal outcome. Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake and oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops.


New technique for gene transfection using laser irradiation.
We have developed a gene transfection system using laser beams. The principle of this procedure is that a small hole is made in a cell membrane by pulse laser irradiation, and a gene contained in a medium is transferred into the cytoplasm through the hole. This hole disappears immediately with the application of laser irradiation of the appropriate power. A pulse-wave Nd:YAG laser with a wavelength of 355 nm was used to make a hole in a cell membrane. To trap a cell, a continuous-wave Nd:YAG laser with a wavelength of 1015 nm was used. Plasmids that encode the enhanced green fluorescent protein (EGFP) gene were contained in a medium and transferred to HuH-7 and NIH/3T3 cells with pulse laser irradiation. We evaluated transfection efficiency on the basis of the number of cells that expressed EGFP. Stimulatory protein 2 cells in suspension were fixed using a trapping laser and the neomycin-resistance gene was transfected by pulse laser irradiation. We examined cell proliferation in the selection medium. Cells that expressed EGFP were recognized in the group that was irradiated by pulse laser. No cells expressed EGFP without irradiation. Transfection efficiency was approximately 10% at a plasmid concentration of 10.0 microg/mL. At concentrations greater than 20 microg/mL, the transfection rate reached a plateau. We also successfully transfected neomycin-resistance genes to cells floating in suspension after fixation that was achieved with trapping laser irradiation. This method enables us to transfect targeted cells, ie, cells in suspension as well as attached cells, with a simple technique that does not involve harmful vectors. The present method is very useful for gene transfection in cellular biotechnology.


Left ventricle and arteries: structure, function, hormones, and disease.
The observation in the 1970s that the performance of the dysfunctional left ventricle was under the influence of aortic impedance led us to exploration of the role of the renin-angiotensin system and other hormonal systems in the progression of heart failure. The apparent efficacy of vasodilator drugs led to the first randomized, controlled trial in heart failure that demonstrated that all impedance-lowering drugs did not exert the same long-term benefit. Differences on the structural remodeling process in the myocardium and arterial vasculature were shown to account for the differential long-term response. We now recognize that the remodeling process in the left ventricle may be inhibited by nitrates, converting enzyme inhibitors, and beta-blockers, and this growth process leads to adverse outcomes. The impedance load on the left ventricle is influenced by vascular remodeling that also may be inhibited by drugs such as converting enzyme inhibitors. Thus, progression of cardiovascular disease is largely a consequence of structural changes that are hormonally mediated and may be inhibited by drug therapy.


Assessing attentional biases with stuttering.
Many adults who stutter presenting for speech treatment experience social anxiety disorder. The presence of mental health disorders in adults who stutter has been implicated in a failure to maintain speech treatment benefits. Contemporary theories of social anxiety disorder propose that the condition is maintained by negative cognitions and information processing biases. Consistent with cognitive theories, the probe detection task has shown that social anxiety is associated with an attentional bias to avoid social information. This information processing bias is suggested to be involved in maintaining anxiety. Evidence is emerging for information processing biases being involved with stuttering. This study investigated information processing in adults who stutter using the probe detection task. Information processing biases have been implicated in anxiety maintenance in social anxiety disorder and therefore may have implications for the assessment and treatment of stuttering. It was hypothesized that stuttering participants compared with control participants would display an attentional bias to avoid attending to social information. Twenty-three adults who stutter and 23 controls completed a probe detection task in which they were presented with pairs of photographs: a face displaying an emotional expression-positive, negative or neutral-and an everyday household object. All participants were subjected to a mild social threat induction being told they would speak to a small group of people on completion of the task. The stuttering group scored significantly higher than controls for trait anxiety, but did not differ from controls on measures of social anxiety. Non-socially anxious adults who stutter did not display an attentional bias to avoid looking at photographs of faces relative to everyday objects. Higher scores on trait anxiety were positively correlated with attention towards photographs of negative faces. Attentional biases as assessed by the probe detection task may not be a characteristic of non-socially anxious adults who stutter. A vigilance to attend to threat information with high trait anxiety is consistent with findings of studies using the emotional Stroop task in stuttering and social anxiety disorder. Future research should investigate attentional processing in people who stutter who are socially anxious. It will also be useful for future studies to employ research paradigms that involve speaking. Continued research is warranted to explore information processing and potential biases that could be involved in the maintenance of anxiety and failure to maintain the benefits of speech treatment outcomes.


MiR-24 alleviates cardiomyocyte apoptosis after myocardial infarction via targeting BIM.
Ischemia hypoxia induces cardiomyocyte (CM) apoptosis in the process of acute myocardial infarction (AMI). It was showed that pro-apoptosis factor BIM participates in regulating tumor cell apoptosis under ischemia or hypoxia condition, while its role in CM apoptosis after AMI is still unclear. It was revealed that miR-24 expression was significantly reduced in myocardial tissue after AMI. Bioinformatics analysis exhibits that miR-24 is targeted to the 3'-UTR of BIM. This study aims to investigate the role of miR-24 in mediating BIM expression and CM apoptosis. Dual-luciferase assay was used to confirm the targeted regulation between miR-24 and BIM. Cells were cultured under ischemia hypoxia for 12 h after transfection for 48 h. Cell apoptosis was tested by using flow cytometry. The caspase activity was detected by using spectrophotometry. Wistar rats were divided into four groups, including Sham, AMI, AMI + agomir-control, and AMI + agomir-24 groups. Cardiac function was evaluated by using echocardiography. CM apoptosis was determined by using TUNEL. Infarction area was measured by using evans blue staining. MiR-24 targeted suppressed BIM expression. MiR-24 mimic and/or si-BIM transfection significantly declined the BIM expression, inhibited caspase-9 and caspase-3 activities, and reduced cell apoptosis in H9C2 cells. MiR-24 expression was decreased, while BIM levels were up-regulated in myocardium after AMI. Agomir-24 injection down-regulated the BIM expression in myocardium, reduced CM apoptosis, narrowed infarction area, and improved cardiac function in rats. MiR-24 was reduced, whereas BIM was enhanced in the CM after AMI. MiR-24 up-regulation plays a critical role in decreasing BIM expression, reducing CM apoptosis, and improving cardiac function after AMI.